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Sample records for reduces net protein

  1. Resistance training reduces whole-body protein turnover and improves net protein retention in untrained young males.

    Science.gov (United States)

    Hartman, Joseph W; Moore, Daniel R; Phillips, Stuart M

    2006-10-01

    It is thought that resistance exercise results in an increased need for dietary protein; however, data also exists to support the opposite conclusion. The purpose of this study was to determine the impact of resistance exercise training on protein metabolism in novices with the hypothesis that resistance training would reduce protein turnover and improve whole-body protein retention. Healthy males (n = 8, 22 +/- 1 y, BMI = 25.3 +/- 1.8 kg.m(-2)) participated in a progressive whole-body split routine resistance-training program 5d/week for 12 weeks. Before (PRE) and after (POST) the training, oral [15N]-glycine ingestion was used to assess nitrogen flux (Q), protein synthesis (PS), protein breakdown (PB), and net protein balance (NPB = PS-PB). Macronutrient intake was controlled over a 5d period PRE and POST, while estimates of protein turnover and urinary nitrogen balance (N(bal) = N(in) - urine N(out)) were conducted. Bench press and leg press increased 40% and 50%, respectively (p training-induced increases in both NPB (PRE = 0.22 +/- 0.13 g.kg(-1).d(-1); POST = 0.54 +/- 0.08 g.kg(-1).d(-1)) and urinary nitrogen balance (PRE = 2.8 +/- 1.7 g N.d(-1); POST = 6.5 +/- 0.9 g N.d(-1)) were observed. A program of resistance training that induced significant muscle hypertrophy resulted in reductions of both whole-body PS and PB, but an improved NPB, which favoured the accretion of skeletal muscle protein. Urinary nitrogen balance increased after training. The reduction in PS and PB and a higher NPB in combination with an increased nitrogen balance after training suggest that dietary requirements for protein in novice resistance-trained athletes are not higher, but lower, after resistance training.

  2. Administration of structured lipid composed of MCT and fish oil reduces net protein catabolism in enterally fed burned rats.

    Science.gov (United States)

    Teo, T C; DeMichele, S J; Selleck, K M; Babayan, V K; Blackburn, G L; Bistrian, B R

    1989-01-01

    The effects of enteral feeding with safflower oil or a structured lipid (SL) derived from 60% medium-chain triglyceride (MCT) and 40% fish oil (MCT/fish oil) on protein and energy metabolism were compared in gastrostomy-fed burned rats (30% body surface area) by measuring oxygen consumption, carbon dioxide production, nitrogen balance, total liver protein, whole-body leucine kinetics, and rectus muscle and liver protein fractional synthetic rates (FSR, %/day). Male Sprague-Dawley rats (195 +/- 5g) received 50 ml/day of an enteral regimen containing 50 kcal, 2 g amino acids, and 40% nonprotein calories as lipid for three days. Protein kinetics were estimated by using a continuous L-[1-14C] leucine infusion technique on day 2. Thermally injured rats enterally fed MCT/fish oil yielded significantly higher daily and cumulative nitrogen balances (p less than or equal to 0.025) and rectus muscle (39%) FSR (p less than or equal to 0.05) when compared with safflower oil. MCT/fish oil showed a 22% decrease (p less than or equal to 0.005) in per cent flux oxidized and a 7% (p less than or equal to 0.05) decrease in total energy expenditure (TEE) versus safflower oil. A 15% increase in liver FSR was accompanied by a significant elevation (p less than or equal to 0.025) in total liver protein with MCT/fish oil. This novel SL shares the properties of other structured lipids in that it reduces the net protein catabolic effects of burn injury, in part, by influencing tissue protein synthetic rates. The reduction in TEE is unique to MCT/fish oil and may relate to the ability of fish oil to diminish the injury response. PMID:2500898

  3. AFM characterization of protein net formation on a fibrous medium

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    Assis O.B.G.

    2000-01-01

    Full Text Available Lysozyme protein net is set on a glass fiber support using the self-assembly technique. Enzymatic film formation is followed by surface imaging via atomic force microscopy (AFM. Change in roughness as a function of deposition time is used as an indirect indicator of film formation. The objective was to form a protein film that would have no effect on the permeability of the medium, aiming at its application as a bioactive membrane or reactor suitable for bacteria and chemical interactions in aqueous media.

  4. The Potential for Forestry to Reduce Net CO2 Emissions

    International Nuclear Information System (INIS)

    Eriksson, Erik

    2006-01-01

    Forestry may have an important role to play in attempts to reduce atmospheric CO 2 levels, since countries may choose to account for forest management activities to fulfil their commitments under the Kyoto Protocol. However, the effectiveness of such efforts may depend on the forest management strategies applied. This thesis is based on four separate studies in which the potential for forest management strategies to decrease net CO 2 emissions was considered. Long-term field experiments and models were used to: evaluate the impact of different thinning regimes; study broad-leaved stands growing on abandoned farmland with different rotation lengths; predict the effects of using different rotation lengths on carbon accumulation and fossil fuel substitution; and perform an integrated analysis of forest management practices and the potential to substitute fossil fuels by wood products. To evaluate the effects of the management regimes considered, carbon stocks in the investigated stands and the potential of the resulting biomass to substitute fossil fuel were estimated. No significant differences were found in biomass production between the thinning regimes for Norway spruce (Picea abies (L.) Karst.) stands, but the standing biomass was significantly larger in unthinned stands, indicating that to maximize the carbon stock in tree biomass thinnings should be avoided. For Scots pine (Pinus sylvestris L.), thinned and fertilized stands produced significantly more biomass (2.60-2.72 ton d.w./ha/yr) than unthinned and unfertilized stands (2.17-2.34 ton d.w./ha/yr) in the northern regions. These findings indicate that fertilization might be a viable measure to increase production of biomass with the potential to replace fossil fuel and energy-intensive material. In addition, for broad-leaved trees stands on abandoned farmland, management regimes with a short rotation were found to be better for maximizing the substitution of fossil fuel than regimes with a long rotation

  5. SynechoNET: integrated protein-protein interaction database of a model cyanobacterium Synechocystis sp. PCC 6803

    OpenAIRE

    Kim, Woo-Yeon; Kang, Sungsoo; Kim, Byoung-Chul; Oh, Jeehyun; Cho, Seongwoong; Bhak, Jong; Choi, Jong-Soon

    2008-01-01

    Background Cyanobacteria are model organisms for studying photosynthesis, carbon and nitrogen assimilation, evolution of plant plastids, and adaptability to environmental stresses. Despite many studies on cyanobacteria, there is no web-based database of their regulatory and signaling protein-protein interaction networks to date. Description We report a database and website SynechoNET that provides predicted protein-protein interactions. SynechoNET shows cyanobacterial domain-domain interactio...

  6. Improved feed protein fractionation schemes for formulating rations with the cornell net carbohydrate and protein system.

    Science.gov (United States)

    Lanzas, C; Broderick, G A; Fox, D G

    2008-12-01

    Adequate predictions of rumen-degradable protein (RDP) and rumen-undegradable protein (RUP) supplies are necessary to optimize performance while minimizing losses of excess nitrogen (N). The objectives of this study were to evaluate the original Cornell Net Carbohydrate Protein System (CNCPS) protein fractionation scheme and to develop and evaluate alternatives designed to improve its adequacy in predicting RDP and RUP. The CNCPS version 5 fractionates CP into 5 fractions based on solubility in protein precipitant agents, buffers, and detergent solutions: A represents the soluble nonprotein N, B1 is the soluble true protein, B2 represents protein with intermediate rates of degradation, B3 is the CP insoluble in neutral detergent solution but soluble in acid detergent solution, and C is the unavailable N. Model predictions were evaluated with studies that measured N flow data at the omasum. The N fractionation scheme in version 5 of the CNCPS explained 78% of the variation in RDP with a root mean square prediction error (RMSPE) of 275 g/d, and 51% of the RUP variation with RMSPE of 248 g/d. Neutral detergent insoluble CP flows were overpredicted with a mean bias of 128 g/d (40% of the observed mean). The greatest improvements in the accuracy of RDP and RUP predictions were obtained with the following 2 alternative schemes. Alternative 1 used the inhibitory in vitro system to measure the fractional rate of degradation for the insoluble protein fraction in which A = nonprotein N, B1 = true soluble protein, B2 = insoluble protein, C = unavailable protein (RDP: R(2) = 0.84 and RMSPE = 167 g/d; RUP: R(2) = 0.61 and RMSPE = 209 g/d), whereas alternative 2 redefined A and B1 fractions as the non-amino-N and amino-N in the soluble fraction respectively (RDP: R(2) = 0.79 with RMSPE = 195 g/d and RUP: R(2) = 0.54 with RMSPE = 225 g/d). We concluded that implementing alternative 1 or 2 will improve the accuracy of predicting RDP and RUP within the CNCPS framework.

  7. InSilico Proteomics System: Integration and Application of Protein and Protein-Protein Interaction Data using Microsoft .NET

    Directory of Open Access Journals (Sweden)

    Straßer Wolfgang

    2006-12-01

    Full Text Available In the last decades, biological databases became the major knowledge resource for researchers in the field of molecular biology. The distribution of information among these databases is one of the major problems. An overview about the subject area of data access and representation of protein and protein-protein interaction data within public biological databases is described. For a comprehensive and consistent way of searching and analysing integrated protein and protein-protein interaction data, the InSilico Proteomics (ISP project has been initiated. Its three main objectives are (1 to provide an integrated knowledge pool for data investigation and global network analysis functions for a better understanding of a cell’s interactome, (2 employment of public data for plausibility analysis and validation of in-house experimental data and (3 testing the applicability of Microsoft’s .NET architecture for bioinformatics applications. Data integrated into the ISP database can be queried through the Web portal PRIMOS (PRotein Interaction and MOlecule Search which is freely available at http://biomis.fh-hagenberg.at/isp/primos.

  8. Ambient UV-B radiation reduces PSII performance and net photosynthesis in high Arctic Salix arctica

    DEFF Research Database (Denmark)

    Albert, Kristian Rost; Mikkelsen, Teis Nørgaard; Ro-Poulsen, H.

    2011-01-01

    , nitrogen and UV-B absorbing compounds. Compared to a 60% reduced UV-B irradiance, the ambient solar UV-B reduced net photosynthesis in Salix arctica leaves fixed in the 45° position which exposed leaves to maximum natural irradiance. Also a reduced Calvin Cycle capacity was found, i.e. the maximum rate...... across position in the vegetation. These findings add to the evidence that the ambient solar UV-B currently is a significant stress factor for plants in high Arctic Greenland....

  9. Diminished UV-absorbing nets reduce the Spreads and population density of Macrosiphum euphorbiae in lettuce.

    OpenAIRE

    Legarrea, S.; Díaz, B. M.; Plaza, M.; Barrios, L.; Morales, Ignacio; Viñuela Sandoval, Elisa; Fereres Castiel, Alberto

    2012-01-01

    UV-absorbing covers reduce the incidence of injurious insect pests and viruses in protected crops. In the present study, the effect of a UV-absorbing net (Bionet) on the spatio-temporal dynamics of the potato aphid on lettuce plants was evaluated. A field experiment was conducted during three seasons in two identical tunnels divided in four plots. A set of lettuce plants were artificially infested with Macrosiphum euphorbiae adults and the population was estimated by counting aphids on ev...

  10. vaccination using profilin and NetB proteins in Montanide IMS adjuvant increases protective immunity against experimentally-induced necrotic enteritis

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    Hyun Soon Lillehoj

    2017-10-01

    Full Text Available Objective The effects of vaccinating 18-day-old chicken embryos with the combination of recombinant Eimeria profilin plus Clostridium perfringens (C. perfringens NetB proteins mixed in the Montanide IMS adjuvant on the chicken immune response to necrotic enteritis (NE were investigated using an Eimeria maxima (E. maxima/C. perfringens co-infection NE disease model that we previously developed. Methods Eighteen-day-old broiler embryos were injected with 100 μL of phosphate-buffered saline, profilin, profilin plus necrotic enteritis B-like (NetB, profilin plus NetB/Montanide adjuvant (IMS 106, and profilin plus Net-B/Montanide adjuvant (IMS 101. After post-hatch birds were challenged with our NE experimental disease model, body weights, intestinal lesions, serum antibody levels to NetB, and proinflammatory cytokine and chemokine mRNA levels in intestinal intraepithelial lymphocytes were measured. Results Chickens in ovo vaccinated with recombinant profilin plus NetB proteins/IMS106 and recombinant profilin plus NetB proteins/IMS101 showed significantly increased body weight gains and reduced gut damages compared with the profilin-only group, respectively. Greater antibody response to NetB toxin were observed in the profilin plus NetB/IMS 106, and profilin plus NetB/IMS 101 groups compared with the other three vaccine/adjuvant groups. Finally, diminished levels of transcripts encoding for proinflammatory cytokines such as lipopolysaccharide-induced tumor necrosis factor-α factor, tumor necrosis factor superfamily 15, and interleukin-8 were observed in the intestinal lymphocytes of chickens in ovo injected with profilin plus NetB toxin in combination with IMS 106, and profilin plus NetB toxin in combination with IMS 101 compared with profilin protein alone bird. Conclusion These results suggest that the Montanide IMS adjuvants potentiate host immunity to experimentally-induced avian NE when administered in ovo in conjunction with the profilin and

  11. Rain events decrease boreal peatland net CO2 uptake through reduced light availability.

    Science.gov (United States)

    Nijp, Jelmer J; Limpens, Juul; Metselaar, Klaas; Peichl, Matthias; Nilsson, Mats B; van der Zee, Sjoerd E A T M; Berendse, Frank

    2015-06-01

    Boreal peatlands store large amounts of carbon, reflecting their important role in the global carbon cycle. The short-term exchange and the long-term storage of atmospheric carbon dioxide (CO2 ) in these ecosystems are closely associated with the permanently wet surface conditions and are susceptible to drought. Especially, the single most important peat forming plant genus, Sphagnum, depends heavily on surface wetness for its primary production. Changes in rainfall patterns are expected to affect surface wetness, but how this transient rewetting affects net ecosystem exchange of CO2 (NEE) remains unknown. This study explores how the timing and characteristics of rain events during photosynthetic active periods, that is daytime, affect peatland NEE and whether rain event associated changes in environmental conditions modify this response (e.g. water table, radiation, vapour pressure deficit, temperature). We analysed an 11-year time series of half-hourly eddy covariance and meteorological measurements from Degerö Stormyr, a boreal peatland in northern Sweden. Our results show that daytime rain events systematically decreased the sink strength of peatlands for atmospheric CO2 . The decrease was best explained by rain associated reduction in light, rather than by rain characteristics or drought length. An average daytime growing season rain event reduced net ecosystem CO2 uptake by 0.23-0.54 gC m(-2) . On an annual basis, this reduction of net CO2 uptake corresponds to 24% of the annual net CO2 uptake (NEE) of the study site, equivalent to a 4.4% reduction of gross primary production (GPP) during the growing season. We conclude that reduced light availability associated with rain events is more important in explaining the NEE response to rain events than rain characteristics and changes in water availability. This suggests that peatland CO2 uptake is highly sensitive to changes in cloud cover formation and to altered rainfall regimes, a process hitherto largely

  12. Positive muscle protein net balance and differential regulation of atrogene expression after resistance exercise and milk protein supplementation

    DEFF Research Database (Denmark)

    Reitelseder, Søren; Agergaard, Jakob; Doessing, Simon

    2014-01-01

    Purpose Resistance exercise and amino acid availability are positive regulators of muscle protein net balance (NB). However, anabolic responses to resistance exercise and protein supplementation deserve further elucidation. The purpose was to compare intakes of whey, caseinate (both: 0.30 g/kg lean...... body mass), or a non-caloric control after heavy resistance exercise on protein turnover and mRNA expressions of forkhead homeobox type O (FOXO) isoforms, muscle RING finger 1 (MuRF1), and Atrogin1 in young healthy males. Methods Protein turnover was determined by stable isotope-labeled leucine...

  13. Prehydrolyzed dietary protein reduces gastrocnemial DNA without ...

    African Journals Online (AJOL)

    Prehydrolyzed dietary protein reduces gastrocnemial DNA without impairing physical capacity in the rat. Viviane Costa Silva Zaffani, Carolina Cauduro Bensabath Carneiro-Leão, Giovana Ermetice de Almeida Costa, Pablo Christiano Barboza Lollo, Emilianne Miguel Salomão, Maria Cristina Cintra Gomes-Marcondes, ...

  14. Accelerating Net Terrestrial Carbon Uptake During the Warming Hiatus Due to Reduced Respiration

    Science.gov (United States)

    Ballantyne, Ashley; Smith, William; Anderegg, William; Kauppi, Pekka; Sarmiento, Jorge; Tans, Pieter; Shevliakova, Elena; Pan, Yude; Poulter, Benjamin; Anav, Alessandro; hide

    2017-01-01

    The recent warming hiatus presents an excellent opportunity to investigate climate sensitivity of carbon cycle processes. Here we combine satellite and atmospheric observations to show that the rate of net biome productivity (NBP) has significantly accelerated from - 0.007 +/- 0.065 PgC yr(exp -2) over the warming period (1982 to 1998) to 0.119 +/- 0.071 PgC yr(exp -2) over the warming hiatus (19982012). This acceleration in NBP is not due to increased primary productivity, but rather reduced respiration that is correlated (r = 0.58; P = 0.0007) and sensitive ( y = 4.05 to 9.40 PgC yr(exp -1) per C) to land temperatures. Global land models do not fully capture this apparent reduced respiration over the warming hiatus; however, an empirical model including soil temperature and moisture observations better captures the reduced respiration.

  15. Ambient UV-B radiation reduces PSII performance and net photosynthesis in high Arctic Salix arctica

    DEFF Research Database (Denmark)

    Albert, Kristian Rost; Mikkelsen, Teis Nørgaard; Ro-Poulsen, Helge

    2011-01-01

    Ambient ultraviolet-B (UV-B) radiation potentially impacts the photosynthetic performance of high Arctic plants. We conducted an UV-B exclusion experiment in a dwarf shrub heath in NE Greenland (74°N), with open control, filter control, UV-B filtering and UV-AB filtering, all in combination......, nitrogen and UV-B absorbing compounds. Compared to a 60% reduced UV-B irradiance, the ambient solar UV-B reduced net photosynthesis in Salix arctica leaves fixed in the 45° position which exposed leaves to maximum natural irradiance. Also a reduced Calvin Cycle capacity was found, i.e. the maximum rate...... across position in the vegetation. These findings add to the evidence that the ambient solar UV-B currently is a significant stress factor for plants in high Arctic Greenland....

  16. Optimization of crude protein in diets for Nile tilapia reared in net pens: performance, hematology, and water quality

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    Débora Del Puppo

    Full Text Available ABSTRACT: Two experiments were conducted to evaluate the effects of reducing dietary crude protein (CP, based on the ideal protein concept for Nile tilapia reared in net pens. The experimental (isocaloric, isocalcium, and isophosphoric diets were formulated to contain 270, 300, 330, and 360g kg-1 CP. In experiment 1, 4320 Nile tilapia (13.5±0.82g were used to evaluate the performance and hematological parameters. The experimental design was completely randomized and the fish were distributed in 24 net pens (1.0m3, with four diets, six replicates, and 180 fishes per experimental unit. In experiment 2, 40 Nile tilapia (22.5±0.56g were used to evaluate the ammonia excretion. Fish were distributed in 40 aquaria (3.0L, with one fish per aquarium (n=10. No protein reduction effect was observed in feed intake and the hematocrit and hemoglobin values. Regarding the statistic models used in the present study, difference was observed between CP values. The optimal level estimated by the quadratic equation first interception with the linear response plateau (LRP as a response to CP changes in the diet was determined for weight gain (324.3g kg-1 and feed conversion (317.8g kg-1. After reduction in the CP levels, a linear reduction was observed in the ammonia excretion in water. Based on the ideal protein concept for Nile tilapia reared in net pens, reducing the CP levels in the diets is possible, without change in the performance and hematological parameters, and with a reduction in the levels of ammonia excretion in water, since amino acids are supplemented.

  17. Petri net-based prediction of therapeutic targets that recover abnormally phosphorylated proteins in muscle atrophy.

    Science.gov (United States)

    Jung, Jinmyung; Kwon, Mijin; Bae, Sunghwa; Yim, Soorin; Lee, Doheon

    2018-03-05

    Muscle atrophy, an involuntary loss of muscle mass, is involved in various diseases and sometimes leads to mortality. However, therapeutics for muscle atrophy thus far have had limited effects. Here, we present a new approach for therapeutic target prediction using Petri net simulation of the status of phosphorylation, with a reasonable assumption that the recovery of abnormally phosphorylated proteins can be a treatment for muscle atrophy. The Petri net model was employed to simulate phosphorylation status in three states, i.e. reference, atrophic and each gene-inhibited state based on the myocyte-specific phosphorylation network. Here, we newly devised a phosphorylation specific Petri net that involves two types of transitions (phosphorylation or de-phosphorylation) and two types of places (activation with or without phosphorylation). Before predicting therapeutic targets, the simulation results in reference and atrophic states were validated by Western blotting experiments detecting five marker proteins, i.e. RELA, SMAD2, SMAD3, FOXO1 and FOXO3. Finally, we determined 37 potential therapeutic targets whose inhibition recovers the phosphorylation status from an atrophic state as indicated by the five validated marker proteins. In the evaluation, we confirmed that the 37 potential targets were enriched for muscle atrophy-related terms such as actin and muscle contraction processes, and they were also significantly overlapping with the genes associated with muscle atrophy reported in the Comparative Toxicogenomics Database (p-value net. We generated a list of the potential therapeutic targets whose inhibition recovers abnormally phosphorylated proteins in an atrophic state. They were evaluated by various approaches, such as Western blotting, GO terms, literature, known muscle atrophy-related genes and shortest path analysis. We expect the new proposed strategy to provide an understanding of phosphorylation status in muscle atrophy and to provide assistance towards

  18. Net herbage accumulation rate and crude protein content of Urochloa brizantha cultivars under shade intensities

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    Paulo Roberto de Lima Meirelles

    2013-12-01

    Full Text Available The use of silvopastoral systems is a sustainable alternative for animal production in various regions of the Brazil. However to obtain satisfactory results in these systems, the selection of forage species that grows well in the shade should be done. The tolerance of plants to light restriction and the correctly choice of species, considering good nutritional values for these conditions has great importance. The study of artificial shading for forage production helps the clarification of issues related to the behavior of plants under reduced light prior to use in integrations with forests. The aim of the study was to evaluate the net herbage accumulation rate of forage (HAR and crude protein (CP of Urochloa brizantha cultivars (Marandu and Piatã under natural light and shading of 30 and 60%. The experiment was conducted at FMVZ - UNESP, Botucatu. The experimental design was a randomized block in factorial arrangement 3 x 2 (three shading levels: 0, 30 and 60%, two cultivars: Marandu and Piatã with three replications and repeated measures (3 cuts. Sample collection occurred when the cultivars reached 35 cm in height. The treatments with shading showed lower cutting intervals as compared to those subjected to full sunlight, because they have reached in a shorter time to time as determined cut-off criterion (mean of 37, 45 and 61 days for reduction of 60%, reduction of 30% and full sun. Significant effects (P<0.05 interaction cultivar x shade x cut on the net herbage accumulation rate (HAR. Most HAR (P<0.05 was observed for cv. Marandu 60% reduction in lightness (127 kg/ha/day due to increased production of stem during the first growing cycle. The lower HAR also occurred to Marandu, but under natural light in the third cut (34 kg/ha/day due to adverse weather conditions during the growth interval. The shadow effect and the cutting (P<0.05 affected CP. The percentage of CP on cultivars showed the highest values (average value of 9.27% in 60

  19. Heating Has No Effect on the Net Protein Utilisation from Egg Whites in Rats

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    Ryosuke Matsuoka

    2017-01-01

    Full Text Available Egg whites (EW are a good source of protein; however, they are typically heated prior to consumption. Therefore, we investigated the effects of different heating conditions on the protein utilisation rate of EW. Male Sprague-Dawley rats (n=36, 198±1 g were divided into six groups and fed American Institute of Nutrition-76 chow containing unheated EW, soft-boiled EW, boiled EW, milk whey protein, soybean protein, or no protein over a 10-day period using pair-feeding. Urine and faeces were sampled daily beginning on day 5 to measure nitrogen content and the net protein utilisation (NPU rate. The soybean protein group had a significantly lower level of food intake and was thus excluded from subsequent analyses. The NPU value was similar among the unheated, soft-boiled, and boiled EW groups (97.5±0.4, 96.5±0.1, and 96.5±0.7, resp.. The EW group values were significantly higher than the whey group values (90.5±1.0. These results show that EW serve as a good source of protein, irrespective of heating.

  20. The relative effectiveness of managed care penetration and the healthcare safety net in reducing avoidable hospitalizations.

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    Pracht, Etienne E; Orban, Barbara L; Comins, Meg M; Large, John T; Asin-Oostburg, Virginia

    2011-01-01

    Avoidable hospitalizations represent a key indicator for access to, and the quality of, primary care. Therefore, understanding their behavior is essential in terms of management of healthcare resources and costs. This analysis examines the affect of 2 healthcare strategies on the rate of avoidable hospitalization, managed care and the healthcare safety net. The avoidable hospitalizations definition developed by Weissman et al. (1992) was used to identify relevant inpatient episodes. A 2-stage simultaneous equations multivariate regression model with instrumental variables was used to estimate the relative influence of HMO penetration and the composition of local hospital markets on the rate of avoidable hospitalizations. Control variables in the model include healthcare supply and demand, demographic, socioeconomic, and health status characteristics. Increased market presence of public hospitals significantly reduced avoidable hospitalizations. HMO penetration did not influence the rate of avoidable hospitalizations. The results suggest that public investments in healthcare facilities and infrastructure are more effective in reducing avoidable hospitalizations. © 2011 National Association for Healthcare Quality.

  1. [Effects of reduced solar radiation on winter wheat flag leaf net photosynthetic rate].

    Science.gov (United States)

    Zheng, You-Fei; Ni, Yan-Li; Mai, Bo-Ru; Wu, Rong-Jun; Feng, Yan; Sun, Jian; Li, Jian; Xu, Jing-Xin

    2011-06-01

    Taking winter wheat Triticum aestivum L. (cv. Yangmai 13) as test material, a field experiment was conducted in Nanjing City to study the effects of simulated reduced solar radiation on the diurnal variation of winter wheat flag leaf photosynthetic rate and the main affecting factors. Five treatments were installed, i. e., 15% (T15), 20% (T20) , 40% (T40), 60% (T60), and 100% (CK) of total incident solar radiation. Reduced solar irradiance increased the chlorophyll and lutein contents significantly, but decreased the net photosynthetic rate (Pn). Under different solar irradiance, the diurnal variation of Pn had greater difference, and the daily maximum Pn was in the order of CK > T60 > T40 > T 20 > T15. In CK, the Pn exhibited a double peak diurnal curve; while in the other four treatments, the Pn showed a single peak curve, and the peak was lagged behind that of CK. Correlation analysis showed that reduced solar irradiance was the main factor affecting the diurnal variation of Pn, but the physiological parameters also played important roles in determining the diurnal variation of Pn. In treatments T60 and T40, the photosynthesis active radiation (PAR), leaf temperature (T1) , stomatal conductance (Gs) , and transpiration rate (Tr) were significantly positively correlated with Pn, suggesting their positive effects on Pn. The intercellular CO2 concentration (Ci) and stomatal limitation (Ls) had significant negative correlations with Pn in treatments T60 and T40 but significant positive correlations with Pn in treatments T20 and T15, implying that the Ci and Ls had negative (or positive) effects on Pn when the solar irradiance was higher (or lower) than 40% of incident solar irradiance.

  2. Systematic mutagenesis of genes encoding predicted autotransported proteins of Burkholderia pseudomallei identifies factors mediating virulence in mice, net intracellular replication and a novel protein conferring serum resistance.

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    Natalie R Lazar Adler

    Full Text Available Burkholderia pseudomallei is the causative agent of the severe tropical disease melioidosis, which commonly presents as sepsis. The B. pseudomallei K96243 genome encodes eleven predicted autotransporters, a diverse family of secreted and outer membrane proteins often associated with virulence. In a systematic study of these autotransporters, we constructed insertion mutants in each gene predicted to encode an autotransporter and assessed them for three pathogenesis-associated phenotypes: virulence in the BALB/c intra-peritoneal mouse melioidosis model, net intracellular replication in J774.2 murine macrophage-like cells and survival in 45% (v/v normal human serum. From the complete repertoire of eleven autotransporter mutants, we identified eight mutants which exhibited an increase in median lethal dose of 1 to 2-log10 compared to the isogenic parent strain (bcaA, boaA, boaB, bpaA, bpaC, bpaE, bpaF and bimA. Four mutants, all demonstrating attenuation for virulence, exhibited reduced net intracellular replication in J774.2 macrophage-like cells (bimA, boaB, bpaC and bpaE. A single mutant (bpaC was identified that exhibited significantly reduced serum survival compared to wild-type. The bpaC mutant, which demonstrated attenuation for virulence and net intracellular replication, was sensitive to complement-mediated killing via the classical and/or lectin pathway. Serum resistance was rescued by in trans complementation. Subsequently, we expressed recombinant proteins of the passenger domain of four predicted autotransporters representing each of the phenotypic groups identified: those attenuated for virulence (BcaA, those attenuated for virulence and net intracellular replication (BpaE, the BpaC mutant with defects in virulence, net intracellular replication and serum resistance and those displaying wild-type phenotypes (BatA. Only BcaA and BpaE elicited a strong IFN-γ response in a restimulation assay using whole blood from seropositive donors

  3. The establishment of a database of Italian feeds for the Cornell Net Carbohydrate and Protein System

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    Enzo Tartari

    2010-01-01

    Full Text Available A field application of the Cornell Net Carbohydrate and Protein System (CNCPS in Italy has been limited because thefeed bank is based on North American feedstuffs and still few laboratories are able to analyze feeds as requested by theCNCPS. Moreover, the standardization of analytical procedures is still not homogeneous among laboratories. This workwas carried out to establish a first database for feeds commonly used in Italy, providing nutritionists and producers anaccurate and current feed composition, also indicating methods and apparatus for analytical procedures potentially availablefor routine analysis. A total of 909 samples of hays, silages and raw materials (protein feeds, cereals and by-productswere analyzed through 1999 and 2002; analysis included protein solubility and degradability, protein fractions,structural carbohydrate fractions and the calculation of neutral detergent structural carbohydrates. When possible, averagedata were compared with those included in the feed bank of CNCPS ver. 3 and with those obtained by another Italianlaboratory. The main differences were observed in chemical composition of forages and silages, whose composition largelydepends on environmental conditions and physiological stage; protein feeds, cereals and by-products showed somedifferences in crude protein, soluble protein and protein fractions even in feeds of national origin.The intent to modify the feed bank values of CNCPS for establishing an Italian data base of feeds will require a collaborativestudy of many laboratories not only for forages, hays and silages samples - whose composition is greatly dependenton environmental factors and agronomic techniques - but also for protein fractions, whose values are largely influencedby even small changes in analytical techniques.

  4. Evaluation of certain crop residues for carbohydrate and protein fractions by cornell net carbohydrate and protein system

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    Venkateswarulu Swarna

    2015-06-01

    Full Text Available Four locally available crop residues viz., jowar stover (JS, maize stover (MS, red gram straw (RGS and black gram straw (BGS were evaluated for carbohydrate and protein fractions using Cornell Net Carbohydrate and Protein (CNCP system. Lignin (% NDF was higher in legume straws as compared to cereal stovers while Non-structural carbohydrates (NSC (% DM followed the reverse trend. The carbohydrate fractions A and B1 were higher in BGS while B2 was higher in MS as compared to other crop residues. The unavailable cell wall fraction (C was higher in legume straws when compared to cereal stovers. Among protein fractions, B1 was higher in legume straws when compared to cereal stovers while B2 was higher in cereal stovers as compared to legume straws. Fraction B3 largely, bypass protein was highest in MS as compared to other crop residues. Acid detergent insoluble crude protein (ADICP (% CP or unavailable protein fraction C was lowest in MS and highest in BGS. It is concluded that MS is superior in nutritional value for feeding ruminants as compared to other crop residues.

  5. Bayesian Inference using Neural Net Likelihood Models for Protein Secondary Structure Prediction

    Directory of Open Access Journals (Sweden)

    Seong-Gon Kim

    2011-06-01

    Full Text Available Several techniques such as Neural Networks, Genetic Algorithms, Decision Trees and other statistical or heuristic methods have been used to approach the complex non-linear task of predicting Alpha-helicies, Beta-sheets and Turns of a proteins secondary structure in the past. This project introduces a new machine learning method by using an offline trained Multilayered Perceptrons (MLP as the likelihood models within a Bayesian Inference framework to predict secondary structures proteins. Varying window sizes are used to extract neighboring amino acid information and passed back and forth between the Neural Net models and the Bayesian Inference process until there is a convergence of the posterior secondary structure probability.

  6. Levels of digestible protein to surubim (Pseudoplatystoma sp. reared in net cages

    Directory of Open Access Journals (Sweden)

    Claucia Aparecida Honorato

    2014-10-01

    Full Text Available The Pseudoplatystoma sp. is species of carnivorous fish that require special attention in the diet offered. This work had the objective to determine the digestible protein requirement of juvenile the Pseudoplatystoma sp. reared in net cages. The test consisted of four isoenergetic diets (2606.69 ± 39.16 kcal kg-1 of digestible energy containing increasing levels of digestible protein (23, 24, 26 and 28%PD provided to juveniles of surubim (157.35±11.23g for five months. The parameters of growth, fillet composition, metabolic liver enzymes and morphometry of the intestine and liver were analyzed in completely randomized design with four treatments and four replicates. An increase of protein in the diet provided better weight gain. The metabolic liver enzymes increased in fish fed 24PD. The histopathological changes were not observed in the liver of the fish. The bowel histology showed adaptation to increased protein in the diet until the 26 level PD. juveniles of Pseudoplatystoma sp. Were demanding in digestible protein, showing the best results of production performance and nutrient use efficiency with the diet containing 28%PD.

  7. Warmer temperatures reduce net carbon uptake, but not water use, in a mature southern Appalachian forest

    Science.gov (United States)

    Increasing air temperature is expected to extend growing season length in temperate, broadleaf forests, leading to potential increases in evapotranspiration and net carbon uptake. However, other key processes affecting water and carbon cycles are also highly temperature-dependent...

  8. Evaluating alternative prescribed burning policies to reduce net economic damages from wildfire

    Science.gov (United States)

    D. Evan Mercer; Jeffrey P. Prestemon; David T. Butry; John M. Pye

    2007-01-01

    We estimate a wildfire risk model with a new measure of wildfire output, intensity-weighted risk and use it in Monte Carlo simulations to estimate welfare changes from alternative prescribed burning policies. Using Volusia County, Florida as a case study, an annual prescribed burning rate of 13% of all forest lands maximizes net welfare; ignoring the effects on...

  9. Evaluating Alternative Prescribed Burning Policies to Reduce Net Economic Damages from Wildfire

    OpenAIRE

    D. Evan Mercer; Jeffrey P. Prestemon; David T. Butry; John M. Pye

    2007-01-01

    We estimate a wildfire risk model with a new measure of wildfire output, intensity-weighted risk and use it in Monte Carlo simulations to estimate welfare changes from alternative prescribed burning policies. Using Volusia County, Florida as a case study, an annual prescribed burning rate of 13% of all forest lands maximizes net welfare; ignoring the effects on wildfire intensity may underestimate optimal rates of prescribed burning. Our estimated supply function for prescribed fire services ...

  10. potential for quality protein maize for reducing protein- energy

    African Journals Online (AJOL)

    ACSS

    social systems hampering QPM promotion and adoption and to identify ... affects growth and development. Protein- energy ... to purchase QPM seed leading to PEU reduction. Education ..... decision support framework “targetCSA”. Agricultural ...

  11. Intestinal remodelling in mink fed with reduced protein content

    DEFF Research Database (Denmark)

    Chen, Pengmin; Zhao, Jingbo; Nielsen, Vivi Hunnicke

    2009-01-01

    Low protein intake occurs in humans in relation to diseases, starvation and post-operatively. Low-protein diets may affect the gastrointestinal structure and mechanical function. The aim was to study the passive biomechanical properties and tissue remodelling of the intestine in minks on reduced...... protein diets. Twenty-seven male minks were divided into three groups receiving different protein level in the diet for 6 weeks: High protein level (group H, 55% energy from protein), moderate protein level (group M, 30% energy from protein) and low protein level (group L, 15% energy from protein) (n=9...... groups. Feeding the low-protein diet shifted the stress-strain curves to the right for the circumferential direction, indicating the wall become softer in the circumferential direction. However, no significant difference was observed in the longitudinal direction for any of the intestinal segments...

  12. Net protein and metabolizable protein requirements for maintenance and growth of early-weaned Dorper crossbred male lambs

    Institute of Scientific and Technical Information of China (English)

    Tao Ma; Kaidong Deng; Yan Tu; Naifeng Zhang; Bingwen Si; Guishan Xu; Qiyu Diao

    2017-01-01

    Background:Dorper is an important breed for meat purpose and widely used in the livestock industry of the world.However,the protein requirement of Dorper crossbred has not been investigated.The current paper reports the net protein (NP) and metabolizable protein (MP) requirements of Dorper crossbred ram lambs from 20 to 35 kg BW.Methods:Thirty-five Dorper × thin-tailed Han crossbred lambs weaned at approximately 50 d of age (20.3 ± 2.15 kg of BW) were used.Seven lambs of 25 kg BW were slaughtered as the baseline animals at the start of the trial.An intermediate group of seven randomly selected lambs fed ad libitum was slaughtered at 28.6 kg BW.The remaining 21 lambs were randomly divided into three levels of dry matter intake:ad libitum or 70% or 40% of ad libitum intake.Those lambs were slaughtered when the lambs fed ad libitum reached 35 kg BW.Total body N and N retention were measured.Results:The daily NP and MP requirements for maintenance were 1.89 and 4.52 g/kg metabolic shrunk BW (SBW0.75).The partial efficiency of MP utilization for maintenance was 0.42.The NP requirement for growth ranged from 12.1 to 43.5 g/d,for the lambs gaining 100 to 350 g/d,and the partial efficiency of MP utilization for growth was 0.86.Conclusions:The NP and MP requirements for the maintenance and growth of Dorper crossbred male lambs were lower than the recommendations of American and British nutritional systems.

  13. Biochar amendment reduces paddy soil nitrogen leaching but increases net global warming potential in Ningxia irrigation, China.

    Science.gov (United States)

    Wang, Yongsheng; Liu, Yansui; Liu, Ruliang; Zhang, Aiping; Yang, Shiqi; Liu, Hongyuan; Zhou, Yang; Yang, Zhengli

    2017-05-09

    The efficacy of biochar as an environmentally friendly agent for non-point source and climate change mitigation remains uncertain. Our goal was to test the impact of biochar amendment on paddy rice nitrogen (N) uptake, soil N leaching, and soil CH 4 and N 2 O fluxes in northwest China. Biochar was applied at four rates (0, 4.5, 9 and13.5 t ha -1 yr -1 ). Biochar amendment significantly increased rice N uptake, soil total N concentration and the abundance of soil ammonia-oxidizing archaea (AOA), but it significantly reduced the soil NO 3 - -N concentration and soil bulk density. Biochar significantly reduced NO 3 - -N and NH 4 + -N leaching. The C2 and C3 treatments significantly increased the soil CH 4 flux and reduced the soil N 2 O flux, leading to significantly increased net global warming potential (GWP). Soil NO 3 - -N rather than NH 4 + -N was the key integrator of the soil CH 4 and N 2 O fluxes. Our results indicate that a shift in abundance of the AOA community and increased rice N uptake are closely linked to the reduced soil NO 3 - -N concentration under biochar amendment. Furthermore, soil NO 3 - -N availability plays an important role in regulating soil inorganic N leaching and net GWP in rice paddies in northwest China.

  14. Spatial repellents on strips of camouflage netting reduce mosquito collections in a field environment

    Science.gov (United States)

    Barrier treatments can be effective in reducing host seeking mosquito vectors and provide an additional layer of passive defense, reducing disease risk. Devices designed to release spatial repellents or direct application of spatial repellents to artificial surfaces can serve as efficient barriers r...

  15. How are proteins reduced in the endoplasmic reticulum?

    DEFF Research Database (Denmark)

    Ellgaard, Lars; Sevier, Carolyn S.; Bulleid, Neil J.

    2018-01-01

    The reversal of thiol oxidation in proteins within the endoplasmic reticulum (ER) is crucial for protein folding, degradation, chaperone function, and the ER stress response. Our understanding of this process is generally poor but progress has been made. Enzymes performing the initial reduction...... of client proteins, as well as the ultimate electron donor in the pathway, have been identified. Most recently, a role for the cytosol in ER protein reduction has been revealed. Nevertheless, how reducing equivalents are transferred from the cytosol to the ER lumen remains an open question. We review here...... why proteins are reduced in the ER, discuss recent data on catalysis of steps in the pathway, and consider the implications for redox homeostasis within the early secretory pathway....

  16. Genomic testing interacts with reproductive surplus in reducing genetic lag and increasing economic net return

    DEFF Research Database (Denmark)

    Hjortø, Line; Ettema, Jehan Frans; Kargo, Morten

    2015-01-01

    Until now, genomic information has mainly been used to improve the accuracy of genomic breeding values for breeding animals at a population level. However, we hypothesize that the use of information from genotyped females also opens up the possibility of reducing genetic lag in a dairy herd......, especially if genomic tests are used in combination with sexed semen or a high management level for reproductive performance, because both factors provide the opportunity for generating a reproductive surplus in the herd. In this study, sexed semen is used in combination with beef semen to produce high......-value crossbred beef calves. Thus, on average there is no surplus of and selection among replacement heifers whether to go into the herd or to be sold. In this situation, the selection opportunities arise when deciding which cows to inseminate with sexed semen, conventional semen, or beef semen. We tested...

  17. NetPhosYeast: prediction of protein phosphorylation sites in yeast

    DEFF Research Database (Denmark)

    Ingrell, C.R.; Miller, Martin Lee; Jensen, O.N.

    2007-01-01

    sites compared to those in humans, suggesting the need for an yeast-specific phosphorylation site predictor. NetPhosYeast achieves a correlation coefficient close to 0.75 with a sensitivity of 0.84 and specificity of 0.90 and outperforms existing predictors in the identification of phosphorylation sites...

  18. A Patient Navigator Intervention to Reduce Hospital Readmissions among High-Risk Safety-Net Patients: A Randomized Controlled Trial.

    Science.gov (United States)

    Balaban, Richard B; Galbraith, Alison A; Burns, Marguerite E; Vialle-Valentin, Catherine E; Larochelle, Marc R; Ross-Degnan, Dennis

    2015-07-01

    Evidence-based interventions to reduce hospital readmissions may not generalize to resource-constrained safety-net hospitals. To determine if an intervention by patient navigators (PNs), hospital-based Community Health Workers, reduces readmissions among high risk, low socioeconomic status patients. Randomized controlled trial. General medicine inpatients having at least one of the following readmission risk factors: (1) age ≥60 years, (2) any in-network inpatient admission within the past 6 months, (3) length of stay ≥3 days, (4) admission diagnosis of heart failure, or (5) chronic obstructive pulmonary disease. The analytic sample included 585 intervention patients and 925 controls. PNs provided coaching and assistance in navigating the transition from hospital to home through hospital visits and weekly telephone outreach, supporting patients for 30 days post-discharge with discharge preparation, medication management, scheduling of follow-up appointments, communication with primary care, and symptom management. The primary outcome was in-network 30-day hospital readmissions. Secondary outcomes included rates of outpatient follow-up. We evaluated outcomes for the entire cohort and stratified by patient age >60 years (425 intervention/584 controls) and ≤60 years (160 intervention/341 controls). Overall, 30-day readmission rates did not differ between intervention and control patients. However, the two age groups demonstrated marked differences. Intervention patients >60 years showed a statistically significant adjusted absolute 4.1% decrease [95% CI: -8.0%, -0.2%] in readmission with an increase in 30-day outpatient follow-up. Intervention patients ≤60 years showed a statistically significant adjusted absolute 11.8% increase [95% CI: 4.4%, 19.0%] in readmission with no change in 30-day outpatient follow-up. A patient navigator intervention among high risk, safety-net patients decreased readmission among older patients while increasing readmissions

  19. SynSysNet: integration of experimental data on synaptic protein-protein interactions with drug-target relations

    NARCIS (Netherlands)

    von Eichborn, J.; Dunkel, M.; Gohlke, B.O.; Preissner, S.C.; Hoffmann, M.F.; Bauer, J.M.J.; Armstrong, J.D.; Schaefer, M.H.; Andrade-Navarro, M.A.; Le Novere, N.; Croning, M.D.R.; Grant, S.G.N.; van Nierop, P.; Smit, A.B.; Preissner, R.

    2013-01-01

    We created SynSysNet, available online at http://bioinformatics.charite.de/ synsysnet, to provide a platform that creates a comprehensive 4D network of synaptic interactions. Neuronal synapses are fundamental structures linking nerve cells in the brain and they are responsible for neuronal

  20. Experimental determination of net protein charge and A(tot) and K(a) of nonvolatile buffers in canine plasma.

    Science.gov (United States)

    Constable, Peter D; Stämpfli, Henry R

    2005-01-01

    Acid-base abnormalities frequently are present in sick dogs. The mechanism for an acid-base disturbance can be determined with the simplified strong ion approach, which requires accurate values for the total concentration of plasma nonvolatile buffers (A(tot)) and the effective dissociation constant for plasma weak acids (K(a)). The aims of this study were to experimentally determine A(tot) and K(a) values for canine plasma. Plasma was harvested from 10 healthy dogs; the concentrations of quantitatively important strong ions (Na+, K+, Ca2+, Mg2+, Cl-, L-lactate) and nonvolatile buffer ions (total protein, albumin, phosphate) were determined; and the plasma was tonometered with CO2 at 37 degrees C. Strong ion difference (SID) was calculated from the measured strong ion concentrations, and nonlinear regression was used to estimate values for A(tot) and K(a), which were validated with data from an in vitro and in vivo study. Mean (+/- SD) values for canine plasma were A(tot) = (17.4 +/- 8.6) mM (equivalent to 0.273 mmol/g of total protein or 0.469 mmol/g of albumin); K(a) = (0.17 +/- 0.11) x 10(-7); pK(a) = 7.77. The calculated SID for normal canine plasma (pH = 7.40; P(CO2) = 37 mm Hg; [total protein] = 64 g/L) was 27 mEq/L. The net protein charge for normal canine plasma was 0.25 mEq/g of total protein or 0.42 mEq/g of albumin. Application of the experimentally determined values for A(tot), K(a), and net protein charge should improve understanding of the mechanism for complex acid-base disturbances in dogs.

  1. Experimental determination of net protein charge, [A]tot, and Ka of nonvolatile buffers in bird plasma.

    Science.gov (United States)

    Stämpfli, Henry; Taylor, Michael; McNicoll, Carl; Gancz, Ady Y; Constable, Peter D

    2006-06-01

    The quantitative mechanistic acid-base approach to clinical assessment of acid-base status requires species-specific values for [A]tot (the total concentration of nonvolatile buffers in plasma) and Ka (the effective dissociation constant for weak acids in plasma). The aim of this study was to determine [A]tot and Ka values for plasma in domestic pigeons. Plasma from 12 healthy commercial domestic pigeons was tonometered with 20% CO2 at 37 degrees C. Plasma pH, Pco2, and plasma concentrations of strong cations (Na, K, Ca), strong anions (Cl, L-lactate), and nonvolatile buffer ions (total protein, albumin, phosphate) were measured over a pH range of 6.8-7.7. Strong ion difference (SID) (SID5=Na+K+Ca-Cl-lactate) was used to calculate [A]tot and Ka from the measured pH and Pco2 and SID5. Mean (+/-SD) values for bird plasma were as follows: [A]tot=7.76+/-2.15 mmol/l (equivalent to 0.32 mmol/g of total protein, 0.51 mmol/g of albumin, 0.23 mmol/g of total solids); Ka=2.15+/-1.15x10(-7); and pKa=6.67. The net protein charge at normal pH (7.43) was estimated to be 6 meq/l; this value indicates that pigeon plasma has a much lower anion gap value than mammals after adjusting for high mean L-lactate concentrations induced by restraint during blood sampling. This finding indicates that plasma proteins in pigeons have a much lower net anion charge than mammalian plasma protein. An incidental finding was that total protein concentration measured by a multianalyzer system was consistently lower than the value for total solids measured by refractometer.

  2. Experimental determination of net protein charge and A(tot) and K(a) of nonvolatile buffers in human plasma.

    Science.gov (United States)

    Staempfli, Henry R; Constable, Peter D

    2003-08-01

    The mechanism for an acid-base disturbance can be determined by using the strong ion approach, which requires species-specific values for the total concentration of plasma nonvolatile buffers (Atot) and the effective dissociation constant for plasma weak acids (Ka). The aim of this study was to experimentally determine Atot and Ka values for human plasma by using in vitro CO2 tonometry. Plasma Pco2 was systematically varied from 25 to 145 Torr at 37 degrees C, thereby altering plasma pH over the physiological range of 6.90-7.55, and plasma pH, Pco2, and concentrations of quantitatively important strong ions (Na+, K+, Ca2+, Mg2+, Cl-, lactate) and buffer ions (total protein, albumin, phosphate) were measured. Strong ion difference was estimated, and nonlinear regression was used to calculate Atot and Ka from the measured pH and Pco2 and estimated strong ion difference; the Atot and Ka values were then validated by using a published data set (Figge J, Rossing TH, and Fencl V, J Lab Clin Med 117: 453-467, 1991). The values (mean +/- SD) were as follows: Atot = 17.2 +/- 3.5 mmol/l (equivalent to 0.224 mmol/g of protein or 0.378 mmol/g of albumin); Ka = 0.80 +/- 0.60 x 10-7; negative log of Ka = 7.10. Mean estimates were obtained for strong ion difference (37 meq/l) and net protein charge (13+.0 meq/l). The experimentally determined values for Atot, Ka, and net protein charge should facilitate the diagnosis and treatment of acid-base disturbances in critically ill humans.

  3. Heat-treatment reduces anti-nutritional phytochemicals and maintains protein quality in genetically improved hulled soybean flour

    Directory of Open Access Journals (Sweden)

    Ariela Werneck de Carvalho

    2013-06-01

    Full Text Available The soybean is a protein source of high biological value. However, the presence of anti-nutritional factors affects its protein quality and limits the bioavailability of other nutrients. The effect of heat-treatment, 150 ºC for 30 minutes, on hulled and hull-less soybean flour from the cultivar UFVTN 105AP on urease, trypsin inhibitor activity, protein solubility, amino acid profile, and in vivo protein quality was investigated. The treatment reduced the trypsin inhibitor activity and urease, but it did not affect protein solubility. Protein Efficiency Coefficient (PER values of the flours were similar, and the PER of the hull-less soybean flour did not differ from casein. The Net Protein Ratio (NPR did not differ between the experimental groups. The True Digestibility (TD of the flours did not differ, but both were lower in casein and the Protein Digestibility Corrected Amino Acid Score (PDCCAS was lower than the TD, due to limited valine determined by the chemical score. Therefore, the flours showed reduced anti-nutritional phytochemicals and similar protein quality, and therefore the whole flours can be used as a source of high quality protein.

  4. Low affinity uniporter carrier proteins can increase net substrate uptake rate by reducing efflux

    NARCIS (Netherlands)

    Bosdriesz, Evert; Wortel, Meike T.; Haanstra, Jurgen R.; Wagner, Marijke J.; De La Torre Cortés, Pilar; Teusink, Bas

    2018-01-01

    Many organisms have several similar transporters with different affinities for the same substrate. Typically, high-affinity transporters are expressed when substrate is scarce and low-affinity ones when it is abundant. The benefit of using low instead of high-affinity transporters remains unclear,

  5. Low affinity uniporter carrier proteins can increase net substrate uptake rate by reducing efflux

    NARCIS (Netherlands)

    Bosdriesz, Evert; Wortel, M.T.; Haanstra, Jurgen R.; Wagner, Marijke J.; De La Torre, P.; Teusink, Bas

    2018-01-01

    Many organisms have several similar transporters with different affinities for the same substrate. Typically, high-affinity transporters are expressed when substrate is scarce and low-affinity ones when it is abundant. The benefit of using low instead of high-affinity transporters remains

  6. Expression and Function of Transmembrane-4 Superfamily (Tetraspanin Proteins in Osteoclasts: Reciprocal Roles of Tspan-5 and NET-6 during Osteoclastogenesis

    Directory of Open Access Journals (Sweden)

    Kaori Iwai

    2007-01-01

    Conclusions: These data indicate that a diversity of tetraspanins is expressed in osteoclast precursors, and that cell fusion during osteoclastogenesis is regulated by cooperation of distinct tetraspanin family proteins such as Tspan-5 and NET-6. This study indicates that functional alterations of tetraspanin family proteins may have therapeutic potential in diseases where osteoclasts play a major role, such as rheumatoid arthritis and osteoporosis.

  7. Petri Net-Based Model of Helicobacter pylori Mediated Disruption of Tight Junction Proteins in Stomach Lining during Gastric Carcinoma

    Directory of Open Access Journals (Sweden)

    Anam Naz

    2017-09-01

    Full Text Available Tight junctions help prevent the passage of digestive enzymes and microorganisms through the space between adjacent epithelial cells lining. However, Helicobacter pylori encoded virulence factors negatively regulate these tight junctions and contribute to dysfunction of gastric mucosa. Here, we have predicted the regulation of important tight junction proteins, such as Zonula occludens-1, Claudin-2 and Connexin32 in the presence of pathogenic proteins. Molecular events such as post translational modifications and crosstalk between phosphorylation, O-glycosylation, palmitoylation and methylation are explored which may compromise the integrity of these tight junction proteins. Furthermore, the signaling pathways disrupted by dysregulated kinases, proteins and post-translational modifications are reviewed to design an abstracted computational model showing the situation-dependent dynamic behaviors of these biological processes and entities. A qualitative hybrid Petri Net model is therefore constructed showing the altered host pathways in the presence of virulence factor cytotoxin-associated gene A, leading to the disruption of tight junction proteins. The model is qualitative logic-based, which does not depend on any kinetic parameter and quantitative data and depends on knowledge derived from experiments. The designed model provides insights into the tight junction disruption and disease progression. Model is then verified by the available experimental data, nevertheless formal in vitro experimentation is a promising way to ensure its validation. The major findings propose that H. pylori activated kinases are responsible to trigger specific post translational modifications within tight junction proteins, at specific sites. These modifications may favor alterations in gastric barrier and provide a route to bacterial invasion into host cells.

  8. The incineration, a net benefit to reduce the greenhouse effect; L'incineration, un benefice net pour reduire l'effet de serre

    Energy Technology Data Exchange (ETDEWEB)

    Chefdebien, H. de [CNIM, Dir. des Relations Institutionnelles, 75 - Paris (France)

    2007-07-01

    Many sources indicate that the wastes incineration contributes to reduce the greenhouse gases emissions. Meanwhile data appear very different from a study to another. It can result of different situations and hypothesis, or because the elements taking into account are not the same. This document aims to give some markers in the domain. (A.L.B.)

  9. LOGIC WITH EXCEPTION ON THE ALGEBRA OF FOURIER-DUAL OPERATIONS: NEURAL NET MECHANISM OF COGNITIVE DISSONANCE REDUCING

    Directory of Open Access Journals (Sweden)

    A. V. Pavlov

    2014-01-01

    Full Text Available A mechanism of cognitive dissonance reducing is demonstrated with approach for non-monotonic fuzzy-valued logics by Fourier-holography technique implementation developing. Cognitive dissonance occurs under perceiving of new information that contradicts to the existing subjective pattern of the outside world, represented by double Fourier-transform cascade with a hologram – neural layers interconnections matrix of inner information representation and logical conclusion. The hologram implements monotonic logic according to “General Modus Ponens” rule. New information is represented by a hologram of exclusion that implements interconnections of logical conclusion and exclusion for neural layers. The latter are linked by Fourier transform that determines duality of the algebra forming operations of conjunction and disjunction. Hologram of exclusion forms conclusion that is dual to the “General Modus Ponens” conclusion. It is shown, that trained for the main rule and exclusion system can be represented by two-layered neural network with separate interconnection matrixes for direct and inverse iterations. The network energy function is involved determining the cyclic dynamics character; dissipative factor causing convergence type of the dynamics is analyzed. Both “General Modus Ponens” and exclusion holograms recording conditions on the dynamics and convergence of the system are demonstrated. The system converges to a stable status, in which logical conclusion doesn’t depend on the inner information. Such kind of dynamics, leading to tolerance forming, is typical for ordinary kind of thinking, aimed at inner pattern of outside world stability. For scientific kind of thinking, aimed at adequacy of the inner pattern of the world, a mechanism is needed to stop the net relaxation; the mechanism has to be external relative to the model of logic. Computer simulation results for the learning conditions adequate to real holograms recording are

  10. Perineuronal Net Protein Neurocan Inhibits NCAM/EphA3 Repellent Signaling in GABAergic Interneurons.

    Science.gov (United States)

    Sullivan, Chelsea S; Gotthard, Ingo; Wyatt, Elliott V; Bongu, Srihita; Mohan, Vishwa; Weinberg, Richard J; Maness, Patricia F

    2018-04-18

    Perineuronal nets (PNNs) are implicated in closure of critical periods of synaptic plasticity in the brain, but the molecular mechanisms by which PNNs regulate synapse development are obscure. A receptor complex of NCAM and EphA3 mediates postnatal remodeling of inhibitory perisomatic synapses of GABAergic interneurons onto pyramidal cells in the mouse frontal cortex necessary for excitatory/inhibitory balance. Here it is shown that enzymatic removal of PNN glycosaminoglycan chains decreased the density of GABAergic perisomatic synapses in mouse organotypic cortical slice cultures. Neurocan, a key component of PNNs, was expressed in postnatal frontal cortex in apposition to perisomatic synapses of parvalbumin-positive interneurons. Polysialylated NCAM (PSA-NCAM), which is required for ephrin-dependent synapse remodeling, bound less efficiently to neurocan than mature, non-PSA-NCAM. Neurocan bound the non-polysialylated form of NCAM at the EphA3 binding site within the immunoglobulin-2 domain. Neurocan inhibited NCAM/EphA3 association, membrane clustering of NCAM/EphA3 in cortical interneuron axons, EphA3 kinase activation, and ephrin-A5-induced growth cone collapse. These studies delineate a novel mechanism wherein neurocan inhibits NCAM/EphA3 signaling and axonal repulsion, which may terminate postnatal remodeling of interneuron axons to stabilize perisomatic synapses in vivo.

  11. BMRF-Net: a software tool for identification of protein interaction subnetworks by a bagging Markov random field-based method.

    Science.gov (United States)

    Shi, Xu; Barnes, Robert O; Chen, Li; Shajahan-Haq, Ayesha N; Hilakivi-Clarke, Leena; Clarke, Robert; Wang, Yue; Xuan, Jianhua

    2015-07-15

    Identification of protein interaction subnetworks is an important step to help us understand complex molecular mechanisms in cancer. In this paper, we develop a BMRF-Net package, implemented in Java and C++, to identify protein interaction subnetworks based on a bagging Markov random field (BMRF) framework. By integrating gene expression data and protein-protein interaction data, this software tool can be used to identify biologically meaningful subnetworks. A user friendly graphic user interface is developed as a Cytoscape plugin for the BMRF-Net software to deal with the input/output interface. The detailed structure of the identified networks can be visualized in Cytoscape conveniently. The BMRF-Net package has been applied to breast cancer data to identify significant subnetworks related to breast cancer recurrence. The BMRF-Net package is available at http://sourceforge.net/projects/bmrfcjava/. The package is tested under Ubuntu 12.04 (64-bit), Java 7, glibc 2.15 and Cytoscape 3.1.0. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. The GroupHouseNet COST Action: exploiting European synergy to reduce feather pecking in laying hens

    DEFF Research Database (Denmark)

    Rodenburg, T.B.; Berk, J; Dimitrov, I.

    2017-01-01

    The COST Action GroupHouseNet focuses on the reduction of damaging behaviour in laying hens and pigs, benefiting from the fact that there are many similarities in causation and solutions for feather pecking and tail biting. The research in the network focuses on three main topics, addressed by th...

  13. Enriched housing enhances recovery of limb placement ability and reduces aggrecan-containing perineuronal nets in the rat somatosensory cortex after experimental stroke.

    Directory of Open Access Journals (Sweden)

    Alexandre Madinier

    Full Text Available Stroke causes life long disabilities where few therapeutic options are available. Using electrical and magnetic stimulation of the brain and physical rehabilitation, recovery of brain function can be enhanced even late after stroke. Animal models support this notion, and housing rodents in an enriched environment (EE several days after experimental stroke stimulates lost brain function by multisensory mechanisms. We studied the dynamics of functional recovery of rats with a lesion to the fore and hind limb motor areas induced by photothrombosis (PT, and with subsequent housing in either standard (STD or EE. In this model, skilled motor function is not significantly enhanced by enriched housing, while the speed of recovery of sensori-motor function substantially improves over the 9-week study period. In particular, this stroke lesion completely obliterates the fore and hind limb placing ability when visual and whisker guidance is prevented, a deficit that persists for up to 9 weeks of recovery, but that is markedly restored within 2 weeks by enriched housing. Enriched housing after stroke also leads to a significant loss of perineuronal net (PNN immunoreactivity; detection of aggrecan protein backbone with AB1031 antibody was decreased by 13-22%, and labelling of a glycan moiety of aggrecan with Cat-315 antibody was reduced by 25-30% in the peri-infarct area and in the somatosensory cortex, respectively. The majority of these cells are parvalbumin/GABA inhibitory interneurons that are important in sensori-information processing. We conclude that damage to the fore and hind limb motor areas provides a model of loss of limb placing response without visual guidance, a deficit also seen in more than 50% of stroke patients. This loss is amenable to recovery induced by multiple sensory stimulation and correlates with a decrease in aggrecan-containing PNNs around inhibitory interneurons. Modulating the PNN structure after ischemic damage may provide new

  14. A Protein Extract from Chicken Reduces Plasma Homocysteine in Rats

    Directory of Open Access Journals (Sweden)

    Vegard Lysne

    2015-06-01

    Full Text Available The present study aimed to evaluate effects of a water-soluble protein fraction of chicken (CP, with a low methionine/glycine ratio, on plasma homocysteine and metabolites related to homocysteine metabolism. Male Wistar rats were fed either a control diet with 20% w/w casein as the protein source, or an experimental diet where 6, 14 or 20% w/w of the casein was replaced with the same amount of CP for four weeks. Rats fed CP had reduced plasma total homocysteine level and markedly increased levels of the choline pathway metabolites betaine, dimethylglycine, sarcosine, glycine and serine, as well as the transsulfuration pathway metabolites cystathionine and cysteine. Hepatic mRNA level of enzymes involved in homocysteine remethylation, methionine synthase and betaine-homocysteine S-methyltransferase, were unchanged, whereas cystathionine gamma-lyase of the transsulfuration pathway was increased in the CP treated rats. Plasma concentrations of vitamin B2, folate, cobalamin, and the B-6 catabolite pyridoxic acid were increased in the 20% CP-treated rats. In conclusion, the CP diet was associated with lower plasma homocysteine concentration and higher levels of serine, choline oxidation and transsulfuration metabolites compared to a casein diet. The status of related B-vitamins was also affected by CP.

  15. Prechilling of Xanthium strumarium L. Reduces Net Photosynthesis and, Independently, Stomatal Conductance, While Sensitizing the Stomata to CO(2).

    Science.gov (United States)

    Drake, B; Raschke, K

    1974-06-01

    Greenhouse-grown plants of Xanthium strumarium L. were exposed in a growth cabinet to 10 C during days and 5 C during nights for periods of up to 120 hours. Subsequently, CO(2) exchange, transpiration, and leaf temperature were measured on attached leaves and in leaf sections at 25 or 30 C, 19 C dew point of the air, 61 milliwatts per square centimeter irradiance, and CO(2) concentrations between 0 and 1000 microliters per liter ambient air. Net photosynthesis and stomatal conductance decreased and dark respiration increased with increasing duration of prechilling. The reduction in net photosynthesis was not a consequence of decreased stomatal conductance because the intercellular CO(2) concentration in prechilled leaves was equal to or greater than that in greenhouse-grown controls. The intercellular CO(2) concentration at which one-half maximum net photosynthesis occurred remained the same in prechilled leaves and controls (175 to 190 microliters per liter). Stomata of the control plants responded to changes in the CO(2) concentration of the air only slightly. Prechilling for 24 hours or more sensitized stomata to CO(2); they responded to changes in CO(2) concentration in the range from 100 to 1000 microliters per liter.

  16. Prechilling of Xanthium strumarium L. Reduces Net Photosynthesis and, Independently, Stomatal Conductance, While Sensitizing the Stomata to CO21

    Science.gov (United States)

    Drake, B.; Raschke, K.

    1974-01-01

    Greenhouse-grown plants of Xanthium strumarium L. were exposed in a growth cabinet to 10 C during days and 5 C during nights for periods of up to 120 hours. Subsequently, CO2 exchange, transpiration, and leaf temperature were measured on attached leaves and in leaf sections at 25 or 30 C, 19 C dew point of the air, 61 milliwatts per square centimeter irradiance, and CO2 concentrations between 0 and 1000 microliters per liter ambient air. Net photosynthesis and stomatal conductance decreased and dark respiration increased with increasing duration of prechilling. The reduction in net photosynthesis was not a consequence of decreased stomatal conductance because the intercellular CO2 concentration in prechilled leaves was equal to or greater than that in greenhouse-grown controls. The intercellular CO2 concentration at which one-half maximum net photosynthesis occurred remained the same in prechilled leaves and controls (175 to 190 microliters per liter). Stomata of the control plants responded to changes in the CO2 concentration of the air only slightly. Prechilling for 24 hours or more sensitized stomata to CO2; they responded to changes in CO2 concentration in the range from 100 to 1000 microliters per liter. PMID:16658795

  17. Synergistic effect of embryo vaccination with Eimeria profilin and Clostridium perfringens NetB proteins on inducing protective immunity against necrotic enteritis in broiler chickens

    Science.gov (United States)

    The effects of embryo vaccination with Eimeria profilin plus Clostridium perfringens NetB toxin proteins in combination with the Montanide IMS-OVO adjuvant on the chicken immune response to necrotic enteritis were investigated using an E. maxima/C. perfringens co-infection model. Eighteen-day-old br...

  18. Effects of Supplementation of Branched-Chain Amino Acids to Reduced-Protein Diet on Skeletal Muscle Protein Synthesis and Degradation in the Fed and Fasted States in a Piglet Model

    Directory of Open Access Journals (Sweden)

    Liufeng Zheng

    2016-12-01

    Full Text Available Supplementation of branched-chain amino acids (BCAA has been demonstrated to promote skeletal muscle mass gain, but the mechanisms underlying this observation are still unknown. Since the regulation of muscle mass depends on a dynamic equilibrium (fasted losses–fed gains in protein turnover, the aim of this study was to investigate the effects of BCAA supplementation on muscle protein synthesis and degradation in fed/fasted states and the related mechanisms. Fourteen 26- (Experiment 1 and 28-day-old (Experiment 2 piglets were fed reduced-protein diets without or with supplemental BCAA. After a four-week acclimation period, skeletal muscle mass and components of anabolic and catabolic signaling in muscle samples after overnight fasting were determined in Experiment 1. Pigs in Experiment 2 were implanted with carotid arterial, jugular venous, femoral arterial and venous catheters, and fed once hourly along with the intravenous infusion of NaH13CO3 for 2 h, followed by a 6-h infusion of [1-13C]leucine. Muscle leucine kinetics were measured using arteriovenous difference technique. The mass of most muscles was increased by BCAA supplementation. During feeding, BCAA supplementation increased leucine uptake, protein synthesis, protein degradation and net transamination. The greater increase in protein synthesis than in protein degradation resulted in elevated protein deposition. Protein synthesis was strongly and positively correlated with the intramuscular net production of α-ketoisocaproate (KIC and protein degradation. Moreover, BCAA supplementation enhanced the fasted-state phosphorylation of protein translation initiation factors and inhibited the protein-degradation signaling of ubiquitin-proteasome and autophagy-lysosome systems. In conclusion, supplementation of BCAA to reduced-protein diet increases fed-state protein synthesis and inhibits fasted-state protein degradation, both of which could contribute to the elevation of skeletal muscle

  19. Can the collection of expired long-lasting insecticidal nets reduce their coverage and use? Sociocultural aspects related to LLIN life cycle management and use in four districts in Madagascar.

    Science.gov (United States)

    Ramanantsoa, Ambinina; Wilson-Barthes, Marta; Rahenintsoa, Rindra; Hoibak, Sarah; Ranaivoharimina, Harilala; Rahelimalala, Martha Delphine; Rakotomanga, Avotiana; Finlay, Alyssa; Muela Ribera, Joan; Peeters Grietens, Koen

    2017-10-10

    There is growing awareness of the likely impact increased numbers of LLINs will have on the environment, if not disposed of or recycled appropriately. As part of a World Health Organization (WHO) and United Nations Environment Programme (UNEP) pilot study to assess environmentally-sound and cost-effective LLIN recycling strategies, the USAID-Deliver Project collected 22,559 used bed nets in Madagascar. A social science study was conducted to provide data on socio-cultural factors related to collection and replacement of LLINs, including impact on primary and other net uses. Ethnographic exploratory research was carried out following the pilot USAID-Deliver net collection and recycling campaign in Betioky, Tsihombe, Fenerive Est and Ambanja districts of Madagascar, triangulating participant observation, interviewing and group discussions. Sampling was theoretical and data analysis was a continuous and iterative process concurrent to data collection. Final analysis was conducted using NVivo10. The following themes emerged as contributing to the success of collecting expired LLINs in the community for recycling purposes: (i) net adequacy and preference: characteristic differences between collected and newly distributed nets lead to communities' reticence to relinquish old nets before confirming new nets were appropriate for intended use. Where newly distributed nets failed to meet local requirements, this was expected to increase alternative uses and decrease household turn over. (ii) Net collection strategies: the net collection campaign brought net use out of the private sphere and into the public arena. Net owners reported feeling ashamed when presenting damaged nets in public for collection, leading to reduced net relinquishment. (iii) Net lifecycle: communities perceived nets as being individually owned and economic value was attributed both to good-condition nets for sleeping and to worn nets for alternative/secondary purposes. Collecting nets at the stage of

  20. Net requirements of energy, protein and macrominerals for weight gain of grazing beef cattle castrated at different ages, with and without supplementation

    Directory of Open Access Journals (Sweden)

    Anilza Andréia da Rocha

    2012-02-01

    Full Text Available The objective of this experiment was to estimate the requirements of energy, protein and macrominerals of grazing crossbreds calves, in Brachiaria decumbens Stapf pasture, castrated at different ages, with and without supplementation. Forty-seven young calves at initial age of 120±30.1 days and 115.3±1.97 kg of live weight were used. To estimate net energy requirements for weight gain, a regression equation between energy retained in the gain and empty body weight gain and metabolic empty body weight was obtained. For estimation of net protein requirements for weight gain, a regression equation was adjusted between protein retained in gain and empty body weight gain and energy content of this gain. Net requirements of Ca, P, Mg and Na for weight gain were determined by the equation Y' = a.b. Xb-1, in which a and b represent the intercept and the coefficient of the alometric equation of macromineral body content prediction, respectively. Neither castration nor concentrate supplementation affects body weight gain net requirements, except the ones of Ca, which were higher for non-castrated animals.

  1. Implementing reduced-risk integrated pest management in fresh-market cabbage: improved net returns via scouting and timing of effective control.

    Science.gov (United States)

    Burkness, Eric C; Hutchison, W D

    2008-04-01

    During 1998-2001, field studies were done to assess the efficacy of an integrated pest management (IPM) program using an action threshold and "reduced-risk" insecticides. The IPM program was compared with a conventional grower-based program. Program performance was evaluated based on management of Trichoplusia ni (Hiibner), Pieris (=Artogeia) rapae (L.), and Plutella xylostella (L.), as well as the economic impact of each program on net returns. The action threshold used in the IPM program consisted of 10% plants infested with T. ni larvae, based on previous small-plot experiment station trials. In all years of the study, the IPM program resulted in significantly lower percentages of plants infested than the conventional program or untreated check. The mean reduction in insecticide applications for the IPM program compared with the conventional program was 23.5%, whereas, on average, the costs of the IPM program were 46.0% higher than the conventional program. Pest reduction in the IPM program resulted in an average of 10.5% higher marketable yields than the conventional program. Percentages of marketable heads in the IPM program ranged from 82 to 99% and from 63 to 96% in the conventional program. Mean net returns for the IPM program exceeded the conventional program by $984.20/ha. These results indicated that the IPM program reduced insecticide use overall, even though costs of the IPM program, with either spinosad or indoxacarb, were sometimes higher. Overall, net returns of the IPM program were higher due to active pest scouting, improved application timing, and increases in marketable yield. Given the potential decrease in insecticide applications and increases in net profit resulting from this IPM program, additional analyses should be conducted to quantify the economic risk, or consistency of the results, to fully evaluate the benefits of the IPM program compared with a conventional program.

  2. Salivary Thromboxane A2-Binding Proteins from Triatomine Vectors of Chagas Disease Inhibit Platelet-Mediated Neutrophil Extracellular Traps (NETs Formation and Arterial Thrombosis.

    Directory of Open Access Journals (Sweden)

    Daniella M Mizurini

    Full Text Available The saliva of blood-feeding arthropods contains a notable diversity of molecules that target the hemostatic and immune systems of the host. Dipetalodipin and triplatin are triatomine salivary proteins that exhibit high affinity binding to prostanoids, such as TXA2, thus resulting in potent inhibitory effect on platelet aggregation in vitro. It was recently demonstrated that platelet-derived TXA2 mediates the formation of neutrophil extracellular traps (NETs, a newly recognized link between inflammation and thrombosis that promote thrombus growth and stability.This study evaluated the ability of dipetalodipin and triplatin to block NETs formation in vitro. We also investigated the in vivo antithrombotic activity of TXA2 binding proteins by employing two murine models of experimental thrombosis. Remarkably, we observed that both inhibitors abolished the platelet-mediated formation of NETs in vitro. Dipetalodipin and triplatin significantly increased carotid artery occlusion time in a FeCl3-induced injury model. Treatment with TXA2-binding proteins also protected mice from lethal pulmonary thromboembolism evoked by the intravenous injection of collagen and epinephrine. Effective antithrombotic doses of dipetalodipin and triplatin did not increase blood loss, which was estimated using the tail transection method.Salivary TXA2-binding proteins, dipetalodipin and triplatin, are capable to prevent platelet-mediated NETs formation in vitro. This ability may contribute to the antithrombotic effects in vivo. Notably, both molecules inhibit arterial thrombosis without promoting excessive bleeding. Our results provide new insight into the antihemostatic effects of TXA2-binding proteins and may have important significance in elucidating the mechanisms of saliva to avoid host's hemostatic responses and innate immune system.

  3. Petri Nets

    Indian Academy of Sciences (India)

    In a computer system, for example, typical discrete events ... This project brought out a series of influential reports on Petri net theory in the mid and late ... Technology became a leading centre for Petri net research and from then on, Petri nets ...

  4. Frequent blood feeding enables insecticide-treated nets to reduce transmission by mosquitoes that bite predominately outdoors.

    Science.gov (United States)

    Russell, Tanya L; Beebe, Nigel W; Bugoro, Hugo; Apairamo, Allan; Chow, Weng K; Cooper, Robert D; Collins, Frank H; Lobo, Neil F; Burkot, Thomas R

    2016-03-10

    The effectiveness of vector control on malaria transmission by long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) depends on the vectors entering houses to blood feed and rest when people are inside houses. In the Solomon Islands, significant reductions in malaria have been achieved in the past 20 years with insecticide-treated bed nets, IRS, improved diagnosis and treatment with artemisinin combination therapies; despite the preference of the primary vector, Anopheles farauti, to feed outdoors and early in the evening and thereby avoid potential exposure to insecticides. Rational development of tools to complement LLINs and IRS by attacking vectors outdoor requires detailed knowledge of the biology and behaviours of the target species. Malaria transmission in Central Province, Solomon Islands was estimated by measuring the components comprising the entomological inoculation rate (EIR) as well as the vectorial capacity of An. farauti. In addition, the daily and seasonal biting behaviour of An. farauti, was examined and the duration of the feeding cycle was estimated with a mark-release-recapture experiment. Anopheles farauti was highly exophagic with 72% captured by human landing catches (HLC) outside of houses. Three-quarters (76%) of blood feeding on humans was estimated to occur before 21.00 h. When the hourly location of humans was considered, the proportion of exposure to mosquito bites on humans occurring indoors (πi) was only 0.130 ± 0.129. Peak densities of host seeking An. farauti occurred between October and January. The annual EIR was estimated to be 2.5 for 2012 and 33.2 for 2013. The length of the feeding cycle was 2.1 days. The short duration of the feeding cycle by this species offers an explanation for the substantial control of malaria that has been achieved in the Solomon Islands by LLINs and IRS. Anopheles farauti is primarily exophagic and early biting, with 13% of mosquitoes entering houses to feed late at night during

  5. High dietary protein intake, reducing or eliciting insulin resistance?

    NARCIS (Netherlands)

    Rietman, A.; Schwarz, J.; Tome, D.; Kok, F.J.; Mensink, M.R.

    2014-01-01

    Dietary proteins have an insulinotropic effect and thus promote insulin secretion, which indeed leads to enhanced glucose clearance from the blood. In the long term, however, a high dietary protein intake is associated with an increased risk of type 2 diabetes. Moreover, branched-chain amino acids

  6. Insecticide-treated bed nets reduce plasma antibody levels and limit the repertoire of antibodies to Plasmodium falciparum variant surface antigens

    DEFF Research Database (Denmark)

    Askjaer, N; Maxwell, C; Chambo, W

    2001-01-01

    The use of insecticide-treated bed nets (ITN) has been documented to reduce malaria morbidity and mortality in areas with endemic malaria, but concerns have been raised that ITN usage could affect the acquisition of malaria immunity. Several lines of evidence have indicated that antibodies against...... variant surface antigens (VSA) are important in the development of naturally acquired immunity to Plasmodium falciparum malaria and may thus be good indicators of immune status. We have compared the levels of VSA antibodies in plasma from children who have used ITN for 4 years to levels in plasma from...

  7. Skeletal muscle protein accretion rates and hindlimb growth are reduced in late gestation intrauterine growth-restricted fetal sheep.

    Science.gov (United States)

    Rozance, Paul J; Zastoupil, Laura; Wesolowski, Stephanie R; Goldstrohm, David A; Strahan, Brittany; Cree-Green, Melanie; Sheffield-Moore, Melinda; Meschia, Giacomo; Hay, William W; Wilkening, Randall B; Brown, Laura D

    2018-01-01

    Adults who were affected by intrauterine growth restriction (IUGR) suffer from reductions in muscle mass, which may contribute to insulin resistance and the development of diabetes. We demonstrate slower hindlimb linear growth and muscle protein synthesis rates that match the reduced hindlimb blood flow and oxygen consumption rates in IUGR fetal sheep. These adaptations resulted in hindlimb blood flow rates in IUGR that were similar to control fetuses on a weight-specific basis. Net hindlimb glucose uptake and lactate output rates were similar between groups, whereas amino acid uptake was significantly lower in IUGR fetal sheep. Among all fetuses, blood O 2 saturation and plasma glucose, insulin and insulin-like growth factor-1 were positively associated and norepinephrine was negatively associated with hindlimb weight. These results further our understanding of the metabolic and hormonal adaptations to reduced oxygen and nutrient supply with placental insufficiency that develop to slow hindlimb growth and muscle protein accretion. Reduced skeletal muscle mass in the fetus with intrauterine growth restriction (IUGR) persists into adulthood and may contribute to increased metabolic disease risk. To determine how placental insufficiency with reduced oxygen and nutrient supply to the fetus affects hindlimb blood flow, substrate uptake and protein accretion rates in skeletal muscle, late gestation control (CON) (n = 8) and IUGR (n = 13) fetal sheep were catheterized with aortic and femoral catheters and a flow transducer around the external iliac artery. Muscle protein kinetic rates were measured using isotopic tracers. Hindlimb weight, linear growth rate, muscle protein accretion rate and fractional synthetic rate were lower in IUGR compared to CON (P fetal norepinephrine and reduced IGF-1 and insulin. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

  8. SUPPLEMENTARY FEEDING ON THE NUTRIENT BALANCE OF LACTATING DAIRY COW AT CONTRASTING TEMPERATURE REGIMES: ASSESSMENT USING CORNELL NET CARBOHYDRATE AND PROTEIN SYSTEM (CNCPS) MODEL

    OpenAIRE

    A. Jayanegara; A. Sofyan

    2014-01-01

    Dairy cows often do not receive adequate nutrient supply during their lactation period. This condition caneven be worse if the environmental temperature is not in comfortable range which may occur especially intropical regions. The present research was aimed to simulate the effect of supplementary feeding on nutrientbalance of lactating dairy cow at contrasting temperature regimes using Cornell Net Carbohydrate andProtein System (CNCPS) model. Treatments consisted of feeds (R1: Pennisetum pur...

  9. Net zero water

    CSIR Research Space (South Africa)

    Lindeque, M

    2013-01-01

    Full Text Available the national grid. The unfortunate situation with water is that there is no replacement technology for water. Water can be supplied from many different sources. A net zero energy development will move closer to a net zero water development by reducing...

  10. Reliability ensemble averaging of 21st century projections of terrestrial net primary productivity reduces global and regional uncertainties

    Science.gov (United States)

    Exbrayat, Jean-François; Bloom, A. Anthony; Falloon, Pete; Ito, Akihiko; Smallman, T. Luke; Williams, Mathew

    2018-02-01

    Multi-model averaging techniques provide opportunities to extract additional information from large ensembles of simulations. In particular, present-day model skill can be used to evaluate their potential performance in future climate simulations. Multi-model averaging methods have been used extensively in climate and hydrological sciences, but they have not been used to constrain projected plant productivity responses to climate change, which is a major uncertainty in Earth system modelling. Here, we use three global observationally orientated estimates of current net primary productivity (NPP) to perform a reliability ensemble averaging (REA) method using 30 global simulations of the 21st century change in NPP based on the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP) business as usual emissions scenario. We find that the three REA methods support an increase in global NPP by the end of the 21st century (2095-2099) compared to 2001-2005, which is 2-3 % stronger than the ensemble ISIMIP mean value of 24.2 Pg C y-1. Using REA also leads to a 45-68 % reduction in the global uncertainty of 21st century NPP projection, which strengthens confidence in the resilience of the CO2 fertilization effect to climate change. This reduction in uncertainty is especially clear for boreal ecosystems although it may be an artefact due to the lack of representation of nutrient limitations on NPP in most models. Conversely, the large uncertainty that remains on the sign of the response of NPP in semi-arid regions points to the need for better observations and model development in these regions.

  11. Effects of reducing dietary crude protein and metabolic energy in ...

    African Journals Online (AJOL)

    The objective of this experiment was to determine the effects of a pure reduction in the dietary crude protein (CP) and metabolic energy (ME) contents on growth performance, nutrient digestibility, blood profile, faecal microflora and odour gas emission in weaned pigs. A total of 80 weaned piglets ((Landrace × Yorkshire) ...

  12. NetTurnP--neural network prediction of beta-turns by use of evolutionary information and predicted protein sequence features.

    Directory of Open Access Journals (Sweden)

    Bent Petersen

    Full Text Available UNLABELLED: β-turns are the most common type of non-repetitive structures, and constitute on average 25% of the amino acids in proteins. The formation of β-turns plays an important role in protein folding, protein stability and molecular recognition processes. In this work we present the neural network method NetTurnP, for prediction of two-class β-turns and prediction of the individual β-turn types, by use of evolutionary information and predicted protein sequence features. It has been evaluated against a commonly used dataset BT426, and achieves a Matthews correlation coefficient of 0.50, which is the highest reported performance on a two-class prediction of β-turn and not-β-turn. Furthermore NetTurnP shows improved performance on some of the specific β-turn types. In the present work, neural network methods have been trained to predict β-turn or not and individual β-turn types from the primary amino acid sequence. The individual β-turn types I, I', II, II', VIII, VIa1, VIa2, VIba and IV have been predicted based on classifications by PROMOTIF, and the two-class prediction of β-turn or not is a superset comprised of all β-turn types. The performance is evaluated using a golden set of non-homologous sequences known as BT426. Our two-class prediction method achieves a performance of: MCC=0.50, Qtotal=82.1%, sensitivity=75.6%, PPV=68.8% and AUC=0.864. We have compared our performance to eleven other prediction methods that obtain Matthews correlation coefficients in the range of 0.17-0.47. For the type specific β-turn predictions, only type I and II can be predicted with reasonable Matthews correlation coefficients, where we obtain performance values of 0.36 and 0.31, respectively. CONCLUSION: The NetTurnP method has been implemented as a webserver, which is freely available at http://www.cbs.dtu.dk/services/NetTurnP/. NetTurnP is the only available webserver that allows submission of multiple sequences.

  13. NetTurnP – Neural Network Prediction of Beta-turns by Use of Evolutionary Information and Predicted Protein Sequence Features

    Science.gov (United States)

    Petersen, Bent; Lundegaard, Claus; Petersen, Thomas Nordahl

    2010-01-01

    β-turns are the most common type of non-repetitive structures, and constitute on average 25% of the amino acids in proteins. The formation of β-turns plays an important role in protein folding, protein stability and molecular recognition processes. In this work we present the neural network method NetTurnP, for prediction of two-class β-turns and prediction of the individual β-turn types, by use of evolutionary information and predicted protein sequence features. It has been evaluated against a commonly used dataset BT426, and achieves a Matthews correlation coefficient of 0.50, which is the highest reported performance on a two-class prediction of β-turn and not-β-turn. Furthermore NetTurnP shows improved performance on some of the specific β-turn types. In the present work, neural network methods have been trained to predict β-turn or not and individual β-turn types from the primary amino acid sequence. The individual β-turn types I, I', II, II', VIII, VIa1, VIa2, VIba and IV have been predicted based on classifications by PROMOTIF, and the two-class prediction of β-turn or not is a superset comprised of all β-turn types. The performance is evaluated using a golden set of non-homologous sequences known as BT426. Our two-class prediction method achieves a performance of: MCC  = 0.50, Qtotal = 82.1%, sensitivity  = 75.6%, PPV  = 68.8% and AUC  = 0.864. We have compared our performance to eleven other prediction methods that obtain Matthews correlation coefficients in the range of 0.17 – 0.47. For the type specific β-turn predictions, only type I and II can be predicted with reasonable Matthews correlation coefficients, where we obtain performance values of 0.36 and 0.31, respectively. Conclusion The NetTurnP method has been implemented as a webserver, which is freely available at http://www.cbs.dtu.dk/services/NetTurnP/. NetTurnP is the only available webserver that allows submission of multiple sequences. PMID:21152409

  14. NetTurnP--neural network prediction of beta-turns by use of evolutionary information and predicted protein sequence features.

    Science.gov (United States)

    Petersen, Bent; Lundegaard, Claus; Petersen, Thomas Nordahl

    2010-11-30

    β-turns are the most common type of non-repetitive structures, and constitute on average 25% of the amino acids in proteins. The formation of β-turns plays an important role in protein folding, protein stability and molecular recognition processes. In this work we present the neural network method NetTurnP, for prediction of two-class β-turns and prediction of the individual β-turn types, by use of evolutionary information and predicted protein sequence features. It has been evaluated against a commonly used dataset BT426, and achieves a Matthews correlation coefficient of 0.50, which is the highest reported performance on a two-class prediction of β-turn and not-β-turn. Furthermore NetTurnP shows improved performance on some of the specific β-turn types. In the present work, neural network methods have been trained to predict β-turn or not and individual β-turn types from the primary amino acid sequence. The individual β-turn types I, I', II, II', VIII, VIa1, VIa2, VIba and IV have been predicted based on classifications by PROMOTIF, and the two-class prediction of β-turn or not is a superset comprised of all β-turn types. The performance is evaluated using a golden set of non-homologous sequences known as BT426. Our two-class prediction method achieves a performance of: MCC=0.50, Qtotal=82.1%, sensitivity=75.6%, PPV=68.8% and AUC=0.864. We have compared our performance to eleven other prediction methods that obtain Matthews correlation coefficients in the range of 0.17-0.47. For the type specific β-turn predictions, only type I and II can be predicted with reasonable Matthews correlation coefficients, where we obtain performance values of 0.36 and 0.31, respectively. The NetTurnP method has been implemented as a webserver, which is freely available at http://www.cbs.dtu.dk/services/NetTurnP/. NetTurnP is the only available webserver that allows submission of multiple sequences.

  15. NetTurnP – Neural Network Prediction of Beta-turns by Use of Evolutionary Information and Predicted Protein Sequence Features

    DEFF Research Database (Denmark)

    Petersen, Bent; Lundegaard, Claus; Petersen, Thomas Nordahl

    2010-01-01

    is the highest reported performance on a two-class prediction of β-turn and not-β-turn. Furthermore NetTurnP shows improved performance on some of the specific β-turn types. In the present work, neural network methods have been trained to predict β-turn or not and individual β-turn types from the primary amino......β-turns are the most common type of non-repetitive structures, and constitute on average 25% of the amino acids in proteins. The formation of β-turns plays an important role in protein folding, protein stability and molecular recognition processes. In this work we present the neural network method...... NetTurnP, for prediction of two-class β-turns and prediction of the individual β-turn types, by use of evolutionary information and predicted protein sequence features. It has been evaluated against a commonly used dataset BT426, and achieves a Matthews correlation coefficient of 0.50, which...

  16. Water-saving ground cover rice production system reduces net greenhouse gas fluxes in an annual rice-based cropping system

    Science.gov (United States)

    Yao, Z.; Du, Y.; Tao, Y.; Zheng, X.; Liu, C.; Lin, S.; Butterbach-Bahl, K.

    2014-11-01

    To safeguard food security and preserve precious water resources, the technology of water-saving ground cover rice production system (GCRPS) is being increasingly adopted for rice cultivation. However, changes in soil water status and temperature under GCRPS may affect soil biogeochemical processes that control the biosphere-atmosphere exchanges of methane (CH4), nitrous oxide (N2O) and carbon dioxide (CO2). The overall goal of this study is to better understand how net ecosystem greenhouse gas exchanges (NEGE) and grain yields are affected by GCRPS in an annual rice-based cropping system. Our evaluation was based on measurements of the CH4 and N2O fluxes and soil heterotrophic respiration (CO2 emissions) over a complete year, and the estimated soil carbon sequestration intensity for six different fertilizer treatments for conventional paddy and GCRPS. The fertilizer treatments included urea application and no N fertilization for both conventional paddy (CUN and CNN) and GCRPS (GUN and GNN), and solely chicken manure (GCM) and combined urea and chicken manure applications (GUM) for GCRPS. Averaging across all the fertilizer treatments, GCRPS increased annual N2O emission and grain yield by 40 and 9%, respectively, and decreased annual CH4 emission by 69%, while GCRPS did not affect soil CO2 emissions relative to the conventional paddy. The annual direct emission factors of N2O were 4.01, 0.09 and 0.50% for GUN, GCM and GUM, respectively, and 1.52% for the conventional paddy (CUN). The annual soil carbon sequestration intensity under GCRPS was estimated to be an average of -1.33 Mg C ha-1 yr-1, which is approximately 44% higher than the conventional paddy. The annual NEGE were 10.80-11.02 Mg CO2-eq ha-1 yr-1 for the conventional paddy and 3.05-9.37 Mg CO2-eq ha-1 yr-1 for the GCRPS, suggesting the potential feasibility of GCRPS in reducing net greenhouse effects from rice cultivation. Using organic fertilizers for GCRPS considerably reduced annual emissions of CH4

  17. Net Neutrality

    DEFF Research Database (Denmark)

    Savin, Andrej

    2017-01-01

    Repealing “net neutrality” in the US will have no bearing on Internet freedom or security there or anywhere else.......Repealing “net neutrality” in the US will have no bearing on Internet freedom or security there or anywhere else....

  18. Membrane Compartmentalization Reducing the Mobility of Lipids and Proteins within a Model Plasma Membrane.

    Science.gov (United States)

    Koldsø, Heidi; Reddy, Tyler; Fowler, Philip W; Duncan, Anna L; Sansom, Mark S P

    2016-09-01

    The cytoskeleton underlying cell membranes may influence the dynamic organization of proteins and lipids within the bilayer by immobilizing certain transmembrane (TM) proteins and forming corrals within the membrane. Here, we present coarse-grained resolution simulations of a biologically realistic membrane model of asymmetrically organized lipids and TM proteins. We determine the effects of a model of cytoskeletal immobilization of selected membrane proteins using long time scale coarse-grained molecular dynamics simulations. By introducing compartments with varying degrees of restraints within the membrane models, we are able to reveal how compartmentalization caused by cytoskeletal immobilization leads to reduced and anomalous diffusional mobility of both proteins and lipids. This in turn results in a reduced rate of protein dimerization within the membrane and of hopping of membrane proteins between compartments. These simulations provide a molecular realization of hierarchical models often invoked to explain single-molecule imaging studies of membrane proteins.

  19. Petri Nets

    Indian Academy of Sciences (India)

    GENERAL I ARTICLE ... In Part 1 of this two-part article, we have seen im- ..... mable logic controller and VLSI arrays, office automation systems, workflow management systems, ... complex discrete event and real-time systems; and Petri nets.

  20. Toward a rigorous network of protein-protein interactions of the model sulfate reducer Desulfovibrio vulgaris Hildenborough

    Energy Technology Data Exchange (ETDEWEB)

    Chhabra, S.R.; Joachimiak, M.P.; Petzold, C.J.; Zane, G.M.; Price, M.N.; Gaucher, S.; Reveco, S.A.; Fok, V.; Johanson, A.R.; Batth, T.S.; Singer, M.; Chandonia, J.M.; Joyner, D.; Hazen, T.C.; Arkin, A.P.; Wall, J.D.; Singh, A.K.; Keasling, J.D.

    2011-05-01

    Protein–protein interactions offer an insight into cellular processes beyond what may be obtained by the quantitative functional genomics tools of proteomics and transcriptomics. The aforementioned tools have been extensively applied to study E. coli and other aerobes and more recently to study the stress response behavior of Desulfovibrio 5 vulgaris Hildenborough, a model anaerobe and sulfate reducer. In this paper we present the first attempt to identify protein-protein interactions in an obligate anaerobic bacterium. We used suicide vector-assisted chromosomal modification of 12 open reading frames encoded by this sulfate reducer to append an eight amino acid affinity tag to the carboxy-terminus of the chosen proteins. Three biological replicates of the 10 ‘pulled-down’ proteins were separated and analyzed using liquid chromatography-mass spectrometry. Replicate agreement ranged between 35% and 69%. An interaction network among 12 bait and 90 prey proteins was reconstructed based on 134 bait-prey interactions computationally identified to be of high confidence. We discuss the biological significance of several unique metabolic features of D. vulgaris revealed by this protein-protein interaction data 15 and protein modifications that were observed. These include the distinct role of the putative carbon monoxide-induced hydrogenase, unique electron transfer routes associated with different oxidoreductases, and the possible role of methylation in regulating sulfate reduction.

  1. NetSig

    DEFF Research Database (Denmark)

    Horn, Heiko; Lawrence, Michael S; Chouinard, Candace R

    2018-01-01

    Methods that integrate molecular network information and tumor genome data could complement gene-based statistical tests to identify likely new cancer genes; but such approaches are challenging to validate at scale, and their predictive value remains unclear. We developed a robust statistic (Net......Sig) that integrates protein interaction networks with data from 4,742 tumor exomes. NetSig can accurately classify known driver genes in 60% of tested tumor types and predicts 62 new driver candidates. Using a quantitative experimental framework to determine in vivo tumorigenic potential in mice, we found that Net......Sig candidates induce tumors at rates that are comparable to those of known oncogenes and are ten-fold higher than those of random genes. By reanalyzing nine tumor-inducing NetSig candidates in 242 patients with oncogene-negative lung adenocarcinomas, we find that two (AKT2 and TFDP2) are significantly amplified...

  2. A novel one-pot process for near-net-shape fabrication of open-porous resorbable hydroxyapatite/protein composites and in vivo assessment

    International Nuclear Information System (INIS)

    Mueller, Berit; Koch, Dietmar; Lutz, Rainer; Schlegel, Karl A.; Treccani, Laura; Rezwan, Kurosch

    2014-01-01

    We present a mild one-pot freeze gelation process for fabricating near-net, complex-shaped hydroxyapatite scaffolds and to directly incorporate active proteins during scaffold processing. In particular, the direct protein incorporation enables a simultaneous adjustment and control of scaffold microstructure, porosity, resorbability and enhancement of initial mechanical and handling stability. Two proteins, serum albumin and lysozyme, are selected and their effect on scaffold stability and microstructure investigated by biaxial strength tests, electron microscopy, and mercury intrusion porosimetry. The resulting hydroxyapatite/protein composites feature adjustable porosities from 50% to 70% and a mechanical strength ranging from 2 to 6 MPa comparable to that of human spongiosa without any sintering step. Scaffold degradation behaviour and protein release are assessed by in vitro studies. A preliminary in vivo assessment of scaffold biocompatibility and resorption behaviour in adult domestic pigs is discussed. After implantation, composites were resorbed up to 50% after only 4 weeks and up to 65% after 8 weeks. In addition, 14% new bone formation after 4 weeks and 37% after 8 weeks were detected. All these investigations demonstrate the outstanding suitability of the one-pot-process to create, in a customisable and reliable way, biocompatible scaffolds with sufficient mechanical strength for handling and surgical insertion, and for potential use as biodegradable bone substitutes and versatile platform for local drug delivery. - Highlights: • We present a one-pot process for directly incorporating protein into HAp scaffolds. • The effect of two model proteins, BSA and LSZ, on scaffold properties is analysed. • HAp/protein scaffolds feature a mechanical strength comparable to human spongiosa. • BSA incorporation in scaffolds leads to strength increase despite porosity increment. • New bone formation in-vivo exceeds established xenograft bone substitutes

  3. Ubiquilin overexpression reduces GFP-polyalanine-induced protein aggregates and toxicity

    International Nuclear Information System (INIS)

    Wang Hongmin; Monteiro, Mervyn J.

    2007-01-01

    Several human disorders are associated with an increase in a continuous stretch of alanine amino acids in proteins. These so-called polyalanine expansion diseases share many similarities with polyglutamine-related disorders, including a length-dependent reiteration of amino acid induction of protein aggregation and cytotoxicity. We previously reported that overexpression of ubiquilin reduces protein aggregates and toxicity of expanded polyglutamine proteins. Here, we demonstrate a similar role for ubiquilin toward expanded polyalanine proteins. Overexpression of ubiquilin-1 in HeLa cells reduced protein aggregates and the cytotoxicity associated with expression of a transfected nuclear-targeted GFP-fusion protein containing 37-alanine repeats (GFP-A37), in a dose dependent manner. Ubiquilin coimmunoprecipitated more with GFP proteins containing a 37-polyalanine tract compared to either 7 (GFP-A7), or no alanine tract (GFP). Moreover, overexpression of ubiquilin suppressed the increased vulnerability of HeLa cell lines stably expressing the GFP-A37 fusion protein to oxidative stress-induced cell death compared to cell lines expressing GFP or GFP-A7 proteins. By contrast, siRNA knockdown of ubiquilin expression in the GFP-A37 cell line was associated with decreased cellular proliferation, and increases in GFP protein aggregates, nuclear fragmentation, and cell death. Our results suggest that boosting ubiquilin levels in cells might provide a universal and attractive strategy to prevent toxicity of proteins containing reiterative expansions of amino acids involved in many human diseases

  4. Towards a rigorous network of protein-protein interactions of the model sulfate reducer Desulfovibrio vulgaris Hildenborough.

    Directory of Open Access Journals (Sweden)

    Swapnil R Chhabra

    Full Text Available Protein-protein interactions offer an insight into cellular processes beyond what may be obtained by the quantitative functional genomics tools of proteomics and transcriptomics. The aforementioned tools have been extensively applied to study Escherichia coli and other aerobes and more recently to study the stress response behavior of Desulfovibrio vulgaris Hildenborough, a model obligate anaerobe and sulfate reducer and the subject of this study. Here we carried out affinity purification followed by mass spectrometry to reconstruct an interaction network among 12 chromosomally encoded bait and 90 prey proteins based on 134 bait-prey interactions identified to be of high confidence. Protein-protein interaction data are often plagued by the lack of adequate controls and replication analyses necessary to assess confidence in the results, including identification of potential false positives. We addressed these issues through the use of biological replication, exponentially modified protein abundance indices, results from an experimental negative control, and a statistical test to assign confidence to each putative interacting pair applicable to small interaction data studies. We discuss the biological significance of metabolic features of D. vulgaris revealed by these protein-protein interaction data and the observed protein modifications. These include the distinct role of the putative carbon monoxide-induced hydrogenase, unique electron transfer routes associated with different oxidoreductases, and the possible role of methylation in regulating sulfate reduction.

  5. RESTful NET

    CERN Document Server

    Flanders, Jon

    2008-01-01

    RESTful .NET is the first book that teaches Windows developers to build RESTful web services using the latest Microsoft tools. Written by Windows Communication Foundation (WFC) expert Jon Flanders, this hands-on tutorial demonstrates how you can use WCF and other components of the .NET 3.5 Framework to build, deploy and use REST-based web services in a variety of application scenarios. RESTful architecture offers a simpler approach to building web services than SOAP, SOA, and the cumbersome WS- stack. And WCF has proven to be a flexible technology for building distributed systems not necessa

  6. Improved netting

    International Nuclear Information System (INIS)

    Bramley, A.; Clabburn, R.J.T.

    1976-01-01

    A method is described for producing netting composed of longitudinal and transverse threads of irradiation cross linked thermoplastic material, the threads being joined together at their crossings by moulded masses of cross linked thermoplastic material. The thread may be formed of polyethylene filaments, subjected to a radiation dose of 15 to 25 MR. The moulding can be conducted at 245 0 to 260 0 C or higher. The product is claimed to be an improved quality of netting, with bonds of increased strength between crossing threads. (U.K.)

  7. Beta-carotene encapsulated in food protein nanoparticles reduces peroxyl radical oxidation in Caco-2 cells

    Science.gov (United States)

    Beta-carotene (BC) was encapsulated by sodium caseinate (SC), whey protein isolate (WPI), and soybean protein isolate (SPI) by the homogenization-evaporation method forming nanoparticles of 78, 90 and 370 nm diameter. Indices of the chemical antioxidant assays, the reducing power, DPPH radical scave...

  8. Petri Nets

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 4; Issue 9. Petri Nets - Applications. Y Narahari. General Article Volume 4 Issue 9 September 1999 pp 44-52 ... Author Affiliations. Y Narahari1. Department of Computer Science and Automation, Indian Institute of Science, Bangalore 560 012, India.

  9. Net Gain

    International Development Research Centre (IDRC) Digital Library (Canada)

    Describing the effect of tax incentives for import, production, and sale of nets and insecticides; and ..... So far, China is the only country where a system for the routine treatment of ...... 1993), and the trials in Ecuador and Peru (Kroeger et al.

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

    Science.gov (United States)

    Nester, Robert T.

    1987-01-01

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

  11. Graphene as a protein crystal mounting material to reduce background scatter.

    Science.gov (United States)

    Wierman, Jennifer L; Alden, Jonathan S; Kim, Chae Un; McEuen, Paul L; Gruner, Sol M

    2013-10-01

    The overall signal-to-noise ratio per unit dose for X-ray diffraction data from protein crystals can be improved by reducing the mass and density of all material surrounding the crystals. This article demonstrates a path towards the practical ultimate in background reduction by use of atomically thin graphene sheets as a crystal mounting platform for protein crystals. The results show the potential for graphene in protein crystallography and other cases where X-ray scatter from the mounting material must be reduced and specimen dehydration prevented, such as in coherent X-ray diffraction imaging of microscopic objects.

  12. Fish protein hydrolysate elevates plasma bile acids and reduces visceral adipose tissue mass in rats

    DEFF Research Database (Denmark)

    Liaset, Bjørn; Madsen, Lise; Hao, Qin

    2009-01-01

    levels relative to rats fed soy protein or casein. Concomitantly, the saithe FPH fed rats had reduced liver lipids and fasting plasma TAG levels. Furthermore, visceral adipose tissue mass was reduced and expression of genes involved in fatty acid oxidation and energy expenditure was induced in perirenal....../retroperitoneal adipose tissues of rats fed saithe FPH. Our results provide the first evidence that dietary protein sources with different amino acid compositions can modulate the level of plasma bile acids and our data suggest potential novel mechanisms by which dietary protein sources can affect energy metabolism....

  13. An autoclave treatment reduces the solubility and antigenicity of an allergenic protein found in buckwheat flour.

    Science.gov (United States)

    Tomotake, Hiroyuki; Yamazaki, Rikio; Yamato, Masayuki

    2012-06-01

    The effects of an autoclave treatment of buckwheat flour on a 24-kDa allergenic protein were investigated by measuring reduction in solubility and antibody binding. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed that the intensity of the major bands, including that of the 24-kDa allergen, was reduced by the autoclave treatment. The protein solubility in buckwheat flour was variably decreased by the autoclave treatment. Enzyme-linked immunosorbent assay analysis using a monoclonal antibody specific for buckwheat 24-kDa protein showed that the reactivity of protein extracts (10 μg/ml) from buckwheat flour was lowered by the autoclave treatment. The autoclave treatment may reduce the major allergen content of buckwheat. Future studies will determine if autoclaving treatments affect the allergenicity of the 24-kDa buckwheat protein.

  14. Chenodeoxycholic Acid Reduces Hypoxia Inducible Factor-1α Protein and Its Target Genes.

    Directory of Open Access Journals (Sweden)

    Yunwon Moon

    Full Text Available This study evaluated HIF-1α inhibitors under different hypoxic conditions, physiological hypoxia (5% O2 and severe hypoxia (0.1% O2. We found that chenodeoxy cholic acid (CDCA reduced the amount of HIF-1α protein only under physiological hypoxia but not under severe hypoxia without decreasing its mRNA level. By using a proteasome inhibitor MG132 and a translation inhibitor cyclohexamide, we showed that CDCA reduced HIF-1α protein by decreasing its translation but not by enhancing its degradation. The following findings indicated that farnesoid X receptor (FXR, a CDCA receptor and its target gene, Small heterodimer partner (SHP are not involved in this effect of CDCA. Distinctly from CDCA, MG132 prevented SHP and an exogenous FXR agonist, GW4064 from reducing HIF-1α protein. Furthermore a FXR antagonist, guggulsterone failed to prevent CDCA from decreasing HIF-1α protein. Furthermore, guggulsterone by itself reduced HIF-1α protein even in the presence of MG132. These findings suggested that CDCA and guggulsterone reduced the translation of HIF-1α in a mechanism which FXR and SHP are not involved. This study reveals novel therapeutic functions of traditional nontoxic drugs, CDCA and guggulsterone, as inhibitors of HIF-1α protein.

  15. Reduced synaptic vesicle protein degradation at lysosomes curbs TBC1D24/sky-induced neurodegeneration.

    Science.gov (United States)

    Fernandes, Ana Clara; Uytterhoeven, Valerie; Kuenen, Sabine; Wang, Yu-Chun; Slabbaert, Jan R; Swerts, Jef; Kasprowicz, Jaroslaw; Aerts, Stein; Verstreken, Patrik

    2014-11-24

    Synaptic demise and accumulation of dysfunctional proteins are thought of as common features in neurodegeneration. However, the mechanisms by which synaptic proteins turn over remain elusive. In this paper, we study Drosophila melanogaster lacking active TBC1D24/Skywalker (Sky), a protein that in humans causes severe neurodegeneration, epilepsy, and DOOR (deafness, onychdystrophy, osteodystrophy, and mental retardation) syndrome, and identify endosome-to-lysosome trafficking as a mechanism for degradation of synaptic vesicle-associated proteins. In fly sky mutants, synaptic vesicles traveled excessively to endosomes. Using chimeric fluorescent timers, we show that synaptic vesicle-associated proteins were younger on average, suggesting that older proteins are more efficiently degraded. Using a genetic screen, we find that reducing endosomal-to-lysosomal trafficking, controlled by the homotypic fusion and vacuole protein sorting (HOPS) complex, rescued the neurotransmission and neurodegeneration defects in sky mutants. Consistently, synaptic vesicle proteins were older in HOPS complex mutants, and these mutants also showed reduced neurotransmission. Our findings define a mechanism in which synaptic transmission is facilitated by efficient protein turnover at lysosomes and identify a potential strategy to suppress defects arising from TBC1D24 mutations in humans. © 2014 Fernandes et al.

  16. Reduced protein oxidation in Wistar rats supplemented with marine ω3 PUFAs.

    Science.gov (United States)

    Méndez, Lucía; Pazos, Manuel; Gallardo, José M; Torres, Josep L; Pérez-Jiménez, Jara; Nogués, Rosa; Romeu, Marta; Medina, Isabel

    2013-02-01

    The potential effects of various dietary eicosapentaenoic acid (EPA; 20:5) and docosahexaenoic acid (DHA; 22:6) ratios (1:1, 2:1, and 1:2, respectively) on protein redox states from plasma, kidney, skeletal muscle, and liver were investigated in Wistar rats. Dietary fish oil groups were compared with animals fed soybean and linseed oils, vegetable oils enriched in ω6 linoleic acid (LA; 18:2) and ω3 α-linolenic acid (ALA; 18:3), respectively. Fish oil treatments were effective at reducing the level of total fatty acids in plasma and enriching the plasmatic free fatty acid fraction and erythrocyte membranes in EPA and DHA. A proteomic approach consisting of fluorescein 5-thiosemicarbazide (FTSC) labeling of protein carbonyls, FTSC intensity visualization on 1-DE or 2-DE gels, and protein identification by MS/MS was used for the protein oxidation assessment. Albumin was found to be the most carbonylated protein in plasma for all dietary groups, and its oxidation level was significantly modulated by dietary interventions. Supplementation with an equal EPA:DHA ratio (1:1) showed the lowest oxidation score for plasma albumin, followed in increasing order of carbonylation by 1:2 proteins and cytosolic proteins from kidney and liver also indicated a protective effect on proteins for the fish oil treatments, the 1:1 ratio exhibiting the lowest protein oxidation scores. The effect of fish oil treatments at reducing carbonylation on specific proteins from plasma (albumin), skeletal muscle (actin), and liver (albumin, argininosuccinate synthetase, 3-α-hydroxysteroid dehydrogenase) was remarkable. This investigation highlights the efficiency of dietary fish oil at reducing in vivo oxidative damage of proteins compared to oils enriched in the 18-carbon polyunsaturated fatty acids ω3 ALA and ω6 LA, and such antioxidant activity may differ among different fish oil sources because of variations in EPA/DHA content. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Net Locality

    DEFF Research Database (Denmark)

    de Souza e Silva, Adriana Araujo; Gordon, Eric

    Provides an introduction to the new theory of Net Locality and the profound effect on individuals and societies when everything is located or locatable. Describes net locality as an emerging form of location awareness central to all aspects of digital media, from mobile phones, to Google Maps......, to location-based social networks and games, such as Foursquare and facebook. Warns of the threats these technologies, such as data surveillance, present to our sense of privacy, while also outlining the opportunities for pro-social developments. Provides a theory of the web in the context of the history...... of emerging technologies, from GeoCities to GPS, Wi-Fi, Wiki Me, and Google Android....

  18. The Gcn4 transcription factor reduces protein synthesis capacity and extends yeast lifespan.

    Science.gov (United States)

    Mittal, Nitish; Guimaraes, Joao C; Gross, Thomas; Schmidt, Alexander; Vina-Vilaseca, Arnau; Nedialkova, Danny D; Aeschimann, Florian; Leidel, Sebastian A; Spang, Anne; Zavolan, Mihaela

    2017-09-06

    In Saccharomyces cerevisiae, deletion of large ribosomal subunit protein-encoding genes increases the replicative lifespan in a Gcn4-dependent manner. However, how Gcn4, a key transcriptional activator of amino acid biosynthesis genes, increases lifespan, is unknown. Here we show that Gcn4 acts as a repressor of protein synthesis. By analyzing the messenger RNA and protein abundance, ribosome occupancy and protein synthesis rate in various yeast strains, we demonstrate that Gcn4 is sufficient to reduce protein synthesis and increase yeast lifespan. Chromatin immunoprecipitation reveals Gcn4 binding not only at genes that are activated, but also at genes, some encoding ribosomal proteins, that are repressed upon Gcn4 overexpression. The promoters of repressed genes contain Rap1 binding motifs. Our data suggest that Gcn4 is a central regulator of protein synthesis under multiple perturbations, including ribosomal protein gene deletions, calorie restriction, and rapamycin treatment, and provide an explanation for its role in longevity and stress response.The transcription factor Gcn4 is known to regulate yeast amino acid synthesis. Here, the authors show that Gcn4 also acts as a repressor of protein biosynthesis in a range of conditions that enhance yeast lifespan, such as ribosomal protein knockout, calorie restriction or mTOR inhibition.

  19. Proteomic detection of oxidized and reduced thiol proteins in cultured cells.

    Science.gov (United States)

    Cuddihy, Sarah L; Baty, James W; Brown, Kristin K; Winterbourn, Christine C; Hampton, Mark B

    2009-01-01

    The oxidation and reduction of cysteine residues is emerging as an important post-translational control of protein function. We describe a method for fluorescent labelling of either reduced or oxidized thiols in combination with two-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis (2DE) to detect changes in the redox proteome of cultured cells. Reduced thiols are labelled with the fluorescent compound 5-iodoacetamidofluorescein. To monitor oxidized thiols, the reduced thiols are first blocked with N-ethyl-maleimide, then the oxidized thiols reduced with dithiothreitol and labelled with 5-iodoacetamidofluorescein. The method is illustrated by treating Jurkat T-lymphoma cells with hydrogen peroxide and monitoring increased labelling of oxidized thiol proteins. A decrease in labelling can also be detected, and this is attributed to the formation of higher oxidation states of cysteine that are not reduced by dithiothreitol.

  20. Effective computation of stochastic protein kinetic equation by reducing stiffness via variable transformation

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Lijin, E-mail: ljwang@ucas.ac.cn [School of Mathematical Sciences, University of Chinese Academy of Sciences, Beijing 100049 (China)

    2016-06-08

    The stochastic protein kinetic equations can be stiff for certain parameters, which makes their numerical simulation rely on very small time step sizes, resulting in large computational cost and accumulated round-off errors. For such situation, we provide a method of reducing stiffness of the stochastic protein kinetic equation by means of a kind of variable transformation. Theoretical and numerical analysis show effectiveness of this method. Its generalization to a more general class of stochastic differential equation models is also discussed.

  1. High protein flexibility and reduced hydration water dynamics are key pressure adaptive strategies in prokaryotes

    KAUST Repository

    Martinez, N.

    2016-09-06

    Water and protein dynamics on a nanometer scale were measured by quasi-elastic neutron scattering in the piezophile archaeon Thermococcus barophilus and the closely related pressure-sensitive Thermococcus kodakarensis, at 0.1 and 40 MPa. We show that cells of the pressure sensitive organism exhibit higher intrinsic stability. Both the hydration water dynamics and the fast protein and lipid dynamics are reduced under pressure. In contrast, the proteome of T. barophilus is more pressure sensitive than that of T. kodakarensis. The diffusion coefficient of hydration water is reduced, while the fast protein and lipid dynamics are slightly enhanced with increasing pressure. These findings show that the coupling between hydration water and cellular constituents might not be simply a master-slave relationship. We propose that the high flexibility of the T. barophilus proteome associated with reduced hydration water may be the keys to the molecular adaptation of the cells to high hydrostatic pressure.

  2. High protein flexibility and reduced hydration water dynamics are key pressure adaptive strategies in prokaryotes

    KAUST Repository

    Martinez, N.; Michoud, Gregoire; Cario, A.; Ollivier, J.; Franzetti, B.; Jebbar, M.; Oger, P.; Peters, J.

    2016-01-01

    Water and protein dynamics on a nanometer scale were measured by quasi-elastic neutron scattering in the piezophile archaeon Thermococcus barophilus and the closely related pressure-sensitive Thermococcus kodakarensis, at 0.1 and 40 MPa. We show that cells of the pressure sensitive organism exhibit higher intrinsic stability. Both the hydration water dynamics and the fast protein and lipid dynamics are reduced under pressure. In contrast, the proteome of T. barophilus is more pressure sensitive than that of T. kodakarensis. The diffusion coefficient of hydration water is reduced, while the fast protein and lipid dynamics are slightly enhanced with increasing pressure. These findings show that the coupling between hydration water and cellular constituents might not be simply a master-slave relationship. We propose that the high flexibility of the T. barophilus proteome associated with reduced hydration water may be the keys to the molecular adaptation of the cells to high hydrostatic pressure.

  3. Reconfiguration of distribution nets

    International Nuclear Information System (INIS)

    Latorre Bayona, Gerardo; Angarita Marquez, Jorge Luis

    2000-01-01

    Starting of the location of the reconfiguration problem inside the context of the operation of distribution nets, of the quality indicators definition and of the presentation of the alternatives more used for reduction of technical losses, they are related diverse reconfiguration methodologies proposed in the technical literature, pointing out their three principals limitations; also are presents the results of lost obtained starting from simulation works carried out in distribution circuits of the ESSA ESP, which permitting to postulate the reconfiguration of nets like an excellent alternative to reduce technical losses

  4. Nuclear protein import is reduced in cells expressing nuclear envelopathy-causing lamin A mutants

    International Nuclear Information System (INIS)

    Busch, Albert; Kiel, Tilman; Heupel, Wolfgang-M.; Wehnert, Manfred; Huebner, Stefan

    2009-01-01

    Lamins, which form the nuclear lamina, not only constitute an important determinant of nuclear architecture, but additionally play essential roles in many nuclear functions. Mutations in A-type lamins cause a wide range of human genetic disorders (laminopathies). The importance of lamin A (LaA) in the spatial arrangement of nuclear pore complexes (NPCs) prompted us to study the role of LaA mutants in nuclear protein transport. Two mutants, causing prenatal skin disease restrictive dermopathy (RD) and the premature aging disease Hutchinson Gilford progeria syndrome, were used for expression in HeLa cells to investigate their impact on the subcellular localization of NPC-associated proteins and nuclear protein import. Furthermore, dynamics of the LaA mutants within the nuclear lamina were studied. We observed affected localization of NPC-associated proteins, diminished lamina dynamics for both LaA mutants and reduced nuclear import of representative cargo molecules. Intriguingly, both LaA mutants displayed similar effects on nuclear morphology and functions, despite their differences in disease severity. Reduced nuclear protein import was also seen in RD fibroblasts and impaired lamina dynamics for the nucleoporin Nup153. Our data thus represent the first study of a direct link between LaA mutant expression and reduced nuclear protein import.

  5. Modulation of GDP-fucose level for generating proteins with reduced rate of fucosylation (WO2010141855).

    Science.gov (United States)

    Taupin, Philippe

    2011-09-01

    The application (WO2010141855) is in the field of glycobiology, and involves the control of the rate of fucosylation of proteins by exogenous factors. It aims at controlling the rate of protein fucosylation with inhibitors (drugs or nucleic acid antagonists) of enzymes involved in the synthesis of GDP-fucose. Mammalian cell lines were cultured in the presence of inhibitors, for example, siRNA. The rates of GDP-fucose in cells and during protein fucosylation were characterized. The level of protein fucosylation decreases rapidly in response to a decrease in GDP-fucose level. The relationship between the rate of fucosylation of proteins and the level of GDP-fucose in a cell is non-linear. Reduction in the rate of protein fucosylation can be achieved with a minimal reduction of the level of GDP-fucose in cells. The paradigm may be used to synthesize proteins and antibodies, with a reduced rate of fucosylation. The application claims that the use of drugs or nucleic acid antagonists that inhibit the enzymes involved in GDP-fucose biosynthesis optimizes the level of GDP-fucose present in cells, and reduces the rate of fucosylation of glycoproteins.

  6. Sodium 4-Phenylbutyrate Attenuates Myocardial Reperfusion Injury by Reducing the Unfolded Protein Response.

    Science.gov (United States)

    Takatori, Osamu; Usui, Soichiro; Okajima, Masaki; Kaneko, Shuichi; Ootsuji, Hiroshi; Takashima, Shin-Ichiro; Kobayashi, Daisuke; Murai, Hisayoshi; Furusho, Hiroshi; Takamura, Masayuki

    2017-05-01

    The unfolded protein response (UPR) plays a pivotal role in ischemia-reperfusion (I/R) injury in various organs such as heart, brain, and liver. Sodium 4-phenylbutyrate (PBA) reportedly acts as a chemical chaperone that reduces UPR. In the present study, we evaluated the effect of PBA on reducing the UPR and protecting against myocardial I/R injury in mice. Male C57BL/6 mice were subjected to 30-minute myocardial I/R, and were treated with phosphate-buffered saline (as a vehicle) or PBA. At 4 hours after reperfusion, mice treated with PBA had reduced serum cardiac troponin I levels and numbers of apoptotic cells in left ventricles (LVs) in myocardial I/R. Infarct size had also reduced in mice treated with PBA at 48 hours after reperfusion. At 2 hours after reperfusion, UPR markers, including eukaryotic initiation of the factor 2α-subunit, activating transcription factor-6, inositol-requiring enzyme-1, glucose-regulated protein 78, CCAAT/enhancer-binding protein (C/EBP) homologous protein, and caspase-12, were significantly increased in mice treated with vehicle compared to sham-operated mice. Administration of PBA significantly reduced the I/R-induced increases of these markers. Cardiac function and dimensions were assessed at 21 days after I/R. Sodium 4-phenylbutyrate dedicated to the improvement of cardiac parameters deterioration including LV end-diastolic diameter and LV fractional shortening. Consistently, PBA reduced messenger RNA expression levels of cardiac remodeling markers such as collagen type 1α1, brain natriuretic peptide, and α skeletal muscle actin in LV at 21 days after I/R. Unfolded protein response mediates myocardial I/R injury. Administration of PBA reduces the UPR, apoptosis, infarct size, and preserved cardiac function. Hence, PBA may be a therapeutic option to attenuate myocardial I/R injury in clinical practice.

  7. Digestibility of gluten proteins is reduced by baking and enhanced by starch digestion.

    Science.gov (United States)

    Smith, Frances; Pan, Xiaoyan; Bellido, Vincent; Toole, Geraldine A; Gates, Fred K; Wickham, Martin S J; Shewry, Peter R; Bakalis, Serafim; Padfield, Philip; Mills, E N Clare

    2015-10-01

    Resistance of proteins to gastrointestinal digestion may play a role in determining immune-mediated adverse reactions to foods. However, digestion studies have largely been restricted to purified proteins and the impact of food processing and food matrices on protein digestibility is poorly understood. Digestibility of a total gliadin fraction (TGF), flour (cv Hereward), and bread was assessed using in vitro batch digestion with simulated oral, gastric, and duodenal phases. Protein digestion was monitored by SDS-PAGE and immunoblotting using monoclonal antibodies specific for celiac-toxic sequences (QQSF, QPFP) and starch digestion by measuring undigested starch. Whereas the TGF was rapidly digested during the gastric phase the gluten proteins in bread were virtually undigested and digested rapidly during the duodenal phase only if amylase was included. Duodenal starch digestion was also slower in the absence of duodenal proteases. The baking process reduces the digestibility of wheat gluten proteins, including those containing sequences active in celiac disease. Starch digestion affects the extent of protein digestion, probably because of gluten-starch complex formation during baking. Digestion studies using purified protein fractions alone are therefore not predictive of digestion in complex food matrices. © 2015 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Reduced uncertainty of regional scale CLM predictions of net carbon fluxes and leaf area indices with estimated plant-specific parameters

    Science.gov (United States)

    Post, Hanna; Hendricks Franssen, Harrie-Jan; Han, Xujun; Baatz, Roland; Montzka, Carsten; Schmidt, Marius; Vereecken, Harry

    2016-04-01

    Reliable estimates of carbon fluxes and states at regional scales are required to reduce uncertainties in regional carbon balance estimates and to support decision making in environmental politics. In this work the Community Land Model version 4.5 (CLM4.5-BGC) was applied at a high spatial resolution (1 km2) for the Rur catchment in western Germany. In order to improve the model-data consistency of net ecosystem exchange (NEE) and leaf area index (LAI) for this study area, five plant functional type (PFT)-specific CLM4.5-BGC parameters were estimated with time series of half-hourly NEE data for one year in 2011/2012, using the DiffeRential Evolution Adaptive Metropolis (DREAM) algorithm, a Markov Chain Monte Carlo (MCMC) approach. The parameters were estimated separately for four different plant functional types (needleleaf evergreen temperate tree, broadleaf deciduous temperate tree, C3-grass and C3-crop) at four different sites. The four sites are located inside or close to the Rur catchment. We evaluated modeled NEE for one year in 2012/2013 with NEE measured at seven eddy covariance sites in the catchment, including the four parameter estimation sites. Modeled LAI was evaluated by means of LAI derived from remotely sensed RapidEye images of about 18 days in 2011/2012. Performance indices were based on a comparison between measurements and (i) a reference run with CLM default parameters, and (ii) a 60 instance CLM ensemble with parameters sampled from the DREAM posterior probability density functions (pdfs). The difference between the observed and simulated NEE sum reduced 23% if estimated parameters instead of default parameters were used as input. The mean absolute difference between modeled and measured LAI was reduced by 59% on average. Simulated LAI was not only improved in terms of the absolute value but in some cases also in terms of the timing (beginning of vegetation onset), which was directly related to a substantial improvement of the NEE estimates in

  9. An Analysis of the Role of Social Safety Net Scholarships in Reducing School Drop-Out during the Indonesian Economic Crisis. Innocenti Working Papers.

    Science.gov (United States)

    Cameron, Lisa A.

    This paper uses regression and matching techniques to evaluate Indonesia's Social Safety Net Scholarships Programme. The scholarships program was developed to try to prevent large numbers of children from dropping out of school as a result of the Asian financial crisis. The expectation was that many families would find it difficult to keep their…

  10. Reduced expression of G protein-coupled receptor kinases in schizophrenia but not in schizoaffective disorder

    Science.gov (United States)

    Bychkov, ER; Ahmed, MR; Gurevich, VV; Benovic, JL; Gurevich, EV

    2011-01-01

    Alterations of multiple G protein-mediated signaling pathways are detected in schizophrenia. G protein-coupled receptor kinases (GRKs) and arrestins terminate signaling by G protein-coupled receptors exerting powerful influence on receptor functions. Modifications of arrestin and/or GRKs expression may contribute to schizophrenia pathology. Cortical expression of arrestins and GRKs was measured postmortem in control and subjects with schizophrenia or schizoaffective disorder. Additionally, arrestin/GRK expression was determined in elderly patients with schizophrenia and age-matched control. Patients with schizophrenia, but not schizoaffective disorder, displayed reduced concentration of arrestin and GRK mRNAs and GRK3 protein. Arrestins and GRK significantly decreased with age. In elderly patients, GRK6 was reduced, with other GRKs and arrestins unchanged. Reduced cortical concentration of GRKs in schizophrenia (resembling that in aging) may result in altered G protein-dependent signaling, thus contributing to prefrontal deficits in schizophrenia. The data suggest distinct molecular mechanisms underlying schizophrenia and schizoaffective disorder. PMID:21784156

  11. Whey protein reduces early life weight gain in mice fed a high-fat diet

    DEFF Research Database (Denmark)

    Tranberg, Britt; Hellgren, Lars; Lykkesfeldt, Jens

    2013-01-01

    An increasing number of studies indicate that dairy products, including whey protein, alleviate several disorders of the metabolic syndrome. Here, we investigated the effects of whey protein isolate (whey) in mice fed a high-fat diet hypothesising that the metabolic effects of whey would...... be associated with changes in the gut microbiota composition. Five-week-old male C57BL/6 mice were fed a high-fat diet ad libitum for 14 weeks with the protein source being either whey or casein. Faeces were collected at week 0, 7, and 13 and the fecal microbiota was analysed by denaturing gradient gel...... reduced weight gain in young C57BL/6 mice fed a high-fat diet compared to casein. Although the effect on weight gain ceased, whey alleviated glucose intolerance, improved insulin sensitivity and reduced plasma cholesterol. These findings could not be explained by changes in food intake or gut microbiota...

  12. Gestational diabetes is characterized by reduced mitochondrial protein expression and altered calcium signaling proteins in skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Kristen E Boyle

    Full Text Available The rising prevalence of gestational diabetes mellitus (GDM affects up to 18% of pregnant women with immediate and long-term metabolic consequences for both mother and infant. Abnormal glucose uptake and lipid oxidation are hallmark features of GDM prompting us to use an exploratory proteomics approach to investigate the cellular mechanisms underlying differences in skeletal muscle metabolism between obese pregnant women with GDM (OGDM and obese pregnant women with normal glucose tolerance (ONGT. Functional validation was performed in a second cohort of obese OGDM and ONGT pregnant women. Quantitative proteomic analysis in rectus abdominus skeletal muscle tissue collected at delivery revealed reduced protein content of mitochondrial complex I (C-I subunits (NDUFS3, NDUFV2 and altered content of proteins involved in calcium homeostasis/signaling (calcineurin A, α1-syntrophin, annexin A4 in OGDM (n = 6 vs. ONGT (n = 6. Follow-up analyses showed reduced enzymatic activity of mitochondrial complexes C-I, C-III, and C-IV (-60-75% in the OGDM (n = 8 compared with ONGT (n = 10 subjects, though no differences were observed for mitochondrial complex protein content. Upstream regulators of mitochondrial biogenesis and oxidative phosphorylation were not different between groups. However, AMPK phosphorylation was dramatically reduced by 75% in the OGDM women. These data suggest that GDM is associated with reduced skeletal muscle oxidative phosphorylation and disordered calcium homeostasis. These relationships deserve further attention as they may represent novel risk factors for development of GDM and may have implications on the effectiveness of physical activity interventions on both treatment strategies for GDM and for prevention of type 2 diabetes postpartum.

  13. The protein C omega-loop substitution Asn2Ile is associated with reduced protein C anticoagulant activity.

    LENUS (Irish Health Repository)

    Preston, Roger J S

    2012-02-01

    We report a kindred with heritable protein C (PC) deficiency in which two siblings with severe thrombosis showed a composite type I and IIb PC deficiency phenotype, identified using commercial PC assays (proband: PC antigen 42 u\\/dl, amidolytic activity 40 u\\/dl, anticoagulant activity 9 u\\/dl). The independent PROC nucleotide variations c.669C>A (predictive of Ser181Arg) and c.131C>T (predictive of Asn2Ile) segregated with the type I and type IIb PC deficiency phenotypes respectively, but co-segregated in the siblings with severe thrombosis. Soluble thrombomodulin (sTM)-mediated inhibition of plasma thrombin generation from an individual with PC-Asn2Ile was lower (endogenous thrombin potential (ETP) 56 +\\/- 1% that of ETP determined without sTM) than control plasma (ETP 15 +\\/- 2%) indicating reduced PC anticoagulant activity. Recombinant APC-Asn2Ile exhibited normal amidolytic activity but impaired anticoagulant activity. Protein S (PS)-dependent anticoagulant activity of recombinant APC-Asn2Ile and binding of recombinant APC-Asn2Ile to endothelial protein C receptor (EPCR) were reduced compared to recombinant wild-type APC. Asn2 lies within the omega-loop of the PC\\/APC Gla domain and this region is critical for calcium-induced folding and subsequent interactions with anionic phospholipids, EPCR and PS. The disruption of these interactions in this naturally-occurring PC variant highlights their collective importance in mediating APC anticoagulant activity in vivo.

  14. Stabilizing salt-bridge enhances protein thermostability by reducing the heat capacity change of unfolding.

    Directory of Open Access Journals (Sweden)

    Chi-Ho Chan

    Full Text Available Most thermophilic proteins tend to have more salt bridges, and achieve higher thermostability by up-shifting and broadening their protein stability curves. While the stabilizing effect of salt-bridge has been extensively studied, experimental data on how salt-bridge influences protein stability curves are scarce. Here, we used double mutant cycles to determine the temperature-dependency of the pair-wise interaction energy and the contribution of salt-bridges to ΔC(p in a thermophilic ribosomal protein L30e. Our results showed that the pair-wise interaction energies for the salt-bridges E6/R92 and E62/K46 were stabilizing and insensitive to temperature changes from 298 to 348 K. On the other hand, the pair-wise interaction energies between the control long-range ion-pair of E90/R92 were negligible. The ΔC(p of all single and double mutants were determined by Gibbs-Helmholtz and Kirchhoff analyses. We showed that the two stabilizing salt-bridges contributed to a reduction of ΔC(p by 0.8-1.0 kJ mol⁻¹ K⁻¹. Taken together, our results suggest that the extra salt-bridges found in thermophilic proteins enhance the thermostability of proteins by reducing ΔC(p, leading to the up-shifting and broadening of the protein stability curves.

  15. Frequency distribution of the reduced unit cells of centred lattices from the Protein Data Bank.

    Science.gov (United States)

    Swaminathan, Kunchithapadam

    2012-03-01

    In crystallography, a centred conventional lattice unit cell has its corresponding reduced primitive unit cell. This study presents the frequency distribution of the reduced unit cells of all centred lattice entries of the Protein Data Bank (as of 23 August 2011) in four unit-cell-dimension-based groups and seven interaxial-angle-based subgroups. This frequency distribution is an added layer of support during space-group assignment in new crystals. In addition, some interesting patterns of distribution are discussed as well as how some reduced unit cells could be wrongly accepted as primitive lattices in a different crystal system.

  16. Pickering nuclear fish diversion net

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, J.; Lew, A. [Ontario Power Generation, Toronto, Ontario (Canada)

    2013-07-01

    Pickering Fish Diversion Net - An Engineered Environmental Solution that has significantly reduced fish impingement at the Pickering Nuclear Facility. Note: As a recent urgent request/discussed by Mark Elliot, CNE-OPG and Jacques Plourde, CNS.

  17. SUPPLEMENTARY FEEDING ON THE NUTRIENT BALANCE OF LACTATING DAIRY COW AT CONTRASTING TEMPERATURE REGIMES: ASSESSMENT USING CORNELL NET CARBOHYDRATE AND PROTEIN SYSTEM (CNCPS MODEL

    Directory of Open Access Journals (Sweden)

    A. Jayanegara

    2014-10-01

    Full Text Available Dairy cows often do not receive adequate nutrient supply during their lactation period. This condition caneven be worse if the environmental temperature is not in comfortable range which may occur especially intropical regions. The present research was aimed to simulate the effect of supplementary feeding on nutrientbalance of lactating dairy cow at contrasting temperature regimes using Cornell Net Carbohydrate andProtein System (CNCPS model. Treatments consisted of feeds (R1: Pennisetum purpureum, R2: P.purpureum + concentrate (60:40, R3: P. purpureum + Gliricidia sepium + Leucaena leucocephala(60:20:20, R4: P. purpureum + concentrate + G. sepium + L. leucocephala (60:20:10:10 and environmentaltemperatures (T1: 20 oC, T2: 30 oC. The dairy cow inputs in CNCPS were Holstein breed, body weight of500 kg, feed intake of 15 kg (dry matter basis per day and produced milk 15 kg/day. Based on the CNCPSmodel, there were negative balances of metabolisable energy (ME and metabolisable protein (MP if alactating dairy cow fed only by P. purpureum. The ME balance was worse at higher temperature, while theMP balance was remain unchanged. Addition of concentrate mixture (R2 fulfilled the ME and MPrequirements as well as other nutrients. Addition of leguminous tree leaves (R3 and R4 improved thenutritional status of the lactating cow model compared to R1, but did not better than R2. It was concludedthat supplementary feeding is necessary for improving the nutrient balance of lactating dairy cow, especiallywhen the cow is maintained under uncomfortable environmental temperature.

  18. Scoring predictive models using a reduced representation of proteins: model and energy definition.

    Science.gov (United States)

    Fogolari, Federico; Pieri, Lidia; Dovier, Agostino; Bortolussi, Luca; Giugliarelli, Gilberto; Corazza, Alessandra; Esposito, Gennaro; Viglino, Paolo

    2007-03-23

    Reduced representations of proteins have been playing a keyrole in the study of protein folding. Many such models are available, with different representation detail. Although the usefulness of many such models for structural bioinformatics applications has been demonstrated in recent years, there are few intermediate resolution models endowed with an energy model capable, for instance, of detecting native or native-like structures among decoy sets. The aim of the present work is to provide a discrete empirical potential for a reduced protein model termed here PC2CA, because it employs a PseudoCovalent structure with only 2 Centers of interactions per Amino acid, suitable for protein model quality assessment. All protein structures in the set top500H have been converted in reduced form. The distribution of pseudobonds, pseudoangle, pseudodihedrals and distances between centers of interactions have been converted into potentials of mean force. A suitable reference distribution has been defined for non-bonded interactions which takes into account excluded volume effects and protein finite size. The correlation between adjacent main chain pseudodihedrals has been converted in an additional energetic term which is able to account for cooperative effects in secondary structure elements. Local energy surface exploration is performed in order to increase the robustness of the energy function. The model and the energy definition proposed have been tested on all the multiple decoys' sets in the Decoys'R'us database. The energetic model is able to recognize, for almost all sets, native-like structures (RMSD less than 2.0 A). These results and those obtained in the blind CASP7 quality assessment experiment suggest that the model compares well with scoring potentials with finer granularity and could be useful for fast exploration of conformational space. Parameters are available at the url: http://www.dstb.uniud.it/~ffogolari/download/.

  19. Pharmacological inhibition of dynamin II reduces constitutive protein secretion from primary human macrophages.

    Directory of Open Access Journals (Sweden)

    Maaike Kockx

    Full Text Available Dynamins are fission proteins that mediate endocytic and exocytic membrane events and are pharmacological therapeutic targets. These studies investigate whether dynamin II regulates constitutive protein secretion and show for the first time that pharmacological inhibition of dynamin decreases secretion of apolipoprotein E (apoE and several other proteins constitutively secreted from primary human macrophages. Inhibitors that target recruitment of dynamin to membranes (MiTMABs or directly target the GTPase domain (Dyngo or Dynole series, dose- and time- dependently reduced the secretion of apoE. SiRNA oligo's targeting all isoforms of dynamin II confirmed the involvement of dynamin II in apoE secretion. Inhibition of secretion was not mediated via effects on mRNA or protein synthesis. 2D-gel electrophoresis showed that inhibition occurred after apoE was processed and glycosylated in the Golgi and live cell imaging showed that inhibited secretion was associated with reduced post-Golgi movement of apoE-GFP-containing vesicles. The effect was not restricted to macrophages, and was not mediated by the effects of the inhibitors on microtubules. Inhibition of dynamin also altered the constitutive secretion of other proteins, decreasing the secretion of fibronectin, matrix metalloproteinase 9, Chitinase-3-like protein 1 and lysozyme but unexpectedly increasing the secretion of the inflammatory mediator cyclophilin A. We conclude that pharmacological inhibitors of dynamin II modulate the constitutive secretion of macrophage apoE as a class effect, and that their capacity to modulate protein secretion may affect a range of biological processes.

  20. High-fiber diets with reduced crude protein for commercial layers

    Directory of Open Access Journals (Sweden)

    MFFM Praes

    2014-06-01

    Full Text Available This study aimed at evaluating diets containing different fiber sources and two crude protein levels on the performance, egg quality, and nitrogen metabolism of commercial layers. In total, 392 48-wk-old Isa Brown layers were distributed according to a completely randomized experimental design in a 3x2+1 (control factorial arrangement, resulting in seven treatments with seven replicates of eight birds each. Treatments consisted of three fiber feedstuffs (cottonseed hulls, soybean hulls, and rice hulls and two dietary crude protein levels (12% and 16%. Cottonseed hulls associated with the high crude protein level (16% resulted in the worst feed conversion ratio per dozen eggs. Diets with 16% crude protein resulted in the highest feed intake, egg production, egg weight, egg mass values, and improved feed conversion ratio (kg eggs/kg feed. The dietary inclusion of soybean hulls determined low yolk pigmentation, and of rice hulls, low egg specific gravity. The 16% crude protein diet with rice hulls promoted the best feed conversion ratio. Hens fed the reference diet presented higher egg mass and better feed conversion ratio per kg eggs and per dozen eggs. Hens fed the diets with low crude protein level (12% had reduced nitrogen excretion, but presented worse egg production.

  1. A reduced amino acid alphabet for understanding and designing protein adaptation to mutation.

    Science.gov (United States)

    Etchebest, C; Benros, C; Bornot, A; Camproux, A-C; de Brevern, A G

    2007-11-01

    Protein sequence world is considerably larger than structure world. In consequence, numerous non-related sequences may adopt similar 3D folds and different kinds of amino acids may thus be found in similar 3D structures. By grouping together the 20 amino acids into a smaller number of representative residues with similar features, sequence world simplification may be achieved. This clustering hence defines a reduced amino acid alphabet (reduced AAA). Numerous works have shown that protein 3D structures are composed of a limited number of building blocks, defining a structural alphabet. We previously identified such an alphabet composed of 16 representative structural motifs (5-residues length) called Protein Blocks (PBs). This alphabet permits to translate the structure (3D) in sequence of PBs (1D). Based on these two concepts, reduced AAA and PBs, we analyzed the distributions of the different kinds of amino acids and their equivalences in the structural context. Different reduced sets were considered. Recurrent amino acid associations were found in all the local structures while other were specific of some local structures (PBs) (e.g Cysteine, Histidine, Threonine and Serine for the alpha-helix Ncap). Some similar associations are found in other reduced AAAs, e.g Ile with Val, or hydrophobic aromatic residues Trp with Phe and Tyr. We put into evidence interesting alternative associations. This highlights the dependence on the information considered (sequence or structure). This approach, equivalent to a substitution matrix, could be useful for designing protein sequence with different features (for instance adaptation to environment) while preserving mainly the 3D fold.

  2. Whey protein reduces early life weight gain in mice fed a high-fat diet

    DEFF Research Database (Denmark)

    Tranberg, Britt; Hellgren, Lars; Lykkesfeldt, Jens

    2013-01-01

    An increasing number of studies indicate that dairy products, including whey protein, alleviate several disorders of the metabolic syndrome. Here, we investigated the effects of whey protein isolate (whey) in mice fed a high-fat diet hypothesising that the metabolic effects of whey would...... be associated with changes in the gut microbiota composition. Five-week-old male C57BL/6 mice were fed a high-fat diet ad libitum for 14 weeks with the protein source being either whey or casein. Faeces were collected at week 0, 7, and 13 and the fecal microbiota was analysed by denaturing gradient gel...... electrophoresis analyses of PCR-derived 16S rRNA gene (V3-region) amplicons. At the end of the study, plasma samples were collected and assayed for glucose, insulin and lipids. Whey significantly reduced body weight gain during the first four weeks of the study compared with casein (P

  3. Benzylglucosinolate Derived Isothiocyanate from Tropaeolum majus Reduces Gluconeogenic Gene and Protein Expression in Human Cells.

    Directory of Open Access Journals (Sweden)

    Valentina Guzmán-Pérez

    Full Text Available Nasturtium (Tropaeolum majus L. contains high concentrations of benzylglcosinolate. We found that a hydrolysis product of benzyl glucosinolate-the benzyl isothiocyanate (BITC-modulates the intracellular localization of the transcription factor Forkhead box O 1 (FOXO1. FoxO transcription factors can antagonize insulin effects and trigger a variety of cellular processes involved in tumor suppression, longevity, development and metabolism. The current study evaluated the ability of BITC-extracted as intact glucosinolate from nasturtium and hydrolyzed with myrosinase-to modulate i the insulin-signaling pathway, ii the intracellular localization of FOXO1 and, iii the expression of proteins involved in gluconeogenesis, antioxidant response and detoxification. Stably transfected human osteosarcoma cells (U-2 OS with constitutive expression of FOXO1 protein labeled with GFP (green fluorescent protein were used to evaluate the effect of BITC on FOXO1. Human hepatoma HepG2 cell cultures were selected to evaluate the effect on gluconeogenic, antioxidant and detoxification genes and protein expression. BITC reduced the phosphorylation of protein kinase B (AKT/PKB and FOXO1; promoted FOXO1 translocation from cytoplasm into the nucleus antagonizing the insulin effect; was able to down-regulate the gene and protein expression of gluconeogenic enzymes; and induced the gene expression of antioxidant and detoxification enzymes. Knockdown analyses with specific siRNAs showed that the expression of gluconeogenic genes was dependent on nuclear factor (erythroid derived-like2 (NRF2 and independent of FOXO1, AKT and NAD-dependent deacetylase sirtuin-1 (SIRT1. The current study provides evidence that BITC might have a role in type 2 diabetes T2D by reducing hepatic glucose production and increasing antioxidant resistance.

  4. Ultraviolet-ozone treatment reduces levels of disease-associated prion protein and prion infectivity

    Science.gov (United States)

    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.

  5. RNAi reduces expression and intracellular retention of mutant cartilage oligomeric matrix protein.

    Directory of Open Access Journals (Sweden)

    Karen L Posey

    2010-04-01

    Full Text Available Mutations in cartilage oligomeric matrix protein (COMP, a large extracellular glycoprotein expressed in musculoskeletal tissues, cause two skeletal dysplasias, pseudoachondroplasia and multiple epiphyseal dysplasia. These mutations lead to massive intracellular retention of COMP, chondrocyte death and loss of growth plate chondrocytes that are necessary for linear growth. In contrast, COMP null mice have only minor growth plate abnormalities, normal growth and longevity. This suggests that reducing mutant and wild-type COMP expression in chondrocytes may prevent the toxic cellular phenotype causing the skeletal dysplasias. We tested this hypothesis using RNA interference to reduce steady state levels of COMP mRNA. A panel of shRNAs directed against COMP was tested. One shRNA (3B reduced endogenous and recombinant COMP mRNA dramatically, regardless of expression levels. The activity of the shRNA against COMP mRNA was maintained for up to 10 weeks. We also demonstrate that this treatment reduced ER stress. Moreover, we show that reducing steady state levels of COMP mRNA alleviates intracellular retention of other extracellular matrix proteins associated with the pseudoachondroplasia cellular pathology. These findings are a proof of principle and the foundation for the development of a therapeutic intervention based on reduction of COMP expression.

  6. Protein energy malnutrition alters mucosal IgA responses and reduces mucosal vaccine efficacy in mice.

    Science.gov (United States)

    Rho, Semi; Kim, Heejoo; Shim, Seung Hyun; Lee, Seung Young; Kim, Min Jung; Yang, Bo-Gie; Jang, Myoung Ho; Han, Byung Woo; Song, Man Ki; Czerkinsky, Cecil; Kim, Jae-Ouk

    2017-10-01

    Oral vaccine responsiveness is often lower in children from less developed countries. Childhood malnutrition may be associated with poor immune response to oral vaccines. The present study was designed to investigate whether protein energy malnutrition (PEM) impairs B cell immunity and ultimately reduces oral vaccine efficacy in a mouse model. Purified isocaloric diets containing low protein (1/10 the protein of the control diet) were used to determine the effect of PEM. PEM increased both nonspecific total IgA and oral antigen-specific IgA in serum without alteration of gut permeability. However, PEM decreased oral antigen-specific IgA in feces, which is consistent with decreased expression of polymeric Immunoglobulin receptor (pIgR) in the small intestine. Of note, polymeric IgA was predominant in serum under PEM. In addition, PEM altered B cell development status in the bone marrow and increased the frequency of IgA-secreting B cells, as well as IgA secretion by long-lived plasma cells in the small intestinal lamina propria. Moreover, PEM reduced the protective efficacy of the mucosally administered cholera vaccine and recombinant attenuated Salmonella enterica serovar Typhimurium vaccine in a mouse model. Our results suggest that PEM can impair mucosal immunity where IgA plays an important role in host protection and may partly explain the reduced efficacy of oral vaccines in malnourished subjects. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  7. Small molecule proteostasis regulators that reprogram the ER to reduce extracellular protein aggregation

    Science.gov (United States)

    Plate, Lars; Cooley, Christina B; Chen, John J; Paxman, Ryan J; Gallagher, Ciara M; Madoux, Franck; Genereux, Joseph C; Dobbs, Wesley; Garza, Dan; Spicer, Timothy P; Scampavia, Louis; Brown, Steven J; Rosen, Hugh; Powers, Evan T; Walter, Peter; Hodder, Peter; Wiseman, R Luke; Kelly, Jeffery W

    2016-01-01

    Imbalances in endoplasmic reticulum (ER) proteostasis are associated with etiologically-diverse degenerative diseases linked to excessive extracellular protein misfolding and aggregation. Reprogramming of the ER proteostasis environment through genetic activation of the Unfolded Protein Response (UPR)-associated transcription factor ATF6 attenuates secretion and extracellular aggregation of amyloidogenic proteins. Here, we employed a screening approach that included complementary arm-specific UPR reporters and medium-throughput transcriptional profiling to identify non-toxic small molecules that phenocopy the ATF6-mediated reprogramming of the ER proteostasis environment. The ER reprogramming afforded by our molecules requires activation of endogenous ATF6 and occurs independent of global ER stress. Furthermore, our molecules phenocopy the ability of genetic ATF6 activation to selectively reduce secretion and extracellular aggregation of amyloidogenic proteins. These results show that small molecule-dependent ER reprogramming, achieved through preferential activation of the ATF6 transcriptional program, is a promising strategy to ameliorate imbalances in ER function associated with degenerative protein aggregation diseases. DOI: http://dx.doi.org/10.7554/eLife.15550.001 PMID:27435961

  8. Amyloid β-sheet mimics that antagonize protein aggregation and reduce amyloid toxicity

    Science.gov (United States)

    Cheng, Pin-Nan; Liu, Cong; Zhao, Minglei; Eisenberg, David; Nowick, James S.

    2012-11-01

    The amyloid protein aggregation associated with diseases such as Alzheimer's, Parkinson's and type II diabetes (among many others) features a bewildering variety of β-sheet-rich structures in transition from native proteins to ordered oligomers and fibres. The variation in the amino-acid sequences of the β-structures presents a challenge to developing a model system of β-sheets for the study of various amyloid aggregates. Here, we introduce a family of robust β-sheet macrocycles that can serve as a platform to display a variety of heptapeptide sequences from different amyloid proteins. We have tailored these amyloid β-sheet mimics (ABSMs) to antagonize the aggregation of various amyloid proteins, thereby reducing the toxicity of amyloid aggregates. We describe the structures and inhibitory properties of ABSMs containing amyloidogenic peptides from the amyloid-β peptide associated with Alzheimer's disease, β2-microglobulin associated with dialysis-related amyloidosis, α-synuclein associated with Parkinson's disease, islet amyloid polypeptide associated with type II diabetes, human and yeast prion proteins, and Tau, which forms neurofibrillary tangles.

  9. "Watts per person" paradigm to design net zero energy buildings: Examining technology interventions and integrating occupant feedback to reduce plug loads in a commercial building

    Science.gov (United States)

    Yagi Kim, Mika

    As building envelopes have improved due to more restrictive energy codes, internal loads have increased largely due to the proliferation of computers, electronics, appliances, imaging and audio visual equipment that continues to grow in commercial buildings. As the dependency on the internet for information and data transfer increases, the electricity demand will pose a challenge to design and operate Net Zero Energy Buildings (NZEBs). Plug Loads (PLs) as a proportion of the building load has become the largest non-regulated building energy load and represents the third highest electricity end-use in California's commercial office buildings, accounting for 23% of the total building electricity consumption (Ecova 2011,2). In the Annual Energy Outlook 2008 (AEO2008), prepared by the Energy Information Administration (EIA) that presents long-term projections of energy supply and demand through 2030 states that office equipment and personal computers are the "fastest growing electrical end uses" in the commercial sector. This thesis entitled "Watts Per Person" Paradigm to Design Net Zero Energy Buildings, measures the implementation of advanced controls and behavioral interventions to study the reduction of PL energy use in the commercial sector. By integrating real world data extracted from an energy efficient commercial building of its energy use, the results produce a new methodology on estimating PL energy use by calculating based on "Watts Per Person" and analyzes computational simulation methods to design NZEBs.

  10. Eco-Friendly Nets and Floating Row Covers Reduce Pest Infestation and Improve Tomato (Solanum lycopersicum L. Yields for Smallholder Farmers in Kenya

    Directory of Open Access Journals (Sweden)

    Elisha O. Gogo

    2014-01-01

    Full Text Available Tomato (Solanum lycopersicum L. is an important vegetable for supplying vitamins, minerals and fiber in human diets worldwide. Successful open field production of tomato in the tropics is limited by insect pests among other constraints. Two trials were conducted at the Horticulture Research and Teaching Field, Egerton University, Kenya with the objective of evaluating the effects of agricultural nets (agronets herein called eco-friendly nets (EFNs and floating row covers (FRCs on pest population and yield of tomatoes. A randomized complete block design with five replications was used. Tomato plants were protected with either fine mesh EFN (0.4-mm pore diameter, large mesh EFN (0.9-mm pore diameter or FRC. The EFN and FRC were maintained permanently closed or opened thrice a week from 9 am to 3 pm. Two control treatments were used: open unsprayed (untreated control or open and sprayed with alpha-cypermethrin based insecticide (treated control. The use of EFN and FRC helped to manage pests with the lowest pest population obtained under FRC maintained permanently covered and the highest population recorded in the untreated control. Covering tomato plants with EFN or FRC also resulted in more marketable fruit and lower yield losses compared with the unprotected systems. The EFN and FRC offer great potential as part of integrated systems for pest management and yield improvement in tomato production in regions with a tropical climate.

  11. AMP-activated protein kinase reduces inflammatory responses and cellular senescence in pulmonary emphysema.

    Science.gov (United States)

    Cheng, Xiao-Yu; Li, Yang-Yang; Huang, Cheng; Li, Jun; Yao, Hong-Wei

    2017-04-04

    Current drug therapy fails to reduce lung destruction of chronic obstructive pulmonary disease (COPD). AMP-activated protein kinase (AMPK) has emerged as an important integrator of signals that control energy balance and lipid metabolism. However, there are no studies regarding the role of AMPK in reducing inflammatory responses and cellular senescence during the development of emphysema. Therefore, we hypothesize that AMPK reduces inflammatroy responses, senescence, and lung injury. To test this hypothesis, human bronchial epithelial cells (BEAS-2B) and small airway epithelial cells (SAECs) were treated with cigarette smoke extract (CSE) in the presence of a specific AMPK activator (AICAR, 1 mM) and inhibitor (Compound C, 5 μM). Elastase injection was performed to induce mouse emphysema, and these mice were treated with a specific AMPK activator metformin as well as Compound C. AICAR reduced, whereas Compound C increased CSE-induced increase in IL-8 and IL-6 release and expression of genes involved in cellular senescence. Knockdown of AMPKα1/α2 increased expression of pro-senescent genes (e.g., p16, p21, and p66shc) in BEAS-2B cells. Prophylactic administration of an AMPK activator metformin (50 and 250 mg/kg) reduced while Compound C (4 and 20 mg/kg) aggravated elastase-induced airspace enlargement, inflammatory responses and cellular senescence in mice. This is in agreement with therapeutic effect of metformin (50 mg/kg) on airspace enlargement. Furthermore, metformin prophylactically protected against but Compound C further reduced mitochondrial proteins SOD2 and SIRT3 in emphysematous lungs. In conclusion, AMPK reduces abnormal inflammatory responses and cellular senescence, which implicates as a potential therapeutic target for COPD/emphysema.

  12. EFFECTS OF PROTEIN-XANTHOPHYLL (PX CONCENTRATE OF ALFALFA ADDITIVE TO CRUDE PROTEIN-REDUCED DIETS ON NITROGEN EXCRETION, GROWTH PERFORMANCE AND MEAT QUALITY OF PIGS

    Directory of Open Access Journals (Sweden)

    Eugeniusz GRELA

    2009-06-01

    Full Text Available The infl uence of protein-xanthophyll (PX concentrate of alfalfa supplement to crude protein-reduced diets was examined in relation to nitrogen excretion, performance parameters and pig meat quality. The investigations included 60 growers (PL x PLW x Duroc crossbreeds assigned to 3 groups. The conclusion is that there is a large potential to decrease nitrogen emission to the environment by 10% lowering of dietary crude protein intake along with reduced animal growth rate and elevated mixture utilization. Inclusion of a protein-xanthophyll concentrate (PX of alfalfa to the diet is likely to diminish disadvantageous productive parameters arising from limiting of total crude protein level in relation to the requirements of pigs feeding norms [1993]. At the same time, it improves feed nitrogen utilization and reduces noxious odour emissions from a piggery. The components of a protein-xanthophyll concentrate (PX contribute to increased liver and kidney weight.

  13. Whey protein consumption after resistance exercise reduces energy intake at a post-exercise meal.

    Science.gov (United States)

    Monteyne, Alistair; Martin, Alex; Jackson, Liam; Corrigan, Nick; Stringer, Ellen; Newey, Jack; Rumbold, Penny L S; Stevenson, Emma J; James, Lewis J

    2018-03-01

    Protein consumption after resistance exercise potentiates muscle protein synthesis, but its effects on subsequent appetite in this context are unknown. This study examined appetite and energy intake following consumption of protein- and carbohydrate-containing drinks after resistance exercise. After familiarisation, 15 resistance training males (age 21 ± 1 years, body mass 78.0 ± 11.9 kg, stature 1.78 ± 0.07 m) completed two randomised, double-blind trials, consisting of lower-body resistance exercise, followed by consumption of a whey protein (PRO 23.9 ± 3.6 g protein) or dextrose (CHO 26.5 ± 3.8 g carbohydrate) drink in the 5 min post-exercise. An ad libitum meal was served 60 min later, with subjective appetite measured throughout. Drinks were flavoured and matched for energy content and volume. The PRO drink provided 0.3 g/kg body mass protein. Ad libitum energy intake (PRO 3742 ± 994 kJ; CHO 4172 ± 1132 kJ; P = 0.007) and mean eating rate (PRO 339 ± 102 kJ/min; CHO 405 ± 154 kJ/min; P = 0.009) were lower during PRO. The change in eating rate was associated with the change in energy intake (R = 0.661, P = 0.007). No interaction effects were observed for subjective measures of appetite. The PRO drink was perceived as creamier and thicker, and less pleasant, sweet and refreshing (P consumption after resistance exercise reduces subsequent energy intake, and this might be partially mediated by a reduced eating rate. Whilst this reduced energy intake is unlikely to impair hypertrophy, it may be of value in supporting an energy deficit for weight loss.

  14. Enzymatic Hydrolysis Does Not Reduce the Biological Reactivity of Soybean Proteins for All Allergic Subjects.

    Science.gov (United States)

    Panda, Rakhi; Tetteh, Afua O; Pramod, Siddanakoppalu N; Goodman, Richard E

    2015-11-04

    Many soybean protein products are processed by enzymatic hydrolysis to attain desirable functional food properties or in some cases to reduce allergenicity. However, few studies have investigated the effects of enzymatic hydrolysis on the allergenicity of soybean products. In this study the allergenicity of soybean protein isolates (SPI) hydrolyzed by Alcalase, trypsin, chymotrypsin, bromelain, or papain was evaluated by IgE immunoblots using eight soybean-allergic patient sera. The biological relevance of IgE binding was evaluated by a functional assay using a humanized rat basophilic leukemia (hRBL) cell line and serum from one subject. Results indicated that hydrolysis of SPI by the enzymes did not reduce the allergenicity, and hydrolysis by chymotrypsin or bromelain has the potential to increase the allergenicity of SPI. Two-dimensional (2D) immunoblot and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of the chymotrypsin-hydrolyzed samples indicated fragments of β-conglycinin protein are responsible for the apparent higher allergenic potential of digested SPI.

  15. Heterozygous RFX6 protein truncating variants are associated with MODY with reduced penetrance.

    Science.gov (United States)

    Patel, Kashyap A; Kettunen, Jarno; Laakso, Markku; Stančáková, Alena; Laver, Thomas W; Colclough, Kevin; Johnson, Matthew B; Abramowicz, Marc; Groop, Leif; Miettinen, Päivi J; Shepherd, Maggie H; Flanagan, Sarah E; Ellard, Sian; Inagaki, Nobuya; Hattersley, Andrew T; Tuomi, Tiinamaija; Cnop, Miriam; Weedon, Michael N

    2017-10-12

    Finding new causes of monogenic diabetes helps understand glycaemic regulation in humans. To find novel genetic causes of maturity-onset diabetes of the young (MODY), we sequenced MODY cases with unknown aetiology and compared variant frequencies to large public databases. From 36 European patients, we identify two probands with novel RFX6 heterozygous nonsense variants. RFX6 protein truncating variants are enriched in the MODY discovery cohort compared to the European control population within ExAC (odds ratio = 131, P = 1 × 10 -4 ). We find similar results in non-Finnish European (n = 348, odds ratio = 43, P = 5 × 10 -5 ) and Finnish (n = 80, odds ratio = 22, P = 1 × 10 -6 ) replication cohorts. RFX6 heterozygotes have reduced penetrance of diabetes compared to common HNF1A and HNF4A-MODY mutations (27, 70 and 55% at 25 years of age, respectively). The hyperglycaemia results from beta-cell dysfunction and is associated with lower fasting and stimulated gastric inhibitory polypeptide (GIP) levels. Our study demonstrates that heterozygous RFX6 protein truncating variants are associated with MODY with reduced penetrance.Maturity-onset diabetes of the young (MODY) is the most common subtype of familial diabetes. Here, Patel et al. use targeted DNA sequencing of MODY patients and large-scale publically available data to show that RFX6 heterozygous protein truncating variants cause reduced penetrance MODY.

  16. Whey Protein Reduces Early Life Weight Gain in Mice Fed a High-Fat Diet

    Science.gov (United States)

    Tranberg, Britt; Hellgren, Lars I.; Lykkesfeldt, Jens; Sejrsen, Kristen; Jeamet, Aymeric; Rune, Ida; Ellekilde, Merete; Nielsen, Dennis S.; Hansen, Axel Kornerup

    2013-01-01

    An increasing number of studies indicate that dairy products, including whey protein, alleviate several disorders of the metabolic syndrome. Here, we investigated the effects of whey protein isolate (whey) in mice fed a high-fat diet hypothesising that the metabolic effects of whey would be associated with changes in the gut microbiota composition. Five-week-old male C57BL/6 mice were fed a high-fat diet ad libitum for 14 weeks with the protein source being either whey or casein. Faeces were collected at week 0, 7, and 13 and the fecal microbiota was analysed by denaturing gradient gel electrophoresis analyses of PCR-derived 16S rRNA gene (V3-region) amplicons. At the end of the study, plasma samples were collected and assayed for glucose, insulin and lipids. Whey significantly reduced body weight gain during the first four weeks of the study compared with casein (Pwhey group relative to casein (34.0±1.0 g vs. 40.2±1.3 g, Pwhey group (Pwhey compared to casein (Pwhey and casein. In conclusion, whey initially reduced weight gain in young C57BL/6 mice fed a high-fat diet compared to casein. Although the effect on weight gain ceased, whey alleviated glucose intolerance, improved insulin sensitivity and reduced plasma cholesterol. These findings could not be explained by changes in food intake or gut microbiota composition. Further studies are needed to clarify the mechanisms behind the metabolic effects of whey. PMID:23940754

  17. Reduced endothelial thioredoxin-interacting protein protects arteries from damage induced by metabolic stress in vivo.

    Science.gov (United States)

    Bedarida, Tatiana; Domingues, Alison; Baron, Stephanie; Ferreira, Chrystophe; Vibert, Francoise; Cottart, Charles-Henry; Paul, Jean-Louis; Escriou, Virginie; Bigey, Pascal; Gaussem, Pascale; Leguillier, Teddy; Nivet-Antoine, Valerie

    2018-06-01

    Although thioredoxin-interacting protein (TXNIP) is involved in a variety of biologic functions, the contribution of endothelial TXNIP has not been well defined. To investigate the endothelial function of TXNIP, we generated a TXNIP knockout mouse on the Cdh5-cre background (TXNIP fl/fl cdh5 cre ). Control (TXNIP fl/fl ) and TXNIP fl/fl cdh5 cre mice were fed a high protein-low carbohydrate (HP-LC) diet for 3 mo to induce metabolic stress. We found that TXNIP fl/fl and TXNIP fl/fl cdh5 cre mice on an HP-LC diet displayed impaired glucose tolerance and dyslipidemia concretizing the metabolic stress induced. We evaluated the impact of this metabolic stress on mice with reduced endothelial TXNIP expression with regard to arterial structure and function. TXNIP fl/fl cdh5 cre mice on an HP-LC diet exhibited less endothelial dysfunction than littermate mice on an HP-LC diet. These mice were protected from decreased aortic medial cell content, impaired aortic distensibility, and increased plasminogen activator inhibitor 1 secretion. This protective effect came with lower oxidative stress and lower inflammation, with a reduced NLRP3 inflammasome expression, leading to a decrease in cleaved IL-1β. We also show the major role of TXNIP in inflammation with a knockdown model, using a TXNIP-specific, small interfering RNA included in a lipoplex. These findings demonstrate a key role for endothelial TXNIP in arterial impairments induced by metabolic stress, making endothelial TXNIP a potential therapeutic target.-Bedarida, T., Domingues, A., Baron, S., Ferreira, C., Vibert, F., Cottart, C.-H., Paul, J.-L., Escriou, V., Bigey, P., Gaussem, P., Leguillier, T., Nivet-Antoine, V. Reduced endothelial thioredoxin-interacting protein protects arteries from damage induced by metabolic stress in vivo.

  18. Surfactant Protein-B 121ins2 Heterozygosity, Reduced Pulmonary Function and COPD in Smokers

    DEFF Research Database (Denmark)

    Bækvad-Hansen, Marie; Dahl, Morten; Tybjærg-Hansen, Anne

    2010-01-01

    .2-4.8) for spirometry defined COPD and of 2.2(1.0-5.1) for hospitalization due to COPD. Among never smokers, 121ins2 heterozygotes did not differ from wildtypes in lung function or risk of COPD. CONCLUSIONS: Surfactant protein-B 121ins2 heterozygosity is associated with reduced lung function and increased risk for COPD......2 mutation have reduced lung function and increased risk for chronic obstructive pulmonary disease (COPD) among smokers. METHODS: We genotyped 47,600 individuals from the adult Danish general population and recorded smoking habits, spirometry and hospital admissions due to COPD. The study...... that the effect of genotype differ by smoking status. Among smokers, 121ins2 heterozygotes had 9% reduced FEV1%predicted(p=0.0008), 6% reduced FVC%predicted(p=0.01) and 6% reduced FEV1/FVC(p=0.00007), compared with wildtypes. Also among smokers, 121ins2 heterozygotes had odds ratios of 2.4(95%CI 1...

  19. Turkey's net energy consumption

    International Nuclear Information System (INIS)

    Soezen, Adnan; Arcaklioglu, Erol; Oezkaymak, Mehmet

    2005-01-01

    The main goal of this study is to develop the equations for forecasting net energy consumption (NEC) using an artificial neural-network (ANN) technique in order to determine the future level of energy consumption in Turkey. In this study, two different models were used in order to train the neural network. In one of them, population, gross generation, installed capacity and years are used in the input layer of the network (Model 1). Other energy sources are used in input layer of network (Model 2). The net energy consumption is in the output layer for two models. Data from 1975 to 2003 are used for the training. Three years (1981, 1994 and 2003) are used only as test data to confirm this method. The statistical coefficients of multiple determinations (R 2 -value) for training data are equal to 0.99944 and 0.99913 for Models 1 and 2, respectively. Similarly, R 2 values for testing data are equal to 0.997386 and 0.999558 for Models 1 and 2, respectively. According to the results, the net energy consumption using the ANN technique has been predicted with acceptable accuracy. Apart from reducing the whole time required, with the ANN approach, it is possible to find solutions that make energy applications more viable and thus more attractive to potential users. It is also expected that this study will be helpful in developing highly applicable energy policies

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

    Science.gov (United States)

    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.

  1. Reduced influenza viral neutralizing activity of natural human trimers of surfactant protein D

    DEFF Research Database (Denmark)

    Hartshorn, Kevan L; White, Mitchell R; Tecle, Tesfaldet

    2007-01-01

    BACKGROUND: Surfactant protein D (SP-D) plays important roles in innate host defense against influenza A virus (IAV) infection. Common human polymorphisms of SP-D have been found in many human populations and associated with increased risk of certain infections. We recently reported that the Thr...... on the CRD of SP-D were found to have differing effects on antiviral activity. Using an mAb that did not interfere with antiviral activity of SP-D, we confirm that natural SP-D trimers had reduced ability to bind to IAV. In addition, the trimers had reduced ability to neutralize IAV as compared to natural...... indicate that a common human polymorphic form of SP-D may modulate host defense against IAV and give impetus to clinical studies correlating this genotype with risk for IAV infection in susceptible groups. We also show that mAbs directed against different areas on the carbohydrate recognition domain of SP...

  2. Whey protein reduces early life weight gain in mice fed a high-fat diet.

    Directory of Open Access Journals (Sweden)

    Britt Tranberg

    Full Text Available An increasing number of studies indicate that dairy products, including whey protein, alleviate several disorders of the metabolic syndrome. Here, we investigated the effects of whey protein isolate (whey in mice fed a high-fat diet hypothesising that the metabolic effects of whey would be associated with changes in the gut microbiota composition. Five-week-old male C57BL/6 mice were fed a high-fat diet ad libitum for 14 weeks with the protein source being either whey or casein. Faeces were collected at week 0, 7, and 13 and the fecal microbiota was analysed by denaturing gradient gel electrophoresis analyses of PCR-derived 16S rRNA gene (V3-region amplicons. At the end of the study, plasma samples were collected and assayed for glucose, insulin and lipids. Whey significantly reduced body weight gain during the first four weeks of the study compared with casein (P<0.001-0.05. Hereafter weight gain was similar resulting in a 15% lower final body weight in the whey group relative to casein (34.0±1.0 g vs. 40.2±1.3 g, P<0.001. Food intake was unaffected by protein source throughout the study period. Fasting insulin was lower in the whey group (P<0.01 and glucose clearance was improved after an oral glucose challenge (P<0.05. Plasma cholesterol was lowered by whey compared to casein (P<0.001. The composition of the fecal microbiota differed between high- and low-fat groups at 13 weeks (P<0.05 whereas no difference was seen between whey and casein. In conclusion, whey initially reduced weight gain in young C57BL/6 mice fed a high-fat diet compared to casein. Although the effect on weight gain ceased, whey alleviated glucose intolerance, improved insulin sensitivity and reduced plasma cholesterol. These findings could not be explained by changes in food intake or gut microbiota composition. Further studies are needed to clarify the mechanisms behind the metabolic effects of whey.

  3. Absence of residual structure in the intrinsically disordered regulatory protein CP12 in its reduced state

    Energy Technology Data Exchange (ETDEWEB)

    Launay, Hélène; Barré, Patrick [Laboratory of integrative Structural and Chemical Biology (iSCB), Centre de Recherche en Cancérologie de Marseille (CRCM), CNRS UMR 7258, INSERM U 1068, Institut Paoli-Calmettes, Aix-Marseille Universités, Marseille 13009 (France); Puppo, Carine [Aix-Marseille Université, Centre National de la Recherche Scientifique, UMR 7281, Laboratoire de Bioénergétique et Ingénierie des Protéines, 31 Chemin Joseph Aiguier, 13402, Marseille Cedex 20 (France); Manneville, Stéphanie [Laboratory of integrative Structural and Chemical Biology (iSCB), Centre de Recherche en Cancérologie de Marseille (CRCM), CNRS UMR 7258, INSERM U 1068, Institut Paoli-Calmettes, Aix-Marseille Universités, Marseille 13009 (France); Gontero, Brigitte [Aix-Marseille Université, Centre National de la Recherche Scientifique, UMR 7281, Laboratoire de Bioénergétique et Ingénierie des Protéines, 31 Chemin Joseph Aiguier, 13402, Marseille Cedex 20 (France); Receveur-Bréchot, Véronique, E-mail: veronique.brechot@inserm.fr [Laboratory of integrative Structural and Chemical Biology (iSCB), Centre de Recherche en Cancérologie de Marseille (CRCM), CNRS UMR 7258, INSERM U 1068, Institut Paoli-Calmettes, Aix-Marseille Universités, Marseille 13009 (France)

    2016-08-12

    The redox switch protein CP12 is a key player of the regulation of the Benson–Calvin cycle. Its oxidation state is controlled by the formation/dissociation of two intramolecular disulphide bridges during the day/night cycle. CP12 was known to be globally intrinsically disordered on a large scale in its reduced state, while being partly ordered in the oxidised state. By combining Nuclear Magnetic Resonance and Small Angle X-ray Scattering experiments, we showed that, contrary to secondary structure or disorder predictions, reduced CP12 is fully disordered, with no transient or local residual structure likely to be precursor of the structures identified in the oxidised active state and/or in the bound state with GAPDH or PRK. These results highlight the diversity of the mechanisms of regulation of conditionally disordered redox switches, and question the stability of oxidised CP12 scaffold. - Highlights: • CP12 is predicted to form two helices in its N-terminal sequence. • Reduced CP12 is disordered as a random coil according to SAXS. • Limited or no transient structures are observed in reduced CP12 by NMR.

  4. Absence of residual structure in the intrinsically disordered regulatory protein CP12 in its reduced state

    International Nuclear Information System (INIS)

    Launay, Hélène; Barré, Patrick; Puppo, Carine; Manneville, Stéphanie; Gontero, Brigitte; Receveur-Bréchot, Véronique

    2016-01-01

    The redox switch protein CP12 is a key player of the regulation of the Benson–Calvin cycle. Its oxidation state is controlled by the formation/dissociation of two intramolecular disulphide bridges during the day/night cycle. CP12 was known to be globally intrinsically disordered on a large scale in its reduced state, while being partly ordered in the oxidised state. By combining Nuclear Magnetic Resonance and Small Angle X-ray Scattering experiments, we showed that, contrary to secondary structure or disorder predictions, reduced CP12 is fully disordered, with no transient or local residual structure likely to be precursor of the structures identified in the oxidised active state and/or in the bound state with GAPDH or PRK. These results highlight the diversity of the mechanisms of regulation of conditionally disordered redox switches, and question the stability of oxidised CP12 scaffold. - Highlights: • CP12 is predicted to form two helices in its N-terminal sequence. • Reduced CP12 is disordered as a random coil according to SAXS. • Limited or no transient structures are observed in reduced CP12 by NMR.

  5. Reduced myelin basic protein and actin-related gene expression in visual cortex in schizophrenia.

    Science.gov (United States)

    Matthews, Paul R; Eastwood, Sharon L; Harrison, Paul J

    2012-01-01

    Most brain gene expression studies of schizophrenia have been conducted in the frontal cortex or hippocampus. The extent to which alterations occur in other cortical regions is not well established. We investigated primary visual cortex (Brodmann area 17) from the Stanley Neuropathology Consortium collection of tissue from 60 subjects with schizophrenia, bipolar disorder, major depression, or controls. We first carried out a preliminary array screen of pooled RNA, and then used RT-PCR to quantify five mRNAs which the array identified as differentially expressed in schizophrenia (myelin basic protein [MBP], myelin-oligodendrocyte glycoprotein [MOG], β-actin [ACTB], thymosin β-10 [TB10], and superior cervical ganglion-10 [SCG10]). Reduced mRNA levels were confirmed by RT-PCR for MBP, ACTB and TB10. The MBP reduction was limited to transcripts containing exon 2. ACTB and TB10 mRNAs were also decreased in bipolar disorder. None of the transcripts were altered in subjects with major depression. Reduced MBP mRNA in schizophrenia replicates findings in other brain regions and is consistent with oligodendrocyte involvement in the disorder. The decreases in expression of ACTB, and the actin-binding protein gene TB10, suggest changes in cytoskeletal organisation. The findings confirm that the primary visual cortex shows molecular alterations in schizophrenia and extend the evidence for a widespread, rather than focal, cortical pathophysiology.

  6. [SNACK HIGH WHEY PROTEIN IMPROVES THE LEVEL OF SATIETY AND REDUCES APPETITE HEALTHY WOMEN].

    Science.gov (United States)

    Reyna, Nadia; Moreno-Rojas, Rafael; Mendoza, Laura; Urdaneta, Andrés; Artigas, Carlos; Reyna, Eduardo; Cámara Martos, Fernando

    2015-10-01

    the nutritional content and energy density of foods is related to greater control of appetite, satiety and reducing food intake. the randomized crossover study included 20 healthy women, aged 20 and 30 years with a BMI of 20 to 24.9 kg/m2 and who completed that included 3 day trial comparing 8 hours 130 kcal snacks consumed afternoon: yoghurt with added whey protein (PSL), biscuits and chocolate. Participants consumed a standardized menu; snack was consumed 3 hours after lunch. Perceived hunger and fullness were evaluated during the afternoon until dinner voluntary intake ad libitum. They repeat the same snack 3 times. consumption of yogurt with PSL led to a further reduction of appetite in the afternoon in front of the snack of chocolate and biscuits (p snack, yogurt there was a significant reduction in caloric intake compared to other snacks (p snacks with less energy density and rich in protein (yogurt with PSL) improve the control of appetite, satiety and reduces food intake in healthy women later. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  7. Cooking Chicken Breast Reduces Dialyzable Iron Resulting from Digestion of Muscle Proteins

    Directory of Open Access Journals (Sweden)

    Aditya S. Gokhale

    2014-01-01

    Full Text Available The purpose of this research was to study the effect of cooking chicken breast on the production of dialyzable iron (an in vitro indicator of bioavailable iron from added ferric iron. Chicken breast muscle was cooked by boiling, baking, sautéing, or deep-frying. Cooked samples were mixed with ferric iron and either extracted with acid or digested with pepsin and pancreatin. Total and ferrous dialyzable iron was measured after extraction or digestion and compared to raw chicken samples. For uncooked samples, dialyzable iron was significantly enhanced after both extraction and digestion. All cooking methods led to markedly reduced levels of dialyzable iron both by extraction and digestion. In most cooked, digested samples dialyzable iron was no greater than the iron-only (no sample control. Cooked samples showed lower levels of histidine and sulfhydryls but protein digestibility was not reduced, except for the sautéed sample. The results showed that, after cooking, little if any dialyzable iron results from digestion of muscle proteins. Our research indicates that, in cooked chicken, residual acid-extractable components are the most important source of dialyzable iron.

  8. Cooking Chicken Breast Reduces Dialyzable Iron Resulting from Digestion of Muscle Proteins.

    Science.gov (United States)

    Gokhale, Aditya S; Mahoney, Raymond R

    2014-01-01

    The purpose of this research was to study the effect of cooking chicken breast on the production of dialyzable iron (an in vitro indicator of bioavailable iron) from added ferric iron. Chicken breast muscle was cooked by boiling, baking, sautéing, or deep-frying. Cooked samples were mixed with ferric iron and either extracted with acid or digested with pepsin and pancreatin. Total and ferrous dialyzable iron was measured after extraction or digestion and compared to raw chicken samples. For uncooked samples, dialyzable iron was significantly enhanced after both extraction and digestion. All cooking methods led to markedly reduced levels of dialyzable iron both by extraction and digestion. In most cooked, digested samples dialyzable iron was no greater than the iron-only (no sample) control. Cooked samples showed lower levels of histidine and sulfhydryls but protein digestibility was not reduced, except for the sautéed sample. The results showed that, after cooking, little if any dialyzable iron results from digestion of muscle proteins. Our research indicates that, in cooked chicken, residual acid-extractable components are the most important source of dialyzable iron.

  9. Very Low-Protein Diet (VLPD) Reduces Metabolic Acidosis in Subjects with Chronic Kidney Disease: The "Nutritional Light Signal" of the Renal Acid Load.

    Science.gov (United States)

    Di Iorio, Biagio Raffaele; Di Micco, Lucia; Marzocco, Stefania; De Simone, Emanuele; De Blasio, Antonietta; Sirico, Maria Luisa; Nardone, Luca

    2017-01-17

    Metabolic acidosis is a common complication of chronic kidney disease; current guidelines recommend treatment with alkali if bicarbonate levels are lower than 22 mMol/L. In fact, recent studies have shown that an early administration of alkali reduces progression of CKD. The aim of the study is to evaluate the effect of fruit and vegetables to reduce the acid load in CKD. We conducted a case-control study in 146 patients who received sodium bicarbonate. Of these, 54 patients assumed very low-protein diet (VLPD) and 92 were controls (ratio 1:2). We calculated every three months the potential renal acid load (PRAL) and the net endogenous acid production (NEAP), inversely correlated with serum bicarbonate levels and representing the non-volatile acid load derived from nutrition. Un-paired T -test and Chi-square test were used to assess differences between study groups at baseline and study completion. Two-tailed probability values ≤0.05 were considered statistically significant. At baseline, there were no statistical differences between the two groups regarding systolic blood pressure (SBP), diastolic blood pressure (DBP), protein and phosphate intake, urinary sodium, potassium, phosphate and urea nitrogen, NEAP, and PRAL. VLPD patients showed at 6 and 12 months a significant reduction of SBP ( p protein intake ( p intake ( p intake of acids; nutritional therapy of CKD, that has always taken into consideration a lower protein, salt, and phosphate intake, should be adopted to correct metabolic acidosis, an important target in the treatment of CKD patients. We provide useful indications regarding acid load of food and drinks-the "acid load dietary traffic light".

  10. Subchronic nandrolone administration reduces cardiac oxidative markers during restraint stress by modulating protein expression patterns.

    Science.gov (United States)

    Pergolizzi, Barbara; Carriero, Vitina; Abbadessa, Giuliana; Penna, Claudia; Berchialla, Paola; De Francia, Silvia; Bracco, Enrico; Racca, Silvia

    2017-10-01

    Nandrolone decanoate (ND), an anabolic-androgenic steroid prohibited in collegiate and professional sports, is associated with detrimental cardiovascular effects through redox-dependent mechanisms. We previously observed that high-dose short-term ND administration (15 mg/kg for 2 weeks) did not induce left heart ventricular hypertrophy and, paradoxically, improved postischemic response, whereas chronic ND treatment (5 mg/kg twice a week for 10 weeks) significantly reduced the cardioprotective effect of postconditioning, with an increase in infarct size and a decrease in cardiac performance. We wanted to determine whether short-term ND administration could affect the oxidative redox status in animals exposed to acute restraint stress. Our hypothesis was that, depending on treatment schedule, ND may have a double-edged sword effect. Measurement of malondialdehyde and 4-hydroxynonenal, two oxidative stress markers, in rat plasma and left heart ventricular tissue, revealed that the levels of both markers were increased in animals exposed to restraint stress, whereas no increase in marker levels was noted in animals pretreated with ND, indicating a possible protective action of ND against stress-induced oxidative damage. Furthermore, isolation and identification of proteins extracted from the left heart ventricular tissue samples of rats pretreated or not with ND and exposed to acute stress showed a prevalent expression of enzymes involved in amino acid synthesis and energy metabolism. Among other proteins, peroxiredoxin 6 and alpha B-crystallin, both involved in the oxidative stress response, were predominantly expressed in the left heart ventricular tissues of the ND-pretreated rats. In conclusion, ND seems to reduce oxidative stress by inducing the expression of antioxidant proteins in the hearts of restraint-stressed animals, thus contributing to amelioration of postischemic heart performance.

  11. Macrocyclic peptides decrease c-Myc protein levels and reduce prostate cancer cell growth.

    Science.gov (United States)

    Mukhopadhyay, Archana; Hanold, Laura E; Thayele Purayil, Hamsa; Gisemba, Solomon A; Senadheera, Sanjeewa N; Aldrich, Jane V

    2017-08-03

    The oncoprotein c-Myc is often overexpressed in cancer cells, and the stability of this protein has major significance in deciding the fate of a cell. Thus, targeting c-Myc levels is an attractive approach for developing therapeutic agents for cancer treatment. In this study, we report the anti-cancer activity of the macrocyclic peptides [D-Trp]CJ-15,208 (cyclo[Phe-D-Pro-Phe-D-Trp]) and the natural product CJ-15,208 (cyclo[Phe-D-Pro-Phe-Trp]). [D-Trp]CJ-15,208 reduced c-Myc protein levels in prostate cancer cells and decreased cell proliferation with IC 50 values ranging from 2.0 to 16 µM in multiple PC cell lines. [D-Trp]CJ-15,208 induced early and late apoptosis in PC-3 cells following 48 hours treatment, and growth arrest in the G2 cell cycle phase following both 24 and 48 hours treatment. Down regulation of c-Myc in PC-3 cells resulted in loss of sensitivity to [D-Trp]CJ-15,208 treatment, while overexpression of c-Myc in HEK-293 cells imparted sensitivity of these cells to [D-Trp]CJ-15,208 treatment. This macrocyclic tetrapeptide also regulated PP2A by reducing the levels of its phosphorylated form which regulates the stability of cellular c-Myc protein. Thus [D-Trp]CJ-15,208 represents a new lead compound for the potential development of an effective treatment of prostate cancer.

  12. Coloured Petri Nets

    DEFF Research Database (Denmark)

    Jensen, Kurt

    1987-01-01

    The author describes a Petri net model, called coloured Petri nets (CP-nets), by means of which it is possible to describe large systems without having to cope with unnecessary details. The author introduces CP-nets and provide a first impression of their modeling power and the suitability...

  13. Learning Visual Basic NET

    CERN Document Server

    Liberty, Jesse

    2009-01-01

    Learning Visual Basic .NET is a complete introduction to VB.NET and object-oriented programming. By using hundreds of examples, this book demonstrates how to develop various kinds of applications--including those that work with databases--and web services. Learning Visual Basic .NET will help you build a solid foundation in .NET.

  14. Serum C-reactive protein and thioredoxin levels in subjects with mildly reduced glomerular filtration rate

    Directory of Open Access Journals (Sweden)

    Ishimura Eiji

    2010-04-01

    Full Text Available Abstract Background Chronic kidney disease (CKD is a newly recognized high-risk condition for cardiovascular disease (CVD, and previous studies reported the changes in inflammation and oxidative stress in advanced stages of CKD. We compared the levels of serum biomarkers for inflammation and oxidative stress between subjects with normal and mildly reduced glomerular filtration rate (GFR. Methods The subjects were 182 participants of a health check-up program including those with normal (≥ 90 mL/min/1.73 m2, N = 79 and mildly reduced eGFR (60-89 mL/min/1.73 m2, N = 103 which was calculated based on serum creatinine, age and sex. We excluded those with reduced eGFR 2. No one had proteinuria. We measured serum levels of C-reactive protein (CRP and thioredoxin (TRX as the markers of inflammation and oxidative stress, respectively. Results As compared with subjects with normal eGFR, those with mildly reduced eGFR had increased levels of both CRP and TRX. Also, eGFR was inversely correlated with these biomarkers. The associations of eGFR with these biomarkers remained significant after adjustment for age and sex. When adjustment was done for eight possible confounders, CRP showed significant association with systolic blood pressure, high density lipoprotein cholesterol (HDL-C and non-HDL-C, whereas TRX was associated with sex significantly, and with eGFR and systolic blood pressure at borderline significance. Conclusions We showed the increased levels of CRP and TRX in subjects with mildly reduced eGFR. The eGFR-CRP link and the eGFR-TRX link appeared to be mediated, at least partly, by the alterations in blood pressure and plasma lipids in these subjects.

  15. Mycobacterium tuberculosis PPE18 Protein Reduces Inflammation and Increases Survival in Animal Model of Sepsis.

    Science.gov (United States)

    Ahmed, Asma; Dolasia, Komal; Mukhopadhyay, Sangita

    2018-04-18

    Mycobacterium tuberculosis PPE18 is a member of the PPE family. Previous studies have shown that recombinant PPE18 (rPPE18) protein binds to TLR2 and triggers a signaling cascade which reduces levels of TNF-α and IL-12, and increases IL-10 in macrophages. Because TNF-α is a major mediator of the pathophysiology of sepsis and blocking inflammation is a possible line of therapy in such circumstances, we tested the efficacy of rPPE18 in reducing symptoms of sepsis in a mouse model of Escherichia coli- induced septic peritonitis. rPPE18 significantly decreased levels of serum TNF-α, IL-1β, IL-6, and IL-12 and reduced organ damage in mice injected i.p. with high doses of E. coli Peritoneal cells isolated from rPPE18-treated mice had characteristics of M2 macrophages which are protective in excessive inflammation. Additionally, rPPE18 inhibited disseminated intravascular coagulation, which can cause organ damage resulting in death. rPPE18 was able to reduce sepsis-induced mortality when given prophylactically or therapeutically. Additionally, in a mouse model of cecal ligation and puncture-induced sepsis, rPPE18 reduced TNF-α, alanine transaminase, and creatinine, attenuated organ damage, prevented depletion of monocytes and lymphocytes, and improved survival. Our studies show that rPPE18 has potent anti-inflammatory properties and can serve as a novel therapeutic to control sepsis. Copyright © 2018 by The American Association of Immunologists, Inc.

  16. Lipoxygenase independent hexanal formation in isolated soy proteins induced by reducing agents.

    Science.gov (United States)

    Lei, Q; Boatright, W L

    2008-08-01

    Compared to corresponding controls, 6.5 mM dithiothreitol (DTT) elevated headspace hexanal level over aqueous slurries of both commercial isolated soy proteins (ISP) and laboratory ISP prepared with 80 degrees C treatment. Further analysis revealed that lipoxygenase (LOX) activity was not detected from these ISP, indicating that LOX is not involved in the observed hexanal increase. Levels of the induced headspace hexanal over the ISP aqueous slurries were proportional to the amount of DTT added in the range of 0 to 65 mM. Subsequent systematic investigations with model systems revealed that iron was required for the reducing agent-induced hexanal formation from linoleic acid. Erythorbate, another reducing agent, can also induce hexanal formation in both ISP and model systems. As a comparison, the LOX activity and hexanal synthesis in defatted soy flour were examined. The corresponding results showed that defatted soy flour maintained high LOX activities and that hexanal synthesis in such sample was significantly inhibited by high concentration DTT (above 130 mM). Data from the current investigation demonstrate the existence of LOX independent hexanal formation induced by reducing agents in ISP and the potential requirement of iron as a catalyst.

  17. Reduced protein bound uraemic toxins in vegetarian kidney failure patients treated by haemodiafiltration.

    Science.gov (United States)

    Kandouz, Sakina; Mohamed, Ali Shendi; Zheng, Yishan; Sandeman, Susan; Davenport, Andrew

    2016-10-01

    Introduction Indoxyl sulfate (IS) and p cresyl sulfate (PCS) are protein bound toxins which accumulate with chronic kidney disease. Haemodiafiltration (HDF) increases middle molecule clearances and has been suggested to increase IS and PCS clearance. We therefore wished to establish whether higher convective clearances with HDF would reduce IS and PCS concentrations. Methods We measured total plasma IS and PCS in a cohort of 138 CKD5d patients treated by On-line HDF (Ol-HDF), by high pressure liquid chromatography. Findings Mean patient age was 64.6 ± 16.5 years, 60.1% male, 57.3% diabetic, median dialysis vintage 25.9 months (12.4-62.0). The mean ICS concentration was 79.8 ± 56.4 umol/L and PCS 140.3 ± 101.8 umol/L. On multivariate analysis, IS was associated with serum albumin (β 4.31,P vegetarian diet(β-28.3, P = 0.048) and PCS negatively with log C reactive protein (β-75.8, P vegetarian diet (β-109, P = 0.001). Vegetarian patients had lower IS and PCS levels (median 41.5 (24.2-71.9) vs. 78.1 (49.5-107.5) and PCS (41.6 (14.2-178.3) vs. 127.3 (77.4-205.6) µmol/L, respectively, P Vegetarian patients had lower preOl-HDF serum urea, and phosphate (13.8 ±3.8 vs. 18.4 ± 5.2 mmol/L, and 1.33 ± 0.21 vs. 1.58 ± 0.45 mmol/L), and estimated urea nitrogen intake (1.25 ± 0.28 vs. 1.62 ± 0.5 g/kg/day), respectively, all P vegetarian diet had reduced IS and PCS concentrations. Although this could be due to differences in dietary protein intake, a vegetarian diet may also potentially reduce IS and PCS production by the intestinal microbiome. © 2016 International Society for Hemodialysis.

  18. Inhibition of coagulation and inflammation by activated protein C or antithrombin reduces intestinal ischemia/reperfusion injury in rats

    NARCIS (Netherlands)

    Schoots, Ivo G.; Levi, Marcel; van Vliet, Arlène K.; Maas, Adrie M.; Roossink, E. H. Paulina; van Gulik, Thomas M.

    2004-01-01

    Objective: To examine whether administration of activated protein C or antithrombin reduces local splanchnic derangement of coagulation and inflammation and attenuates intestinal dysfunction and injury following intestinal ischemia/reperfusion. Design: Randomized prospective animal study. Setting:

  19. Leucine supplementation stimulates protein synthesis and reduces degradation signal activation in muscle of newborn pigs during acute endotoxemia

    Science.gov (United States)

    Sepsis disrupts skeletal muscle proteostasis and mitigates the anabolic response to leucine (Leu) in muscle of mature animals. We have shown that Leu stimulates muscle protein synthesis (PS) in healthy neonatal piglets. To determine if supplemental Leu can stimulate PS and reduce protein degradation...

  20. Blunted hypothalamic ghrelin signaling reduces diet intake in rats fed a low-protein diet in late pregnancy

    Science.gov (United States)

    Diet intake in pregnant rats fed a low-protein (LP) diet was significantly reduced during late pregnancy despite elevated plasma levels of ghrelin. In this study, we hypothesized that ghrelin signaling in the hypothalamus is blunted under a low-protein diet condition and therefore, it does not stimu...

  1. Overexpression of protein kinase A - RIalpha reduces lipofection efficiency of cisplatin-resistant human tumor cells.

    Science.gov (United States)

    Son, K K; Rosenblatt, J

    2001-04-10

    Cisplatin-resistant variant A2780CP/vector cells were 4.0-5.3-fold more transfectable and 7.6-fold more resistant to cisplatin than their parent cisplatin-sensitive human ovarian carcinoma A2780/vector cells. Overexpression of cAMP-dependent protein kinase Type I regulatory alpha subunit (PKA-RIalpha) gene in A2780CP cells significantly reduced (maximum 47.0%) the transfection activity, with a slight reduction (maximum 27.3%) of cisplatin resistance, of A2780CP cells. However, RIalpha-overexpressing A2780CP (A2780CP/RIalpha) cells were still 2.5-to 3.0-fold more transfectable and 5.5-fold more resistant to cisplatin than A2780 cells. This results suggest that gene transfer efficiency is associated with cisplatin resistance, in part, through the PKA-mediated cAMP signal transduction pathway.

  2. High-Pressure-High-Temperature Processing Reduces Maillard Reaction and Viscosity in Whey Protein-Sugar Solutions.

    Science.gov (United States)

    Avila Ruiz, Geraldine; Xi, Bingyan; Minor, Marcel; Sala, Guido; van Boekel, Martinus; Fogliano, Vincenzo; Stieger, Markus

    2016-09-28

    The aim of the study was to determine the influence of pressure in high-pressure-high-temperature (HPHT) processing on Maillard reactions and protein aggregation of whey protein-sugar solutions. Solutions of whey protein isolate containing either glucose or trehalose at pH 6, 7, and 9 were treated by HPHT processing or conventional high-temperature (HT) treatments. Browning was reduced, and early and advanced Maillard reactions were retarded under HPHT processing at all pH values compared to HT treatment. HPHT induced a larger pH drop than HT treatments, especially at pH 9, which was not associated with Maillard reactions. After HPHT processing at pH 7, protein aggregation and viscosity of whey protein isolate-glucose/trehalose solutions remained unchanged. It was concluded that HPHT processing can potentially improve the quality of protein-sugar-containing foods, for which browning and high viscosities are undesired, such as high-protein beverages.

  3. Impact of feeding reduced crude protein diets to lactating sows on nitrogen utilizatilon

    DEFF Research Database (Denmark)

    Huber, L; de Lange, C F M; Larsen, Uffe Krogh

    2015-01-01

    -fed; analyzed contents; HCP); 2) 15.7% CP (MHCP); 3) 14.3% CP (MLCP); 4) 13.2% CP (LCP); diet HCP was formulated using soybean meal and corn as the only Lys sources. The reduced CP diets contained CAA to meet requirements of the limiting AA. Sow and piglet BW were measured on d 1, 3, 7, 14, 18, and 21...... of lactation. Nitrogen retention was measured on sows between d 3 and 7 (early) and d 14 and 18 (peak) of lactation. Milk true protein output was calculated from estimated milk yield and analyzed true protein concentration. Sow BW change (overall mean: -4.2 ± 3.37 kg over the 21-d lactation period) and average...... daily DM intake (overall mean: 4.05 ± 0.18 and 6.12 ± 0.20 kg/d, early and peak lactation, respectively) did not differ between diets. Nitrogen intake decreased as dietary CP concentration decreased (114.3, 106.0, 107.4, and 99.0 ± 5.29 g/d and 169.5, 168.3, 161.2, and 145.1 ± 5.29 g/d for HCP, MHCP...

  4. Net Gain: A New Method for Preventing Malaria Deaths | CRDI ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    A finely spun net could prevent as many as one-third of all child deaths in Africa, reports IDRC's new publication, Net Gain. Studies conducted in Gambia, Ghana, and Kenya show that the insecticide-treated mosquito net reduced the mortality rate of children under 5 years of age by up to 63 percent. Net Gain reviews and ...

  5. Effect of malaria transmission reduction by insecticide-treated bed nets (ITNs) on the genetic diversity of Plasmodium falciparum merozoite surface protein (MSP-1) and circumsporozoite (CSP) in western Kenya.

    Science.gov (United States)

    Kariuki, Simon K; Njunge, James; Muia, Ann; Muluvi, Geofrey; Gatei, Wangeci; Ter Kuile, Feiko; Terlouw, Dianne J; Hawley, William A; Phillips-Howard, Penelope A; Nahlen, Bernard L; Lindblade, Kim A; Hamel, Mary J; Slutsker, Laurence; Shi, Ya Ping

    2013-08-27

    Although several studies have investigated the impact of reduced malaria transmission due to insecticide-treated bed nets (ITNs) on the patterns of morbidity and mortality, there is limited information on their effect on parasite diversity. Sequencing was used to investigate the effect of ITNs on polymorphisms in two genes encoding leading Plasmodium falciparum vaccine candidate antigens, the 19 kilodalton blood stage merozoite surface protein-1 (MSP-1(19kDa)) and the Th2R and Th3R T-cell epitopes of the pre-erythrocytic stage circumsporozoite protein (CSP) in a large community-based ITN trial site in western Kenya. The number and frequency of haplotypes as well as nucleotide and haplotype diversity were compared among parasites obtained from children diversity of > 0.7. No MSP-1(19kDa) 3D7 sequence-types were detected in 1996 and the frequency was less than 4% in 2001. The CSP Th2R and Th3R domains were highly polymorphic with a total of 26 and 14 haplotypes, respectively detected in 1996 and 34 and 13 haplotypes in 2001, with an overall haplotype diversity of > 0.9 and 0.75 respectively. The frequency of the most predominant Th2R and Th3R haplotypes was 14 and 36%, respectively. The frequency of Th2R and Th3R haplotypes corresponding to the 3D7 parasite strain was less than 4% at both time points. There was no significant difference in nucleotide and haplotype diversity in parasite isolates collected at both time points. High diversity in these two genes has been maintained overtime despite marked reductions in malaria transmission due to ITNs use. The frequency of 3D7 sequence-types was very low in this area. These findings provide information that could be useful in the design of future malaria vaccines for deployment in endemic areas with high ITN coverage and in interpretation of efficacy data for malaria vaccines based on 3D7 parasite strains.

  6. Reduced homeobox protein MSX1 in human endometrial tissue is linked to infertility.

    Science.gov (United States)

    Bolnick, Alan D; Bolnick, Jay M; Kilburn, Brian A; Stewart, Tamika; Oakes, Jonathan; Rodriguez-Kovacs, Javier; Kohan-Ghadr, Hamid-Reza; Dai, Jing; Diamond, Michael P; Hirota, Yasushi; Drewlo, Sascha; Dey, Sudhansu K; Armant, D Randall

    2016-09-01

    Is protein expression of the muscle segment homeobox gene family member MSX1 altered in the human secretory endometrium by cell type, developmental stage or fertility? MSX1 protein levels, normally elevated in the secretory phase endometrium, were significantly reduced in endometrial biopsies obtained from women of infertile couples. Molecular changes in the endometrium are important for fertility in both animals and humans. Msx1 is expressed in the preimplantation mouse uterus and regulates uterine receptivity for implantation. The MSX protein persists a short time, after its message has been down-regulated. Microarray analysis of the human endometrium reveals a similar pattern of MSX1 mRNA expression that peaks before the receptive period, with depressed expression at implantation. Targeted deletion of uterine Msx1 and Msx2 in mice prevents the loss of epithelial cell polarity during implantation and causes infertility. MSX1 mRNA and cell type-specific levels of MSX1 protein were quantified from two retrospective cohorts during the human endometrial cycle. MSX1 protein expression patterns were compared between fertile and infertile couples. Selected samples were dual-labeled by immunofluorescence microscopy to localize E-cadherin and β-catenin in epithelial cells. MSX1 mRNA was quantified by PCR in endometrium from hysterectomies (n = 14) determined by endometrial dating to be in the late-proliferative (cycle days 10-13), early-secretory (cycle days 14-19) or mid-secretory (cycle days 20-24) phase. MSX1 protein was localized using high-throughput, semi-quantitative immunohistochemistry with sectioned endometrial biopsy tissues from fertile (n = 89) and infertile (n = 89) couples. Image analysis measured stain intensity specifically within the luminal epithelium, glands and stroma during the early-, mid- and late- (cycle days 25-28) secretory phases. MSX1 transcript increased 5-fold (P MSX1 protein displayed strong nuclear localization in the luminal epithelium

  7. Morphine Reduces Myocardial Infarct Size via Heat Shock Protein 90 in Rodents

    Directory of Open Access Journals (Sweden)

    Bryce A. Small

    2015-01-01

    Full Text Available Opioids reduce injury from myocardial ischemia-reperfusion in humans. In experimental models, this mechanism involves GSK3β inhibition. HSP90 regulates mitochondrial protein import, with GSK3β inhibition increasing HSP90 mitochondrial content. Therefore, we determined whether morphine-induced cardioprotection is mediated by HSP90 and if the protective effect is downstream of GSK3β inhibition. Male Sprague-Dawley rats, aged 8–10 weeks, were subjected to an in vivo myocardial ischemia-reperfusion injury protocol involving 30 minutes of ischemia followed by 2 hours of reperfusion. Hemodynamics were continually monitored and myocardial infarct size determined. Rats received morphine (0.3 mg/kg, the GSK3β inhibitor, SB216763 (0.6 mg/kg, or saline, 10 minutes prior to ischemia. Some rats received selective HSP90 inhibitors, radicicol (0.3 mg/kg, or deoxyspergualin (DSG, 0.6 mg/kg alone or 5 minutes prior to morphine or SB216763. Morphine reduced myocardial infarct size when compared to control (42 ± 2% versus 60 ± 1%. This protection was abolished by prior treatment of radicicol or DSG (59 ± 1%, 56 ± 2%. GSK3β inhibition also reduced myocardial infarct size (41 ± 2% with HSP90 inhibition by radicicol or DSG partially inhibiting SB216763-induced infarct size reduction (54 ± 3%, 47 ± 1%, resp.. These data suggest that opioid-induced cardioprotection is mediated by HSP90. Part of this protection afforded by HSP90 is downstream of GSK3β, potentially via the HSP-TOM mitochondrial import pathway.

  8. Planning of nets

    International Nuclear Information System (INIS)

    Carberry, M

    1996-01-01

    The paper is about the planning of nets in areas of low density like it is the case of the rural areas. The author includes economic and technological aspects, planning of nets, demands and management among others

  9. Annotating Coloured Petri Nets

    DEFF Research Database (Denmark)

    Lindstrøm, Bo; Wells, Lisa Marie

    2002-01-01

    Coloured Petri nets (CP-nets) can be used for several fundamentally different purposes like functional analysis, performance analysis, and visualisation. To be able to use the corresponding tool extensions and libraries it is sometimes necessary to include extra auxiliary information in the CP......-net. An example of such auxiliary information is a counter which is associated with a token to be able to do performance analysis. Modifying colour sets and arc inscriptions in a CP-net to support a specific use may lead to creation of several slightly different CP-nets – only to support the different uses...... of the same basic CP-net. One solution to this problem is that the auxiliary information is not integrated into colour sets and arc inscriptions of a CP-net, but is kept separately. This makes it easy to disable this auxiliary information if a CP-net is to be used for another purpose. This paper proposes...

  10. Very Low-Protein Diet (VLPD Reduces Metabolic Acidosis in Subjects with Chronic Kidney Disease: The “Nutritional Light Signal” of the Renal Acid Load

    Directory of Open Access Journals (Sweden)

    Biagio Raffaele Di Iorio

    2017-01-01

    Full Text Available Background: Metabolic acidosis is a common complication of chronic kidney disease; current guidelines recommend treatment with alkali if bicarbonate levels are lower than 22 mMol/L. In fact, recent studies have shown that an early administration of alkali reduces progression of CKD. The aim of the study is to evaluate the effect of fruit and vegetables to reduce the acid load in CKD. Methods: We conducted a case-control study in 146 patients who received sodium bicarbonate. Of these, 54 patients assumed very low-protein diet (VLPD and 92 were controls (ratio 1:2. We calculated every three months the potential renal acid load (PRAL and the net endogenous acid production (NEAP, inversely correlated with serum bicarbonate levels and representing the non-volatile acid load derived from nutrition. Un-paired T-test and Chi-square test were used to assess differences between study groups at baseline and study completion. Two-tailed probability values ≤0.05 were considered statistically significant. Results: At baseline, there were no statistical differences between the two groups regarding systolic blood pressure (SBP, diastolic blood pressure (DBP, protein and phosphate intake, urinary sodium, potassium, phosphate and urea nitrogen, NEAP, and PRAL. VLPD patients showed at 6 and 12 months a significant reduction of SBP (p < 0.0001, DBP (p < 0.001, plasma urea (p < 0.0001 protein intake (p < 0.0001, calcemia (p < 0.0001, phosphatemia (p < 0.0001, phosphate intake (p < 0.0001, urinary sodium (p < 0.0001, urinary potassium (p < 0.002, and urinary phosphate (p < 0.0001. NEAP and PRAL were significantly reduced in VLPD during follow-up. Conclusion: VLPD reduces intake of acids; nutritional therapy of CKD, that has always taken into consideration a lower protein, salt, and phosphate intake, should be adopted to correct metabolic acidosis, an important target in the treatment of CKD patients. We provide useful indications regarding acid load of food and

  11. A NEW METHOD TO QUANTIFY AND REDUCE THE NET PROJECTION ERROR IN WHOLE-SOLAR-ACTIVE-REGION PARAMETERS MEASURED FROM VECTOR MAGNETOGRAMS

    Energy Technology Data Exchange (ETDEWEB)

    Falconer, David A.; Tiwari, Sanjiv K.; Moore, Ronald L. [NASA Marshall Space Flight Center, Huntsville, AL 35812 (United States); Khazanov, Igor, E-mail: David.a.Falconer@nasa.gov [Center for Space Plasma and Aeronomic Research, University of Alabama in Huntsville, Huntsville, AL 35899 (United States)

    2016-12-20

    Projection errors limit the use of vector magnetograms of active regions (ARs) far from the disk center. In this Letter, for ARs observed up to 60° from the disk center, we demonstrate a method for measuring and reducing the projection error in the magnitude of any whole-AR parameter that is derived from a vector magnetogram that has been deprojected to the disk center. The method assumes that the center-to-limb curve of the average of the parameter’s absolute values, measured from the disk passage of a large number of ARs and normalized to each AR’s absolute value of the parameter at central meridian, gives the average fractional projection error at each radial distance from the disk center. To demonstrate the method, we use a large set of large-flux ARs and apply the method to a whole-AR parameter that is among the simplest to measure: whole-AR magnetic flux. We measure 30,845 SDO /Helioseismic and Magnetic Imager vector magnetograms covering the disk passage of 272 large-flux ARs, each having whole-AR flux >10{sup 22} Mx. We obtain the center-to-limb radial-distance run of the average projection error in measured whole-AR flux from a Chebyshev fit to the radial-distance plot of the 30,845 normalized measured values. The average projection error in the measured whole-AR flux of an AR at a given radial distance is removed by multiplying the measured flux by the correction factor given by the fit. The correction is important for both the study of the evolution of ARs and for improving the accuracy of forecasts of an AR’s major flare/coronal mass ejection productivity.

  12. Bone Morphogenetic Protein 9 Reduces Cardiac Fibrosis and Improves Cardiac Function in Heart Failure.

    Science.gov (United States)

    Morine, Kevin J; Qiao, Xiaoying; York, Sam; Natov, Peter S; Paruchuri, Vikram; Zhang, Yali; Aronovitz, Mark J; Karas, Richard H; Kapur, Navin K

    2018-02-27

    Background -Heart failure is a growing cause of morbidity and mortality worldwide. Transforming growth factor beta (TGF-β1) promotes cardiac fibrosis, but also activates counter-regulatory pathways that serve to regulate TGF-β1 activity in heart failure. Bone morphogenetic protein 9 (BMP9) is a member of the TGFβ family of cytokines and signals via the downstream effector protein Smad1. Endoglin is a TGFβ co-receptor that promotes TGF-β1 signaling via Smad3 and binds BMP9 with high affinity. We hypothesized that BMP9 limits cardiac fibrosis by activating Smad1 and attenuating Smad3 and further that neutralizing endoglin activity promotes BMP9 activity. Methods -We examined BMP9 expression and signaling in human cardiac fibroblasts and human subjects with heart failure. We utilized the thoracic aortic constriction (TAC) induced model of heart failure to evaluate the functional effect of BMP9 signaling on cardiac remodeling. Results -BMP9 expression is increased in the circulation and left ventricle (LV) of human subjects with heart failure and is expressed by cardiac fibroblasts. Next, we observed that BMP9 attenuates Type I collagen synthesis in human cardiac fibroblasts using recombinant human BMP9 and an siRNA approach. In BMP9 -/- mice subjected to TAC, loss of BMP9 activity promotes cardiac fibrosis, impairs LV function, and increases LV levels of phosphorylated Smad3 (pSmad3), not pSmad1. In contrast, treatment of wild-type mice subjected to TAC with recombinant BMP9 limits progression of cardiac fibrosis, improves LV function, enhances myocardial capillary density, and increases LV levels of pSmad1, not pSmad3 compared to vehicle treated controls. Since endoglin binds BMP9 with high affinity, we explored the effect of reduced endoglin activity on BMP9 activity. Neutralizing endoglin activity in human cardiac fibroblasts or in wild-type mice subjected to TAC induced heart failure limits collagen production, increases BMP9 protein levels, and increases

  13. Moderate, but not vigorous, intensity exercise training reduces C-reactive protein.

    Science.gov (United States)

    Fedewa, Michael V; Hathaway, Elizabeth D; Higgins, Simon; Forehand, Ronald L; Schmidt, Michael D; Evans, Ellen M

    2018-06-01

    Sprint interval cycle training is a contemporary popular mode of training but its relative efficacy, under conditions of matched energy expenditure, to reduce risk factors for cardiometabolic disease is incompletely characterised, especially in young women. The purpose of this investigation was to determine the relative efficacy of six weeks of moderate-intensity cycling (MOD-C) and vigorous sprint-interval cycling (VIG-SIC) on lipid profile, insulin (INS) and insulin resistance using the homeostatic model assessment (HOMA-IR) and C-reactive protein (CRP) in inactive, overweight/obese (OW/OB) young women. Participants (BMI ≥25 kg/m 2 , waist circumference ≥88 cm) were randomly assigned to MOD-C (20-30 min at 60-70% of heart rate reserve(HRR)) or VIG-SIC (5-7 repeated bouts 30-second maximal effort sprints, followed by four minutes of active recovery) supervised training three days/week for six weeks, with each group matched on energy expenditure. Adiposity (%Fat) was measured using dual x-ray absorptiometry. Forty-four participants (20.4 ± 1.6 years, 65.9% Caucasian, 29.8 ± 4.1 kg/m 2 ) were included in the analysis. The improvement in CRP observed in the MOD-C group was larger than the VIG-C group (p = .034). Overall, high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) levels improved following training (p  .05). These results indicate MOD-C training may be more effective in reducing CRP than VIG-SIC.

  14. A novel mosquito ubiquitin targets viral envelope protein for degradation and reduces virion production during dengue virus infection.

    Science.gov (United States)

    Troupin, Andrea; Londono-Renteria, Berlin; Conway, Michael J; Cloherty, Erin; Jameson, Samuel; Higgs, Stephen; Vanlandingham, Dana L; Fikrig, Erol; Colpitts, Tonya M

    2016-09-01

    Dengue virus (DENV) is a mosquito-borne flavivirus that causes significant human disease and mortality in the tropics and subtropics. By examining the effects of virus infection on gene expression, and interactions between virus and vector, new targets for prevention of infection and novel treatments may be identified in mosquitoes. We previously performed a microarray analysis of the Aedes aegypti transcriptome during infection with DENV and found that mosquito ubiquitin protein Ub3881 (AAEL003881) was specifically and highly down-regulated. Ubiquitin proteins have multiple functions in insects, including marking proteins for proteasomal degradation, regulating apoptosis and mediating innate immune signaling. We used qRT-PCR to quantify gene expression and infection, and RNAi to reduce Ub3881 expression. Mosquitoes were infected with DENV through blood feeding. We transfected DENV protein expression constructs to examine the effect of Ub3881 on protein degradation. We used site-directed mutagenesis and transfection to determine what amino acids are involved in Ub3881-mediated protein degradation. Immunofluorescence, Co-immunoprecipitation and Western blotting were used to examine protein interactions and co-localization. The overexpression of Ub3881, but not related ubiquitin proteins, decreased DENV infection in mosquito cells and live Ae. aegypti. The Ub3881 protein was demonstrated to be involved in DENV envelope protein degradation and reduce the number of infectious virions released. We conclude that Ub3881 has several antiviral functions in the mosquito, including specific viral protein degradation. Our data highlights Ub3881 as a target for future DENV prevention strategies in the mosquito transmission vector. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Reduced immune responses to purified protein derivative and Candida albicans in oral lichen planus.

    Science.gov (United States)

    Simark-Mattsson, Charlotte; Eklund, Christina

    2013-10-01

    Impairment of cellular immunity is reported in lichen planus, an autoimmune disease affecting mucosae and skin. Our aim was to investigate immune responses directed against a set of microbial antigens in patients with oral lichen planus and in matched controls. Venous blood was obtained, and the mononuclear cells were enriched by density gradient centrifugation. The proliferation of peripheral blood mononuclear cells was assessed, following stimulation with purified protein derivative (PPD), Candida albicans, phytohemagglutinin or when cells were left unstimulated, after three or six days of cell culture. The production of interleukin-1ß (IL-1ß), IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α), G-CSF, GM-CSF, MCP-1, MIP-ß was assessed in supernatants using the Bio-plex(®) assay and was complemented with ELISA for selected cytokines. Patients with oral lichen planus demonstrated reduced proliferative responses against PPD (P stimulated supernatants from patients with oral lichen planus. Collectively, the findings suggested that memory lymphocytes from patients with oral lichen planus (OLP) may have an impaired functional ability to react against certain recall antigens, as part of a generalized response, which may reflect immune regulatory processes. Further studies are needed to clarify the mechanisms of down-regulation in OLP pathogenesis and progression. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. A Novel Hemp Seed Meal Protein Hydrolysate Reduces Oxidative Stress Factors in Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Abraham T. Girgih

    2014-12-01

    Full Text Available This report shows the antioxidant effects of a hemp seed meal protein hydrolysate (HMH in spontaneously hypertensive rats (SHR. Defatted hemp seed meal was hydrolyzed consecutively with pepsin and pancreatin to yield HMH, which was incorporated into rat feed as a source of antioxidant peptides. Young (8-week old SHRs were divided into three groups (8 rats/group and fed diets that contained 0.0%, 0.5% or 1.0% (w/w HMH for eight weeks; half of the rats were sacrificed for blood collection. After a 4-week washout period, the remaining 20-week old SHRs were fed for an additional four weeks and sacrificed for blood collection. Plasma total antioxidant capacity (TAC and superoxide dismutase (SOD, catalase (CAT and total peroxides (TPx levels were determined. Results showed that plasma TAC, CAT and SOD levels decreased in the older 20-week old SHRs when compared to the young SHRs. The presence of HMH in the diets led to significant (p < 0.05 increases in plasma SOD and CAT levels in both young and adult SHR groups; these increases were accompanied by decreases in TPx levels. The results suggest that HMH contained antioxidant peptides that reduced the rate of lipid peroxidation in SHRs with enhanced antioxidant enzyme levels and total antioxidant capacity.

  17. Important mitochondrial proteins in human omental adipose tissue show reduced expression in obesity

    Directory of Open Access Journals (Sweden)

    Peter W. Lindinger

    2015-09-01

    Full Text Available Obesity is associated with impaired mitochondrial function. This study compares mitochondrial protein expression in omental fat in obese and non-obese humans. Omental adipose tissue was obtained by surgical biopsy, adipocytes were purified and mitochondria isolated. Using anion-exchange chromatography, SDS-PAGE and mass-spectrometry, 128 proteins with potentially different abundances in patient groups were identified, 62 of the 128 proteins are mainly localized in the mitochondria. Further quantification of 12 of these 62 proteins by immune dot blot analysis revealed four proteins citrate synthase, HADHA, LETM1 and mitofilin being inversely associated with BMI, and mitofilin being inversely correlated with gender.

  18. Important mitochondrial proteins in human omental adipose tissue show reduced expression in obesity.

    Science.gov (United States)

    Lindinger, Peter W; Christe, Martine; Eberle, Alex N; Kern, Beatrice; Peterli, Ralph; Peters, Thomas; Jayawardene, Kamburapola J I; Fearnley, Ian M; Walker, John E

    2015-09-01

    Obesity is associated with impaired mitochondrial function. This study compares mitochondrial protein expression in omental fat in obese and non-obese humans. Omental adipose tissue was obtained by surgical biopsy, adipocytes were purified and mitochondria isolated. Using anion-exchange chromatography, SDS-PAGE and mass-spectrometry, 128 proteins with potentially different abundances in patient groups were identified, 62 of the 128 proteins are mainly localized in the mitochondria. Further quantification of 12 of these 62 proteins by immune dot blot analysis revealed four proteins citrate synthase, HADHA, LETM1 and mitofilin being inversely associated with BMI, and mitofilin being inversely correlated with gender.

  19. Threonine supplementation reduces dietary protein and improves lipid metabolism in Pekin ducks.

    Science.gov (United States)

    Jiang, Y; Tang, J; Xie, M; Wen, Z G; Qiao, S Y; Hou, S S

    2017-12-01

    1. This study was conducted to investigate the efficiency of threonine (Thr) supplementation on reducing dietary crude protein (CP) content and the effects of Thr on lipid metabolism in Pekin ducks. The effects of dietary CP concentration (160, 190 and 220 g/kg) and Thr supplemental concentration (0, 0.7, 1.4, 2.1 and 2.8 g/kg) on growth performance, carcass, liver lipid and plasma profiles were determined in Pekin ducks from 1-21 d of age. 2. A total of 720-d-old male Pekin ducks were randomly allotted to 1 of 15 dietary treatments with 6 replicate cages of 8 birds per cage for each treatment according to average body weight. 3. Dietary Thr supplementation improved growth performance and breast muscle percentage at all CP diets, and ducks fed Thr-supplemented diets had higher plasma concentrations of some plasma amino acids. Thr supplementation reduced the concentrations of total lipid, triglyceride, cholesterol in liver, and plasma low density lipoprotein cholesterin concentration at 160 and 190 g/kg CP, whereas it increased triglyceride concentration at 160 g/kg CP. 4. Thr requirements based on quadratic broken-line model estimation were 6.6 and 7.0 g/kg for optimal average daily gain (ADG), and 6.7 and 7.3 g/kg for breast muscle percentage of Pekin ducks from 1-21 d of age at 190 and 220 g/kg CP, respectively. The dietary Thr requirements and estimated ADG (55.18 vs. 55.86 g/d/bird) and breast muscle percentage (2.79% vs. 2.75%) of Pekin ducks did not differ between 190 and 220 g/kg CP according to the t-test results. 5. Dietary CP level could be reduced to 190 g/kg in Pekin ducks from 1-21 d of age with Thr supplementation to balance dietary amino acids, and Thr supplementation prevented excess liver lipid deposition in this instance.

  20. Feeding broiler breeders a reduced balanced protein diet during the rearing and laying period impairs reproductive performance but enhances broiler offspring performance.

    Science.gov (United States)

    Lesuisse, J; Li, C; Schallier, S; Leblois, J; Everaert, N; Buyse, J

    2017-09-01

    Mammalian studies have shown that nutritional constraints during the perinatal period are able to program the progeny (metabolism, performance). The presented research aimed to investigate if broiler breeders and their offspring performance could be influenced by reducing the dietary crude protein (CP) level with 25%. A total of 160 day-old pure line A breeder females were randomly divided over 2 dietary treatments. The control group was fed commercial diets, whereas the reduced balanced protein (RP) breeders received an isoenergetic diet that was decreased with 25% in dietary CP and amino acid during their entire lifespan. The RP birds required an increased feed allowance, varying between 3 and 15%, to meet the same BW goals as their control fed counterparts. The difference in feed allocations and reduction of the dietary CP level resulted in a net protein reduction varying between 14 and 23%. At wk 27 and 40, the body composition of the breeders was changed as a result of the dietary treatment. At both ages, the proportional abdominal fat pad weight of the RP breeders was increased (P < 0.001), whereas the proportional breast muscle weight was only higher at wk 27 in the control group compared to the RP group (P < 0.001). Egg weight (P < 0.001) and egg production (P < 0.001) was decreased for the RP fed birds. The lower dietary CP level reduced the proportional albumen weight of the RP eggs (P = 0.006). Male offspring from RP breeders were characterized by an increase in BW from 28 d until 35 d of age (P = 0.015). Moreover, female progeny of RP breeders showed a reduced FCR (P = 0.025), whereas male progeny showed a tendency (P = 0.052) towards a lower FCR at 5 wk of age. In conclusion, lowering dietary CP levels in rearing and laying phase of breeders had a negative effect on breeder performance but enhanced live performance of the offspring. © 2017 Poultry Science Association Inc.

  1. Fracionamento dos carboidratos pelas equações do Cornell Net Carbohydrate and Protein System de três cultivares de girassol na presença ou não de irrigação Carbohydrate fractionation of three sunflower cultivars in the presence or absence of irrigation using the Cornell Net Carbohydrate and Protein System equations

    Directory of Open Access Journals (Sweden)

    Mário Adriano Ávila Queiroz

    2008-12-01

    Full Text Available Objetivou-se quantificar as frações de carboidratos pelas equações do Cornell Net Carbohydrate and Protein System (CNCPS de três cultivares de girassol (Helianthus annuus L. cultivados na presença ou não de irrigação. A utilização de uma preparação fibrosa, denominada parede celular (PC, nas equações da CNCPS, em substituição à fibra em detergente neutro (FDN não promoveu diferenças nas frações de carboidratos B1 e C, mas influenciou as frações A e B2. Como os valores da fração B1, obtidos pelo modelo CNCPS foram menores que os teores de amido e pectina determinados em laboratório, supõe-se que a pectina e outros oligossacarídeos da parede celular, solubilizados pela solução de detergente neutro (fibra solúvel, nunca fizeram parte da fração B1, e sim da fração A. Apesar de os carboidratos da fibra solúvel apresentarem elevadas taxas de degradação, não parece adequada a caracterização da fibra solúvel na fração A. Parece mais adequado que a fibra solúvel (que inclui a pectina seja alocada a uma fração exclusivamente sua, que pode ser a fração B2, e que seja criada uma nova fração, a B3, para os carboidratos digeríveis da parede celular. Assim, a fração B1 seria composta apenas de amido. A equação da fração C, que estima os carboidratos indigeríveis da parede celular, pode ser simplificada, relacionando a fração indigerível ao teor de lignina na matéria seca, e não à FDN isenta de cinzas e proteína, como atualmente utilizado. Esta proposta tem implicações práticas, uma vez que a fração indigerível da parede celular tem sido expressa em relação à FDN, e não na MS, com base no fato de que os efeitos inibitórios da lignina ocorrem sobre os componentes fibrosos da parede celular vegetal, e não sobre o conteúdo celular.This work aimed to estimate the carbohydrate fractions in three sunflower (Helianthus annuus L. cultivars in the presence or absence of irrigation, using the

  2. The use of insecticide-treated nets for reducing malaria morbidity among children aged 6-59 months, in an area of high malaria transmission in central Côte d'Ivoire

    Directory of Open Access Journals (Sweden)

    Nsanzabana Christian

    2010-09-01

    Full Text Available Abstract Background Long-lasting insecticidal nets (LLINs are an important tool for controlling malaria. Much attention has been devoted to determine both the effect of LLINs on the reduction of Plasmodium infection rate and on clinically-confirmed malaria cases in sub-Saharan Africa. We carried out an epidemiological study to investigate whether LLINs impact on Plasmodium prevalence rate and the proportion of clinically-confirmed malaria cases, in five villages in the district of Toumodi, central Côte d'Ivoire. Methods From April 2007 to November 2008, a community-based malaria control programme was implemented in the study villages, which involved large-scale distribution of LLINs, and training and sensitization activities within the community. We determined the effect of this programme on Plasmodium prevalence rate, clinically-confirmed malaria cases and proportion of high parasitaemia rates in children aged 6-59 months through a series of cross-sectional surveys starting in April 2007 and repeated once every 6 months. Results We observed a significant decrease in the mean P. falciparum prevalence rate from April 2007 to April 2008 (p = 0.029. An opposite trend was observed from November 2007 to November 2008 when P. falciparum prevalence rate increased significantly (p = 0.003. Highly significant decreases in the proportions of clinical malaria cases were observed between April 2007 and April 2008 (p Conclusions Large-scale distribution of LLINs, accompanied by training and sensitization activities, significantly reduced Plasmodium prevalence rates among young children in the first year of the project, whereas overall clinical malaria rates dropped over the entire 18-month project period. A decrease in community motivation to sleep under bed nets, perhaps along with changing patterns of malaria transmission, might explain the observed increase in the Plasmodium prevalence rate between November 2007 and November 2008.

  3. NetMHCpan, a method for quantitative predictions of peptide binding to any HLA-A and -B locus protein of known sequence

    DEFF Research Database (Denmark)

    Nielsen, Morten; Lundegaard, Claus; Blicher, Thomas

    2007-01-01

    BACKGROUND: Binding of peptides to Major Histocompatibility Complex (MHC) molecules is the single most selective step in the recognition of pathogens by the cellular immune system. The human MHC class I system (HLA-I) is extremely polymorphic. The number of registered HLA-I molecules has now surp...... to provide new basic insights into HLA structure-function relationships. The method is available at http://www.cbs.dtu.dk/services/NetMHCpan....... surpassed 1500. Characterizing the specificity of each separately would be a major undertaking. PRINCIPAL FINDINGS: Here, we have drawn on a large database of known peptide-HLA-I interactions to develop a bioinformatics method, which takes both peptide and HLA sequence information into account...... successfully validate this method. We further demonstrate that the method can be applied to perform a clustering analysis of MHC specificities and suggest using this clustering to select particularly informative novel MHC molecules for future biochemical and functional analysis. CONCLUSIONS: Encompassing all...

  4. Deletion of G-protein-coupled receptor 55 promotes obesity by reducing physical activity.

    Science.gov (United States)

    Meadows, A; Lee, J H; Wu, C-S; Wei, Q; Pradhan, G; Yafi, M; Lu, H-C; Sun, Y

    2016-03-01

    Cannabinoid receptor 1 (CB1) is the best-characterized cannabinoid receptor, and CB1 antagonists are used in clinical trials to treat obesity. Because of the wide range of CB1 functions, the side effects of CB1 antagonists pose serious concerns. G-protein-coupled receptor 55 (GPR55) is an atypical cannabinoid receptor, and its pharmacology and functions are distinct from CB1. GPR55 regulates neuropathic pain, gut, bone, immune functions and motor coordination. GPR55 is expressed in various brain regions and peripheral tissues. However, the roles of GPR55 in energy and glucose homeostasis are unknown. Here we have investigated the roles of GPR55 in energy balance and insulin sensitivity using GPR55-null mice (GPR55(-/-)). Body composition of the mice was measured by EchoMRI. Food intake, feeding behavior, energy expenditure and physical activity of GPR55(-/-) mice were determined by indirect calorimetry. Muscle function was assessed by forced treadmill running test. Insulin sensitivity was evaluated by glucose and insulin tolerance tests. Adipose inflammation was assessed by flow cytometry analysis of adipose tissue macrophages. The expression of inflammatory markers in adipose tissues and orexigenic/anorexigenic peptides in the hypothalamus was also analyzed by real-time PCR. GPR55(-/-) mice had normal total energy intake and feeding pattern (i.e., no changes in meal size, meal number or feeding frequency). Intriguingly, whereas adult GPR55(-/-) mice only showed a modest increase in overall body weight, they exhibited significantly increased fat mass and insulin resistance. The spontaneous locomotor activity of GPR55(-/-) mice was dramatically decreased, whereas resting metabolic rate and non-shivering thermogenesis were unchanged. Moreover, GPR55(-/-) mice exhibited significantly decreased voluntary physical activity, showing reduced running distance on the running wheels, whereas muscle function appeared to be normal. GPR55 has an important role in energy

  5. Reduced Sleep During Social Isolation Leads to Cellular Stress and Induction of the Unfolded Protein Response.

    Science.gov (United States)

    Brown, Marishka K; Strus, Ewa; Naidoo, Nirinjini

    2017-07-01

    Social isolation has a multitude of negative consequences on human health including the ability to endure challenges to the immune system, sleep amount and efficiency, and general morbidity and mortality. These adverse health outcomes are conserved in other social species. In the fruit fly Drosophila melanogaster, social isolation leads to increased aggression, impaired memory, and reduced amounts of daytime sleep. There is a correlation between molecules affected by social isolation and those implicated in sleep in Drosophila. We previously demonstrated that acute sleep loss in flies and mice induced the unfolded protein response (UPR), an adaptive signaling pathway. One mechanism indicating UPR upregulation is elevated levels of the endoplasmic reticular chaperone BiP/GRP78. We previously showed that BiP overexpression in Drosophila led to increased sleep rebound. Increased rebound sleep has also been demonstrated in socially isolated (SI) flies. D. melanogaster were used to study the effect of social isolation on cellular stress. SI flies displayed an increase in UPR markers; there were higher BiP levels, increased phosphorylation of the translation initiation factor eIF2α, and increased splicing of xbp1. These are all indicators of UPR activation. In addition, the effects of isolation on the UPR were reversible; pharmacologically and genetically altering sleep in the flies modulated the UPR. The reduction in sleep observed in SI flies is a cellular stressor that results in UPR induction. © Sleep Research Society 2017. Published by Oxford University Press [on behalf of the Sleep Research Society]. All rights reserved. For permissions, please email: journals.permissions@oup.com

  6. Reduced hemoglobin and increased C-reactive protein are associated with upper gastrointestinal bleeding.

    Science.gov (United States)

    Tomizawa, Minoru; Shinozaki, Fuminobu; Hasegawa, Rumiko; Togawa, Akira; Shirai, Yoshinori; Ichiki, Noboru; Motoyoshi, Yasufumi; Sugiyama, Takao; Yamamoto, Shigenori; Sueishi, Makoto

    2014-02-07

    To investigate the early upper gastrointestinal endoscopy (endoscopy) significantly reduces mortality resulting from upper gastrointestinal (GI) bleeding. Upper GI bleeding was defined as 1a, 1b, 2a, and 2b according to the Forrest classification. The hemoglobin (Hb), and C-reactive protein (CRP) were examined at around the day of endoscopy and 3 mo prior to endoscopy. The rate of change was calculated as follows: (the result of blood examination on the day of endoscopy - the results of blood examination 3 mo prior to endoscopy)/(results of blood examination 3 mo prior to endoscopy). Receiver operating characteristic curves were created to determine threshold values. Seventy-nine men and 77 women were enrolled. There were 17 patients with upper GI bleeding: 12 with a gastric ulcer, 3 with a duodenal ulcer, 1 with an acute gastric mucosal lesion, and 1 with gastric cancer. The area under the curve (AUC), threshold, sensitivity, and specificity of Hb around the day of endoscopy were 0.902, 11.7 g/dL, 94.1%, and 77.1%, respectively, while those of CRP were 0.722, 0.5 mg/dL, 70.5%, and 73%, respectively. The AUC, threshold, sensitivity, and specificity of the rate of change of Hb were 0.851, -21.3%, 76.4%, and 82.6%, respectively, while those of CRP were 0.901, 100%, 100%, and 82.5%, respectively. Predictors for upper GI bleeding were Hb 21.3% and an increase in the CRP > 100%, 3 mo before endoscopy.

  7. Reduced Insulin/IGF-1 Signaling Restores the Dynamic Properties of Key Stress Granule Proteins during Aging

    Directory of Open Access Journals (Sweden)

    Marie C. Lechler

    2017-01-01

    Full Text Available Summary: Low-complexity “prion-like” domains in key RNA-binding proteins (RBPs mediate the reversible assembly of RNA granules. Individual RBPs harboring these domains have been linked to specific neurodegenerative diseases. Although their aggregation in neurodegeneration has been extensively characterized, it remains unknown how the process of aging disturbs RBP dynamics. We show that a wide variety of RNA granule components, including stress granule proteins, become highly insoluble with age in C. elegans and that reduced insulin/insulin-like growth factor 1 (IGF-1 daf-2 receptor signaling efficiently prevents their aggregation. Importantly, stress-granule-related RBP aggregates are associated with reduced fitness. We show that heat shock transcription factor 1 (HSF-1 is a main regulator of stress-granule-related RBP aggregation in both young and aged animals. During aging, increasing DAF-16 activity restores dynamic stress-granule-related RBPs, partly by decreasing the buildup of other misfolded proteins that seed RBP aggregation. Longevity-associated mechanisms found to maintain dynamic RBPs during aging could be relevant for neurodegenerative diseases. : Lechler et al. show that RNA-binding proteins (RBPs including stress granule proteins are prone to aggregate with age in C. elegans. Aggregation of stress granule RBPs with “prion-like” domains is associated with reduced fitness. Their aggregation is prevented by longevity pathways and promoted by the aggregation of other misfolded proteins. Keywords: neurodegenerative diseases, Caenorhabditis elegans, protein aggregation, aging, RNA-binding proteins, stress granules, HSF-1, DAF-2, longevity

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

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Luciana O.; Goto, Renata N. [Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Neto, Marinaldo P.C. [Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Sousa, Lucas O. [Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Curti, Carlos [Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Leopoldino, Andréia M., E-mail: andreiaml@usp.br [Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil)

    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.

  9. Quantum net dynamics

    International Nuclear Information System (INIS)

    Finkelstein, D.

    1989-01-01

    The quantum net unifies the basic principles of quantum theory and relativity in a quantum spacetime having no ultraviolet infinities, supporting the Dirac equation, and having the usual vacuum as a quantum condensation. A correspondence principle connects nets to Schwinger sources and further unifies the vertical structure of the theory, so that the functions of the many hierarchic levels of quantum field theory (predicate algebra, set theory, topology,hor-ellipsis, quantum dynamics) are served by one in quantum net dynamics

  10. Effectiveness of Germination on Protein Hydrolysis as a Way To Reduce Adverse Reactions to Wheat.

    Science.gov (United States)

    Boukid, Fatma; Prandi, Barbara; Buhler, Sofie; Sforza, Stefano

    2017-11-15

    In this work, the aim is to study the effectiveness of germination on wheat protein degradation, with a specific focus on proteins involved in adverse reactions to wheat. The effects of 8 days of germination at 25 °C on the chemical composition and the protein profile were determined. Germination did not have a significant effect on starch, protein, lipid, and ash contents. General protein profile, as indicated by SDS-PAGE analysis, revealed that germination induced a relevant degradation in protein fraction. After in vitro gastrointestinal digestion, gluten peptides involved in celiac disease (CD) were identified and quantified using UPLC/ESI-MS technique. Also, CM3 protein, involved in baker's asthma and intestinal inflammation, was quantified by measuring a marker peptide. Statistical analysis underlined that germination and genotype had significant impact on the amount of both components. Regarding gluten peptides related to CD, germination enabled an average reduction of 47% in peptides eliciting adaptive immune response and 46% in peptides eliciting innate immune response. CM3 protein showed also a high average reduction (56%). Thus, this study suggests that germination might be a good bioalternative to provide a low "impact" raw ingredient for special wheat-based foodstuffs.

  11. Molecular mechanisms used by chaperones to reduce the toxicity of aberrant protein oligomers

    NARCIS (Netherlands)

    Mannini, Benedetta; Cascella, Roberta; Zampagni, Mariagioia; Van Waarde-Verhagen, Maria; Meehan, Sarah; Roodveldt, Cintia; Campioni, Silvia; Boninsegna, Matilde; Penco, Amanda; Relini, Annalisa; Kampinga, Harm H.; Dobson, Christopher M.; Wilson, Mark R.; Cecchi, Cristina; Chiti, Fabrizio

    2012-01-01

    Chaperones are the primary regulators of the proteostasis network and are known to facilitate protein folding, inhibit protein aggregation, and promote disaggregation and clearance of misfolded aggregates inside cells. We have tested the effects of five chaperones on the toxicity of misfolded

  12. Programming NET Web Services

    CERN Document Server

    Ferrara, Alex

    2007-01-01

    Web services are poised to become a key technology for a wide range of Internet-enabled applications, spanning everything from straight B2B systems to mobile devices and proprietary in-house software. While there are several tools and platforms that can be used for building web services, developers are finding a powerful tool in Microsoft's .NET Framework and Visual Studio .NET. Designed from scratch to support the development of web services, the .NET Framework simplifies the process--programmers find that tasks that took an hour using the SOAP Toolkit take just minutes. Programming .NET

  13. Game Coloured Petri Nets

    DEFF Research Database (Denmark)

    Westergaard, Michael

    2006-01-01

    This paper introduces the notion of game coloured Petri nets. This allows the modeler to explicitly model what parts of the model comprise the modeled system and what parts are the environment of the modeled system. We give the formal definition of game coloured Petri nets, a means of reachability...... analysis of this net class, and an application of game coloured Petri nets to automatically generate easy-to-understand visualizations of the model by exploiting the knowledge that some parts of the model are not interesting from a visualization perspective (i.e. they are part of the environment...

  14. Acute high-caffeine exposure increases autophagic flux and reduces protein synthesis in C2C12 skeletal myotubes.

    Science.gov (United States)

    Hughes, M A; Downs, R M; Webb, G W; Crocker, C L; Kinsey, S T; Baumgarner, Bradley L

    2017-04-01

    Caffeine is a highly catabolic dietary stimulant. High caffeine concentrations (1-10 mM) have previously been shown to inhibit protein synthesis and increase protein degradation in various mammalian cell lines. The purpose of this study was to examine the effect of short-term caffeine exposure on cell signaling pathways that regulate protein metabolism in mammalian skeletal muscle cells. Fully differentiated C2C12 skeletal myotubes either received vehicle (DMSO) or 5 mM caffeine for 6 h. Our analysis revealed that caffeine promoted a 40% increase in autolysosome formation and a 25% increase in autophagic flux. In contrast, caffeine treatment did not significantly increase the expression of the skeletal muscle specific ubiquitin ligases MAFbx and MuRF1 or 20S proteasome activity. Caffeine treatment significantly reduced mTORC1 signaling, total protein synthesis and myotube diameter in a CaMKKβ/AMPK-dependent manner. Further, caffeine promoted a CaMKII-dependent increase in myostatin mRNA expression that did not significantly contribute to the caffeine-dependent reduction in protein synthesis. Our results indicate that short-term caffeine exposure significantly reduced skeletal myotube diameter by increasing autophagic flux and promoting a CaMKKβ/AMPK-dependent reduction in protein synthesis.

  15. Can radiation damage to protein crystals be reduced using small-molecule compounds?

    Energy Technology Data Exchange (ETDEWEB)

    Kmetko, Jan [Kenyon College, Gambier, OH 43022 (United States); Warkentin, Matthew; Englich, Ulrich; Thorne, Robert E., E-mail: ret6@cornell.edu [Cornell University, Ithaca, NY 14853 (United States); Kenyon College, Gambier, OH 43022 (United States)

    2011-10-01

    Free-radical scavengers that are known to be effective protectors of proteins in solution are found to increase global radiation damage to protein crystals. Protective mechanisms may become deleterious in the protein-dense environment of a crystal. Recent studies have defined a data-collection protocol and a metric that provide a robust measure of global radiation damage to protein crystals. Using this protocol and metric, 19 small-molecule compounds (introduced either by cocrystallization or soaking) were evaluated for their ability to protect lysozyme crystals from radiation damage. The compounds were selected based upon their ability to interact with radiolytic products (e.g. hydrated electrons, hydrogen, hydroxyl and perhydroxyl radicals) and/or their efficacy in protecting biological molecules from radiation damage in dilute aqueous solutions. At room temperature, 12 compounds had no effect and six had a sensitizing effect on global damage. Only one compound, sodium nitrate, appeared to extend crystal lifetimes, but not in all proteins and only by a factor of two or less. No compound provided protection at T = 100 K. Scavengers are ineffective in protecting protein crystals from global damage because a large fraction of primary X-ray-induced excitations are generated in and/or directly attack the protein and because the ratio of scavenger molecules to protein molecules is too small to provide appreciable competitive protection. The same reactivity that makes some scavengers effective radioprotectors in protein solutions may explain their sensitizing effect in the protein-dense environment of a crystal. A more productive focus for future efforts may be to identify and eliminate sensitizing compounds from crystallization solutions.

  16. Can radiation damage to protein crystals be reduced using small-molecule compounds?

    International Nuclear Information System (INIS)

    Kmetko, Jan; Warkentin, Matthew; Englich, Ulrich; Thorne, Robert E.

    2011-01-01

    Free-radical scavengers that are known to be effective protectors of proteins in solution are found to increase global radiation damage to protein crystals. Protective mechanisms may become deleterious in the protein-dense environment of a crystal. Recent studies have defined a data-collection protocol and a metric that provide a robust measure of global radiation damage to protein crystals. Using this protocol and metric, 19 small-molecule compounds (introduced either by cocrystallization or soaking) were evaluated for their ability to protect lysozyme crystals from radiation damage. The compounds were selected based upon their ability to interact with radiolytic products (e.g. hydrated electrons, hydrogen, hydroxyl and perhydroxyl radicals) and/or their efficacy in protecting biological molecules from radiation damage in dilute aqueous solutions. At room temperature, 12 compounds had no effect and six had a sensitizing effect on global damage. Only one compound, sodium nitrate, appeared to extend crystal lifetimes, but not in all proteins and only by a factor of two or less. No compound provided protection at T = 100 K. Scavengers are ineffective in protecting protein crystals from global damage because a large fraction of primary X-ray-induced excitations are generated in and/or directly attack the protein and because the ratio of scavenger molecules to protein molecules is too small to provide appreciable competitive protection. The same reactivity that makes some scavengers effective radioprotectors in protein solutions may explain their sensitizing effect in the protein-dense environment of a crystal. A more productive focus for future efforts may be to identify and eliminate sensitizing compounds from crystallization solutions

  17. Reduced Wall Acetylation Proteins Play Vital and Distinct Roles in Cell Wall O-Acetylation in Arabidopsis

    DEFF Research Database (Denmark)

    Manabe, Yuzuki; Verhertbruggen, Yves; Gille, Sascha

    2013-01-01

    The Reduced Wall Acetylation (RWA) proteins are involved in cell wall acetylation in plants. Previously, we described a single mutant, rwa2, which has about 20% lower level of O-acetylation in leaf cell walls and no obvious growth or developmental phenotype. In this study, we generated double....... The quadruple rwa mutant can be completely complemented with the RWA2 protein expressed under 35S promoter, indicating the functional redundancy of the RWA proteins. Nevertheless, the degree of acetylation of xylan, (gluco) mannan, and xyloglucan as well as overall cell wall acetylation is affected differently...... in different combinations of triple mutants, suggesting their diversity in substrate preference. The overall degree of wall acetylation in the rwa quadruple mutant was reduced by 63% compared with the wild type, and histochemical analysis of the rwa quadruple mutant stem indicates defects in cell...

  18. Immunotoxicity of nucleic acid reduced BioProtein - a bacterial derived single cell protein - in Wistar rats

    DEFF Research Database (Denmark)

    Mølck, Anne-marie; Poulsen, Morten; Christensen, Hanne Risager

    2002-01-01

    , therefore, a nucleic acid reduced variant (NABP) has been developed by the manufacturer. The purpose of the present study was to establish the safety of NABP in a subchronic toxicity rat study. Groups of 10 male and 10 female Wistar rats were fed diets containing 0, 6, 12 or 24% NABP for 13 weeks. Feeding...

  19. Increased Levels of Antinutritional and/or Defense Proteins Reduced the Protein Quality of a Disease-Resistant Soybean Cultivar.

    Science.gov (United States)

    Sousa, Daniele O B; Carvalho, Ana F U; Oliveira, José Tadeu A; Farias, Davi F; Castelar, Ivan; Oliveira, Henrique P; Vasconcelos, Ilka M

    2015-07-22

    The biochemical and nutritional attributes of two soybean (Glycine max (L.) Merr.) cultivars, one susceptible (Seridó) and the other resistant (Seridó-RCH) to stem canker, were examined to assess whether the resistance to pathogens was related to levels of antinutritional and/or defense proteins in the plant and subsequently affected the nutritional quality. Lectin, urease, trypsin inhibitor, peroxidase and chitinase activities were higher in the resistant cultivar. Growing rats were fed with isocaloric and isoproteic diets prepared with defatted raw soybean meals. Those on the Seridó-RCH diet showed the worst performance in terms of protein quality indicators. Based on regression analysis, lectin, trypsin inhibitor, peroxidase and chitinase appear to be involved in the resistance trait but also in the poorer nutritional quality of Seridó-RCH. Thus, the development of cultivars for disease resistance may lead to higher concentrations of antinutritional compounds, affecting the quality of soybean seeds. Further research that includes the assessment of more cultivars/genotypes is needed.

  20. A scalable and accurate method for classifying protein-ligand binding geometries using a MapReduce approach.

    Science.gov (United States)

    Estrada, T; Zhang, B; Cicotti, P; Armen, R S; Taufer, M

    2012-07-01

    We present a scalable and accurate method for classifying protein-ligand binding geometries in molecular docking. Our method is a three-step process: the first step encodes the geometry of a three-dimensional (3D) ligand conformation into a single 3D point in the space; the second step builds an octree by assigning an octant identifier to every single point in the space under consideration; and the third step performs an octree-based clustering on the reduced conformation space and identifies the most dense octant. We adapt our method for MapReduce and implement it in Hadoop. The load-balancing, fault-tolerance, and scalability in MapReduce allow screening of very large conformation spaces not approachable with traditional clustering methods. We analyze results for docking trials for 23 protein-ligand complexes for HIV protease, 21 protein-ligand complexes for Trypsin, and 12 protein-ligand complexes for P38alpha kinase. We also analyze cross docking trials for 24 ligands, each docking into 24 protein conformations of the HIV protease, and receptor ensemble docking trials for 24 ligands, each docking in a pool of HIV protease receptors. Our method demonstrates significant improvement over energy-only scoring for the accurate identification of native ligand geometries in all these docking assessments. The advantages of our clustering approach make it attractive for complex applications in real-world drug design efforts. We demonstrate that our method is particularly useful for clustering docking results using a minimal ensemble of representative protein conformational states (receptor ensemble docking), which is now a common strategy to address protein flexibility in molecular docking. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. NASA Net Zero Energy Buildings Roadmap

    Energy Technology Data Exchange (ETDEWEB)

    Pless, S.; Scheib, J.; Torcellini, P.; Hendron, B.; Slovensky, M.

    2014-10-01

    In preparation for the time-phased net zero energy requirement for new federal buildings starting in 2020, set forth in Executive Order 13514, NASA requested that the National Renewable Energy Laboratory (NREL) to develop a roadmap for NASA's compliance. NASA detailed a Statement of Work that requested information on strategic, organizational, and tactical aspects of net zero energy buildings. In response, this document presents a high-level approach to net zero energy planning, design, construction, and operations, based on NREL's first-hand experience procuring net zero energy construction, and based on NREL and other industry research on net zero energy feasibility. The strategic approach to net zero energy starts with an interpretation of the executive order language relating to net zero energy. Specifically, this roadmap defines a net zero energy acquisition process as one that sets an aggressive energy use intensity goal for the building in project planning, meets the reduced demand goal through energy efficiency strategies and technologies, then adds renewable energy in a prioritized manner, using building-associated, emission- free sources first, to offset the annual energy use required at the building; the net zero energy process extends through the life of the building, requiring a balance of energy use and production in each calendar year.

  2. Denaturing high-performance liquid chromatography mutation analysis in patients with reduced Protein S levels

    DEFF Research Database (Denmark)

    Bathum, Lise; Münster, Anna-Marie; Nybo, Mads

    2008-01-01

    diagnosis and risk estimation. The aim was to design a high-throughput genetic analysis based on denaturing high-performance liquid chromatography to identify sequence variations in the gene coding for Protein S. PATIENTS: In total, 55 patients referred to the Section of Thrombosis and Haemostasis, Odense......BACKGROUND: Patients with congenital Protein S deficiency have increased risk of venous thromboembolism. However, Protein S levels show large intra-individual variation and the biochemical assays have low accuracy and a high interlaboratory variability. Genetic analysis might aid in a more precise......, giving a precise diagnosis and subsequently a better risk estimation....

  3. Breast cancer resistance protein (Bcrp1/Abcg2) limits net intestinal uptake of quercetin in rats by facilitating apical efflux of glucuronides

    NARCIS (Netherlands)

    Sesink, A.L.A.; Arts, I.C.W.; Boer, de V.C.J.; Breedveld, P.; Schellens, J.H.M.; Hollman, P.C.H.; Russel, F.G.M.

    2005-01-01

    The intestinal absorption of the flavonoid quercetin in rats is limited by the secretion of glucuronidated metabolites back into the gut lumen. The objective of this study was to determine the role of the intestinal efflux transporters breast cancer resistance protein (Bcrp1)/Abcg2 and multidrug

  4. Breast cancer resistance protein (Bcrp1/Abcg2) limits net intestinal uptake of quercetin in rats by facilitating apical efflux of glucuronides.

    NARCIS (Netherlands)

    Sesink, A.L.; Arts, I.C.; Boer, V.C. de; Breedveld, P.; Schellens, J.H.; Hollman, P.C.H.; Russel, F.G.M.

    2005-01-01

    The intestinal absorption of the flavonoid quercetin in rats is limited by the secretion of glucuronidated metabolites back into the gut lumen. The objective of this study was to determine the role of the intestinal efflux transporters breast cancer resistance protein (Bcrp1)/Abcg2 and multidrug

  5. Anabolic sensitivity of postprandial muscle protein synthesis to the ingestion of a protein-dense food is reduced in overweight and obese young adults.

    Science.gov (United States)

    Beals, Joseph W; Sukiennik, Richard A; Nallabelli, Julian; Emmons, Russell S; van Vliet, Stephan; Young, Justin R; Ulanov, Alexander V; Li, Zhong; Paluska, Scott A; De Lisio, Michael; Burd, Nicholas A

    2016-10-01

    Excess body fat diminishes muscle protein synthesis rates in response to hyperinsulinemic-hyperaminoacidemic clamps. However, muscle protein synthetic responses after the ingestion of a protein-dense food source across a range of body mass indexes (BMIs) have not been compared. We compared the myofibrillar protein synthetic response and underlying nutrient-sensing mechanisms after the ingestion of lean pork between obese, overweight, and healthy-weight adults. Ten healthy-weight [HW; BMI (in kg/m 2 ): 22.7 ± 0.4], 10 overweight (OW; BMI: 27.1 ± 0.5), and 10 obese (OB; BMI: 35.9 ± 1.3) adults received primed continuous l-[ring- 13 C 6 ]phenylalanine infusions. Blood and muscle biopsy samples were collected before and after the ingestion of 170 g pork (36 g protein and 3 g fat) to assess skeletal muscle anabolic signaling, amino acid transporters [large neutral and small neutral amino acid transporters (LAT1, SNAT2) and CD98], and myofibrillar protein synthesis. At baseline, OW and OB groups showed greater relative amounts of mammalian target of rapamycin complex 1 (mTORC1) protein than the HW group. Pork ingestion increased mTORC1 phosphorylation only in the HW group (P = 0.001). LAT1 and SNAT2 protein content increased during the postprandial period in all groups (time effect, P anabolic signals, that reduces muscle sensitivity to food ingestion. This trial was registered at clinicaltrials.gov as NCT02613767. © 2016 American Society for Nutrition.

  6. PROTEIN L-ISOASPARTYL METHYLTRANSFERASE2 is differentially expressed in chickpea and enhances seed vigor and longevity by reducing abnormal isoaspartyl accumulation predominantly in seed nuclear proteins.

    Science.gov (United States)

    Verma, Pooja; Kaur, Harmeet; Petla, Bhanu Prakash; Rao, Venkateswara; Saxena, Saurabh C; Majee, Manoj

    2013-03-01

    PROTEIN l-ISOASPARTYL METHYLTRANSFERASE (PIMT) is a widely distributed protein-repairing enzyme that catalyzes the conversion of abnormal l-isoaspartyl residues in spontaneously damaged proteins to normal aspartyl residues. This enzyme is encoded by two divergent genes (PIMT1 and PIMT2) in plants, unlike many other organisms. While the biological role of PIMT1 has been elucidated, the role and significance of the PIMT2 gene in plants is not well defined. Here, we isolated the PIMT2 gene (CaPIMT2) from chickpea (Cicer arietinum), which exhibits a significant increase in isoaspartyl residues in seed proteins coupled with reduced germination vigor under artificial aging conditions. The CaPIMT2 gene is found to be highly divergent and encodes two possible isoforms (CaPIMT2 and CaPIMT2') differing by two amino acids in the region I catalytic domain through alternative splicing. Unlike CaPIMT1, both isoforms possess a unique 56-amino acid amino terminus and exhibit similar yet distinct enzymatic properties. Expression analysis revealed that CaPIMT2 is differentially regulated by stresses and abscisic acid. Confocal visualization of stably expressed green fluorescent protein-fused PIMT proteins and cell fractionation-immunoblot analysis revealed that apart from the plasma membrane, both CaPIMT2 isoforms localize predominantly in the nucleus, while CaPIMT1 localizes in the cytosol. Remarkably, CaPIMT2 enhances seed vigor and longevity by repairing abnormal isoaspartyl residues predominantly in nuclear proteins upon seed-specific expression in Arabidopsis (Arabidopsis thaliana), while CaPIMT1 enhances seed vigor and longevity by repairing such abnormal proteins mainly in the cytosolic fraction. Together, our data suggest that CaPIMT2 has most likely evolved through gene duplication, followed by subfunctionalization to specialize in repairing the nuclear proteome.

  7. Attenuation of iron-binding proteins in ARPE-19 cells reduces their resistance to oxidative stress.

    Science.gov (United States)

    Karlsson, Markus; Kurz, Tino

    2016-09-01

    Oxidative stress-related damage to retinal pigment epithelial (RPE) cells is an important feature in the development of age-related macular degeneration. Iron-catalysed intralysosomal production of hydroxyl radicals is considered a major pathogenic factor, leading to lipofuscin formation with ensuing depressed cellular autophagic capacity, lysosomal membrane permeabilization and apoptosis. Previously, we have shown that cultured immortalized human RPE (ARPE-19) cells are extremely resistant to exposure to bolus doses of hydrogen peroxide and contain considerable amounts of the iron-binding proteins metallothionein (MT), heat-shock protein 70 (HSP70) and ferritin (FT). According to previous findings, autophagy of these proteins depresses lysosomal redox-active iron. The aim of this study was to investigate whether up- or downregulation of these proteins would affect the resistance of ARPE-19 cells to oxidative stress. The sensitivity of ARPE-19 cells to H2 O2 exposure was tested following upregulation of MT, HSP70 and/or FT by pretreatment with ZnSO4 , heat shock or FeCl3 , as well as siRNA-mediated downregulation of the same proteins. Upregulation of MT, HSP70 and FT did not improve survival following exposure to H2 O2 . This was interpreted as existence of an already maximal protection. Combined siRNA-mediated attenuation of both FT chains (H and L), or simultaneous downregulation of all three proteins, made the cells significantly more susceptible to oxidative stress confirming the importance of iron-binding proteins. The findings support our hypothesis that the oxidative stress resistance exhibited by RPE cells may be explained by a high autophagic influx of iron-binding proteins that would keep levels of redox-active lysosomal iron low. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  8. Coloured Petri Nets

    DEFF Research Database (Denmark)

    Jensen, Kurt

    1991-01-01

    This paper describes how Coloured Petri Nets (CP-nets) have been developed — from being a promising theoretical model to being a full-fledged language for the design, specification, simulation, validation and implementation of large software systems (and other systems in which human beings and...

  9. Construction of monophase nets

    International Nuclear Information System (INIS)

    Suarez A, Jose Antonio

    1996-01-01

    The paper refers to the use of monophase loads in commercial residential urbanizations and in small industries, for this reason it is considered unnecessary the construction of three-phase nets. The author makes a historical recount of these nets in Bogota, his capacities, uses and energy savings

  10. Reduced expression of exocytotic proteins caused by anti-cholinesterase pesticides in Brachionus calyciflorus (Rotifera: Monogononta

    Directory of Open Access Journals (Sweden)

    IA Pérez-Legaspi

    Full Text Available AbstractThe organophosphate and carbamate pesticides methyl-parathion and carbaryl have a common action mechanism: they inhibit acetylcholinesterase enzyme by blocking the transmission of nerve impulses. However, they can alter the expression of exocytotic membrane proteins (SNARE, by modifying release of neurotransmitters and other substances. This study evaluated the adverse effects of the pesticides methyl-parathion and carbaryl on expression of SNARE proteins: Syntaxin-1, Syntaxin-4 and SNAP-23 in freshwater rotifer Brachionus calyciflorus. Protein expression of these three proteins was analyzed before and after exposure to these two pesticides by Western Blot. The expression of Syntaxin-1, Syntaxin-4 and SNAP-23 proteins in B. calyciflorussignificantly decreases with increasing concentration of either pesticides. This suggests that organophosphates and carbamates have adverse effects on expression of membrane proteins of exocytosis by altering the recognition, docking and fusion of presynaptic and vesicular membranes involved in exocytosis of neurotransmitters. Our results demonstrate that the neurotoxic effect of anticholinesterase pesticides influences the interaction of syntaxins and SNAP-25 and the proper assembly of the SNARE complex.

  11. Fusion through the NET

    International Nuclear Information System (INIS)

    Spears, B.

    1987-01-01

    The paper concerns the next generation of fusion machines which are intended to demonstrate the technical viability of fusion. In Europe, the device that will follow on from JET is known as NET - the Next European Torus. If the design programme for NET proceeds, Europe could start to build the machine in 1994. The present JET programme hopes to achieve breakeven in the early 1990's. NET hopes to reach ignition in the next century, and so lay the foundation for a demonstration reactor. A description is given of the technical specifications of the components of NET, including: the first wall, the divertors to protect the wall, the array of magnets that provide the fields containing the plasma, the superconducting magnets, and the shield of the machine. NET's research programme is briefly outlined, including the testing programme to optimise conditions in the machine to achieve ignition, and its safety work. (U.K.)

  12. irGPU.proton.Net: Irregular strong charge interaction networks of protonatable groups in protein molecules--a GPU solver using the fast multipole method and statistical thermodynamics.

    Science.gov (United States)

    Kantardjiev, Alexander A

    2015-04-05

    A cluster of strongly interacting ionization groups in protein molecules with irregular ionization behavior is suggestive for specific structure-function relationship. However, their computational treatment is unconventional (e.g., lack of convergence in naive self-consistent iterative algorithm). The stringent evaluation requires evaluation of Boltzmann averaged statistical mechanics sums and electrostatic energy estimation for each microstate. irGPU: Irregular strong interactions in proteins--a GPU solver is novel solution to a versatile problem in protein biophysics--atypical protonation behavior of coupled groups. The computational severity of the problem is alleviated by parallelization (via GPU kernels) which is applied for the electrostatic interaction evaluation (including explicit electrostatics via the fast multipole method) as well as statistical mechanics sums (partition function) estimation. Special attention is given to the ease of the service and encapsulation of theoretical details without sacrificing rigor of computational procedures. irGPU is not just a solution-in-principle but a promising practical application with potential to entice community into deeper understanding of principles governing biomolecule mechanisms. © 2015 Wiley Periodicals, Inc.

  13. Enhanced Temperature During Grain Filling Reduces Protein Concentration of Durum Wheat

    Directory of Open Access Journals (Sweden)

    Franco Miglietta

    2011-02-01

    Full Text Available Durum wheat is cultivated over more than 13 millions of hectares (ha world wide and Italy is the main European producer with 3.5 millions tons per year. The protein concentration of durum wheat is very important, it ensures high nutritional value and is highly appreciated by the pasta production industries. The protein concentration of wheat is determined during the grain filling period when carbon and nitrogen compounds are translocated into the grains. Air temperature affects translocation rates and contributes to final protein concentration of wheat grains. Two common commercial varieties of durum and bread wheat were exposed from anthesis to harvest, to a source of infrared radiation in the field. This allowed to investigate the relative effect of temperature on translocation of carbon and nitrogen compound during grain filling. The heat treatment imposed affected marginally dry mass accumulation of the grains in bread wheat and didn’t affect dry mass in durum wheat. Grain protein was affected by heat treatment in durum but not in bread wheat. Carbon accumulation rate was higher for durum than for bread wheat. The protein concentration was greater in durum than in bread wheat and we can assume that the absolute nitrogen accumulation rates were higher for the former species. Such difference may be either caused by a faster nitrogen uptake rate and translocation or a more efficient relocation of nitrogen accumulated in reserve organs.

  14. Aptamer-Conjugated Calcium Phosphate Nanoparticles for Reducing Diabetes Risk via Retinol Binding Protein 4 Inhibition.

    Science.gov (United States)

    Torabi, Raheleh; Ghourchian, Hedayatollah; Amanlou, Massoud; Pasalar, Parvin

    2017-06-01

    Inhibition of the binding of retinol to its carrier, retinol binding protein 4, is a new strategy for treating type 2 diabetes; for this purpose, we have provided an aptamer-functionalized multishell calcium phosphate nanoparticle. First, calcium phosphate nanoparticles were synthesized and conjugated to the aptamer. The cytotoxicity of nanoparticles releases the process of aptamer from nanoparticles and their inhibition function of binding retinol to retinol binding protein 4. After synthesizing and characterizing the multishell calcium phosphate nanoparticles and observing the noncytotoxicity of conjugate, the optimum time (48 hours) and the pH (7.4) for releasing the aptamer from the nanoparticles was determined. The half-maximum inhibitory concentration (IC 50 ) value for inhibition of retinol binding to retinol binding protein 4 was 210 femtomolar (fmol). The results revealed that the aptamer could prevent connection between retinol and retinol binding protein 4 at a very low IC 50 value (210 fmol) compared to other reported inhibitors. It seems that this aptamer could be used as an efficient candidate not only for decreasing the insulin resistance in type 2 diabetes, but also for inhibiting the other retinol binding protein 4-related diseases. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

  15. Net Zero Energy Buildings

    DEFF Research Database (Denmark)

    Marszal, Anna Joanna; Bourrelle, Julien S.; Gustavsen, Arild

    2010-01-01

    and identify possible renewable energy supply options which may be considered in calculations. Finally, the gap between the methodology proposed by each organisation and their respective national building code is assessed; providing an overview of the possible changes building codes will need to undergo......The international cooperation project IEA SHC Task 40 / ECBCS Annex 52 “Towards Net Zero Energy Solar Buildings”, attempts to develop a common understanding and to set up the basis for an international definition framework of Net Zero Energy Buildings (Net ZEBs). The understanding of such buildings...

  16. Getting to Net Zero

    Energy Technology Data Exchange (ETDEWEB)

    2016-09-01

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

  17. Pro NET Best Practices

    CERN Document Server

    Ritchie, Stephen D

    2011-01-01

    Pro .NET Best Practices is a practical reference to the best practices that you can apply to your .NET projects today. You will learn standards, techniques, and conventions that are sharply focused, realistic and helpful for achieving results, steering clear of unproven, idealistic, and impractical recommendations. Pro .NET Best Practices covers a broad range of practices and principles that development experts agree are the right ways to develop software, which includes continuous integration, automated testing, automated deployment, and code analysis. Whether the solution is from a free and

  18. Ursodeoxycholic acid reduces protein levels and nucleation-promoting activity in human gallbladder bile

    NARCIS (Netherlands)

    van Erpecum, K. J.; Portincasa, P.; Eckhardt, E.; Go, P. M.; vanBerge-Henegouwen, G. P.; Groen, A. K.

    1996-01-01

    Background & Aims: Ursodeoxycholic acid prevents gallstone formation in selected patients. The aim of this study was to examine whether decreased concentration and nucleation-promoting activity of various proteins contribute to this beneficial effect. Methods: Gallbladder bile of 13 patients with

  19. Increasing intake of soybean protein or casein, but not cod meal, reduces nephrocalcinosis in female rats.

    NARCIS (Netherlands)

    Zhang, X.; Beynen, A.C.

    1992-01-01

    Female weanling rats were fed diets with soybean protein, casein or cod meal at 171, 342 or 513 mmol nitrogen/100 g for 3 wk. The diets were isonitrogenous and balanced for fat, cholesterol, calcium, magnesium and phosphorus. Cod meal feeding at 171 and 342 mmol nitrogen/100 g diet produced lower

  20. Histone H1 Differentially Inhibits DNA Bending by Reduced and Oxidized HMGB1 Protein

    Czech Academy of Sciences Publication Activity Database

    Štros, Michal; Muselíková Polanská, Eva; Kučírek, Martin; Pospíšilová, Š.

    2015-01-01

    Roč. 10, č. 9 (2015) E-ISSN 1932-6203 R&D Projects: GA ČR GAP305/12/2475; GA ČR GA15-01354S Institutional support: RVO:68081707 Keywords : GROUP BOX DOMAINS * BINDING PROTEINS * LINKER HISTONES Subject RIV: BO - Biophysics Impact factor: 3.057, year: 2015

  1. Reduced incorporation of the influenza B virus BM2 protein in virus particles decreases infectivity

    International Nuclear Information System (INIS)

    Jackson, David; Zuercher, Thomas; Barclay, Wendy

    2004-01-01

    BM2 is the fourth integral membrane protein encoded by the influenza B virus genome. It is synthesized late in infection and transported to the plasma membrane from where it is subsequently incorporated into progeny virus particles. It has recently been reported that BM2 has ion channel activity and may be the functional homologue of the influenza A virus M2 protein acting as an ion channel involved in viral entry. Using a reverse genetic approach it was not possible to recover virus which lacked BM2. A recombinant influenza B virus was generated in which the BM2 AUG initiation codon was mutated to GUG. This decreased the efficiency of translation of BM2 protein such that progeny virions contained only 1/8 the amount of BM2 seen in wild-type virus. The reduction in BM2 incorporation resulted in a reduction in infectivity although there was no concomitant decrease in the numbers of virions released from the infected cells. These data imply that the incorporation of sufficient BM2 protein into influenza B virions is required for infectivity of the virus particles

  2. Reduced Response to Activated Protein C Is Associated with Increased Risk for Cerebrovascular Disease

    NARCIS (Netherlands)

    Bom, J.G. van der; Bots, M.L.; Haverkate, F.; Slagboom, P.E.; Meijer, P.; Jong, P.T.V.M. de; Hofman, A.; Grobbee, D.E.; Kluft, C.

    1996-01-01

    Background: Resistance to activated protein C (APC), which results from various factors, including a mutation in the gene for coagulant factor V, has been associated with increased risk for venous thrombosis. However, its relation to arterial disease is still not well defined. Objective: To

  3. Intake of Mung Bean Protein Isolate Reduces Plasma Triglyceride Level in Rats

    Directory of Open Access Journals (Sweden)

    Nobuhiko Tachibana

    2013-09-01

    Full Text Available ABSTRACTBackground: Mung bean is well known as a starch source, but the physiological effects of mung bean protein have received little attention. In this study, we isolated mung bean protein from de-starched mung bean solutions, and investigated its influence on lipid metabolism. Objective: The aim of this study is to clarify the influence of the lipid metabolism by consumption of mung bean protein isolate (MPIMethods: Diets containing either mung bean protein isolate (MPI or casein were fed to normal rats for 28 days.Results: Both groups ate the same amount of food, but the plasma triglyceride level, relative liver weight and liver lipid contents (cholesterol and triglyceride pool in the MPI group were significantly lower than in the casein group. In the MPI group, the expression of sterol regulatory-element binding factor 1 (SREBF1 mRNA in the liver was significantly different when compared with the casein group. The significantly lower levels of insulin and free fatty acids in the MPI-fed rats may be due to the regulation of genes related to lipid metabolism in the liver.Conclusions: These results suggest that MPI may improve the plasma lipid profile by normalizing insulin sensitivity.Keywords: mung bean, Vigna radiata L., 8S globulin, triglyceride, β-conglycinin, 7S globulin, insulin sensitivity, SREBF1

  4. Increased protein intake reduces lean body mass loss during weight loss in athletes.

    Science.gov (United States)

    Mettler, Samuel; Mitchell, Nigel; Tipton, Kevin D

    2010-02-01

    To examine the influence of dietary protein on lean body mass loss and performance during short-term hypoenergetic weight loss in athletes. In a parallel design, 20 young healthy resistance-trained athletes were examined for energy expenditure for 1 wk and fed a mixed diet (15% protein, 100% energy) in the second week followed by a hypoenergetic diet (60% of the habitual energy intake), containing either 15% (approximately 1.0 g x kg(-1)) protein (control group, n = 10; CP) or 35% (approximately 2.3 g x kg(-1)) protein (high-protein group, n = 10; HP) for 2 wk. Subjects continued their habitual training throughout the study. Total, lean body, and fat mass, performance (squat jump, maximal isometric leg extension, one-repetition maximum (1RM) bench press, muscle endurance bench press, and 30-s Wingate test) and fasting blood samples (glucose, nonesterified fatty acids (NEFA), glycerol, urea, cortisol, free testosterone, free Insulin-like growth factor-1 (IGF-1), and growth hormone), and psychologic measures were examined at the end of each of the 4 wk. Total (-3.0 +/- 0.4 and -1.5 +/- 0.3 kg for the CP and HP, respectively, P = 0.036) and lean body mass loss (-1.6 +/- 0.3 and -0.3 +/- 0.3 kg, P = 0.006) were significantly larger in the CP compared with those in the HP. Fat loss, performance, and most blood parameters were not influenced by the diet. Urea was higher in HP, and NEFA and urea showed a group x time interaction. Fatigue ratings and "worse than normal" scores on the Daily Analysis of Life Demands for Athletes were higher in HP. These results indicate that approximately 2.3 g x kg(-1) or approximately 35% protein was significantly superior to approximately 1.0 g x kg(-1) or approximately 15% energy protein for maintenance of lean body mass in young healthy athletes during short-term hypoenergetic weight loss.

  5. Disulfide Linkage Characterization of Disulfide Bond-Containing Proteins and Peptides by Reducing Electrochemistry and Mass Spectrometry

    DEFF Research Database (Denmark)

    Cramer, Christian N; Haselmann, Kim F; Olsen, Jesper V

    2016-01-01

    in protein sequencing by tandem MS (MS/MS). Electrochemical (EC) reduction of disulfide bonds has recently been demonstrated to provide efficient reduction efficiencies, significantly enhancing sequence coverages in online coupling with MS characterization. In this study, the potential use of EC disulfide...... link between parent disulfide-linked fragments and free reduced peptides in an LC-EC-MS platform of nonreduced proteolytic protein digestions. Here we report the successful use of EC as a partial reduction approach in mapping of disulfide bonds of intact human insulin (HI) and lysozyme. In addition, we...... established a LC-EC-MS platform advantageous in disulfide characterization of complex and highly disulfide-bonded proteins such as human serum albumin (HSA) by online EC reduction of nonreduced proteolytic digestions....

  6. Recognizing protein–protein interfaces with empirical potentials and reduced amino acid alphabets

    Directory of Open Access Journals (Sweden)

    Wodak Shoshana

    2007-07-01

    Full Text Available Abstract Background In structural genomics, an important goal is the detection and classification of protein–protein interactions, given the structures of the interacting partners. We have developed empirical energy functions to identify native structures of protein–protein complexes among sets of decoy structures. To understand the role of amino acid diversity, we parameterized a series of functions, using a hierarchy of amino acid alphabets of increasing complexity, with 2, 3, 4, 6, and 20 amino acid groups. Compared to previous work, we used the simplest possible functional form, with residue–residue interactions and a stepwise distance-dependence. We used increased computational ressources, however, constructing 290,000 decoys for 219 protein–protein complexes, with a realistic docking protocol where the protein partners are flexible and interact through a molecular mechanics energy function. The energy parameters were optimized to correctly assign as many native complexes as possible. To resolve the multiple minimum problem in parameter space, over 64000 starting parameter guesses were tried for each energy function. The optimized functions were tested by cross validation on subsets of our native and decoy structures, by blind tests on series of native and decoy structures available on the Web, and on models for 13 complexes submitted to the CAPRI structure prediction experiment. Results Performance is similar to several other statistical potentials of the same complexity. For example, the CAPRI target structure is correctly ranked ahead of 90% of its decoys in 6 cases out of 13. The hierarchy of amino acid alphabets leads to a coherent hierarchy of energy functions, with qualitatively similar parameters for similar amino acid types at all levels. Most remarkably, the performance with six amino acid classes is equivalent to that of the most detailed, 20-class energy function. Conclusion This suggests that six carefully chosen amino

  7. GLP-1 analogs reduce hepatocyte steatosis and improve survival by enhancing the unfolded protein response and promoting macroautophagy.

    Directory of Open Access Journals (Sweden)

    Shvetank Sharma

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a known outcome of hepatosteatosis. Free fatty acids (FFA induce the unfolded protein response (UPR or endoplasmic reticulum (ER stress that may induce apoptosis. Recent data indicate ER stress to be a major player in the progression of fatty liver to more aggressive lesions. Autophagy on the other hand has been demonstrated to be protective against ER stress-induced cell death. We hypothesized that exendin-4 (GLP-1 analog treatment of fat loaded hepatocytes can reduce steatosis by autophagy which leads to reduced ER stress-related hepatocyte apoptosis.Primary human hepatocytes were loaded with saturated, cis- and trans-unsaturated fatty acids (palmitic, oleic and elaidic acid respectively. Steatosis, induced with all three fatty acids, was significantly resolved after exendin-4 treatment. Exendin-4 sustained levels of GRP78 expression in fat-loaded cells when compared to untreated fat-loaded cells alone. In contrast, CHOP (C/EBP homologous protein; the penultimate protein that leads to ER stress-related cell death was significantly decreased by exendin-4 in hepatocytes loaded with fatty acids. Finally, exendin-4 in fat loaded hepatocytes clearly promoted gene products associated with macroautophagy as measured by enhanced production of both Beclin-1 and LC3B-II, markers for autophagy; and visualized by transmission electron microscopy (TEM. Similar observations were made in mouse liver lysates after mice were fed with high fat high fructose diet and treated with a long acting GLP-1 receptor agonist, liraglutide.GLP-1 proteins appear to protect hepatocytes from fatty acid-related death by prohibition of a dysfunctional ER stress response; and reduce fatty acid accumulation, by activation of both macro-and chaperone-mediated autophagy. These findings provide a novel role for GLP-1 proteins in halting the progression of more aggressive lesions from underlying steatosis in humans afflicted with NAFLD.

  8. Redução da proteína da dieta com base no conceito de proteína ideal para tilápias-do-nilo (Oreochromis niloticus criadas em tanques-rede Dietary protein reduction based on ideal protein concept for Nile Tilapia (Oreochromis niloticus cultured in net pens

    Directory of Open Access Journals (Sweden)

    Daniele Botaro

    2007-06-01

    levels according to the ideal protein profile and to simulate amino acid levels of the control diet. Fish (34.63±1.19 g were hand-fed one of the four isoenergetic (3,075 kcal of digestible energy/kg, as fed basis experimental diets until apparent satiation, three times a day during 90 days. A completely randomized design with four treatments, three replicates and 25 fishes per experimental unit was utilized. No effects of dietary digestible protein levels on weight gain, feed conversion, protein efficiency ratio, empty carcass weight, carcass yield, fillet weight and yield, survival, and hematocrit were observed. It was observed quadratic effect on feed intake and nitrogen excretion, wich increased up to 24.41 and 24.92% of dietary digestible protein, respectively. The reduction of digestible protein levels resulted in a linear increase of nitrogen retention. It was concluded that it is possible to reduce the dietary digestible protein from 27.0 (29.1% of CP to 24.3% (26.6% of CP in amino acid supplemented diets (based on ideal protein concept, for juvenile Nile tilapia, cultured in net pens, without adverse effects on growth performance, carcass yield and composition, hematological parameters and cost of diet/kg of fillet gain.

  9. Bed rest reduces metabolic protein content and abolishes exercise-induced mRNA responses in human skeletal muscle

    DEFF Research Database (Denmark)

    Jørgensen, Stine Ringholm; Biensø, Rasmus S; Kiilerich, Kristian

    2011-01-01

    Background: The aim was to test the hypothesis that one week of bed rest will reduce mitochondrial number and expression and activity of oxidative proteins in human skeletal muscle, but that exercise-induced intracellular signaling as well as mRNA and microRNA (miR) responses are maintained after......-legged knee extensor exercise performed before and after bed rest. Results: Maximal oxygen uptake decreased 5% and exercise endurance decreased non-significantly 25% by bed rest. Bed rest reduced skeletal muscle mitochondrial DNA/nuclear DNA content 15%, hexokinase II and sirtuin 1 protein content ~45%, 3...... bed rest. Research Design and Methods: Twelve young, healthy, male subjects completed 7 days of bed rest with vastus lateralis muscle biopsies taken before and after bed rest. In addition, muscle biopsies were obtained from 6 of the subjects prior to, immediately after and 3h after 45 min one...

  10. Protein cross-linking by chlorinated polyamines and transglutamylation stabilizes neutrophil extracellular traps.

    Science.gov (United States)

    Csomós, Krisztián; Kristóf, Endre; Jakob, Bernadett; Csomós, István; Kovács, György; Rotem, Omri; Hodrea, Judit; Bagoly, Zsuzsa; Muszbek, Laszlo; Balajthy, Zoltán; Csősz, Éva; Fésüs, László

    2016-08-11

    Neutrophil extracellular trap (NET) ejected from activated dying neutrophils is a highly ordered structure of DNA and selected proteins capable to eliminate pathogenic microorganisms. Biochemical determinants of the non-randomly formed stable NETs have not been revealed so far. Studying the formation of human NETs we have observed that polyamines were incorporated into the NET. Inhibition of myeloperoxidase, which is essential for NET formation and can generate reactive chlorinated polyamines through hypochlorous acid, decreased polyamine incorporation. Addition of exogenous primary amines that similarly to polyamines inhibit reactions catalyzed by the protein cross-linker transglutaminases (TGases) has similar effect. Proteomic analysis of the highly reproducible pattern of NET components revealed cross-linking of NET proteins through chlorinated polyamines and ɛ(γ-glutamyl)lysine as well as bis-γ-glutamyl polyamine bonds catalyzed by the TGases detected in neutrophils. Competitive inhibition of protein cross-linking by monoamines disturbed the cross-linking pattern of NET proteins, which resulted in the loss of the ordered structure of the NET and significantly reduced capacity to trap bacteria. Our findings provide explanation of how NETs are formed in a reproducible and ordered manner to efficiently neutralize microorganisms at the first defense line of the innate immune system.

  11. Structural changes in Mcm5 protein bypass Cdc7-Dbf4 function and reduce replication origin efficiency in Saccharomyces cerevisiae.

    Science.gov (United States)

    Hoang, Margaret L; Leon, Ronald P; Pessoa-Brandao, Luis; Hunt, Sonia; Raghuraman, M K; Fangman, Walton L; Brewer, Bonita J; Sclafani, Robert A

    2007-11-01

    Eukaryotic chromosomal replication is a complicated process with many origins firing at different efficiencies and times during S phase. Prereplication complexes are assembled on all origins in G(1) phase, and yet only a subset of complexes is activated during S phase by DDK (for Dbf4-dependent kinase) (Cdc7-Dbf4). The yeast mcm5-bob1 (P83L) mutation bypasses DDK but results in reduced intrinsic firing efficiency at 11 endogenous origins and at origins located on minichromosomes. Origin efficiency may result from Mcm5 protein assuming an altered conformation, as predicted from the atomic structure of an archaeal MCM (for minichromosome maintenance) homologue. Similarly, an intragenic mutation in a residue predicted to interact with P83L suppresses the mcm5-bob1 bypass phenotype. We propose DDK phosphorylation of the MCM complex normally results in a single, highly active conformation of Mcm5, whereas the mcm5-bob1 mutation produces a number of conformations, only one of which is permissive for origin activation. Random adoption of these alternate states by the mcm5-bob1 protein can explain both how origin firing occurs independently of DDK and why origin efficiency is reduced. Because similar mutations in mcm2 and mcm4 cannot bypass DDK, Mcm5 protein may be a unique Mcm protein that is the final target of DDK regulation.

  12. PhysioNet

    Data.gov (United States)

    U.S. Department of Health & Human Services — The PhysioNet Resource is intended to stimulate current research and new investigations in the study of complex biomedical and physiologic signals. It offers free...

  13. Blanket testing in NET

    International Nuclear Information System (INIS)

    Chazalon, M.; Daenner, W.; Libin, B.

    1989-01-01

    The testing stages in NET for the performance assessment of the various breeding blanket concepts developed at the present time in Europe for DEMO (LiPb and ceramic blankets) and the requirements upon NET to perform these tests are reviewed. Typical locations available in NET for blanket testing are the central outboard segments and the horizontal ports of in-vessel sectors. These test positions will be connectable with external test loops. The number of test loops (helium, water, liquid metal) will be such that each major class of blankets can be tested in NET. The test positions, the boundary conditions and the external test loops are identified and the requirements for test blankets are summarized (author). 6

  14. Programming NET 35

    CERN Document Server

    Liberty, Jesse

    2009-01-01

    Bestselling author Jesse Liberty and industry expert Alex Horovitz uncover the common threads that unite the .NET 3.5 technologies, so you can benefit from the best practices and architectural patterns baked into the new Microsoft frameworks. The book offers a Grand Tour" of .NET 3.5 that describes how the principal technologies can be used together, with Ajax, to build modern n-tier and service-oriented applications. "

  15. NET SALARY ADJUSTMENT

    CERN Multimedia

    Finance Division

    2001-01-01

    On 15 June 2001 the Council approved the correction of the discrepancy identified in the net salary adjustment implemented on 1st January 2001 by retroactively increasing the scale of basic salaries to achieve the 2.8% average net salary adjustment approved in December 2000. We should like to inform you that the corresponding adjustment will be made to your July salary. Full details of the retroactive adjustments will consequently be shown on your pay slip.

  16. Short-Range Electron Transfer in Reduced Flavodoxin: Ultrafast Nonequilibrium Dynamics Coupled with Protein Fluctuations.

    Science.gov (United States)

    Kundu, Mainak; He, Ting-Fang; Lu, Yangyi; Wang, Lijuan; Zhong, Dongping

    2018-05-03

    Short-range electron transfer (ET) in proteins is an ultrafast process on the similar timescales as local protein-solvent fluctuations thus the two dynamics are coupled. Here, we use semiquinone flavodoxin and systematically characterized the photoinduced redox cycle with eleven mutations of different aromatic electron donors (tryptophan and tyrosine) and local residues to change redox properties. We observed the forward and backward ET dynamics in a few picoseconds, strongly following a stretched behavior resulting from a coupling between local environment relaxations and these ET processes. We further observed the hot vibrational-state formation through charge recombination and the subsequent cooling dynamics also in a few picoseconds. Combined with the ET studies in oxidized flavodoxin, these results coherently reveal the evolution of the ET dynamics from single to stretched exponential behaviors and thus elucidate critical timescales for the coupling. The observed hot vibration-state formation is robust and should be considered in all photoinduced back ET processes in flavoproteins.

  17. High-sensitive C-reactive protein is associated with reduced lung function in young adults

    DEFF Research Database (Denmark)

    Rasmussen, Finn; Mikkelsen, Dennis; Hancox, Robert

    2009-01-01

    levels of CRP at age 20 yrs were associated with a greater reduction in both FEV(1) and forced vital capacity between ages 20 and 29 yrs. The findings show that higher levels of C-reactive protein in young adults are associated with subsequent decline in lung function, suggesting that low-grade systemic...... inflammation in young adulthood may lead to impaired lung function independently of the effects of smoking, obesity, cardiorespiratory fitness, asthma and eosinophilic inflammation....

  18. Salivary proline-rich protein may reduce tannin-iron chelation: a systematic narrative review

    OpenAIRE

    Delimont, Nicole M.; Rosenkranz, Sara K.; Haub, Mark D.; Lindshield, Brian L.

    2017-01-01

    Background Tannins are often cited for antinutritional effects, including chelation of non-heme iron. Despite this, studies exploring non-heme iron bioavailability inhibition with long-term consumption have reported mixed results. Salivary proline-rich proteins (PRPs) may mediate tannin-antinutritional effects on non-heme iron bioavailability. Aim To review evidence regarding biochemical binding mechanisms and affinity states between PRPs and tannins, as well as effects of PRPs on non-heme ir...

  19. Increased protein intake and meal frequency reduces abdominal fat during energy balance and energy deficit.

    Science.gov (United States)

    Arciero, Paul J; Ormsbee, Michael J; Gentile, Christopher L; Nindl, Bradley C; Brestoff, Jonathan R; Ruby, Maxwell

    2013-07-01

    Unrefined, complex carbohydrates and lean protein diets are used to combat obesity, although it's unknown whether more frequent meals may improve this response. The effects of consuming traditional (~15%) versus higher (~35%) protein intakes as three or six meals/day on abdominal fat, postprandial thermogenesis (TEM), and cardiometabolic biomarkers in overweight individuals during 28 days of energy balance (BAL) and deficit (NEG), respectively were compared. Overweight individuals (n = 30) were randomized into three groups: two high-protein groups (35% of energy) consumed as three (HP3) or six (HP6) meals/day and one group consumed three meals/day of a traditional intake (TD3). Following a 5-day baseline control (CON), subjects consumed their respective diets throughout a 56-day intervention consisting of two, 28 day phases: a BAL followed by a NEG phase (75% of energy needs). Total body fat (BF) and abdominal BF (ABF), body weight (BW), TEM, and fasting biomarkers were assessed at the end of CON, BAL, and NEG phases. BW remained stable throughout CON and BAL in all groups, whereas BF (P meals/day in overweight individuals during both BAL and NEG. Copyright © 2013 The Obesity Society.

  20. Reduced Fluorescent Protein Switching Fatigue by Binding-Induced Emissive State Stabilization

    Directory of Open Access Journals (Sweden)

    Thijs Roebroek

    2017-09-01

    Full Text Available Reversibly switchable fluorescent proteins (RSFPs enable advanced fluorescence imaging, though the performance of this imaging crucially depends on the properties of the labels. We report on the use of an existing small binding peptide, named Enhancer, to modulate the spectroscopic properties of the recently developed rsGreen series of RSFPs. Fusion constructs of Enhancer with rsGreen1 and rsGreenF revealed an increased molecular brightness and pH stability, although expression in living E. coli or HeLa cells resulted in a decrease of the overall emission. Surprisingly, Enhancer binding also increased off-switching speed and resistance to switching fatigue. Further investigation suggested that the RSFPs can interconvert between fast- and slow-switching emissive states, with the overall protein population gradually converting to the slow-switching state through irradiation. The Enhancer modulates the spectroscopic properties of both states, but also preferentially stabilizes the fast-switching state, supporting the increased fatigue resistance. This work demonstrates how the photo-physical properties of RSFPs can be influenced by their binding to other small proteins, which opens up new horizons for applications that may require such modulation. Furthermore, we provide new insights into the photoswitching kinetics that should be of general consideration when developing new RSFPs with improved or different photochromic properties.

  1. Reduced Fragment Diversity for Alpha and Alpha-Beta Protein Structure Prediction using Rosetta.

    Science.gov (United States)

    Abbass, Jad; Nebel, Jean-Christophe

    2017-01-01

    Protein structure prediction is considered a main challenge in computational biology. The biannual international competition, Critical Assessment of protein Structure Prediction (CASP), has shown in its eleventh experiment that free modelling target predictions are still beyond reliable accuracy, therefore, much effort should be made to improve ab initio methods. Arguably, Rosetta is considered as the most competitive method when it comes to targets with no homologues. Relying on fragments of length 9 and 3 from known structures, Rosetta creates putative structures by assembling candidate fragments. Generally, the structure with the lowest energy score, also known as first model, is chosen to be the "predicted one". A thorough study has been conducted on the role and diversity of 3-mers involved in Rosetta's model "refinement" phase. Usage of the standard number of 3-mers - i.e. 200 - has been shown to degrade alpha and alpha-beta protein conformations initially achieved by assembling 9-mers. Therefore, a new prediction pipeline is proposed for Rosetta where the "refinement" phase is customised according to a target's structural class prediction. Over 8% improvement in terms of first model structure accuracy is reported for alpha and alpha-beta classes when decreasing the number of 3- mers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Composição corporal e exigências líquidas proteicas de ovinos Santa Inês em crescimento Body composition and net protein requirements for growing Santa Inês sheep

    Directory of Open Access Journals (Sweden)

    José Gilson Louzada Regadas Filho

    2011-06-01

    protein requirements of 24 Santa Inês non-castrated growing sheep at average age of 50 days and average body weight of 13.00 ± 0.56 kg. After a ten-day adaptation period, four animals were slaughtered to be used as a reference for estimates of empty body weight (EBW and initial body composition of the other animals. The remaining animals were assigned into a randomized block design with diets containg different levels of metabolizable energy (2.08; 2.28; 2.47 and 2.69 Mcal/kg of DM and crude protein (12.74; 14.36, 15.97 and 17.65% CP of DM with five replicates. The N daily excretion was estimated by extrapolating regression equations of N intake (g/kg BW0.75/day in function of retention (g/kg BW0.75/day for zero intake. The derivative regression of the logarithm of protein content in function of the logarithm of EBW enabled the estimation of net protein requirement for empty body weight gain (EBWG. Daily nitrogen excretion was 277 ± 0.05 mg/kg BW0.75/day and net protein requirement for maintenance was 1.73 g/kg BW0.75/day. Protein content of EBW of animals decreased from 157.83 to 144.33 g/kg of EBW when the BW of the animals increased from 15 to 30 kg, respectively. The amount of protein deposited in the gain decreased from 137.47 to 125.71 g/kg of EBWG with the increase of body weight of the animals from 15 to 30 kg, respectively. Nitrogen fecal excretion and protein net requirement for maintenance of Santa Inês growing lambs was lower than the values commonly cited by the main systems of feed evaluation and nutrient requirements for small ruminants.

  3. Net energy benefits of carbon nanotube applications

    International Nuclear Information System (INIS)

    Zhai, Pei; Isaacs, Jacqueline A.; Eckelman, Matthew J.

    2016-01-01

    Highlights: • Life cycle net energy benefits are examined. • CNT-enabled and the conventional technologies are compared. • Flash memory with CNT switches show significant positive net energy benefit. • Lithium-ion batteries with MWCNT cathodes show positive net energy benefit. • Lithium-ion batteries with SWCNT anodes tend to exhibit negative net energy benefit. - Abstract: Implementation of carbon nanotubes (CNTs) in various applications can reduce material and energy requirements of products, resulting in energy savings. However, processes for the production of carbon nanotubes (CNTs) are energy-intensive and can require extensive purification. In this study, we investigate the net energy benefits of three CNT-enabled technologies: multi-walled CNT (MWCNT) reinforced cement used as highway construction material, single-walled CNT (SWCNT) flash memory switches used in cell phones and CNT anodes and cathodes used in lithium-ion batteries used in electric vehicles. We explore the avoided or additional energy requirement in the manufacturing and use phases and estimate the life cycle net energy benefits for each application. Additional scenario analysis and Monte Carlo simulation of parameter uncertainties resulted in probability distributions of net energy benefits, indicating that net energy benefits are dependent on the application with confidence intervals straddling the breakeven line in some cases. Analysis of simulation results reveals that SWCNT switch flash memory and MWCNT Li-ion battery cathodes have statistically significant positive net energy benefits (α = 0.05) and SWCNT Li-ion battery anodes tend to have negative net energy benefits, while positive results for MWCNT-reinforced cement were significant only under an efficient CNT production scenario and a lower confidence level (α = 0.1).

  4. Rising atmospheric CO2 is reducing the protein concentration of a floral pollen source essential for North American bees.

    Science.gov (United States)

    Ziska, Lewis H; Pettis, Jeffery S; Edwards, Joan; Hancock, Jillian E; Tomecek, Martha B; Clark, Andrew; Dukes, Jeffrey S; Loladze, Irakli; Polley, H Wayne

    2016-04-13

    At present, there is substantive evidence that the nutritional content of agriculturally important food crops will decrease in response to rising levels of atmospheric carbon dioxide, Ca However, whether Ca-induced declines in nutritional quality are also occurring for pollinator food sources is unknown. Flowering late in the season, goldenrod (Solidago spp.) pollen is a widely available autumnal food source commonly acknowledged by apiarists to be essential to native bee (e.g. Bombus spp.) and honeybee (Apis mellifera) health and winter survival. Using floral collections obtained from the Smithsonian Natural History Museum, we quantified Ca-induced temporal changes in pollen protein concentration of Canada goldenrod (Solidago canadensis), the most wide spread Solidago taxon, from hundreds of samples collected throughout the USA and southern Canada over the period 1842-2014 (i.e. a Ca from approx. 280 to 398 ppm). In addition, we conducted a 2 year in situtrial of S. Canadensis populations grown along a continuous Ca gradient from approximately 280 to 500 ppm. The historical data indicated a strong significant correlation between recent increases in Ca and reductions in pollen protein concentration (r(2)= 0.81). Experimental data confirmed this decrease in pollen protein concentration, and indicated that it would be ongoing as Ca continues to rise in the near term, i.e. to 500 ppm (r(2)= 0.88). While additional data are needed to quantify the subsequent effects of reduced protein concentration for Canada goldenrod on bee health and population stability, these results are the first to indicate that increasing Ca can reduce protein content of a floral pollen source widely used by North American bees. © 2016 The Author(s).

  5. Chemotherapeutic treatment reduces circulating levels of surfactant protein-D in children with acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Rathe, Mathias; Sorensen, Grith L; Skov Wehner, Peder

    2017-01-01

    with acute lymphoblastic leukemia (ALL). PROCEDURE: In a prospective study, 43 children receiving treatment for ALL were monitored for mucosal toxicity from diagnosis through the induction phase of treatment. Serial blood draws were taken to determine the levels of SP-D, interleukin-6 (IL-6), C......BACKGROUND: Surfactant protein D (SP-D) is a host defense molecule of the innate immune system that enhances pathogen clearance and modulates inflammatory responses. We hypothesized that circulating SP-D levels are associated with chemotherapy-induced mucositis and infectious morbidity in children...

  6. Sphingosine-1-Phosphate reduces ischemia/reperfusion injury by phosphorylating the gap junction protein Connexin43

    DEFF Research Database (Denmark)

    Morel, Sandrine; Christoffersen, Christina; Axelsen, Lene N

    2016-01-01

    recruitment seems only indirectly affected. Importantly, short-term S1P treatment at the onset of reperfusion was sufficient to reduce ischemia/reperfusion injury in isolated perfused hearts. Mechanistic in vitro and ex vivo studies revealed that 5 min of S1P treatment induced phosphorylation of the gap...

  7. The catechin flavonoid reduces proliferation and induces apoptosis of murine lymphoma cells LB02 through modulation of antiapoptotic proteins

    Directory of Open Access Journals (Sweden)

    Daniela Laura Papademetrio

    2013-06-01

    Full Text Available Flavonoids are products of secondary metabolism of plants. They are present in herbs and trees and also act as natural chemopreventives and anticancer agents. Ligaria cuneifolia (Ruiz & Pav. Tiegh., Loranthaceae, is a hemiparasite species that belongs to Argentine flora. Phytochemical studies have disclosed the presence of quercetin, catechin-4β-ol and pro-anthocyanidine as polyphenolic compounds in the active extracts. We previously demonstrated that ethyl acetate extract was capable of reducing cell proliferation and inducing apoptotic death of lymphoid tumor cells. The aim of the current study is to determine whether or not catechin, isolated from L. cuneifolia extracts can induce leukemia cell death and to determine its effect on the cytoplasmatic proteins that modulate cell survival. Our results show that catechin can reduce proliferation of murine lymphoma cell line LB02. The effect is mediated by apoptosis at concentrations upper to 100 µg/mL. Cell death is related to the loss of mitochondrial membrane potential (ΔΨm and a down regulation of survivin and Bcl-2 together with the increase of pro-apoptotic protein Bax. In summary, the current study indicates that catechin present in the extract of L. cuneifolia is in part, responsible for the anti-proliferative activity of whole extracts by induction of ΔΨm disruption and modulation of the anti-apoptotic proteins over expressed in tumor cells. These results give new findings into the potential anticancer and chemopreventive activities of L. cuneifolia.

  8. The catechin flavonoid reduces proliferation and induces apoptosis of murine lymphoma cells LB02 through modulation of antiapoptotic proteins

    Directory of Open Access Journals (Sweden)

    Daniela Laura Papademetrio

    2013-03-01

    Full Text Available Flavonoids are products of secondary metabolism of plants. They are present in herbs and trees and also act as natural chemopreventives and anticancer agents. Ligaria cuneifolia (Ruiz & Pav. Tiegh., Loranthaceae, is a hemiparasite species that belongs to Argentine flora. Phytochemical studies have disclosed the presence of quercetin, catechin-4β-ol and pro-anthocyanidine as polyphenolic compounds in the active extracts. We previously demonstrated that ethyl acetate extract was capable of reducing cell proliferation and inducing apoptotic death of lymphoid tumor cells. The aim of the current study is to determine whether or not catechin, isolated from L. cuneifolia extracts can induce leukemia cell death and to determine its effect on the cytoplasmatic proteins that modulate cell survival. Our results show that catechin can reduce proliferation of murine lymphoma cell line LB02. The effect is mediated by apoptosis at concentrations upper to 100 µg/mL. Cell death is related to the loss of mitochondrial membrane potential (ΔΨm and a down regulation of survivin and Bcl-2 together with the increase of pro-apoptotic protein Bax. In summary, the current study indicates that catechin present in the extract of L. cuneifolia is in part, responsible for the anti-proliferative activity of whole extracts by induction of ΔΨm disruption and modulation of the anti-apoptotic proteins over expressed in tumor cells. These results give new findings into the potential anticancer and chemopreventive activities of L. cuneifolia.

  9. Protective Immunity and Reduced Renal Colonization Induced by Vaccines Containing Recombinant Leptospira interrogans Outer Membrane Proteins and Flagellin Adjuvant

    Science.gov (United States)

    Monaris, D.; Sbrogio-Almeida, M. E.; Dib, C. C.; Canhamero, T. A.; Souza, G. O.; Vasconcellos, S. A.; Ferreira, L. C. S.

    2015-01-01

    Leptospirosis is a global zoonotic disease caused by different Leptospira species, such as Leptospira interrogans, that colonize the renal tubules of wild and domestic animals. Thus far, attempts to develop effective leptospirosis vaccines, both for humans and animals, have failed to induce immune responses capable of conferring protection and simultaneously preventing renal colonization. In this study, we evaluated the protective immunity induced by subunit vaccines containing seven different recombinant Leptospira interrogans outer membrane proteins, including the carboxy-terminal portion of the immunoglobulinlike protein A (LigAC) and six novel antigens, combined with aluminum hydroxide (alum) or Salmonella flagellin (FliC) as adjuvants. Hamsters vaccinated with the different formulations elicited high antigen-specific antibody titers. Immunization with LigAC, either with alum or flagellin, conferred protective immunity but did not prevent renal colonization. Similarly, animals immunized with LigAC or LigAC coadministered with six leptospiral proteins with alum adjuvant conferred protection but did not reduce renal colonization. In contrast, immunizing animals with the pool of seven antigens in combination with flagellin conferred protection and significantly reduced renal colonization by the pathogen. The present study emphasizes the relevance of antigen composition and added adjuvant in the efficacy of antileptospirosis subunit vaccines and shows the complex relationship between immune responses and renal colonization by the pathogen. PMID:26108285

  10. Association of canine obesity with reduced serum levels of C-reactive protein.

    Science.gov (United States)

    Veiga, Angela P M; Price, Christopher A; de Oliveira, Simone T; Dos Santos, Andréa P; Campos, Rómulo; Barbosa, Patricia R; González, Félix H D

    2008-03-01

    The prevalence of obesity is increasing in dogs as well as in humans. C-reactive protein (CRP) is an important tool for the detection of inflammation and/or early tissue damage and is linked to obesity in humans. The objective of the present study was to determine if serum CRP levels are altered in obese dogs. Fifteen lean (control group) and 16 overweight (obese group) dogs were examined. Blood samples were collected under fasted conditions for serum determination of CRP, glucose, insulin, cholesterol, triglyceride, and fructosamine. Results indicated that obese dogs were insulin resistant because serum insulin and insulin/glucose ratios were higher than in lean dogs (P obese dogs than in controls (P obese group compared with the control group. Based on these results, it can be postulated that CRP production is inhibited by obesity and insulin resistance in dogs.

  11. Short communication: Effect of whey protein addition and transglutaminase treatment on the physical and sensory properties of reduced-fat ice cream.

    Science.gov (United States)

    Danesh, Erfan; Goudarzi, Mostafa; Jooyandeh, Hossein

    2017-07-01

    The effects of whey protein addition and transglutaminase treatment, alone and in combination, on the physical and sensory properties of reduced-fat ice cream were investigated. Adding whey protein with or without enzyme treatment decreased melting rate, overrun, and hardness of the reduced-fat ice cream; however, the enzyme-treated sample had a higher melting rate and overrun and softer texture. Whey protein-fortified samples showed higher melting resistance, but lower overrun and firmer texture compared with the enzyme-treated sample without added whey protein. Whey protein addition with or without transglutaminase treatment caused an increase in apparent viscosity and a decrease in flow index of the reduced-fat ice cream; nevertheless, the flow behavior of full-fat sample was most similar to the enzyme-treated reduced-fat sample with no added whey protein. Descriptive sensory analyses showed that neither whey protein addition nor transglutaminase treatment significantly influenced the flavor and odor of reduced-fat ice cream, but they both noticeably improved the color and texture of the final product. The results of this study suggest that whey protein addition with transglutaminase treatment improves the physical and sensory properties of reduced-fat ice cream more favorably than does whey protein addition or transglutaminase treatment alone. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  12. Reducing crude protein content with supplementation of synthetic lysine and threonine in barley - rapeseed meal - pea diets for growing pigs

    Directory of Open Access Journals (Sweden)

    Jarmo Valaja

    1993-03-01

    Full Text Available This study was conducted to determine the possibility to use synthetic amino acids to lower the nitrogen output from pig production. A performance experiment was carried out with 120triplet-fed growing pigs whose dietary crude protein was reduced from 179 g/feed unit (FU= 0.7 kg starch equivalent to 160, 140 and 122 g/FU, respectively. The diets were supplemented with synthetic lysine and threonine to keep the level of these amino acids constant. Dietary protein reduction did not affect the growth performance or feed conversion ratio of the pigs, but it did linearly increase the portion of fat to lean in the carcass. Significant linear effect was found in back fat (p

  13. A Phospholipid-Protein Complex from Krill with Antioxidative and Immunomodulating Properties Reduced Plasma Triacylglycerol and Hepatic Lipogenesis in Rats

    Directory of Open Access Journals (Sweden)

    Marie S. Ramsvik

    2015-07-01

    Full Text Available Dietary intake of marine omega-3 polyunsaturated fatty acids (n-3 PUFAs can change the plasma profile from atherogenic to cardioprotective. In addition, there is growing evidence that proteins of marine origin may have health benefits. We investigated a phospholipid-protein complex (PPC from krill that is hypothesized to influence lipid metabolism, inflammation, and redox status. Male Wistar rats were fed a control diet (2% soy oil, 8% lard, 20% casein, or diets where corresponding amounts of casein and lard were replaced with PPC at 3%, 6%, or 11% (wt %, for four weeks. Dietary supplementation with PPC resulted in significantly lower levels of plasma triacylglycerols in the 11% PPC-fed group, probably due to reduced hepatic lipogenesis. Plasma cholesterol levels were also reduced at the highest dose of PPC. In addition, the plasma and liver content of n-3 PUFAs increased while n-6 PUFAs decreased. This was associated with increased total antioxidant capacity in plasma and increased liver gene expression of mitochondrial superoxide dismutase (Sod2. Finally, a reduced plasma level of the inflammatory mediator interleukin-2 (IL-2 was detected in the PPC-fed animals. The present data show that PPC has lipid-lowering effects in rats, and may modulate risk factors related to cardiovascular disease progression.

  14. Atorvastatin reduces lipid accumulation in the liver by activating protein kinase A-mediated phosphorylation of perilipin 5.

    Science.gov (United States)

    Gao, Xing; Nan, Yang; Zhao, Yuanlin; Yuan, Yuan; Ren, Bincheng; Sun, Chao; Cao, Kaiyu; Yu, Ming; Feng, Xuyang; Ye, Jing

    2017-12-01

    Statins have been proven to be effective in treating non-alcoholic fatty liver disease (NAFLD). Recently, it was reported that statins decreased the hepatic expression of perilipin 5 (Plin5), a lipid droplet (LD)-associated protein, which plays critical roles in regulating lipid accumulation and lipolysis in liver. However, the function and regulation mechanism of Plin5 have not yet been well-established in NAFLD treatment with statins. In this study, we observed that atorvastatin moderately reduced the expression of Plin5 in livers without changing the protein level of Plin5 in the hepatic LD fraction of mice fed with high-fat diet (HFD). Intriguingly, atorvastatin stimulated the PKA-mediated phosphorylation of Plin5 and reduced the triglyceride (TG) accumulation in hepatocytes with overexpression of wide type (Plin5-WT) compared to serine-155 mutant Plin5 (Plin5-S155A). Moreover, PKA-stimulated FA release of purified LDs carrying Plin5-WT but not Plin5-S155A. Glucagon, a PKA activator, stimulated the phosphorylation of Plin5-WT and inhibited its interaction with CGI-58. The results indicated that atorvastatin promoted lipolysis and reduced TG accumulation in the liver by increasing PKA-mediated phosphorylation of Plin5. This new mechanism of lipid-lowering effects of atorvastatin might provide a new strategy for NAFLD treatment. Copyright © 2017. Published by Elsevier B.V.

  15. Inhibition of Cartilage Acidic Protein 1 Reduces Ultraviolet B Irradiation Induced-Apoptosis through P38 Mitogen-Activated Protein Kinase and Jun Amino-Terminal Kinase Pathways

    Directory of Open Access Journals (Sweden)

    Yinghong Ji

    2016-11-01

    Full Text Available Background/Aims: Ultraviolet B (UVB irradiation can easily induce apoptosis in human lens epithelial cells (HLECs and further lead to various eye diseases including cataract. Here for the first time, we investigated the role of cartilage acidic protein 1 (CRTAC1 gene in UVB irradiation induced-apoptosis in HLECs. Methods: Three groups of HLECs were employed including model group, empty vector group, and CRTAC1 interference group. Results: After UVB irradiation, the percentage of primary apoptotic cells was obviously fewer in CRTAC1 interference group. Meanwhile, inhibition of CRTAC1 also reduced both reactive oxygen species (ROS production and intracellular Ca2+ concentration, but the level of mitochondrial membrane potential (Δψm was increased in HLECs. Further studies indicated that superoxide dismutase (SOD activity and total antioxidative (T-AOC level were significantly increased in CRTAC1-inhibited cells, while the levels of malondialdehyde (MDA and lactate dehydrogenase (LDH were significantly decreased. ELISA analysis of CRTAC1-inhibited cells showed that the concentrations of tumor necrosis factor-α (TNF-α and interleukin-6 (IL-6 were significantly decreased, but the concentration of interleukin-10 (IL-10 was significantly increased. Western blot analyses of eight apoptosis-associated proteins including Bax, Bcl-2, p38, phospho-p38 (p-p38, Jun amino-terminal kinases (JNK1/2, phospho-JNK1/2 (p-JNK1/2, calcium-sensing receptor (CasR, and Ca2+/calmodulin-dependent protein kinase II (CaMKII indicated that the inhibition of CRTAC1 alleviated oxidative stress and inflammation response, inactivated calcium-signaling pathway, p38 and JNK1/2 signal pathways, and eventually reduced UVB irradiation induced-apoptosis in HLECs. Conclusion: These results provided new insights into the mechanism of cataract development, and demonstrated that CRTAC1 could be a potentially novel target for cataract treatment.

  16. Inhibition of Cartilage Acidic Protein 1 Reduces Ultraviolet B Irradiation Induced-Apoptosis through P38 Mitogen-Activated Protein Kinase and Jun Amino-Terminal Kinase Pathways.

    Science.gov (United States)

    Ji, Yinghong; Rong, Xianfang; Li, Dan; Cai, Lei; Rao, Jun; Lu, Yi

    2016-01-01

    Ultraviolet B (UVB) irradiation can easily induce apoptosis in human lens epithelial cells (HLECs) and further lead to various eye diseases including cataract. Here for the first time, we investigated the role of cartilage acidic protein 1 (CRTAC1) gene in UVB irradiation induced-apoptosis in HLECs. Three groups of HLECs were employed including model group, empty vector group, and CRTAC1 interference group. After UVB irradiation, the percentage of primary apoptotic cells was obviously fewer in CRTAC1 interference group. Meanwhile, inhibition of CRTAC1 also reduced both reactive oxygen species (ROS) production and intracellular Ca2+ concentration, but the level of mitochondrial membrane potential (Δψm) was increased in HLECs. Further studies indicated that superoxide dismutase (SOD) activity and total antioxidative (T-AOC) level were significantly increased in CRTAC1-inhibited cells, while the levels of malondialdehyde (MDA) and lactate dehydrogenase (LDH) were significantly decreased. ELISA analysis of CRTAC1-inhibited cells showed that the concentrations of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were significantly decreased, but the concentration of interleukin-10 (IL-10) was significantly increased. Western blot analyses of eight apoptosis-associated proteins including Bax, Bcl-2, p38, phospho-p38 (p-p38), Jun amino-terminal kinases (JNK1/2), phospho-JNK1/2 (p-JNK1/2), calcium-sensing receptor (CasR), and Ca2+/calmodulin-dependent protein kinase II (CaMKII) indicated that the inhibition of CRTAC1 alleviated oxidative stress and inflammation response, inactivated calcium-signaling pathway, p38 and JNK1/2 signal pathways, and eventually reduced UVB irradiation induced-apoptosis in HLECs. These results provided new insights into the mechanism of cataract development, and demonstrated that CRTAC1 could be a potentially novel target for cataract treatment. © 2016 The Author(s) Published by S. Karger AG, Basel.

  17. Reduced expression of Jak-1 and Tyk-2 proteins leads to interferon resistance in Hepatitis C virus replicon

    Directory of Open Access Journals (Sweden)

    Luftig Ronald

    2007-09-01

    Full Text Available Abstract Background Alpha interferon in combination with ribavirin is the standard therapy for hepatitis C virus infection. Unfortunately, a significant number of patients fail to eradicate their infection with this regimen. The mechanisms of IFN-resistance are unclear. The aim of this study was to determine the contribution of host cell factors to the mechanisms of interferon resistance using replicon cell lines. Results HCV replicons with high and low activation of the IFN-promoter were cultured for a prolonged period of time in the presence of interferon-alpha (IFN-alpha2b. Stable replicon cell lines with resistant phenotype were isolated and characterized by their ability to continue viral replication in the presence of IFN-alpha. Interferon resistant cell colonies developed only in replicons having lower activation of the IFN promoter and no resistant colonies arose from replicons that exhibit higher activation of the IFN promoter. Individual cell clones were isolated and nine IFN resistant cell lines were established. HCV RNA and protein levels in these cells were not altered by IFN- alpha2b. Reduced signaling and IFN-resistant phenotype was found in all Huh-7 cell lines even after eliminating HCV, suggesting that cellular factors are involved. Resistant phenotype in the replicons is not due to lack of interferon receptor expression. All the cell lines show defect in the JAK-STAT signaling and phosphorylation of STAT 1 and STAT 2 proteins were strongly inhibited due to reduced expression of Tyk2 and Jak-1 protein. Conclusion This in vitro study provides evidence that altered expression of the Jak-Stat signaling proteins can cause IFN resistance using HCV replicon cell clones.

  18. Biological Petri Nets

    CERN Document Server

    Wingender, E

    2011-01-01

    It was suggested some years ago that Petri nets might be well suited to modeling metabolic networks, overcoming some of the limitations encountered by the use of systems employing ODEs (ordinary differential equations). Much work has been done since then which confirms this and demonstrates the usefulness of this concept for systems biology. Petri net technology is not only intuitively understood by scientists trained in the life sciences, it also has a robust mathematical foundation and provides the required degree of flexibility. As a result it appears to be a very promising approach to mode

  19. NET system integration

    International Nuclear Information System (INIS)

    Farfaletti-Casali, F.; Mitchell, N.; Salpietro, E.; Buzzi, U.; Gritzmann, P.

    1985-01-01

    The NET system integration procedure is the process by which the requirements of the various Tokamak machine design areas are brought together to form a compatible machine layout. Each design area produces requirements which generally allow components to be built at minimum cost and operate with minimum technical risk, and the final machine assembly should be achieved with minimum departure from these optimum designs. This is carried out in NET by allowing flexibility in the maintenance and access methods to the machine internal components which must be regularly replaced by remote handling, in segmentation of these internal components and in the number of toroidal field coils

  20. Ursodeoxycholic acid pretreatment reduces oral bioavailability of the multiple drug resistance-associated protein 2 substrate baicalin in rats.

    Science.gov (United States)

    Wu, Tao; Li, Xi-Ping; Xu, Yan-Jiao; Du, Guang; Liu, Dong

    2013-11-01

    Baicalin is a major bioactive component of Scutellaria baicalensis and a substrate of multiple drug resistance-associated protein 2. Expression of multiple drug resistance-associated protein 2 is regulated by NF-E2-related factor 2. The aim of this study was to explore whether ursodeoxycholic acid, an NF-E2-related factor 2 activator, could influence the oral bioavailability of baicalin. A single dose of baicalin (200 mg/kg) was given orally to rats pretreated with ursodeoxycholic acid (75 mg/kg and 150 mg/kg, per day, intragastrically) or normal saline (per day, intragastrically) for six consecutive days. The plasma concentration of baicalin was measured with the HPLC method. The result indicated that the oral bioavailability of baicalin was significantly and dose-dependently reduced in rats pretreated with ursodeoxycholic acid. Compared with control rats, the mean area under concentration-time curve of baicalin was reduced from 13.25 ± 0.24 mg/L h to 7.62 ± 0.15 mg/L h and 4.97 ± 0.21 mg/L h, and the C(max) value was decreased from 1.31 ± 0.03 mg/L to 0.62 ± 0.05 mg/L and 0.36 ± 0.04 mg/L in rats pretreated with ursodeoxycholic acid at doses of 75 mg/kg and 150 mg/kg, respectively, for six consecutive days. Hence, ursodeoxycholic acid treatment reduced the oral bioavailability of baicalin in rats, probably due to the enhanced efflux of baicalin from the intestine and liver by multiple drug resistance-associated protein 2. Georg Thieme Verlag KG Stuttgart · New York.

  1. Glutamine reduces myocardial cell apoptosis in a rat model of sepsis by promoting expression of heat shock protein 90.

    Science.gov (United States)

    Li, Wanxia; Tao, Shaoyu; Wu, Qinghua; Wu, Tao; Tao, Ran; Fan, Jun

    2017-12-01

    Myocardial cell injury and cardiac myocyte apoptosis are associated with sepsis. Glutamine (Gln) has been reported to repair myocardial cell injury. The aim of this study was to explore the role of Gln on cardiac myocytes in a cecal ligation and puncture (CLP) model of sepsis in Wistar rats. Following induction of sepsis in a CLP rat model, viral encoding heat shock protein 90 (Hsp90) gene and Hsp90dsDNA were designed to express and knockdown Hsp90, respectively. Rat cardiac tissues were examined histologically, and apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The expression of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein, Hsp90, p53 upregulated modulator of apoptosis, and p53 was measured by western blotting and real-time polymerase chain reaction. Caspase-3, caspase-8, and caspase-9 were detected by enzyme-linked immunosorbent assay. Rat cardiac myocyte damage induced by CLP was reduced by Gln treatment and Hsp90 overexpression, and these changes were reversed by Hsp90 knockdown. Bcl-2 expression, Bcl-2-associated X protein, p53, p53 upregulated modulator of apoptosis, caspase-8, caspase-9, and caspase-3 activities were significantly upregulated in the CLP model, which were reduced by Gln treatment and Hsp90 overexpression. Gln reduced apoptosis of cardiac myocytes in a rat model of sepsis, by promoting Hsp90 expression. Further studies are needed to determine the possible therapeutic action of Gln in sepsis in human tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Brazilin inhibits amyloid β-protein fibrillogenesis, remodels amyloid fibrils and reduces amyloid cytotoxicity

    Science.gov (United States)

    Du, Wen-Jie; Guo, Jing-Jing; Gao, Ming-Tao; Hu, Sheng-Quan; Dong, Xiao-Yan; Han, Yi-Fan; Liu, Fu-Feng; Jiang, Shaoyi; Sun, Yan

    2015-01-01

    Soluble amyloid β-protein (Aβ) oligomers, the main neurotoxic species, are predominantly formed from monomers through a fibril-catalyzed secondary nucleation. Herein, we virtually screened an in-house library of natural compounds and discovered brazilin as a dual functional compound in both Aβ42 fibrillogenesis inhibition and mature fibril remodeling, leading to significant reduction in Aβ42 cytotoxicity. The potent inhibitory effect of brazilin was proven by an IC50 of 1.5 +/- 0.3 μM, which was smaller than that of (-)-epigallocatechin gallate in Phase III clinical trials and about one order of magnitude smaller than those of curcumin and resveratrol. Most importantly, it was found that brazilin redirected Aβ42 monomers and its mature fibrils into unstructured Aβ aggregates with some β-sheet structures, which could prevent both the primary nucleation and the fibril-catalyzed secondary nucleation. Molecular simulations demonstrated that brazilin inhibited Aβ42 fibrillogenesis by directly binding to Aβ42 species via hydrophobic interactions and hydrogen bonding and remodeled mature fibrils by disrupting the intermolecular salt bridge Asp23-Lys28 via hydrogen bonding. Both experimental and computational studies revealed a different working mechanism of brazilin from that of known inhibitors. These findings indicate that brazilin is of great potential as a neuroprotective and therapeutic agent for Alzheimer's disease.

  3. Subcellular localization of proteins in the anaerobic sulfate reducer Desulfovibrio vulgaris via SNAP-tag labeling and photoconversion

    Energy Technology Data Exchange (ETDEWEB)

    Gorur, A.; Leung, C. M.; Jorgens, D.; Tauscher, A.; Remis, J. P.; Ball, D. A.; Chhabra, S.; Fok, V.; Geller, J. T.; Singer, M.; Hazen, T. C.; Juba, T.; Elias, D.; Wall, J.; Biggin, M.; Downing, K. H.; Auer, M.

    2010-06-01

    Systems Biology studies the temporal and spatial 3D distribution of macromolecular complexes with the aim that such knowledge will allow more accurate modeling of biological function and will allow mathematical prediction of cellular behavior. However, in order to accomplish accurate modeling precise knowledge of spatial 3D organization and distribution inside cells is necessary. And while a number of macromolecular complexes may be identified by its 3D structure and molecular characteristics alone, the overwhelming number of proteins will need to be localized using a reporter tag. GFP and its derivatives (XFPs) have been traditionally employed for subcelllar localization using photoconversion approaches, but this approach cannot be taken for obligate anaerobic bacteria, where the intolerance towards oxygen prevents XFP approaches. As part of the GTL-funded PCAP project (now ENIGMA) genetic tools have been developed for the anaerobe sulfate reducer Desulfovibrio vulgaris that allow the high-throughput generation of tagged-protein mutant strains, with a focus on the commercially available SNAP-tag cell system (New England Biolabs, Ipswich, MA), which is based on a modified O6-alkylguanine-DNA alkyltransferase (AGT) tag, that has a dead-end reaction with a modified O6-benzylguanine (BG) derivative and has been shown to function under anaerobic conditions. After initial challenges with respect to variability, robustness and specificity of the labeling signal we have optimized the labeling. Over the last year, as a result of the optimized labeling protocol, we now obtain robust labeling of 20 out of 31 SNAP strains. Labeling for 13 strains were confirmed at least five times. We have also successfully performed photoconversion on 5 of these 13 strains, with distinct labeling patterns for different strains. For example, DsrC robustly localizes to the periplasmic portion of the inner membrane, where as a DNA-binding protein localizes to the center of the cell, where the

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

    Energy Technology Data Exchange (ETDEWEB)

    Song, Jun [Qilu Hospital, Shandong University, Jinan, Shandong (China); Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX (United States); Texas Heart Institute at St. Luke' s Episcopal Hospital, Houston, TX (United States); Ren, Pingping; Zhang, Lin [Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX (United States); Texas Heart Institute at St. Luke' s Episcopal Hospital, Houston, TX (United States); Wang, Xing Li [Qilu Hospital, Shandong University, Jinan, Shandong (China); Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX (United States); Texas Heart Institute at St. Luke' s Episcopal Hospital, Houston, TX (United States); Chen, Li [Qilu Hospital, Shandong University, Jinan, Shandong (China); Shen, Ying H., E-mail: hyshen@bcm.edu [Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX (United States); Texas Heart Institute at St. Luke' s Episcopal Hospital, Houston, TX (United States)

    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.

  6. Coloured Petri Nets

    CERN Document Server

    Jensen, Kurt

    2009-01-01

    Coloured Petri Nets (CPN) is a graphical language for modelling and validating concurrent and distributed systems, and other systems in which concurrency plays a major role. This book introduces the constructs of the CPN modelling language and presents the related analysis methods. It provides a comprehensive road map for the practical use of CPN.

  7. Safety nets or straitjackets?

    DEFF Research Database (Denmark)

    Ilsøe, Anna

    2012-01-01

    Does regulation of working hours at national and sector level impose straitjackets, or offer safety nets to employees seeking working time flexibility? This article compares legislation and collective agreements in the metal industries of Denmark, Germany and the USA. The industry has historically...

  8. Neuronal nets in robotics

    International Nuclear Information System (INIS)

    Jimenez Sanchez, Raul

    1999-01-01

    The paper gives a generic idea of the solutions that the neuronal nets contribute to the robotics. The advantages and the inconveniences are exposed that have regarding the conventional techniques. It also describe the more excellent applications as the pursuit of trajectories, the positioning based on images, the force control or of the mobile robots management, among others

  9. Net4Care platform

    DEFF Research Database (Denmark)

    2012-01-01

    , that in turn enables general practitioners and clinical staff to view observations. Use the menus above to explore the site's information resources. To get started, follow the short Hello, World! tutorial. The Net4Care project is funded by The Central Denmark Region and EU via Caretech Innovation....

  10. Coloured Petri Nets

    DEFF Research Database (Denmark)

    Jensen, Kurt; Kristensen, Lars Michael

    Coloured Petri Nets (CPN) is a graphical language for modelling and validating concurrent and distributed systems, and other systems in which concurrency plays a major role. The development of such systems is particularly challenging because of inherent intricacies like possible nondeterminism an...

  11. Game Theory .net.

    Science.gov (United States)

    Shor, Mikhael

    2003-01-01

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

  12. BacillusRegNet

    DEFF Research Database (Denmark)

    Misirli, Goksel; Hallinan, Jennifer; Röttger, Richard

    2014-01-01

    As high-throughput technologies become cheaper and easier to use, raw sequence data and corresponding annotations for many organisms are becoming available. However, sequence data alone is not sufficient to explain the biological behaviour of organisms, which arises largely from complex molecular...... the associated BacillusRegNet website (http://bacillus.ncl.ac.uk)....

  13. Boom Booom Net Radio

    DEFF Research Database (Denmark)

    Grimshaw, Mark Nicholas; Yong, Louisa; Dobie, Ian

    1999-01-01

    of an existing Internet radio station; Boom Booom Net Radio. Whilst necessity dictates some use of technology-related terminology, wherever possible we have endeavoured to keep such jargon to a minimum and to either explain it in the text or to provide further explanation in the appended glossary....

  14. Basal-bolus insulin therapy reduces maternal triglycerides in gestational diabetes without modifying cholesteryl ester transfer protein activity.

    Science.gov (United States)

    Olmos, Pablo R; Borzone, Gisella R

    2017-09-01

    Macrosomia in the offspring of overweight/obese mothers with glucose-controlled gestational diabetes mellitus (GDM) is due to excessive rise of maternal triglycerides (TG). We aimed to ascertain whether basal-bolus insulin therapy (BBIT), or other components of the treatment, could reduce TG in GDM. We studied the records of 131 singleton pregnancies with GDM, using stepwise multiple linear regression, Mann-Whitney, χ 2 , and Jonckheere-Terpstra tests. As maternal TG increased steadily during normal pregnancy, these were transformed as z-scores. The atherogenic index of plasma (AIP) was calculated as a measure of cholesteryl ester transfer protein activity. Multiple regression showed that only BBIT (but neither limitation of weight gain nor metformin) reduced maternal TG z-scores (P = 0.011). When the 131 pregnancies were split into two groups - without BBIT (n = 58; HbA1c = 5.3 ± 0.3%) and with BBIT (n = 73; HbA1c = 5.4 ± 0.6; P = 0.2005) - we observed that BBIT (n = 73) reduced maternal TG z-scores in a dose-related fashion (Jonckheere-Terpstra P = 0.03817). The atherogenic index of plasma remained within normal range in both groups. BBIT (but not weight gain control nor metformin) reduced maternal TG in mothers with glucose-controlled GDM. This beneficial effect of BBIT was not related to changes in the cholesteryl ester transfer protein activity. © 2017 Japan Society of Obstetrics and Gynecology.

  15. Monoacylated Cellular Prion Proteins Reduce Amyloid-β-Induced Activation of Cytoplasmic Phospholipase A2 and Synapse Damage

    Directory of Open Access Journals (Sweden)

    Ewan West

    2015-06-01

    Full Text Available Alzheimer’s disease (AD is a progressive neurodegenerative disease characterized by the accumulation of amyloid-β (Aβ and the loss of synapses. Aggregation of the cellular prion protein (PrPC by Aβ oligomers induced synapse damage in cultured neurons. PrPC is attached to membranes via a glycosylphosphatidylinositol (GPI anchor, the composition of which affects protein targeting and cell signaling. Monoacylated PrPC incorporated into neurons bound “natural Aβ”, sequestering Aβ outside lipid rafts and preventing its accumulation at synapses. The presence of monoacylated PrPC reduced the Aβ-induced activation of cytoplasmic phospholipase A2 (cPLA2 and Aβ-induced synapse damage. This protective effect was stimulus specific, as treated neurons remained sensitive to α-synuclein, a protein associated with synapse damage in Parkinson’s disease. In synaptosomes, the aggregation of PrPC by Aβ oligomers triggered the formation of a signaling complex containing the cPLA2.a process, disrupted by monoacylated PrPC. We propose that monoacylated PrPC acts as a molecular sponge, binding Aβ oligomers at the neuronal perikarya without activating cPLA2 or triggering synapse damage.

  16. Functions of innate and acquired immune system are reduced in domestic pigeons (Columba livia domestica) given a low protein diet

    Science.gov (United States)

    Mabuchi, Yuko; Frankel, Theresa L.

    2016-01-01

    Racing pigeons are exposed to and act as carriers of diseases. Dietary protein requirement for their maintenance has not been determined experimentally despite their being domesticated for over 7000 years. A maintenance nitrogen (protein) requirement (MNR) for pigeons was determined in a balance study using diets containing 6, 10 and 14% crude protein (CP). Then, the effects of feeding the diets were investigated to determine whether they were adequate to sustain innate and acquired immune functions. Nitrogen intake from the 6% CP diet was sufficient to maintain nitrogen balance and body weight in pigeons. However, the immune functions of phagocytosis, oxidative burst and lymphocyte proliferation in pigeons fed this diet were reduced compared with those fed 10 and 14% CP diets. Pigeons given the 6 and 10% CP diets had lower antibody titres following inoculation against Newcastle disease (ND) than those on the 14% CP diet. A confounding factor found on autopsy was the presence of intestinal parasites in some of the pigeons given the 6 and 10% CP diets; however, none of the pigeons used to measure MNR or acquired immunity to ND were infested with parasites. In conclusion, neither the 6 nor 10% CP diets adequately sustained acquired immune function of pigeons. PMID:27069640

  17. A carbohydrate-reduced high-protein diet acutely decreases postprandial and diurnal glucose excursions in type 2 diabetes patients

    DEFF Research Database (Denmark)

    Samkani, Amirsalar; Skytte, Mads J; Kandel, Daniel

    2018-01-01

    with T2DM treated with metformin only, fourteen male, with a median age of 65 (43-70) years, HbA1c of 6·5 % (47 mmol/l) (5·5-8·3 % (37-67 mmol/l)) and a BMI of 30 (sd 4·4) kg/m2 participated in the randomised, cross-over study. A carbohydrate-reduced high-protein (CRHP) diet was compared with an iso......The aim of the study was to assess whether a simple substitution of carbohydrate in the conventionally recommended diet with protein and fat would result in a clinically meaningful reduction in postprandial hyperglycaemia in subjects with type 2 diabetes mellitus (T2DM). In all, sixteen subjects......-energetic conventional diabetes (CD) diet. Macronutrient contents of the CRHP/CD diets consisted of 31/54 % energy from carbohydrate, 29/16 % energy from protein and 40/30 % energy from fat, respectively. Each diet was consumed on 2 consecutive days in a randomised order. Postprandial glycaemia, pancreatic and gut...

  18. Metabolic Characterization of Intact Cells Reveals Intracellular Amyloid Beta but Not Its Precursor Protein to Reduce Mitochondrial Respiration

    Science.gov (United States)

    Schaefer, Patrick M.; von Einem, Bjoern; Walther, Paul; Calzia, Enrico; von Arnim, Christine A. F.

    2016-01-01

    One hallmark of Alzheimer´s disease are senile plaques consisting of amyloid beta (Aβ), which derives from the processing of the amyloid precursor protein (APP). Mitochondrial dysfunction has been linked to the pathogenesis of Alzheimer´s disease and both Aβ and APP have been reported to affect mitochondrial function in isolated systems. However, in intact cells, considering a physiological localization of APP and Aβ, it is pending what triggers the mitochondrial defect. Thus, the aim of this study was to dissect the impact of APP versus Aβ in inducing mitochondrial alterations with respect to their subcellular localization. We performed an overexpression of APP or beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), increasing APP and Aβ levels or Aβ alone, respectively. Conducting a comprehensive metabolic characterization we demonstrate that only APP overexpression reduced mitochondrial respiration, despite lower extracellular Aβ levels compared to BACE overexpression. Surprisingly, this could be rescued by a gamma secretase inhibitor, oppositionally indicating an Aβ-mediated mitochondrial toxicity. Analyzing Aβ localization revealed that intracellular levels of Aβ and an increased spatial association of APP/Aβ with mitochondria are associated with reduced mitochondrial respiration. Thus, our data provide marked evidence for a prominent role of intracellular Aβ accumulation in Alzheimer´s disease associated mitochondrial dysfunction. Thereby it highlights the importance of the localization of APP processing and intracellular transport as a decisive factor for mitochondrial function, linking two prominent hallmarks of neurodegenerative diseases. PMID:28005987

  19. Active site mutations in yeast protein disulfide isomerase cause dithiothreitol sensitivity and a reduced rate of protein folding in the endoplasmic reticulum

    DEFF Research Database (Denmark)

    Holst, B; Tachibana, C; Winther, Jakob R.

    1997-01-01

    Aspects of protein disulfide isomerase (PDI) function have been studied in yeast in vivo. PDI contains two thioredoxin-like domains, a and a', each of which contains an active-site CXXC motif. The relative importance of the two domains was analyzed by rendering each one inactive by mutation to SGAS....... Such mutations had no significant effect on growth. The domains however, were not equivalent since the rate of folding of carboxypeptidase Y (CPY) in vivo was reduced by inactivation of the a domain but not the a' domain. To investigate the relevance of PDI redox potential, the G and H positions of each CGHC......-deleted strains overexpressing the yeast PDI homologue EUG1 are viable. Exchanging the wild-type Eug1p C(L/I)HS active site sequences for C(L/I)HC increased the growth rate significantly, however, further highlighting the importance of the oxidizing function for optimal growth....

  20. Inhibition of Cyclic Adenosine Monophosphate (cAMP-response Element-binding Protein (CREB-binding Protein (CBP/β-Catenin Reduces Liver Fibrosis in Mice

    Directory of Open Access Journals (Sweden)

    Yosuke Osawa

    2015-11-01

    Full Text Available Wnt/β-catenin is involved in every aspect of embryonic development and in the pathogenesis of many human diseases, and is also implicated in organ fibrosis. However, the role of β-catenin-mediated signaling on liver fibrosis remains unclear. To explore this issue, the effects of PRI-724, a selective inhibitor of the cAMP-response element-binding protein-binding protein (CBP/β-catenin interaction, on liver fibrosis were examined using carbon tetrachloride (CCl4- or bile duct ligation (BDL-induced mouse liver fibrosis models. Following repetitive CCl4 administrations, the nuclear translocation of β-catenin was observed only in the non-parenchymal cells in the liver. PRI-724 treatment reduced the fibrosis induced by CCl4 or BDL. C-82, an active form of PRI-724, inhibited the activation of isolated primary mouse quiescent hepatic stellate cells (HSCs and promoted cell death in culture-activated HSCs. During the fibrosis resolution period, an increase in F4/80+ CD11b+ and Ly6Clow CD11b+ macrophages was induced by CCl4 and was sustained for two weeks thereafter, even after having stopped CCl4 treatment. PRI-724 accelerated the resolution of CCl4-induced liver fibrosis, and this was accompanied by increased matrix metalloproteinase (MMP-9, MMP-2, and MMP-8 expression in intrahepatic leukocytes. In conclusion, targeting the CBP/β-catenin interaction may become a new therapeutic strategy in treating liver fibrosis.

  1. Brief pressure overload of the left ventricle reduces myocardial infarct size via activation of protein kinase C.

    Science.gov (United States)

    Tang, Chia-Yu; Lai, Chang-Chi; Chiang, Shu-Chiung; Tseng, Kuo-Wei; Huang, Cheng-Hsiung

    2015-09-01

    We have previously reported that brief pressure overload of the left ventricle reduced myocardial infarct (MI) size. However, the role of protein kinase C (PKC) remains uncertain. In this study, we investigated whether pressure overload reduces MI size by activating PKC. MI was induced by a 40-minute occlusion of the left anterior descending coronary artery and a 3-hour reperfusion in anesthetized Sprague-Dawley rats. MI size was determined using triphenyl tetrazolium chloride staining. Brief pressure overload was achieved by two 10-minute partial snarings of the ascending aorta, raising the systolic left ventricular pressure 50% above the baseline value. Ischemic preconditioning was elicited by two 10-minute coronary artery occlusions and 10-minute reperfusions. Dimethyl sulfoxide (vehicle) or calphostin C (0.1 mg/kg, a specific inhibitor of PKC) was administered intravenously as pretreatment. The MI size, expressed as the percentage of the area at risk, was significantly reduced in the pressure overload group and the ischemic preconditioning group (19.0 ± 2.9% and 18.7 ± 3.0% vs. 26.1 ± 2.6% in the control group, where p overload and ischemic preconditioning (25.2 ± 2.4% and 25.0 ± 2.3%, where p overload of the left ventricle reduced MI size. Since calphostin C significantly limited the decrease of MI size, our results suggested that brief pressure overload reduces MI size via activation of PKC. Copyright © 2015. Published by Elsevier Taiwan.

  2. Direct, simple derivatization of disulfide bonds in proteins with organic mercury in alkaline medium without any chemical pre-reducing agents

    Energy Technology Data Exchange (ETDEWEB)

    Campanella, Beatrice; Onor, Massimo [National Research Council of Italy, C.N.R., Istituto di Chimica dei Composti Organo Metallici-ICCOM- UOS Pisa, Area di Ricerca, Via G. Moruzzi 1, 56124 Pisa (Italy); Ferrari, Carlo [National Research Council of Italy, C.N.R., Istituto Nazionale di Ottica, INO-UOS Pisa, Area di Ricerca, Via G. Moruzzi 1, 56124 Pisa (Italy); D’Ulivo, Alessandro [National Research Council of Italy, C.N.R., Istituto di Chimica dei Composti Organo Metallici-ICCOM- UOS Pisa, Area di Ricerca, Via G. Moruzzi 1, 56124 Pisa (Italy); Bramanti, Emilia, E-mail: bramanti@pi.iccom.cnr.it [National Research Council of Italy, C.N.R., Istituto di Chimica dei Composti Organo Metallici-ICCOM- UOS Pisa, Area di Ricerca, Via G. Moruzzi 1, 56124 Pisa (Italy)

    2014-09-16

    Highlights: • A simple procedure for the derivatization of proteins disulfide bonds. • Cysteine groups in several proteins derivatised with pHMB in alkaline media. • 75–100% labelling of cysteines in proteins with pHMB. - Abstract: In this work we have studied the derivatization of protein disulfide bonds with p-Hydroxymercurybenzoate (pHMB) in strong alkaline medium without any preliminary reduction. The reaction has been followed by the determination of the protein–pHMB complex using size exclusion chromatography coupled to a microwave/UV mercury oxidation system for the on-line oxidation of free and protein-complexed pHMB and atomic fluorescence spectrometry (SEC–CVG–AFS) detection. The reaction has been optimized by an experimental design using lysozyme as a model protein and applied to several thiolic proteins. The proposed method reports, for the first time, that it is possible to label 75–100% cysteines of proteins and, thus, to determine thiolic proteins without the need of any reducing step to obtain reduced -SH groups before mercury labelling. We obtained a detection limit of 100 nmol L{sup −1} based on a signal-to-noise ratio of 3 for unbound and complexed pHMB, corresponding to a detection limit of proteins ranged between 3 and 360 nmol L{sup −1}, depending on the number of cysteines in the protein sequence.

  3. Direct, simple derivatization of disulfide bonds in proteins with organic mercury in alkaline medium without any chemical pre-reducing agents

    International Nuclear Information System (INIS)

    Campanella, Beatrice; Onor, Massimo; Ferrari, Carlo; D’Ulivo, Alessandro; Bramanti, Emilia

    2014-01-01

    Highlights: • A simple procedure for the derivatization of proteins disulfide bonds. • Cysteine groups in several proteins derivatised with pHMB in alkaline media. • 75–100% labelling of cysteines in proteins with pHMB. - Abstract: In this work we have studied the derivatization of protein disulfide bonds with p-Hydroxymercurybenzoate (pHMB) in strong alkaline medium without any preliminary reduction. The reaction has been followed by the determination of the protein–pHMB complex using size exclusion chromatography coupled to a microwave/UV mercury oxidation system for the on-line oxidation of free and protein-complexed pHMB and atomic fluorescence spectrometry (SEC–CVG–AFS) detection. The reaction has been optimized by an experimental design using lysozyme as a model protein and applied to several thiolic proteins. The proposed method reports, for the first time, that it is possible to label 75–100% cysteines of proteins and, thus, to determine thiolic proteins without the need of any reducing step to obtain reduced -SH groups before mercury labelling. We obtained a detection limit of 100 nmol L −1 based on a signal-to-noise ratio of 3 for unbound and complexed pHMB, corresponding to a detection limit of proteins ranged between 3 and 360 nmol L −1 , depending on the number of cysteines in the protein sequence

  4. SolNet

    DEFF Research Database (Denmark)

    Jordan, Ulrike; Vajen, Klaus; Bales, Chris

    2014-01-01

    -accompanying Master courses, placements of internships, and PhD scholarship projects. A new scholarship project, “SHINE”, was launched in autumn 2013 in the frame work of the Marie Curie program of the European Union (Initial Training Network, ITN). 13 PhD-scholarships on solar district heating, solar heat......SolNet, founded in 2006, is the first coordinated International PhD education program on Solar Thermal Engineering. The SolNet network is coordinated by the Institute of Thermal Engineering at Kassel University, Germany. The network offers PhD courses on solar heating and cooling, conference...... for industrial processes, as well as sorption stores and materials started in December 2013. Additionally, the project comprises a training program with five PhD courses and several workshops on solar thermal engineering that will be open also for other PhD students working in the field. The research projects...

  5. High levels of vitamin D in relation to reduced risk of schizophrenia with elevated C-reactive protein.

    Science.gov (United States)

    Zhu, Dao-min; Liu, Yong; Zhang, Ai-guo; Chu, Zhao-xue; Wu, Qing; Li, Hui; Ge, Jin-fang; Dong, Yi; Zhu, Peng

    2015-08-30

    There is growing evidence on the novel role of vitamin D in reducing inflammation. This study aimed to examine the hypothesis that vitamin D is inversely associated with C-reactive protein (CRP) in patients with schizophrenia, and high levels of vitamin D may be linked to reduced risk of schizophrenia with elevated CRP. Ninety-three patients with schizophrenia and 93 family-matched controls were recruited in this cross-sectional study. Plasma concentrations of CRP and 25-hydroxyvitamin D [25(OH)D] were measured using commercial kits. Information about demographic characteristics and clinic data were obtained by interviews or medical records. Mean levels of CRP and 25(OH)D were 43.3% higher and 26.7% lower for patients compared to controls, respectively. 25(OH)D were inversely associated with CRP in the patients, but not in the controls. The proportions of patients significantly increased with increasing quartiles of CRP, while significantly decreased with increasing quartiles of 25(OH)D. Among individuals with high CRP, participants with high 25(OH)D have significantly lower proportion (adjusted OR =0.217, 95% CI 0.063, 0.751) of schizophrenia compared to those with low 25(OH)D. The evidence suggested that high levels of vitamin D may be linked to reduced risk of schizophrenia with elevated CRP. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Activation of PAD4 in NET formation

    Directory of Open Access Journals (Sweden)

    Amanda eRohrbach

    2012-11-01

    Full Text Available Peptidyl arginine deiminases, or PADs, convert arginine residues to the non-ribosomally encoded amino acid citrulline in a variety of protein substrates. PAD4 is expressed in granulocytes and is essential for the formation of neutrophil extracellular traps (NETs via PAD4-mediated histone citrullination. Citrullination of histones is thought to promote NET formation by inducing chromatin decondensation and facilitating the expulsion of chromosomal DNA that is coated with antimicrobial molecules. Numerous stimuli have been reported to lead to PAD4 activation and NET formation. However, how this signaling process proceeds and how PAD4 becomes activated in cells is largely unknown. Herein, we describe the various stimuli and signaling pathways that have been implicated in PAD4 activation and NET formation, including the role of reactive oxygen species generation. To provide a foundation for the above discussion, we first describe PAD4 structure and function, and how these studies led to the development of PAD-specific inhibitors. A comprehensive survey of the receptors and signaling pathways that regulate PAD4 activation will be important for our understanding of innate immunity, and the identification of signaling intermediates in PAD4 activation may also lead to the generation of pharmaceuticals to target NET-related pathogenesis.

  7. Reduced amyloidogenic processing of the amyloid beta-protein precursor by the small-molecule Differentiation Inducing Factor-1.

    Science.gov (United States)

    Myre, Michael A; Washicosky, Kevin; Moir, Robert D; Tesco, Giuseppina; Tanzi, Rudolph E; Wasco, Wilma

    2009-04-01

    The detection of cell cycle proteins in Alzheimer's disease (AD) brains may represent an early event leading to neurodegeneration. To identify cell cycle modifiers with anti-Abeta properties, we assessed the effect of Differentiation-Inducing Factor-1 (DIF-1), a unique, small-molecule from Dictyostelium discoideum, on the proteolysis of the amyloid beta-protein precursor (APP) in a variety of different cell types. We show that DIF-1 slows cell cycle progression through G0/G1 that correlates with a reduction in cyclin D1 protein levels. Western blot analysis of DIF-treated cells and conditioned medium revealed decreases in the levels of secreted APP, mature APP, and C-terminal fragments. Assessment of conditioned media by sandwich ELISA showed reduced levels of Abeta40 and Abeta42, also demonstrating that treatment with DIF-1 effectively decreases the ratio of Abeta42 to Abeta40. In addition, DIF-1 significantly diminished APP phosphorylation at residue T668. Interestingly, site-directed mutagenesis of APP residue Thr668 to alanine or glutamic acid abolished the effect of DIF-1 on APP proteolysis and restored secreted levels of Abeta. Finally, DIF-1 prevented the accumulation of APP C-terminal fragments induced by the proteasome inhibitor lactacystin, and calpain inhibitor N-acetyl-leucyl-leucyl-norleucinal (ALLN). Our findings suggest that DIF-1 affects G0/G1-associated amyloidogenic processing of APP by a gamma-secretase-, proteasome- and calpain-insensitive pathway, and that this effect requires the presence of residue Thr668.

  8. Reduced amyloidogenic processing of the amyloid β-protein precursor by the small-molecule Differentiation Inducing Factor-1

    Science.gov (United States)

    Myre, Michael A.; Washicosky, Kevin; Moir, Robert D.; Tesco, Giuseppina; Tanzi, Rudolph E.; Wasco, Wilma

    2013-01-01

    The detection of cell cycle proteins in Alzheimer’s disease (AD) brains may represent an early event leading to neurodegeneration. To identify cell cycle modifiers with anti-Aβ properties, we assessed the effect of Differentiation-Inducing Factor-1 (DIF-1), a unique, small-molecule from Dictyostelium discoideum, on the proteolysis of the amyloid β-protein precursor (APP) in a variety of different cell types. We show that DIF-1 slows cell cycle progression through G0/G1 that correlates with a reduction in cyclin D1 protein levels. Western blot analysis of DIF-treated cells and conditioned medium revealed decreases in the levels of secreted APP, mature APP, and C-terminal fragments. Assessment of conditioned media by sandwich ELISA showed reduced levels of Aβ40 and Aβ42, also demonstrating that treatment with DIF-1 effectively decreases the ratio of Aβ42 to Aβ40. In addition, DIF-1 significantly diminished APP phosphorylation at residue T668. Interestingly, site-directed mutagenesis of APP residue Thr668 to alanine or glutamic acid abolished the effect of DIF-1 on APP proteolysis and restored secreted levels of Aβ. Finally, DIF-1 prevented the accumulation of APP C-terminal fragments induced by the proteasome inhibitor lactacystin, and calpain inhibitor N-acetyl-leucyl-leucyl-norleucinal (ALLN). Our findings suggest that DIF-1 affects G0/G1-associated amyloidogenic processing of APP by a γ-secretase-, proteasome- and calpain-insensitive pathway, and that this effect requires the presence of residue Thr668. PMID:19154786

  9. Net one, net two: the primary care network income statement.

    Science.gov (United States)

    Halley, M D; Little, A W

    1999-10-01

    Although hospital-owned primary care practices have been unprofitable for most hospitals, some hospitals are achieving competitive advantage and sustainable practice operations. A key to the success of some has been a net income reporting tool that separates practice operating expenses from the costs of creating and operating a network of practices to help healthcare organization managers, physicians, and staff to identify opportunities to improve the network's financial performance. This "Net One, Net Two" reporting allows operations leadership to be held accountable for Net One expenses and strategic leadership to be held accountable for Net Two expenses.

  10. Proof Nets for Lambek Calculus

    NARCIS (Netherlands)

    Roorda, Dirk

    1992-01-01

    The proof nets of linear logic are adapted to the non-commutative Lambek calculus. A different criterion for soundness of proof nets is given, which gives rise to new algorithms for proof search. The order sensitiveness of the Lambek calculus is reflected by the planarity condition on proof nets;

  11. Net metering: zero electricity bill

    International Nuclear Information System (INIS)

    Mangi, A.; Khan, Z.

    2011-01-01

    Worldwide move towards renewable energy sources, environmental concerns and decentralization of the power sector have made net metering an attractive option for power generation at small scale. This paper discusses the net metering, economical issues of renewable sources in Pakistan, technical aspects, installation suitability according to varying terrain, existing utility rules and formulation of legislation for net metering making it economically attractive. (author)

  12. The Net Advance of Physics

    Science.gov (United States)

    THE NET ADVANCE OF PHYSICS Review Articles and Tutorials in an Encyclopædic Format Established 1995 [Link to MIT] Computer support for The Net Advance of Physics is furnished by The Massachusetts Newest Additions SPECIAL FEATURES: Net Advance RETRO: Nineteenth Century Physics History of Science

  13. Dietary supplementation of branched-chain amino acids increases muscle net amino acid fluxes through elevating their substrate availability and intramuscular catabolism in young pigs.

    Science.gov (United States)

    Zheng, Liufeng; Zuo, Fangrui; Zhao, Shengjun; He, Pingli; Wei, Hongkui; Xiang, Quanhang; Pang, Jiaman; Peng, Jian

    2017-04-01

    Branched-chain amino acids (BCAA) have been clearly demonstrated to have anabolic effects on muscle protein synthesis. However, little is known about their roles in the regulation of net AA fluxes across skeletal muscle in vivo. This study was aimed to investigate the effect and related mechanisms of dietary supplementation of BCAA on muscle net amino acid (AA) fluxes using the hindlimb flux model. In all fourteen 4-week-old barrows were fed reduced-protein diets with or without supplemental BCAA for 28 d. Pigs were implanted with carotid arterial, femoral arterial and venous catheters, and fed once hourly with intraarterial infusion of p-amino hippurate. Arterial and venous plasma and muscle samples were obtained for the measurement of AA, branched-chain α-keto acids (BCKA) and 3-methylhistidine (3-MH). Metabolomes of venous plasma were determined by HPLC-quadrupole time-of-flight-MS. BCAA-supplemented group showed elevated muscle net fluxes of total essential AA, non-essential AA and AA. As for individual AA, muscle net fluxes of each BCAA and their metabolites (alanine, glutamate and glutamine), along with those of histidine, methionine and several functional non-essential AA (glycine, proline and serine), were increased by BCAA supplementation. The elevated muscle net AA fluxes were associated with the increase in arterial and intramuscular concentrations of BCAA and venous metabolites including BCKA and free fatty acids, and were also related to the decrease in the intramuscular concentration of 3-MH. Correlation analysis indicated that muscle net AA fluxes are highly and positively correlated with arterial BCAA concentrations and muscle net BCKA production. In conclusion, supplementing BCAA to reduced-protein diet increases the arterial concentrations and intramuscular catabolism of BCAA, both of which would contribute to an increase of muscle net AA fluxes in young pigs.

  14. Reduced Contractility and Motility of Prostatic Cancer-Associated Fibroblasts after Inhibition of Heat Shock Protein 90

    Directory of Open Access Journals (Sweden)

    Alex Henke

    2016-08-01

    Full Text Available Background: Prostate cancer-associated fibroblasts (CAF can stimulate malignant progression and invasion of prostatic tumour cells via several mechanisms including those active in extracellular matrix; Methods: We isolated CAF from prostate cancer patients of Gleason Score 6–10 and confirmed their cancer-promoting activity using an in vivo tumour reconstitution assay comprised of CAF and BPH1 cells. We tested the effects of heat shock protein 90 (HSP90 inhibitors upon reconstituted tumour growth in vivo. Additionally, CAF contractility was measured in a 3D collagen contraction assay and migration was measured by scratch assay; Results: HSP90 inhibitors dipalmitoyl-radicicol and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG reduced tumour size and proliferation in CAF/BPH1 reconstituted tumours in vivo. We observed that the most contractile CAF were derived from patients with lower Gleason Score and of younger age compared with the least contractile CAF. HSP90 inhibitors radicicol and 17-DMAG inhibited contractility and reduced the migration of CAF in scratch assays. Intracellular levels of HSP70 and HSP90 were upregulated upon treatment with HSP90 inhibitors. Inhibition of HSP90 also led to a specific increase in transforming growth factor beta 2 (TGFβ2 levels in CAF; Conclusions: We suggest that HSP90 inhibitors act not only upon tumour cells, but also on CAF in the tumour microenvironment.

  15. Cromolyn Reduces Levels of the Alzheimer's Disease-Associated Amyloid β-Protein by Promoting Microglial Phagocytosis.

    Science.gov (United States)

    Zhang, Can; Griciuc, Ana; Hudry, Eloise; Wan, Yu; Quinti, Luisa; Ward, Joseph; Forte, Angela M; Shen, Xunuo; Ran, ChongZhao; Elmaleh, David R; Tanzi, Rudolph E

    2018-01-18

    Amyloid-beta protein (Aβ) deposition is a pathological hallmark of Alzheimer's disease (AD). Aβ deposition triggers both pro-neuroinflammatory microglial activation and neurofibrillary tangle formation. Cromolyn sodium is an asthma therapeutic agent previously shown to reduce Aβ levels in transgenic AD mouse brains after one-week of treatment. Here, we further explored these effects as well as the mechanism of action of cromolyn, alone, and in combination with ibuprofen in APP Swedish -expressing Tg2576 mice. Mice were treated for 3 months starting at 5 months of age, when the earliest stages of β-amyloid deposition begin. Cromolyn, alone, or in combination with ibuprofen, almost completely abolished longer insoluble Aβ species, i.e. Aβ40 and Aβ42, but increased insoluble Aβ38 levels. In addition to its anti-aggregation effects on Aβ, cromolyn, alone, or plus ibuprofen, but not ibuprofen alone, increased microglial recruitment to, and phagocytosis of β-amyloid deposits in AD mice. Cromolyn also promoted Aβ42 uptake in microglial cell-based assays. Collectively, our data reveal robust effects of cromolyn, alone, or in combination with ibuprofen, in reducing aggregation-prone Aβ levels and inducing a neuroprotective microglial activation state favoring Aβ phagocytosis versus a pro-neuroinflammatory state. These findings support the use of cromolyn, alone, or with ibuprofen, as a potential AD therapeutic.

  16. Master Robotic Net

    Directory of Open Access Journals (Sweden)

    Vladimir Lipunov

    2010-01-01

    Full Text Available The main goal of the MASTER-Net project is to produce a unique fast sky survey with all sky observed over a single night down to a limiting magnitude of 19-20. Such a survey will make it possible to address a number of fundamental problems: search for dark energy via the discovery and photometry of supernovae (including SNIa, search for exoplanets, microlensing effects, discovery of minor bodies in the Solar System, and space-junk monitoring. All MASTER telescopes can be guided by alerts, and we plan to observe prompt optical emission from gamma-ray bursts synchronously in several filters and in several polarization planes.

  17. Near-Net Forging Technology Demonstration Program

    Science.gov (United States)

    Hall, I. Keith

    1996-01-01

    Significant advantages in specific mechanical properties, when compared to conventional aluminum (Al) alloys, make aluminum-lithium (Al-Li) alloys attractive candidate materials for use in cryogenic propellant tanks and dry bay structures. However, the cost of Al-Li alloys is typically five times that of 2219 aluminum. If conventional fabrication processes are employed to fabricate launch vehicle structure, the material costs will restrict their utilization. In order to fully exploit the potential cost and performance benefits of Al-Li alloys, it is necessary that near-net manufacturing methods be developed to off-set or reduce raw material costs. Near-net forging is an advanced manufacturing method that uses elevated temperature metal movement (forging) to fabricate a single piece, near-net shape, structure. This process is termed 'near-net' because only a minimal amount of post-forge machining is required. The near-net forging process was developed to reduce the material scrap rate (buy-to-fly ratio) and fabrication costs associated with conventional manufacturing methods. The goal for the near-net forging process, when mature, is to achieve an overall cost reduction of approximately 50 percent compared with conventional manufacturing options for producing structures fabricated from Al-Li alloys. This NASA Marshall Space Flight Center (MSFC) sponsored program has been a part of a unique government / industry partnership, coordinated to develop and demonstrate near-net forging technology. The objective of this program was to demonstrate scale-up of the near-net forging process. This objective was successfully achieved by fabricating four integrally stiffened, 170- inch diameter by 20-inch tall, Al-Li alloy 2195, Y-ring adapters. Initially, two 2195 Al-Li ingots were converted and back extruded to produce four cylindrical blockers. Conventional ring rolling of the blockers was performed to produce ring preforms, which were then contour ring rolled to produce

  18. Activation of PKA and Epac proteins by cyclic AMP depletes intracellular calcium stores and reduces calcium availability for vasoconstriction.

    Science.gov (United States)

    Cuíñas, Andrea; García-Morales, Verónica; Viña, Dolores; Gil-Longo, José; Campos-Toimil, Manuel

    2016-06-15

    We investigated the implication of PKA and Epac proteins in the endothelium-independent vasorelaxant effects of cyclic AMP (cAMP). Cytosolic Ca(2+) concentration ([Ca(2+)]c) was measured by fura-2 imaging in rat aortic smooth muscle cells (RASMC). Contraction-relaxation experiments were performed in rat aortic rings deprived of endothelium. In extracellular Ca(2+)-free solution, cAMP-elevating agents induced an increase in [Ca(2+)]c in RASMC that was reproduced by PKA and Epac activation and reduced after depletion of intracellular Ca(2+) reservoirs. Arginine-vasopressin (AVP)-evoked increase of [Ca(2+)]c and store-operated Ca(2+) entry (SOCE) were inhibited by cAMP-elevating agents, PKA or Epac activation in these cells. In aortic rings, the contractions induced by phenylephrine in absence of extracellular Ca(2+) were inhibited by cAMP-elevating agents, PKA or Epac activation. In these conditions, reintroduction of Ca(2+) induced a contraction that was inhibited by cAMP-elevating agents, an effect reduced by PKA inhibition and reproduced by PKA or Epac activators. Our results suggest that increased cAMP depletes intracellular, thapsigargin-sensitive Ca(2+) stores through activation of PKA and Epac in RASMC, thus reducing the amount of Ca(2+) released by IP3-generating agonists during the contraction of rat aorta. cAMP rise also inhibits the contraction induced by depletion of intracellular Ca(2+), an effect mediated by reduction of SOCE after PKA or Epac activation. Both effects participate in the cAMP-induced endothelium-independent vasorelaxation. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Electrophysiology of glioma: a Rho GTPase-activating protein reduces tumor growth and spares neuron structure and function.

    Science.gov (United States)

    Vannini, Eleonora; Olimpico, Francesco; Middei, Silvia; Ammassari-Teule, Martine; de Graaf, Erik L; McDonnell, Liam; Schmidt, Gudula; Fabbri, Alessia; Fiorentini, Carla; Baroncelli, Laura; Costa, Mario; Caleo, Matteo

    2016-12-01

    Glioblastomas are the most aggressive type of brain tumor. A successful treatment should aim at halting tumor growth and protecting neuronal cells to prevent functional deficits and cognitive deterioration. Here, we exploited a Rho GTPase-activating bacterial protein toxin, cytotoxic necrotizing factor 1 (CNF1), to interfere with glioma cell growth in vitro and vivo. We also investigated whether this toxin spares neuron structure and function in peritumoral areas. We performed a microarray transcriptomic and in-depth proteomic analysis to characterize the molecular changes triggered by CNF1 in glioma cells. We also examined tumor cell senescence and growth in vehicle- and CNF1-treated glioma-bearing mice. Electrophysiological and morphological techniques were used to investigate neuronal alterations in peritumoral cortical areas. Administration of CNF1 triggered molecular and morphological hallmarks of senescence in mouse and human glioma cells in vitro. CNF1 treatment in vivo induced glioma cell senescence and potently reduced tumor volumes. In peritumoral areas of glioma-bearing mice, neurons showed a shrunken dendritic arbor and severe functional alterations such as increased spontaneous activity and reduced visual responsiveness. CNF1 treatment enhanced dendritic length and improved several physiological properties of pyramidal neurons, demonstrating functional preservation of the cortical network. Our findings demonstrate that CNF1 reduces glioma volume while at the same time maintaining the physiological and structural properties of peritumoral neurons. These data indicate a promising strategy for the development of more effective antiglioma therapies. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Limitations of shallow nets approximation.

    Science.gov (United States)

    Lin, Shao-Bo

    2017-10-01

    In this paper, we aim at analyzing the approximation abilities of shallow networks in reproducing kernel Hilbert spaces (RKHSs). We prove that there is a probability measure such that the achievable lower bound for approximating by shallow nets can be realized for all functions in balls of reproducing kernel Hilbert space with high probability, which is different with the classical minimax approximation error estimates. This result together with the existing approximation results for deep nets shows the limitations for shallow nets and provides a theoretical explanation on why deep nets perform better than shallow nets. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Shielding calculations for NET

    International Nuclear Information System (INIS)

    Verschuur, K.A.; Hogenbirk, A.

    1991-05-01

    In the European Fusion Technology Programme there is only a small activity on research and development for fusion neutronics. Never-the-less, looking further than blanket design now, as ECN is getting involved in design of radiation shields for the coils and biological shields, it becomes apparent that fusion neutronics as a whole still needs substantial development. Existing exact codes for calculation of complex geometries like MCNP and DORT/TORT are put over the limits of their numerical capabilities, whilst approximate codes for complex geometries like FURNACE and MERCURE4 are put over the limits of their modelling capabilities. The main objective of this study is just to find out how far we can get with existing codes in obtaining reliable values for the radiation levels inside and outside the cryostat/shield during operation and after shut-down. Starting with a 1D torus model for preliminary parametric studies, more dimensional approximation of the torus or parts of it including the main heterogeneities should follow. Regular contacts with the NET-Team are kept, to be aware of main changes in NET design that might affect our calculation models. Work on the contract started 1 July 1990. The technical description of the contract is given. (author). 14 refs.; 4 figs.; 1 tab

  2. Engineering properties of fibres from waste fishing nets

    DEFF Research Database (Denmark)

    Bertelsen, Ida Maria Gieysztor; Ottosen, Lisbeth M.

    2016-01-01

    This study is part of the international project Circular Ocean and focuses on reducing marine plastic waste within the Northern Periphery and Arctic (NPA) region by developing new sustainable solutions for the reuse of discarded waste fishing nets. Recycled plastic fibres from waste fishing nets...

  3. 42 CFR 422.382 - Minimum net worth amount.

    Science.gov (United States)

    2010-10-01

    ... that CMS considers appropriate to reduce, control or eliminate start-up administrative costs. (b) After... section. (c) Calculation of the minimum net worth amount—(1) Cash requirement. (i) At the time of application, the organization must maintain at least $750,000 of the minimum net worth amount in cash or cash...

  4. Sublingual immunization with the phosphate-binding-protein (PstS) reduces oral colonization by Streptococcus mutans.

    Science.gov (United States)

    Ferreira, E L; Batista, M T; Cavalcante, R C M; Pegos, V R; Passos, H M; Silva, D A; Balan, A; Ferreira, L C S; Ferreira, R C C

    2016-10-01

    Bacterial ATP-binding cassette (ABC) transporters play a crucial role in the physiology and pathogenicity of different bacterial species. Components of ABC transporters have also been tested as target antigens for the development of vaccines against different bacterial species, such as those belonging to the Streptococcus genus. Streptococcus mutans is the etiological agent of dental caries, and previous studies have demonstrated that deletion of the gene encoding PstS, the substrate-binding component of the phosphate uptake system (Pst), reduced the adherence of the bacteria to abiotic surfaces. In the current study, we generated a recombinant form of the S. mutans PstS protein (rPstS) with preserved structural features, and we evaluated the induction of antibody responses in mice after sublingual mucosal immunization with a formulation containing the recombinant protein and an adjuvant derived from the heat-labile toxin from enterotoxigenic Escherichia coli strains. Mice immunized with rPstS exhibited systemic and secreted antibody responses, measured by the number of immunoglobulin A-secreting cells in draining lymph nodes. Serum antibodies raised in mice immunized with rPstS interfered with the adhesion of bacteria to the oral cavity of naive mice challenged with S. mutans. Similarly, mice actively immunized with rPstS were partially protected from oral colonization after challenge with the S. mutans NG8 strain. Therefore, our results indicate that S. mutans PstS is a potential target antigen capable of inducing specific and protective antibody responses after sublingual administration. Overall, these observations raise interesting perspectives for the development of vaccines to prevent dental caries. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Science.gov (United States)

    Wang, Jing; Yu, ShuXia; Du, YuYue

    2015-01-01

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

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

    Science.gov (United States)

    Wang, Jing; Yu, ShuXia; Du, YuYue

    2015-01-01

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

  7. Skeletal muscle neuronal nitric oxide synthase micro protein is reduced in people with impaired glucose homeostasis and is not normalized by exercise training.

    Science.gov (United States)

    Bradley, Scott J; Kingwell, Bronwyn A; Canny, Benedict J; McConell, Glenn K

    2007-10-01

    Skeletal muscle inducible nitric oxide synthase (NOS) protein is greatly elevated in people with type 2 diabetes mellitus, whereas endothelial NOS is at normal levels. Diabetic rat studies suggest that skeletal muscle neuronal NOS (nNOS) micro protein expression may be reduced in human insulin resistance. The aim of this study was to determine whether skeletal muscle nNOSmicro protein expression is reduced in people with impaired glucose homeostasis and whether exercise training increases nNOSmicro protein expression in these individuals because exercise training increases skeletal muscle nNOSmicro protein in rats. Seven people with type 2 diabetes mellitus or prediabetes (impaired fasting glucose and/or impaired glucose tolerance) and 7 matched (sex, age, fitness, body mass index, blood pressure, lipid profile) healthy controls aged 36 to 60 years participated in this study. Vastus lateralis muscle biopsies for nNOSmicro protein determination were obtained, aerobic fitness was measured (peak pulmonary oxygen uptake [Vo(2) peak]), and glucose tolerance and insulin homeostasis were assessed before and after 1 and 4 weeks of cycling exercise training (60% Vo(2) peak, 50 minutes x 5 d wk(-1)). Skeletal muscle nNOSmicro protein was significantly lower (by 32%) in subjects with type 2 diabetes mellitus or prediabetes compared with that in controls before training (17.7 +/- 1.2 vs 26.2 +/- 3.4 arbitrary units, P glucose homeostasis have reduced skeletal muscle nNOSmicro protein content. However, because exercise training improves insulin sensitivity without influencing skeletal muscle nNOSmicro protein expression, it seems that changes in skeletal muscle nNOSmicro protein are not central to the control of insulin sensitivity in humans and therefore may be a consequence rather than a cause of diabetes.

  8. Pristanic acid provokes lipid, protein, and DNA oxidative damage and reduces the antioxidant defenses in cerebellum of young rats.

    Science.gov (United States)

    Busanello, Estela Natacha Brandt; Lobato, Vannessa Gonçalves Araujo; Zanatta, Ângela; Borges, Clarissa Günther; Tonin, Anelise Miotti; Viegas, Carolina Maso; Manfredini, Vanusa; Ribeiro, César Augusto João; Vargas, Carmen Regla; de Souza, Diogo Onofre Gomes; Wajner, Moacir

    2014-12-01

    Zellweger syndrome (ZS) and some peroxisomal diseases are severe inherited disorders mainly characterized by neurological symptoms and cerebellum abnormalities, whose pathogenesis is poorly understood. Biochemically, these diseases are mainly characterized by accumulation of pristanic acid (Prist) and other fatty acids in the brain and other tissues. In this work, we evaluated the in vitro influence of Prist on redox homeostasis by measuring lipid, protein, and DNA damage, as well as the antioxidant defenses and the activities of aconitase and α-ketoglutarate dehydrogenase in cerebellum of 30-day-old rats. The effect of Prist on DNA damage was also evaluated in blood of these animals. Some parameters were also evaluated in cerebellum from neonatal rats and in cerebellum neuronal cultures. Prist significantly increased malondialdehyde (MDA) levels and carbonyl formation and reduced sulfhydryl content and glutathione (GSH) concentrations in cerebellum of young rats. It also caused DNA strand damage in cerebellum and induced a high micronuclei frequency in blood. On the other hand, this fatty acid significantly reduced α-ketoglutarate dehydrogenase and aconitase activities in rat cerebellum. We also verified that Prist-induced increase of MDA levels was totally prevented by melatonin and attenuated by α-tocopherol but not by the nitric oxide synthase inhibitor N(ω)-nitro-L-arginine methyl ester, indicating the involvement of reactive oxygen species in this effect. Cerebellum from neonate rats also showed marked alterations of redox homeostasis, including an increase of MDA levels and a decrease of sulfhydryl content and GSH concentrations elicited by Prist. Finally, Prist provoked an increase of dichlorofluorescein (DCFH) oxidation in cerebellum-cultivated neurons. Our present data indicate that Prist compromises redox homeostasis in rat cerebellum and blood and inhibits critical enzymes of the citric acid cycle that are susceptible to free radical attack. The

  9. Art/Net/Work

    DEFF Research Database (Denmark)

    Andersen, Christian Ulrik; Lindstrøm, Hanne

    2006-01-01

    The seminar Art|Net|Work deals with two important changes in our culture. On one side, the network has become essential in the latest technological development. The Internet has entered a new phase, Web 2.0, including the occurrence of as ‘Wiki’s’, ‘Peer-2-Peer’ distribution, user controlled...... on the ‘network’ itself as a phenomenon and are often using technological networks as a mean of production and distribution. This changes the artistic practice and the distribution channels of art works – and the traditional notions of ‘work’, ‘origin’ and ‘rights’ are increasingly perceived as limiting...... the praxis of the artist. We see different kinds of interventions and activism (including ‘hacktivism’) using the network as a way of questioning the invisible rules that govern public and semi-public spaces. Who ‘owns’ them? What kind of social relationships do they generate? On what principle...

  10. Net4Care

    DEFF Research Database (Denmark)

    Christensen, Henrik Bærbak; Hansen, Klaus Marius

    2012-01-01

    , health centers are getting larger and more distributed, and the number of healthcare professionals does not follow the trend in chronic diseases. All of this leads to a need for telemedical and mobile health applications. In a Danish context, these applications are often developed through local...... (innovative) initiatives with little regards for national and global (standardization) initiatives. A reason for this discrepancy is that the software architecture for national (and global) systems and standards are hard to understand, hard to develop systems based on, and hard to deploy. To counter this, we...... propose a software ecosystem approach for telemedicine applications, providing a framework, Net4Care, encapsulating national/global design decisions with respect to standardization while allowing for local innovation. This paper presents an analysis of existing systems, of requirements for a software...

  11. High-Pressure-High-Temperature Processing Reduces Maillard Reaction and Viscosity in Whey Protein-Sugar Solutions

    NARCIS (Netherlands)

    Avila Ruiz, Geraldine; Xi, Bingyan; Minor, Marcel; Sala, Guido; Boekel, van Tiny; Fogliano, Vincenzo; Stieger, Markus

    2016-01-01

    The aim of the study was to determine the influence of pressure in high-pressure-high-temperature (HPHT) processing on Maillard reactions and protein aggregation of whey protein-sugar solutions. Solutions of whey protein isolate containing either glucose or trehalose at pH 6, 7, and 9 were

  12. Surfactant protein-B 121ins2 heterozygosity, reduced pulmonary function, and chronic obstructive pulmonary disease in smokers

    DEFF Research Database (Denmark)

    Bækvad-Hansen, Marie; Dahl, Morten; Tybjaerg-Hansen, Anne

    2010-01-01

    Hereditary surfactant protein-B deficiency is an autosomal recessive disorder that causes fatal respiratory distress syndrome in newborns. Seventy percent of the cases of hereditary surfactant protein-B deficiency are caused by homozygosity for the 121ins2 mutation in the surfactant protein-B gen...

  13. A High-Protein Diet Reduces Weight Gain, Decreases Food Intake, Decreases Liver Fat Deposition, and Improves Markers of Muscle Metabolism in Obese Zucker Rats.

    Science.gov (United States)

    French, William W; Dridi, Sami; Shouse, Stephanie A; Wu, Hexirui; Hawley, Aubree; Lee, Sun-Ok; Gu, Xuan; Baum, Jamie I

    2017-06-08

    A primary factor in controlling and preventing obesity is through dietary manipulation. Diets higher in protein have been shown to improve body composition and metabolic health during weight loss. The objective of this study was to examine the effects of a high-protein diet versus a moderate-protein diet on muscle, liver and fat metabolism and glucose regulation using the obese Zucker rat. Twelve-week old, male, Zucker (fa/fa) and lean control (Fa/fa) rats were randomly assigned to either a high-protein (40% energy) or moderate-protein (20% energy) diet for 12 weeks, with a total of four groups: lean 20% protein (L20; n = 8), lean 40% protein (L40; n = 10), obese 20% protein (O20; n = 8), and obese 40% protein (O40; n = 10). At the end of 12 weeks, animals were fasted and euthanized. There was no difference in food intake between L20 and L40. O40 rats gained less weight and had lower food intake ( p diet rats, respectively. O40 had decreased skeletal muscle mechanistic target of rapamycin complex 1 (mTORC1) phosphorylation and peroxisome proliferator-activated receptor gamma (PPARγ) mRNA expression compared to O20 ( p protein kinase (AMPK), eukaryotic translation initiation factor 4E binding protein 1 (4EBP1), protein kinase B (Akt) or p70 ribosomal S6 kinase (p70S6K) phosphorylation. The data suggest that high-protein diets have the potential to reduce weight gain and alter metabolism, possibly through regulation of an mTORC1-dependent pathway in skeletal muscle.

  14. Label-free and direct detection of C-reactive protein using reduced graphene oxide-nanoparticle hybrid impedimetric sensor.

    Science.gov (United States)

    Yagati, Ajay Kumar; Pyun, Jae-Chul; Min, Junhong; Cho, Sungbo

    2016-02-01

    For label-free and direct detection of C-reactive protein (CRP), an impedimetric sensor based on an indium tin oxide (ITO) electrode array functionalized with reduced graphene oxide-nanoparticle (rGO-NP) hybrid was fabricated and evaluated. Analytical measurements were performed to examine the properties of rGO-NP-modified ITO microelectrodes and to determine the influence upon sensory performance of using nanostructures modified for antibody immobilization and for recognition of CRP binding events. Impedimetric measurements in the presence of the redox couple [Fe(CN)6](3-/4-) showed significant changes in charge transfer resistance upon binding of CRP. The impedance measurements were highly target specific, linear with logarithmic CRP concentrations in PBS and human serum across a 1 ng mL(-1) and 1000 ng mL(-1) range and associated with a detection limits of 0.06 and 0.08 ng mL(-1) respectively. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Loss of monocyte chemoattractant protein-1 alters macrophage polarization and reduces NFκB activation in the foreign body response.

    Science.gov (United States)

    Moore, Laura Beth; Sawyer, Andrew J; Charokopos, Antonios; Skokos, Eleni A; Kyriakides, Themis R

    2015-01-01

    Implantation of biomaterials elicits a foreign body response characterized by fusion of macrophages to form foreign body giant cells and fibrotic encapsulation. Studies of the macrophage polarization involved in this response have suggested that alternative (M2) activation is associated with more favorable outcomes. Here we investigated this process in vivo by implanting mixed cellulose ester filters or polydimethylsiloxane disks in the peritoneal cavity of wild-type (WT) and monocyte chemoattractant protein-1 (MCP-1) knockout mice. We analyzed classical (M1) and alternative (M2) gene expression via quantitative polymerase chain reaction, immunohistochemistry and enzyme-linked immunosorbent assay in both non-adherent cells isolated by lavage and implant-adherent cells. Our results show that macrophages undergo unique activation that displays features of both M1 and M2 polarization including induction of tumor necrosis factor α (TNF), which induces the expression and nuclear translocation of p50 and RelA determined by immunofluorescence and Western blot. Both processes were compromised in fusion-deficient MCP-1 KO macrophages in vitro and in vivo. Furthermore, inclusion of BAY 11-7028, an inhibitor of NFκB activation, reduced nuclear translocation of RelA and fusion in WT macrophages. Our studies suggest that peritoneal implants elicit a unique macrophage polarization phenotype leading to induction of TNF and activation of the NFκB pathway. Published by Elsevier Ltd.

  16. Minor cell-death defects but reduced tumor latency in mice lacking the BH3-only proteins Bad and Bmf.

    Science.gov (United States)

    Baumgartner, F; Woess, C; Pedit, V; Tzankov, A; Labi, V; Villunger, A

    2013-01-31

    Proapoptotic Bcl-2 family members of the Bcl-2 homology (BH)3-only subgroup are critical for the establishment and maintenance of tissue homeostasis and can mediate apoptotic cell death in response to developmental cues or exogenously induced forms of cell stress. On the basis of the biochemical experiments as well as genetic studies in mice, the BH3-only proteins Bad and Bmf have been implicated in different proapoptotic events such as those triggered by glucose- or trophic factor-deprivation, glucocorticoids, or histone deacetylase inhibition, as well as suppression of B-cell lymphomagenesis upon aberrant expression of c-Myc. To address possible redundancies in cell death regulation and tumor suppression, we generated compound mutant mice lacking both genes. Our studies revealed lack of redundancy in most paradigms of lymphocyte apoptosis tested in tissue culture. Only spontaneous cell death of thymocytes kept in low glucose or that of pre-B cells deprived of cytokines was significantly delayed when both genes were lacking. Of note, despite these minor apoptosis defects we observed compromised lymphocyte homeostasis in vivo that affected mainly the B-cell lineage. Long-term follow-up revealed significantly reduced latency to spontaneous tumor formation in aged mice when both genes were lacking. Together our study suggests that Bad and Bmf co-regulate lymphocyte homeostasis and limit spontaneous transformation by mechanisms that may not exclusively be linked to the induction of lymphocyte apoptosis.

  17. Life cycle assessment as a tool to evaluate the impact of reducing crude protein in pig diets

    Directory of Open Access Journals (Sweden)

    Alessandra Nardina Trícia Rigo Monteiro

    Full Text Available ABSTRACT: Environmental impacts of livestock systems, especially pig production, have come under increasing debate in recent years. The challenge is in meeting the growing demand for food at an affordable cost, without compromising environmental integrity. Previous studies have shown that feed production is responsible for the majority of CO2-eq. emission resulting from pig farming systems. This seems to indicate that feed strategies could be an effective tool to achieve the sustainability of the pork chain. Therefore, dietary crude protein reduction, through the addition of industrial amino acids, lessens the nitrogen excretion by pigs and, consequently, could mitigate the effects on the environment of pig production. In this sense, to effectively evaluate the environmental impacts of pig production systems, life cycle assessment has been widely used in agriculture, but the effects of feed are still understudied in Brazilian conditions. Owing to the importance and the great concern in this research area, we presented in this paper an updated review focusing on the nutritional techniques and their potential to reduce the global warming potential of pig production, considering both the direct effects, related to the choice of feed ingredients and the indirect effects, related to changes in the efficiency of use of nutrient by the animals.

  18. Reducing dietary protein in pond production of hybrid striped bass - study shows a significant reduction is possible in digestible protein level in commercial diets

    Science.gov (United States)

    In previous work, we demonstrated that diets containing 40% digestible protein (DP) (45% crude protein) and 18 %lipid supplemented with Met and Lys resulted in superior performance and nutrient retentions in hybrid striped bass compared to less energy-dense diets when rearing hybrid striped bass at ...

  19. High-level Petri Nets

    DEFF Research Database (Denmark)

    various journals and collections. As a result, much of this knowledge is not readily available to people who may be interested in using high-level nets. Within the Petri net community this problem has been discussed many times, and as an outcome this book has been compiled. The book contains reprints...... of some of the most important papers on the application and theory of high-level Petri nets. In this way it makes the relevant literature more available. It is our hope that the book will be a useful source of information and that, e.g., it can be used in the organization of Petri net courses. To make......High-level Petri nets are now widely used in both theoretical analysis and practical modelling of concurrent systems. The main reason for the success of this class of net models is that they make it possible to obtain much more succinct and manageable descriptions than can be obtained by means...

  20. Net neutrality and audiovisual services

    OpenAIRE

    van Eijk, N.; Nikoltchev, S.

    2011-01-01

    Net neutrality is high on the European agenda. New regulations for the communication sector provide a legal framework for net neutrality and need to be implemented on both a European and a national level. The key element is not just about blocking or slowing down traffic across communication networks: the control over the distribution of audiovisual services constitutes a vital part of the problem. In this contribution, the phenomenon of net neutrality is described first. Next, the European a...

  1. NetView technical research

    Science.gov (United States)

    1993-01-01

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

  2. Initial CAD investigations for NET

    International Nuclear Information System (INIS)

    Katz, F.; Leinemann, K.; Ludwig, A.; Marek, U.; Olbrich, W.; Schlechtendahl, E.G.

    1985-11-01

    This report summarizes the work done under contract no. 164/84-7/FU-D-/NET between the Commission of the European Communities and KfK during the period from June 1, 1984, through May 31, 1985. The following topics are covered in this report: Initial modelling of NET version NET2A, CAD system extension for remote handling studies, analysis of the CAD information structure, work related to the transfer of CAD information between KfK and the NET team. (orig.) [de

  3. Understanding Net Zero Energy Buildings

    DEFF Research Database (Denmark)

    Salom, Jaume; Widén, Joakim; Candanedo, José

    2011-01-01

    Although several alternative definitions exist, a Net-Zero Energy Building (Net ZEB) can be succinctly described as a grid-connected building that generates as much energy as it uses over a year. The “net-zero” balance is attained by applying energy conservation and efficiency measures...... and by incorporating renewable energy systems. While based on annual balances, a complete description of a Net ZEB requires examining the system at smaller time-scales. This assessment should address: (a) the relationship between power generation and building loads and (b) the resulting interaction with the power grid...

  4. Transcriptomic changes underlie altered egg protein production and reduced fecundity in an estuarine model fish exposed to bifenthrin.

    Science.gov (United States)

    Brander, Susanne M; Jeffries, Ken M; Cole, Bryan J; DeCourten, Bethany M; White, J Wilson; Hasenbein, Simone; Fangue, Nann A; Connon, Richard E

    2016-05-01

    PCR demonstrated that bifenthrin downregulates a number of estrogen-related transcripts, particularly at the lowest exposure level. Choriogenin protein also decreased with exposure to increasing concentrations of bifenthrin, and adult M. beryllina exposed to 0.5ng/L had significantly reduced reproductive output (fertilized eggs per female). This reduction in fecundity is consistent with observed changes in endocrine-related gene expression and choriogenin production. Taken together, our results demonstrate that environmental concentrations of bifenthrin have potential to interfere with metabolic processes, endocrine signaling, and to decrease reproductive output. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Which nets are being used: factors associated with mosquito net use in Amhara, Oromia and Southern Nations, Nationalities and Peoples' Regions of Ethiopia.

    Science.gov (United States)

    Ngondi, Jeremiah M; Graves, Patricia M; Gebre, Teshome; Mosher, Aryc W; Shargie, Estifanos B; Emerson, Paul M; Richards, Frank O

    2011-04-17

    There has been recent large scale-up of malaria control interventions in Ethiopia where transmission is unstable. While household ownership of long-lasting insecticidal nets (LLIN) has increased greatly, there are concerns about inadequate net use. This study aimed to investigate factors associated with net use at two time points, before and after mass distribution of nets. Two cross sectional surveys were carried out in 2006 and 2007 in Amhara, Oromia and SNNP regions. The latter was a sub-sample of the national Malaria Indicator Survey (MIS 3R). Each survey wave used multi-stage cluster random sampling with 25 households per cluster (224 clusters with 5,730 households in Baseline 2006 and 245 clusters with 5,910 households in MIS 3R 2007). Net ownership was assessed by visual inspection while net utilization was reported as use of the net the previous night. This net level analysis was restricted to households owning at least one net of any type. Logistic regression models of association between net use and explanatory variables including net type, age, condition, cost and other household characteristics were undertaken using generalized linear latent and mixed models (GLLAMM). A total of 3,784 nets in 2,430 households were included in the baseline 2006 analysis while the MIS 3R 2007 analysis comprised 5,413 nets in 3,328 households. The proportion of nets used the previous night decreased from 85.1% to 56.0% between baseline 2006 and MIS 3R 2007, respectively. Factors independently associated with increased proportion of nets used were: LLIN net type (at baseline 2006); indoor residual spraying (at MIS 3R 2007); and increasing wealth index at both surveys. At both baseline 2006 and MIS 3R 2007, reduced proportion of nets used was independently associated with increasing net age, increasing damage of nets, increasing household net density, and increasing altitude (>2,000 m). This study identified modifiable factors affecting use of nets that were consistent

  6. Which nets are being used: factors associated with mosquito net use in Amhara, Oromia and Southern Nations, Nationalities and Peoples' Regions of Ethiopia

    Directory of Open Access Journals (Sweden)

    Mosher Aryc W

    2011-04-01

    Full Text Available Abstract Background There has been recent large scale-up of malaria control interventions in Ethiopia where transmission is unstable. While household ownership of long-lasting insecticidal nets (LLIN has increased greatly, there are concerns about inadequate net use. This study aimed to investigate factors associated with net use at two time points, before and after mass distribution of nets. Methods Two cross sectional surveys were carried out in 2006 and 2007 in Amhara, Oromia and SNNP regions. The latter was a sub-sample of the national Malaria Indicator Survey (MIS 3R. Each survey wave used multi-stage cluster random sampling with 25 households per cluster (224 clusters with 5,730 households in Baseline 2006 and 245 clusters with 5,910 households in MIS 3R 2007. Net ownership was assessed by visual inspection while net utilization was reported as use of the net the previous night. This net level analysis was restricted to households owning at least one net of any type. Logistic regression models of association between net use and explanatory variables including net type, age, condition, cost and other household characteristics were undertaken using generalized linear latent and mixed models (GLLAMM. Results A total of 3,784 nets in 2,430 households were included in the baseline 2006 analysis while the MIS 3R 2007 analysis comprised 5,413 nets in 3,328 households. The proportion of nets used the previous night decreased from 85.1% to 56.0% between baseline 2006 and MIS 3R 2007, respectively. Factors independently associated with increased proportion of nets used were: LLIN net type (at baseline 2006; indoor residual spraying (at MIS 3R 2007; and increasing wealth index at both surveys. At both baseline 2006 and MIS 3R 2007, reduced proportion of nets used was independently associated with increasing net age, increasing damage of nets, increasing household net density, and increasing altitude (>2,000 m. Conclusion This study identified

  7. Petri nets SM-cover-based on heuristic coloring algorithm

    Science.gov (United States)

    Tkacz, Jacek; Doligalski, Michał

    2015-09-01

    In the paper, coloring heuristic algorithm of interpreted Petri nets is presented. Coloring is used to determine the State Machines (SM) subnets. The present algorithm reduces the Petri net in order to reduce the computational complexity and finds one of its possible State Machines cover. The proposed algorithm uses elements of interpretation of Petri nets. The obtained result may not be the best, but it is sufficient for use in rapid prototyping of logic controllers. Found SM-cover will be also used in the development of algorithms for decomposition, and modular synthesis and implementation of parallel logic controllers. Correctness developed heuristic algorithm was verified using Gentzen formal reasoning system.

  8. Rare, but challenging tumors: NET

    International Nuclear Information System (INIS)

    Ivanova, D.; Balev, B.

    2013-01-01

    Full text: Introduction: Gastroenteropancreatic Neuroendocrine Tumors (GEP - NET) are a heterogeneous group of tumors with different locations and many different clinical, histological, and imaging performance. In a part of them a secretion of various organic substances is present. The morbidity of GEP - NET in the EU is growing, and this leads to increase the attention to them. What you will learn: Imaging methods used for localization and staging of GEP - NET, characteristics of the study’s protocols; Classification of GEP - NET; Demonstration of typical and atypical imaging features of GEP - NET in patients registered at the NET Center at University Hospital ‘St. Marina’, Varna; Features of metastatic NET, The role of imaging in the evaluation of treatment response and follow-up of the patients. Discussion: The image semiotics analysis is based on 19 cases of GEP - NET registered NET Center at University Hospital ‘St. Marina’. The main imaging method is multidetector CT (MDCT), and magnetic resonance imaging (MRI ) has advantages in the evaluation of liver lesions and the local prevalence of anorectal tumors. In patients with advanced disease and liver lesions the assessment of skeletal involvement (MRI/ nuclear medical method) is mandatory. The majority of GEP - NET have not any specific imaging findings. Therefore it is extremely important proper planning and conducting of the study (MDCT and MR enterography; accurate assessment phase of scanning, positive and negative contrast). Conclusion: GEP - NET is a major diagnostic challenge due to the absence of typical imaging characteristics and often an overlap with those of the tumors of different origin can be observed. Therefore, a good knowledge of clinical and imaging changes occurring at different locations is needed. MDCT is the basis for the diagnosis, staging and follow-up of these neoplasms

  9. Disulfide scrambling in superoxide dismutase 1 reduces its cytotoxic effect in cultured cells and promotes protein aggregation.

    Directory of Open Access Journals (Sweden)

    Lina Leinartaitė

    Full Text Available Mutations in the gene coding for superoxide dismutase 1 (SOD1 are associated with familiar forms of the neurodegenerative disease amyotrophic lateral sclerosis (ALS. These mutations are believed to result in a "gain of toxic function", leading to neuronal degeneration. The exact mechanism is still unknown, but misfolding/aggregation events are generally acknowledged as important pathological events in this process. Recently, we observed that demetallated apoSOD1, with cysteine 6 and 111 substituted for alanine, is toxic to cultured neuroblastoma cells. This toxicity depended on an intact, high affinity Zn(2+ site. It was therefor contradictory to discover that wild-type apoSOD1 was not toxic, despite of its high affinity for Zn(2+. This inconsistency was hypothesized to originate from erroneous disulfide formation involving C6 and C111. Using high resolution non-reducing SDS-PAGE, we have in this study demonstrated that the inability of wild-type apoSOD1 to cause cell death stems from formation of non-native intra-molecular disulfides. Moreover, monomeric apoSOD1 variants capable of such disulfide scrambling aggregated into ThT positive oligomers under physiological conditions without agitation. The oligomers were stabilized by inter-molecular disulfides and morphologically resembled what has in other neurodegenerative diseases been termed protofibrils. Disulfide scrambling thus appears to be an important event for misfolding and aggregation of SOD1, but may also be significant for protein function involving cysteines, e.g. mitochondrial import and copper loading.

  10. Structural analogs of human insulin-like growth factor I with reduced affinity for serum binding proteins and the type 2 insulin-like growth factor receptor

    International Nuclear Information System (INIS)

    Bayne, M.L.; Applebaum, J.; Chicchi, G.G.; Hayes, N.S.; Green, B.G.; Cascieri, M.A.

    1988-01-01

    Four structural analogs of human insulin-like growth factor I (hIGF-I) have been prepared by site-directed mutagenesis of a synthetic IGF-I gene and subsequent expression and purification of the mutant protein from the conditioned media of transformed yeast. [Phe -1 , Val 1 , Asn 2 , Gln 3 , His 4 , Ser 8 , His 9 , Glu 12 , Tyr 15 , Leu 16 ]IGF-I (B-chain mutant), in which the first 16 amino acids of hIGF-I were replaced with the first 17 amino acids of the B-chain of insulin, has >1000-, 100-, and 2-fold reduced potency for human serum binding proteins, the rat liver type 2 IGF receptor, and the human placental type 1 IGF receptor, respectively. The B-chain mutant also has 4-fold increased affinity for the human placental insulin receptor. [Gln 3 , Ala 4 ] IGF-I has 4-fold reduced affinity for human serum binding proteins, but is equipotent to hIGF-I at the types 1 and 2 IGF and insulin receptors. [Tyr 15 , Leu 16 ] IGH-I has 4-fold reduced affinity for human serum binding proteins and 10-fold increased affinity for the insulin receptor. The peptide in which these four-point mutations are combined, [Gln 3 , Ala 4 , Tyr 15 ,Leu 16 ]IGF-I, has 600-fold reduced affinity for the serum binding proteins. All four of these mutants stimulate DNA synthesis in the rat vascular smooth muscle cell line A10 with potencies reflecting their potency at the type 1 IGF receptor. These studies identify some of the domains of hIGF-I which are responsible for maintaining high affinity binding with the serum binding protein and the type 2 IGF receptor. In addition, These peptides will be useful in defining the role of the type 2 IGF receptor and serum binding proteins in the physiological actions of hIGF-I

  11. Liquid metal cooled blanket concept for NET

    International Nuclear Information System (INIS)

    Malang, S.; Casal, V.; Arheidt, K.; Fischer, U.; Link, W.; Rust, K.

    1986-01-01

    A blanket concept for NET using liquid lithium-lead both as breeder material and as coolant is described. The need for inboard breeding is avoided by using beryllium as neutron multiplier in the outboard blanket. Novel flow channel inserts are employed in all poloidal ducts to reduce the MHD pressure drop. The concept offers a simple mechanical design and a higher tritium breeding ratio compared to water- and gas-cooled blankets. (author)

  12. Chloroplastic and stomatal aspects of ozone-induced reduction of net photosynthesis in plants

    Energy Technology Data Exchange (ETDEWEB)

    Torsethaugen, Gro

    1998-09-01

    The present thesis relates to ozone-induced reduction of photosynthesis in plants. As a photochemical oxidant O{sub 3} is formed by the interaction of hydrocarbons, nitrogen oxides and oxygen in sunlight. Ozone (O{sub 3}) is the most phytotoxic of all the air pollutants and is known to reduce plant growth and net photosynthesis, cause stomatal closure, induce visible injury, accelerate senescence and induce or inhibit transcription of a variety of genes with a corresponding increase/decrease in protein products. The underlying cellular mechanisms for many of these changes are unknown. Following fields are investigated: Ozone-induced reduction of net photosynthesis; ozone and the photosynthetic apparatus in the chloroplasts; ozone and stomata; ozone effects on plant membranes; protection against ozone injury in plants. 249 refs., 22 figs., 4 tabs.

  13. Optimization of elution salt concentration in stepwise elution of protein chromatography using linear gradient elution data. Reducing residual protein A by cation-exchange chromatography in monoclonal antibody purification.

    Science.gov (United States)

    Ishihara, Takashi; Kadoya, Toshihiko; Endo, Naomi; Yamamoto, Shuichi

    2006-05-05

    Our simple method for optimization of the elution salt concentration in stepwise elution was applied to the actual protein separation system, which involves several difficulties such as detection of the target. As a model separation system, reducing residual protein A by cation-exchange chromatography in human monoclonal antibody (hMab) purification was chosen. We carried out linear gradient elution experiments and obtained the data for the peak salt concentration of hMab and residual protein A, respectively. An enzyme-linked immunosorbent assay was applied to the measurement of the residual protein A. From these data, we calculated the distribution coefficient of the hMab and the residual protein A as a function of salt concentration. The optimal salt concentration of stepwise elution to reduce the residual protein A from the hMab was determined based on the relationship between the distribution coefficient and the salt concentration. Using the optimized condition, we successfully performed the separation, resulting in high recovery of hMab and the elimination of residual protein A.

  14. Linear Logic on Petri Nets

    DEFF Research Database (Denmark)

    Engberg, Uffe Henrik; Winskel, Glynn

    This article shows how individual Petri nets form models of Girard's intuitionistic linear logic. It explores questions of expressiveness and completeness of linear logic with respect to this interpretation. An aim is to use Petri nets to give an understanding of linear logic and give some apprai...

  15. Net neutrality and audiovisual services

    NARCIS (Netherlands)

    van Eijk, N.; Nikoltchev, S.

    2011-01-01

    Net neutrality is high on the European agenda. New regulations for the communication sector provide a legal framework for net neutrality and need to be implemented on both a European and a national level. The key element is not just about blocking or slowing down traffic across communication

  16. Moderate alcohol consumption reduces plasma C-reactive protein and fibrinogen levels : a randomized, diet-controlled intervention study

    NARCIS (Netherlands)

    Sierksma, A.; Gaag, M.S. van der; Kluft, C.; Hendriks, H.F.J.

    2002-01-01

    Objective: To evaluate the effect of moderate alcohol consumption on the acute phase proteins C-reactive protein and fibrinogen. Design: Randomized, diet-controlled, cross-over study. Setting: The study was performed at TNO Nutrition and Food Research, Zeist, The Netherlands. Subjects: Ten

  17. Protein Exposed Hydrophobicity Reduces the Kinetic Barrier for Adsorption of Ovalbumin to the Air-Water Interface

    NARCIS (Netherlands)

    Wierenga, P.A.; Meinders, M.B.J.; Egmond, M.R.; Voragen, F.A.G.J.; Jongh, H.H.J. de

    2003-01-01

    Using native and caprylated ovalbumin, the role of exposed hydrophobicity on the kinetics of protein adsorption to the air - water interface is studied. First, changes in the chemical properties of the protein upon caprylation were characterized followed by measurement of the changes in adsorption

  18. Protein exposed hydrophobicity reduces the kinetic barrier for adsoption of ovalbumin to the air-water interface.

    NARCIS (Netherlands)

    Wierenga, P.A.; Meinders, M.B.J.; Egmond, M.R.; Voragen, A.G.J.

    2003-01-01

    Using native and caprylated ovalbumin, the role of exposed hydrophobicity on the kinetics of protein adsorption to the air-water interface is studied. First, changes in the chemical properties of the protein upon caprylation were characterized followed by measurement of the changes in adsorption

  19. Milk protein enriched beverage reduces post-exercise energy intakes in women with higher levels of cognitive dietary restraint

    NARCIS (Netherlands)

    Virgilio, Nicolina; Donno, De Roberta; Bandini, Enrica; Napolitano, Aurora; Fogliano, Vincenzo; Vitaglione, Paola

    2017-01-01

    Objective: The aim of this study was to assess the satiating efficacy of milk proteins compared to carbohydrates in twenty women during post-exercise period. Methods: A milk protein-enriched beverage (MPB), and an isocaloric carbohydrate-enriched beverage (CB) containing respectively 9.3. g and 0.3.

  20. Properties of porous netted materials

    International Nuclear Information System (INIS)

    Daragan, V.D.; Drozdov, B.G.; Kotov, A.Yu.; Mel'nikov, G.N.; Pustogarov, A.V.

    1987-01-01

    Hydraulic and strength characteristics, efficient heat conduction and inner heat exchange coefficient are experimentally studied for porous netted materials on the base of the brass nets as dependent on porosity, cell size and method of net laying. Results of the studies are presented. It is shown that due to anisotropy of the material properties the hydraulic resistance in the direction parallel to the nets plane is 1.3-1.6 times higher than in the perpendicular one. Values of the effective heat conduction in the direction perpendicular to the nets plane at Π>0.45 agree with the data from literature, at Π<0.45 a deviation from the calculated values is marked in the direction of the heat conduction decrease

  1. NET remote workstation

    International Nuclear Information System (INIS)

    Leinemann, K.

    1990-10-01

    The goal of this NET study was to define the functionality of a remote handling workstation and its hardware and software architecture. The remote handling workstation has to fulfill two basic functions: (1) to provide the man-machine interface (MMI), that means the interface to the control system of the maintenance equipment and to the working environment (telepresence) and (2) to provide high level (task level) supporting functions (software tools) during the maintenance work and in the preparation phase. Concerning the man-machine interface, an important module of the remote handling workstation besides the standard components of man-machine interfacing is a module for graphical scene presentation supplementing viewing by TV. The technique of integrated viewing is well known from JET BOOM and TARM control using the GBsim and KISMET software. For integration of equipment dependent MMI functions the remote handling workstation provides a special software module interface. Task level support of the operator is based on (1) spatial (geometric/kinematic) models, (2) remote handling procedure models, and (3) functional models of the equipment. These models and the related simulation modules are used for planning, programming, execution monitoring, and training. The workstation provides an intelligent handbook guiding the operator through planned procedures illustrated by animated graphical sequences. For unplanned situations decision aids are available. A central point of the architectural design was to guarantee a high flexibility with respect to hardware and software. Therefore the remote handling workstation is designed as an open system based on widely accepted standards allowing the stepwise integration of the various modules starting with the basic MMI and the spatial simulation as standard components. (orig./HP) [de

  2. Identification of thioredoxin h-reducible disulphides in proteornes by differential labelling of cysteines: Insight into recognition and regulation of proteins in barley seeds by thioredoxin h

    DEFF Research Database (Denmark)

    Maeda, Kenji; Finnie, Christine; Svensson, Birte

    2005-01-01

    alpha-amylase/subtilisin inhibitor (BASI) by barley thioredoxin h isoform 1 was analysed. Furthermore, the method was coupled with two-dimensional electrophoresis for convenient thioredoxin h-reducible disulphide identification in barley seed extracts without the need for protein purification...... or production of recombinant proteins. Mass shifts of 15 peptides, induced by treatment with thioredoxin h and differential alkylation, identified specific reduction of nine disulphides in BASI, four alpha-amylase/trypsin inhibitors and a protein of unknown function. Two specific disulphides, located...... structurally close to the alpha-amylase binding surfaces of BASI and alpha-amylase inhibitor BMAI-1 were demonstrated to be reduced to a particularly high extent. For the first time, specificity of thioredoxin h for particular disulphide bonds is demonstrated, providing a basis to study structural aspects...

  3. Optimizing sampling design to deal with mist-net avoidance in Amazonian birds and bats.

    Directory of Open Access Journals (Sweden)

    João Tiago Marques

    Full Text Available Mist netting is a widely used technique to sample bird and bat assemblages. However, captures often decline with time because animals learn and avoid the locations of nets. This avoidance or net shyness can substantially decrease sampling efficiency. We quantified the day-to-day decline in captures of Amazonian birds and bats with mist nets set at the same location for four consecutive days. We also evaluated how net avoidance influences the efficiency of surveys under different logistic scenarios using re-sampling techniques. Net avoidance caused substantial declines in bird and bat captures, although more accentuated in the latter. Most of the decline occurred between the first and second days of netting: 28% in birds and 47% in bats. Captures of commoner species were more affected. The numbers of species detected also declined. Moving nets daily to minimize the avoidance effect increased captures by 30% in birds and 70% in bats. However, moving the location of nets may cause a reduction in netting time and captures. When moving the nets caused the loss of one netting day it was no longer advantageous to move the nets frequently. In bird surveys that could even decrease the number of individuals captured and species detected. Net avoidance can greatly affect sampling efficiency but adjustments in survey design can minimize this. Whenever nets can be moved without losing netting time and the objective is to capture many individuals, they should be moved daily. If the main objective is to survey species present then nets should still be moved for bats, but not for birds. However, if relocating nets causes a significant loss of netting time, moving them to reduce effects of shyness will not improve sampling efficiency in either group. Overall, our findings can improve the design of mist netting sampling strategies in other tropical areas.

  4. Glycation inhibitors extend yeast chronological lifespan by reducing advanced glycation end products and by back regulation of proteins involved in mitochondrial respiration.

    Science.gov (United States)

    Kazi, Rubina S; Banarjee, Reema M; Deshmukh, Arati B; Patil, Gouri V; Jagadeeshaprasad, Mashanipalya G; Kulkarni, Mahesh J

    2017-03-06

    Advanced Glycation End products (AGEs) are implicated in aging process. Thus, reducing AGEs by using glycation inhibitors may help in attenuating the aging process. In this study using Saccharomyces cerevisiae yeast system, we show that Aminoguanidine (AMG), a well-known glycation inhibitor, decreases the AGE modification of proteins in non-calorie restriction (NR) (2% glucose) and extends chronological lifespan (CLS) similar to that of calorie restriction (CR) condition (0.5% glucose). Proteomic analysis revealed that AMG back regulates the expression of differentially expressed proteins especially those involved in mitochondrial respiration in NR condition, suggesting that it switches metabolism from fermentation to respiration, mimicking CR. AMG induced back regulation of differentially expressed proteins could be possibly due to its chemical effect or indirectly by glycation inhibition. To delineate this, Metformin (MET), a structural analog of AMG and a mild glycation inhibitor and Hydralazine (HYD), another potent glycation inhibitor but not structural analog of AMG were used. HYD was more effective than MET in mimicking AMG suggesting that glycation inhibition was responsible for restoration of differentially expressed proteins. Thus glycation inhibitors particularly AMG, HYD and MET extend yeast CLS by reducing AGEs, modulating the expression of proteins involved in mitochondrial respiration and possibly by scavenging glucose. This study reports the role of glycation in aging process. In the non-caloric restriction condition, carbohydrates such as glucose promote protein glycation and reduce CLS. While, the inhibitors of glycation such as AMG, HYD, MET mimic the caloric restriction condition by back regulating deregulated proteins involved in mitochondrial respiration which could facilitate shift of metabolism from fermentation to respiration and extend yeast CLS. These findings suggest that glycation inhibitors can be potential molecules that can be used

  5. BAG3 down-modulation reduces anaplastic thyroid tumor growth by enhancing proteasome-mediated degradation of BRAF protein.

    Science.gov (United States)

    Chiappetta, Gennaro; Basile, Anna; Arra, Claudio; Califano, Daniela; Pasquinelli, Rosa; Barbieri, Antonio; De Simone, Veronica; Rea, Domenica; Giudice, Aldo; Pezzullo, Luciano; De Laurenzi, Vincenzo; Botti, Gerardo; Losito, Simona; Conforti, Daniela; Turco, Maria Caterina

    2012-01-01

    Anaplastic thyroid tumors (ATC) express high levels of BAG3, a member of the BAG family of cochaperone proteins that is involved in regulating cell apoptosis through multiple mechanisms. The objective of the study was the investigation of the influence of B-cell lymphoma-2-associated athanogene 3 (BAG3) on ATC growth. We investigated the effects of BAG3 down-modulation, obtained by using a specific small interfering RNA, on in vitro and in vivo growth of the human ATC cell line 8505C. Because BRAF protein plays an important role in ATC cell growth, we analyzed the effects of BAG3 down-modulation on BRAF protein levels. Furthermore, by using a proteasome inhibitor, we verified whether BAG3-mediated regulation of BRAF levels involved a proteasome-dependent mechanism. BAG3 down-modulation significantly inhibits ATC growth in vitro and in vivo. BAG3 coimmunoprecipitates with BRAF protein, and its down-modulation results in a significant reduction of BRAF protein levels, which can be reverted by incubation with the proteasome inhibitor MG132. BAG3 protein sustains ATC growth in vitro and in vivo. The underlying molecular mechanism appears to rely on BAG3 binding to BRAF, thus protecting it from proteasome-dependent degradation. These results are in line with the reported ability of BAG3 to interfere with the proteasomal delivery of a number of other client proteins.

  6. Residues at a Single Site Differentiate Animal Cryptochromes from Cyclobutane Pyrimidine Dimer Photolyases by Affecting the Proteins' Preferences for Reduced FAD.

    Science.gov (United States)

    Xu, Lei; Wen, Bin; Wang, Yuan; Tian, Changqing; Wu, Mingcai; Zhu, Guoping

    2017-06-19

    Cryptochromes (CRYs) and photolyases belong to the cryptochrome/photolyase family (CPF). Reduced FAD is essential for photolyases to photorepair UV-induced cyclobutane pyrimidine dimers (CPDs) or 6-4 photoproducts in DNA. In Drosophila CRY (dCRY, a type I animal CRY), FAD is converted to the anionic radical but not to the reduced state upon illumination, which might induce a conformational change in the protein to relay the light signal downstream. To explore the foundation of these differences, multiple sequence alignment of 650 CPF protein sequences was performed. We identified a site facing FAD (Ala377 in Escherichia coli CPD photolyase and Val415 in dCRY), hereafter referred to as "site 377", that was distinctly conserved across these sequences: CPD photolyases often had Ala, Ser, or Asn at this site, whereas animal CRYs had Ile, Leu, or Val. The binding affinity for reduced FAD, but not the photorepair activity of E. coli photolyase, was dramatically impaired when replacing Ala377 with any of the three CRY residues. Conversely, in V415S and V415N mutants of dCRY, FAD was photoreduced to its fully reduced state after prolonged illumination, and light-dependent conformational changes of these mutants were severely inhibited. We speculate that the residues at site 377 play a key role in the different preferences of CPF proteins for reduced FAD, which differentiate animal CRYs from CPD photolyases. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. High plasma cholesteryl ester transfer protein levels may favour reduced incidence of cardiovascular events in men with low triglycerides

    NARCIS (Netherlands)

    Borggreve, Susanna E.; Hillege, Hans L.; Dallinga-Thie, Geesje M.; de Jong, Paul E.; Wolffenbuttel, Bruce H. R.; Grobbee, Diederik E.; van Tol, Arie; Dullaart, Robin P. F.

    2007-01-01

    High cholesteryl ester transfer protein (CETP) concentrations are associated with increased risk of cardiovascular disease (CVD) in subjects with high triglycerides. We determined the relationship of plasma CETP with incident CVD in a population with relatively low triglycerides. A nested

  8. PPARγ activates ABCA1 gene transcription but reduces the level of ABCA1 protein in HepG2 cells

    International Nuclear Information System (INIS)

    Mogilenko, Denis A.; Shavva, Vladimir S.; Dizhe, Ella B.; Orlov, Sergey V.; Perevozchikov, Andrej P.

    2010-01-01

    Research highlights: → PPARγ activates ABCA1 gene expression but decreases ABCA1 protein content in human hepatoma cell line HepG2. → Treatment of HepG2 cells with PPARγ agonist GW1929 leads to dissociation of LXRβ from ABCA1-LXRβ complex. → Inhibition of protein kinases MEK1/2 abolishes PPARγ-mediated dissociation of LXRβ from ABCA1/LXRβ complex. → Activation of PPARγ leads to increasing of the level of LXRβ associated with LXRE within ABCA1 gene promoter. -- Abstract: Synthesis of ABCA1 protein in liver is necessary for high-density lipoproteins (HDL) formation in mammals. Nuclear receptor PPARγ is known as activator of ABCA1 expression, but details of PPARγ-mediated regulation of ABCA1 at both transcriptional and post-transcriptional levels in hepatocytes have not still been well elucidated. In this study we have shown, that PPARγ activates ABCA1 gene transcription in human hepatoma cells HepG2 through increasing of LXRβ binding with promoter region of ABCA1 gene. Treatment of HepG2 cells with PPARγ agonist GW1929 leads to dissociation of LXRβ from ABCA1/LXRβ complex and to nuclear translocation of this nuclear receptor resulting in reduction of ABCA1 protein level 24 h after treatment. Inhibition of protein kinases MEK1/2 abolishes PPARγ-mediated dissociation of LXRβ from ABCA1/LXRβ complex, but does not block PPARγ-dependent down-regulation of ABCA1 protein in HepG2 cells. These data suggest that PPARγ may be important for regulation of the level of hepatic ABCA1 protein and indicate the new interplays between PPARγ, LXRβ and MEK1/2 in regulation of ABCA1 mRNA and protein expression.

  9. Design of Protein Multi-specificity Using an Independent Sequence Search Reduces the Barrier to Low Energy Sequences.

    Directory of Open Access Journals (Sweden)

    Alexander M Sevy

    2015-07-01

    Full Text Available Computational protein design has found great success in engineering proteins for thermodynamic stability, binding specificity, or enzymatic activity in a 'single state' design (SSD paradigm. Multi-specificity design (MSD, on the other hand, involves considering the stability of multiple protein states simultaneously. We have developed a novel MSD algorithm, which we refer to as REstrained CONvergence in multi-specificity design (RECON. The algorithm allows each state to adopt its own sequence throughout the design process rather than enforcing a single sequence on all states. Convergence to a single sequence is encouraged through an incrementally increasing convergence restraint for corresponding positions. Compared to MSD algorithms that enforce (constrain an identical sequence on all states the energy landscape is simplified, which accelerates the search drastically. As a result, RECON can readily be used in simulations with a flexible protein backbone. We have benchmarked RECON on two design tasks. First, we designed antibodies derived from a common germline gene against their diverse targets to assess recovery of the germline, polyspecific sequence. Second, we design "promiscuous", polyspecific proteins against all binding partners and measure recovery of the native sequence. We show that RECON is able to efficiently recover native-like, biologically relevant sequences in this diverse set of protein complexes.

  10. Conformal Nets II: Conformal Blocks

    Science.gov (United States)

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

    2017-08-01

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

  11. Pro asynchronous programming with .NET

    CERN Document Server

    Blewett, Richard; Ltd, Rock Solid Knowledge

    2014-01-01

    Pro Asynchronous Programming with .NET teaches the essential skill of asynchronous programming in .NET. It answers critical questions in .NET application development, such as: how do I keep my program responding at all times to keep my users happy how do I make the most of the available hardware how can I improve performanceIn the modern world, users expect more and more from their applications and devices, and multi-core hardware has the potential to provide it. But it takes carefully crafted code to turn that potential into responsive, scalable applications.With Pro Asynchronous Programming

  12. 康奈尔净碳水化合物-蛋白质体系预测小肠可消化粗蛋白质含量%Predicting Utilizable Crude Protein Content in Small Intestine by Cornell Net Carbohydrate and Protein System

    Institute of Scientific and Technical Information of China (English)

    王燕; 杨方; 陈常栋; 王海威; 张微微; 张永根

    2012-01-01

    This study was conducted to establish mathematical models of predicting utilizable crude protein (uCP) content in feed for dairy cows using Cornell net carbohydrate and protein system (CNCPS). Contents of protein fractions of 13 kinds of common feeds were analyzed using CNCPS, and uCP of feeds was determined using mobile nylon bag method, and three Holstein dairy cows with permanent ruminal and duodenal cannulas were used in a single factor experimental design. The results showed as follows: 1) contents of uCP in soybean meal, cottonseed meal, rapeseed meal, sunflower seed meal, sesame meal, corn germ meal, rice bran, rice bran cake, rice bran meal, barley, wheat bran, corn and corn gluten feed were 390. 32, 321. 90, 297.21, 230.50, 388.62, 177.49, 85.53, 116.78, 134.74, 80.47, 128.26, 70.28 and 66. 65 g/kg, respectively. 2) The regression equation of contents of measured uCP and CNCPS fractions in all experimental feeds was uCP = -4.11 + 6.48PA+7.73PB, + 5.72PB2 +8.26PB3 +5. UPC (R2 =0.997 2, P<0.01) ; the regression equation of contents of measured uCP and CNCPS fractions in protein feed was uCP =12. 79 + 5. 47PA +7. 04PBl +9. 74PB2 +8. 14PB3 (R2 = 0. 998 7, P < 0. 01) ; the regression equation of contents of measured uCP and CNCPS fractions in energy feed was uCP = 14. 80 +8. 55PA +6. 27PB2 +17. 64PB3(R2 = 0.987 4, P<0.01). 3) Regression coefficients (R2) between CNCPS fractions contents and measured uCP contents in protein feed, energy feed and all experimental feed were all higher than 0. 95, and regression coefficient between measured uCP content and CNCPS fractions contents in protein feed was higher than that in energy feed. In conclusion, it is feasible that using contents of protein components subdivided by CNCPS to predict uCP content, and the prediction result in protein feed is more accurate than that in energy feed.%本试验旨在建立奶牛饲料的康奈尔净碳水化合物-蛋白质体系(Cornell net carbohydrate and protein system,CNCPS)预测

  13. Lower Squalene Epoxidase and Higher Scavenger Receptor Class B Type 1 Protein Levels Are Involved in Reduced Serum Cholesterol Levels in Stroke-Prone Spontaneously Hypertensive Rats.

    Science.gov (United States)

    Michihara, Akihiro; Mido, Mayuko; Matsuoka, Hiroshi; Mizutani, Yurika

    2015-01-01

    A lower serum cholesterol level was recently shown to be one of the causes of stroke in an epidemiological study. Spontaneously hypertensive rats stroke-prone (SHRSP) have lower serum cholesterol levels than normotensive Wistar-Kyoto rats (WKY). To elucidate the mechanisms responsible for the lower serum cholesterol levels in SHRSP, we determined whether the amounts of cholesterol biosynthetic enzymes or the receptor and transporter involved in cholesterol uptake and efflux in the liver were altered in SHRSP. When the mRNA levels of seven cholesterol biosynthetic enzymes were measured using real-time polymerase chain reaction (PCR), farnesyl pyrophosphate synthase and squalene epoxidase (SQE) levels in the liver of SHRSP were significantly lower than those in WKY. SQE protein levels were significantly reduced in tissues other than the brain of SHRSP. No significant differences were observed in low-density lipoprotein (LDL) receptor (uptake of serum LDL-cholesterol) or ATP-binding cassette transporter A1 (efflux of cholesterol from the liver/formation of high-density lipoprotein (HDL)) protein levels in the liver and testis between SHRSP and WKY, whereas scavenger receptor class B type 1 (SRB1: uptake of serum HDL-cholesterol) protein levels were higher in the livers of SHRSP. These results indicated that the lower protein levels of SQE and higher protein levels of SRB1 in the liver were involved in the reduced serum cholesterol levels in SHRSP.

  14. Net load forecasting for high renewable energy penetration grids

    International Nuclear Information System (INIS)

    Kaur, Amanpreet; Nonnenmacher, Lukas; Coimbra, Carlos F.M.

    2016-01-01

    We discuss methods for net load forecasting and their significance for operation and management of power grids with high renewable energy penetration. Net load forecasting is an enabling technology for the integration of microgrid fleets with the macrogrid. Net load represents the load that is traded between the grids (microgrid and utility grid). It is important for resource allocation and electricity market participation at the point of common coupling between the interconnected grids. We compare two inherently different approaches: additive and integrated net load forecast models. The proposed methodologies are validated on a microgrid with 33% annual renewable energy (solar) penetration. A heuristics based solar forecasting technique is proposed, achieving skill of 24.20%. The integrated solar and load forecasting model outperforms the additive model by 10.69% and the uncertainty range for the additive model is larger than the integrated model by 2.2%. Thus, for grid applications an integrated forecast model is recommended. We find that the net load forecast errors and the solar forecasting errors are cointegrated with a common stochastic drift. This is useful for future planning and modeling because the solar energy time-series allows to infer important features of the net load time-series, such as expected variability and uncertainty. - Highlights: • Net load forecasting methods for grids with renewable energy generation are discussed. • Integrated solar and load forecasting outperforms the additive model by 10.69%. • Net load forecasting reduces the uncertainty between the interconnected grids.

  15. A High-Protein Diet Reduces Weight Gain, Decreases Food Intake, Decreases Liver Fat Deposition, and Improves Markers of Muscle Metabolism in Obese Zucker Rats

    Directory of Open Access Journals (Sweden)

    William W. French

    2017-06-01

    Full Text Available A primary factor in controlling and preventing obesity is through dietary manipulation. Diets higher in protein have been shown to improve body composition and metabolic health during weight loss. The objective of this study was to examine the effects of a high-protein diet versus a moderate-protein diet on muscle, liver and fat metabolism and glucose regulation using the obese Zucker rat. Twelve-week old, male, Zucker (fa/fa and lean control (Fa/fa rats were randomly assigned to either a high-protein (40% energy or moderate-protein (20% energy diet for 12 weeks, with a total of four groups: lean 20% protein (L20; n = 8, lean 40% protein (L40; n = 10, obese 20% protein (O20; n = 8, and obese 40% protein (O40; n = 10. At the end of 12 weeks, animals were fasted and euthanized. There was no difference in food intake between L20 and L40. O40 rats gained less weight and had lower food intake (p < 0.05 compared to O20. O40 rats had lower liver weight (p < 0.05 compared to O20. However, O40 rats had higher orexin (p < 0.05 levels compared to L20, L40 and O20. Rats in the L40 and O40 groups had less liver and muscle lipid deposition compared to L20 and L40 diet rats, respectively. O40 had decreased skeletal muscle mechanistic target of rapamycin complex 1 (mTORC1 phosphorylation and peroxisome proliferator-activated receptor gamma (PPARγ mRNA expression compared to O20 (p < 0.05, with no difference in 5′ AMP-activated protein kinase (AMPK, eukaryotic translation initiation factor 4E binding protein 1 (4EBP1, protein kinase B (Akt or p70 ribosomal S6 kinase (p70S6K phosphorylation. The data suggest that high-protein diets have the potential to reduce weight gain and alter metabolism, possibly through regulation of an mTORC1-dependent pathway in skeletal muscle.

  16. Dehulling reduces toxicity and improves in vivo biological value of proteins in vegetal milk derived from two mucuna (Mucuna pruriens L.) seeds varieties.

    Science.gov (United States)

    Mang, Yannick Dimitry; Njintang, Yanou Nicolas; Abdou, Bouba Armand; Scher, Joel; Bernard, Clémence; Mbofung, Moses C

    2016-06-01

    The present work was carried out to evaluate the nutritive quality (proximate and antinutrients composition) of vegetable milks prepared from whole and dehulled mucuna bean flours. Casein and mucuna milk diets were fed to rats (four weeks old; n = 8 per group) for 28 days to determine protein efficiency ratio (PER), net protein efficiency ratio (NPER), true and apparent digestibility (TD and AD, respectively), organ-to-body weight ratios and hematological parameters. The experimental design was a factorial design with two variety of mucuna (cochinchinensis and veracruz) and two treatments (whole and dehulled beans). Protein, total sugar, dry matter and ash-content of mucuna milks ranged from 6.40 to 12.13 g/100 mL, 10.52 to 13.08 g/100 mL, 8.59 to 12.88 g/100 g and 0.31 to 0.92 g/100 g, respectively. Milks from dehulled flours had lower contents of tannins (80-87.08 %), phytates (76.67-78.16 %) and L-Dopamine (44.45-66.66 %) than that from whole flours. The PER of dehulled mucuna diets were 22.76-21.74 %, but negative PER and low NPER was observed for whole mucuna milk diets. TD for dehulled mucuna milk (85.15-85.96 %) were higher and similar to casein when compared to that of whole mucuna milk (47.87-51.17 %). Rats fed with diets containing whole mucuna milk lost weight and had higher kidney weight. In addition, the rats fed with milk from whole mucuna flours showed significantly lower levels of lymphocytes, granulocytes, red blood cells, hemoglobin and hematocrit than that fed with dehulled mucuna milk.

  17. Automatic pipeline operation using Petri Nets

    Energy Technology Data Exchange (ETDEWEB)

    Moreira, Guilherme O. [PETROBRAS TRANSPORTE S.A., Rio de Janeiro, RJ (Brazil)

    2009-07-01

    A pipeline operation requires several actions, attention and time from the control room operator in each of its operating phases. This article proposition is to use automation as something more than a remote control, drastically reducing the number of repetitive and routine actions needed from the operator to start and stop the system, granting more time for system supervision, decision making during critical conditions and avoiding errors caused due to the need of several actions being executed in a short period of time. To achieve these objectives the pipeline operation will be modeled as a Petri Net consisting of states, event and actions. A methodology for converting this Petri Net into a Ladder controller code will also be proposed. (author)

  18. Net accumulation of the Greenland ice sheet

    DEFF Research Database (Denmark)

    Kiilsholm, Sissi; Christensen, Jens Hesselbjerg; Dethloff, Klaus

    2003-01-01

    High-resolution (50 km) climate change simulations for an area covering the entire Arctic have been conducted with the regional climate model (RCM) HIRHAM. The experiments were forced at the lateral boundary by large-scale atmospheric conditions from transient climate change scenario simulations...... with HIRHAM for periods representing present-day (1961-1990) and the future (2071-2100) in the two scenarios. We find that due to a much better representation of the surface topography in the RCM, the geographical distribution of present-day accumulation rates simulated by the RCM represents a substantial...... improvement compared to the driving OAGCM. Estimates of the regional net balance are also better represented by the RCM. In the future climate the net balance for the Greenland Ice Sheet is reduced in all the simulation, but discrepancies between the amounts when based on ECHAM4/OPYC3 and HIRHAM are found...

  19. Cholesterol Removal from Adult Skeletal Muscle impairs Excitation-Contraction Coupling and Aging reduces Caveolin-3 and alters the Expression of other Triadic Proteins

    Directory of Open Access Journals (Sweden)

    Genaro eBarrientos

    2015-04-01

    Full Text Available Cholesterol and caveolin are integral membrane components that modulate the function/location of many cellular proteins. Skeletal muscle fibers, which have unusually high cholesterol levels in transverse tubules, express the caveolin-3 isoform but its association with transverse tubules remains contentious. Cholesterol removal impairs excitation-contraction coupling in amphibian and mammalian fetal skeletal muscle fibers. Here, we show that treating single muscle fibers from adult mice with the cholesterol removing agent methyl-β-cyclodextrin decreased fiber cholesterol by 26%, altered the location pattern of caveolin-3 and of the voltage dependent calcium channel Cav1.1, and suppressed or reduced electrically evoked Ca2+ transients without affecting membrane integrity or causing sarcoplasmic reticulum calcium depletion. We found that transverse tubules from adult muscle and triad fractions that contain ~10% attached transverse tubules, but not sarcoplasmic reticulum membranes, contained caveolin-3 and Cav1.1; both proteins partitioned into detergent-resistant membrane fractions highly enriched in cholesterol. Aging entails significant deterioration of skeletal muscle function. We found that triad fractions from aged rats had similar cholesterol and RyR1 protein levels compared to triads from young rats, but had lower caveolin-3 and glyceraldehyde 3-phosphate dehydrogenase and increased Na+/K+-ATPase protein levels. Both triad fractions had comparable NADPH oxidase (NOX activity and protein content of NOX2 subunits (p47phox and gp91phox, implying that NOX activity does not increase during aging. These findings show that partial cholesterol removal impairs excitation-contraction coupling and alters caveolin-3 and Cav1.1 location pattern, and that aging reduces caveolin-3 protein content and modifies the expression of other triadic proteins. We discuss the possible implications of these findings for skeletal muscle function in young and aged

  20. Moderate carbohydrate, moderate protein weight loss diet reduces cardiovascular disease risk compared to high carbohydrate, low protein diet in obese adults: A randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Evans Ellen M

    2008-11-01

    Full Text Available Abstract Background To evaluate the metabolic effects of two weight loss diets differing in macronutrient composition on features of dyslipidemia and post-prandial insulin (INS response to a meal challenge in overweight/obese individuals. Methods This study was a parallel-arm randomized 4 mo weight loss trial. Adults (n = 50, 47 ± 7 y matched on BMI (33.6 ± 0.6 kg/m2, P = 0.79 consumed energy restricted diets (deficit ~500 kcal/d: PRO (1.6 g.kg-1.d-1 protein and -1.d-1 protein and > 220 g/d carbohydrate for 4 mos. Meal challenges of respective diets were utilized for determination of blood lipids and post-prandial INS and glucose response at the beginning and end of the study. Results There was a trend for PRO to lose more weight (-9.1% vs. -7.3%, P = 0.07 with a significant reduction in percent fat mass compared to CHO (-8.7% vs. -5.7%; P = 0.03. PRO also favored reductions in triacylglycerol (-34% vs. -14%; P P = 0.05; however, CHO favored reduction in LDL-C (-7% vs. +2.5%; P P P Conclusion A weight loss diet with moderate carbohydrate, moderate protein results in more favorable changes in body composition, dyslipidemia, and post-prandial INS response compared to a high carbohydrate, low protein diet suggesting an additional benefit beyond weight management to include augmented risk reduction for metabolic disease.

  1. Inhibition of Cartilage Acidic Protein 1 Reduces Ultraviolet B Irradiation Induced-Apoptosis through P38 Mitogen-Activated Protein Kinase and Jun Amino-Terminal Kinase Pathways

    OpenAIRE

    Yinghong Ji; Xianfang Rong; Dan Li; Lei Cai; Jun Rao; Yi Lu

    2016-01-01

    Background/Aims: Ultraviolet B (UVB) irradiation can easily induce apoptosis in human lens epithelial cells (HLECs) and further lead to various eye diseases including cataract. Here for the first time, we investigated the role of cartilage acidic protein 1 (CRTAC1) gene in UVB irradiation induced-apoptosis in HLECs. Methods: Three groups of HLECs were employed including model group, empty vector group, and CRTAC1 interference group. Results: After UVB irradiation, the percentage of primary ap...

  2. The potent, indirect adenosine monophosphate-activated protein kinase activator R419 attenuates mitogen-activated protein kinase signaling, inhibits nociceptor excitability, and reduces pain hypersensitivity in mice

    Directory of Open Access Journals (Sweden)

    Galo L. Mejia

    2016-07-01

    Full Text Available Abstract. There is a great need for new therapeutics for the treatment of pain. A possible avenue to development of such therapeutics is to interfere with signaling pathways engaged in peripheral nociceptors that cause these neurons to become hyperexcitable. There is strong evidence that mitogen-activated protein kinases and phosphoinositide 3-kinase (PI3K/mechanistic target of rapamycin signaling pathways are key modulators of nociceptor excitability in vitro and in vivo. Activation of adenosine monophosphate-activated protein kinase (AMPK can inhibit signaling in both of these pathways, and AMPK activators have been shown to inhibit nociceptor excitability and pain hypersensitivity in rodents. R419 is one of, if not the most potent AMPK activator described to date. We tested whether R419 activates AMPK in dorsal root ganglion (DRG neurons and if this leads to decreased pain hypersensitivity in mice. We find that R419 activates AMPK in DRG neurons resulting in decreased mitogen-activated protein kinase signaling, decreased nascent protein synthesis, and enhanced P body formation. R419 attenuates nerve growth factor (NGF-induced changes in excitability in DRG neurons and blocks NGF-induced mechanical pain amplification in vivo. Moreover, locally applied R419 attenuates pain hypersensitivity in a model of postsurgical pain and blocks the development of hyperalgesic priming in response to both NGF and incision. We conclude that R419 is a promising lead candidate compound for the development of potent and specific AMPK activation to inhibit pain hypersensitivity as a result of injury.

  3. KM3NeT

    CERN Multimedia

    KM3NeT is a large scale next-generation neutrino telescope located in the deep waters of the Mediterranean Sea, optimized for the discovery of galactic neutrino sources emitting in the TeV energy region.

  4. PolicyNet Publication System

    Data.gov (United States)

    Social Security Administration — The PolicyNet Publication System project will merge the Oracle-based Policy Repository (POMS) and the SQL-Server CAMP system (MSOM) into a new system with an Oracle...

  5. Net Neutrality: Background and Issues

    National Research Council Canada - National Science Library

    Gilroy, Angele A

    2006-01-01

    .... The move to place restrictions on the owners of the networks that compose and provide access to the Internet, to ensure equal access and nondiscriminatory treatment, is referred to as "net neutrality...

  6. Protein intakes are associated with reduced length of stay: a comparison between Enhanced Recovery After Surgery (ERAS) and conventional care after elective colorectal surgery.

    Science.gov (United States)

    Yeung, Sophia E; Hilkewich, Leslee; Gillis, Chelsia; Heine, John A; Fenton, Tanis R

    2017-07-01

    Background: Protein can modulate the surgical stress response and postoperative catabolism. Enhanced Recovery After Surgery (ERAS) protocols are evidence-based care bundles that reduce morbidity. Objective: In this study, we compared protein adequacy as well as energy intakes, gut function, clinical outcomes, and how well nutritional variables predict length of hospital stay (LOS) in patients receiving ERAS protocols and conventional care. Design: We conducted a prospective cohort study in adult elective colorectal resection patients after conventional ( n = 46) and ERAS ( n = 69) care. Data collected included preoperative Malnutrition Screening Tool (MST) score, 3-d food records, postoperative nausea, LOS, and complications. Multivariable regression analysis assessed whether low protein intakes and the MST score were predictive of LOS. Results: Total protein intakes were significantly higher in the ERAS group due to the inclusion of oral nutrition supplements (conventional group: 0.33 g · kg -1 · d -1 ; ERAS group: 0.54 g · kg -1 · d -1 ; P Nutrition variables were independent predictors of earlier discharge after potential confounders were controlled for. Each unit increase in preoperative MST score predicted longer LOSs of 2.5 d (95% CI: 1.5, 3.5 d; P nutrition supplements. However, total protein intake remained inadequate to meet recommendations. Consumption of ≥60% protein needs after surgery and MST scores were independent predictors of LOS. This trial was registered at clinicaltrials.gov as NCT02940665. © 2017 American Society for Nutrition.

  7. Analisis Determinan Net Ekspor Indonesia

    OpenAIRE

    Daulay, Rahmawaty

    2010-01-01

    This study is to analyzing empirically among Indonesia GDP, trade partnership GDP (Malaysia, Singapore, US and Thailand) and real exchange rate toward Indonesia Net Export. To find out which one from those three variables is significant in order to fluctuating (increasing or decreasing) Indonesia Net Export either in the short run or in the long run. Data collection is obtained using secondary data, namely Indonesia GDP, Malaysia GDP, Singapura GDP, US GDP, Thailand GDP and real exchange rate...

  8. NetBeans GUI Builder

    OpenAIRE

    Pusiankova, Tatsiana

    2009-01-01

    This work aims at making readers familiar with the powerful tool NetBeans IDE GUI Builder and helping them make their first steps to creation of their own graphical user interface in the Java programming language. The work includes theoretical description of NetBeans IDE GUI Builder, its most important characteristics and peculiarities and also a set of practical instructions that will help readers in creation of their first GUI. The readers will be introduced to the environment of this tool ...

  9. PNet: A Python Library for Petri Net Modeling and Simulation

    OpenAIRE

    Zhu En Chay; Bing Feng Goh; Maurice HT Ling

    2016-01-01

    Petri Net is a formalism to describe changes between 2 or more states across discrete time and has been used to model many systems. We present PNet – a pure Python library for Petri Net modeling and simulation in Python programming language. The design of PNet focuses on reducing the learning curve needed to define a Petri Net by using a text-based language rather than programming constructs to define transition rules. Complex transition rules can be refined as regular Python functions. To de...

  10. NetProt: Complex-based Feature Selection.

    Science.gov (United States)

    Goh, Wilson Wen Bin; Wong, Limsoon

    2017-08-04

    Protein complex-based feature selection (PCBFS) provides unparalleled reproducibility with high phenotypic relevance on proteomics data. Currently, there are five PCBFS paradigms, but not all representative methods have been implemented or made readily available. To allow general users to take advantage of these methods, we developed the R-package NetProt, which provides implementations of representative feature-selection methods. NetProt also provides methods for generating simulated differential data and generating pseudocomplexes for complex-based performance benchmarking. The NetProt open source R package is available for download from https://github.com/gohwils/NetProt/releases/ , and online documentation is available at http://rpubs.com/gohwils/204259 .

  11. Multiflavor string-net models

    Science.gov (United States)

    Lin, Chien-Hung

    2017-05-01

    We generalize the string-net construction to multiple flavors of strings, each of which is labeled by the elements of an Abelian group Gi. The same flavor of strings can branch, while different flavors of strings can cross one another and thus they form intersecting string nets. We systematically construct the exactly soluble lattice Hamiltonians and the ground-state wave functions for the intersecting string-net condensed phases. We analyze the braiding statistics of the low-energy quasiparticle excitations and find that our model can realize all the topological phases as the string-net model with group G =∏iGi . In this respect, our construction provides various ways of building lattice models which realize topological order G , corresponding to different partitions of G and thus different flavors of string nets. In fact, our construction concretely demonstrates the Künneth formula by constructing various lattice models with the same topological order. As an example, we construct the G =Z2×Z2×Z2 string-net model which realizes a non-Abelian topological phase by properly intersecting three copies of toric codes.

  12. Optimization of Protein Extraction from Spirulina platensis to Generate a Potential Co-Product and a Biofuel Feedstock with Reduced Nitrogen Content

    Energy Technology Data Exchange (ETDEWEB)

    Parimi, Naga Sirisha; Singh, Manjinder; Kastner, James R.; Das, Keshav C., E-mail: kdas@engr.uga.edu [College of Engineering, The University of Georgia, Athens, GA (United States); Forsberg, Lennart S.; Azadi, Parastoo [Complex Carbohydrate Research Center, The University of Georgia, Athens, GA (United States)

    2015-06-23

    The current work reports protein extraction from Spirulina platensis cyanobacterial biomass in order to simultaneously generate a potential co-product and a biofuel feedstock with reduced nitrogen content. S. platensis cells were subjected to cell disruption by high-pressure homogenization and subsequent protein isolation by solubilization at alkaline pH followed by precipitation at acidic pH. Response surface methodology was used to optimize the process parameters – pH, extraction (solubilization/precipitation) time and biomass concentration for obtaining maximum protein yield. The optimized process conditions were found to be pH 11.38, solubilization time of 35 min and biomass concentration of 3.6% (w/w) solids for the solubilization step, and pH 4.01 and precipitation time of 60 min for the precipitation step. At the optimized conditions, a high protein yield of 60.7% (w/w) was obtained. The protein isolate (co-product) had a higher protein content [80.6% (w/w)], lower ash [1.9% (w/w)] and mineral content and was enriched in essential amino acids, the nutritious γ-linolenic acid and other high-value unsaturated fatty acids compared to the original biomass. The residual biomass obtained after protein extraction had lower nitrogen content and higher total non-protein content than the original biomass. The loss of about 50% of the total lipids from this fraction did not impact its composition significantly owing to the low lipid content of S. platensis (8.03%).

  13. Optimization of Protein Extraction from Spirulina platensis to Generate a Potential Co-Product and a Biofuel Feedstock with Reduced Nitrogen Content

    International Nuclear Information System (INIS)

    Parimi, Naga Sirisha; Singh, Manjinder; Kastner, James R.; Das, Keshav C.; Forsberg, Lennart S.; Azadi, Parastoo

    2015-01-01

    The current work reports protein extraction from Spirulina platensis cyanobacterial biomass in order to simultaneously generate a potential co-product and a biofuel feedstock with reduced nitrogen content. S. platensis cells were subjected to cell disruption by high-pressure homogenization and subsequent protein isolation by solubilization at alkaline pH followed by precipitation at acidic pH. Response surface methodology was used to optimize the process parameters – pH, extraction (solubilization/precipitation) time and biomass concentration for obtaining maximum protein yield. The optimized process conditions were found to be pH 11.38, solubilization time of 35 min and biomass concentration of 3.6% (w/w) solids for the solubilization step, and pH 4.01 and precipitation time of 60 min for the precipitation step. At the optimized conditions, a high protein yield of 60.7% (w/w) was obtained. The protein isolate (co-product) had a higher protein content [80.6% (w/w)], lower ash [1.9% (w/w)] and mineral content and was enriched in essential amino acids, the nutritious γ-linolenic acid and other high-value unsaturated fatty acids compared to the original biomass. The residual biomass obtained after protein extraction had lower nitrogen content and higher total non-protein content than the original biomass. The loss of about 50% of the total lipids from this fraction did not impact its composition significantly owing to the low lipid content of S. platensis (8.03%).

  14. Hydrolysis with Cucurbita ficifolia serine protease reduces antigenic response to bovine whey protein concentrate and αs-casein.

    Science.gov (United States)

    Babij, Konrad; Bajzert, Joanna; Dąbrowska, Anna; Szołtysik, Marek; Zambrowicz, Aleksandra; Lubec, Gert; Stefaniak, Tadeusz; Willak-Janc, Ewa; Chrzanowska, Józefa

    2015-11-01

    In the present study the effect of hydrolysis with non-commercial Cucurbita ficifolia serine protease on a reduction of the IgE and IgG binding capacity of whey protein concentrate and αs-casein was investigated. The intensity of the protein degradation was analyzed by the degree of hydrolysis, the free amino groups content and RP-HPLC. The ability to bind the antibodies by native proteins and their hydrolysates was determined using a competitive ELISA test. Deep hydrolysis contributed to a significant reduction of immunoreactive epitopes present in WPC. In the case of IgE and IgG present in the serum pool of children with CMA, the lowest binding capacity was detected in the 24 h WPC hydrolysate, where the inhibition of the reaction with native WPC was ≤23 and ≤60 %, respectively. The analysis of the IgG reactivity in the antiserum of the immunized goat showed that the lowest antibody binding capacity was exhibited also by 24 h WPC hydrolysate at a concentration of 1000 μg/ml where the inhibition of the reaction with nWPC was ≤47 %. One-hour hydrolysis of α-casein was sufficient to significant reduction of the protein antigenicity, while the longer time (5 h) of hydrolysis probably lead to the appearance of new epitopes reactive with polyclonal.

  15. Interactive effect of reduced pollen availability and Varroa destructor infestation limits growth and protein content of young honey bees

    NARCIS (Netherlands)

    Dooremalen, van C.; Stam, E.; Gerritsen, L.J.M.; Cornelissen, B.; Steen, van der J.J.M.; Langevelde, van F.; Blacquiere, T.

    2013-01-01

    Varroa destructor in combination with one or more stressors, such as low food availability or chemical exposure, is considered to be one of the main causes for honey bee colony losses. We examined the inter-active effect of pollen availability on the protein content and body weight of young bees

  16. High plasma cholesteryl ester transfer protein levels may favour reduced incidence of cardiovascular events in men with low triglycerides

    NARCIS (Netherlands)

    Borggreve, Susanna E.; Hillege, Hans L.; Dallinga-Thie, Geesje M.; de Jong, Paul E.; Wolffenbuttel, Bruce H. R.; Grobbee, Diederik E.; van Tol, Arie; Dullaart, Robin P. F.

    Aims High cholesteryl ester transfer protein (CETP) concentrations are associated with increased risk of cardiovascular disease (CVD) in subjects with high triglycerides. We determined the relationship of plasma CETP with incident CVD in a population with relatively low triglycerides. Methods and

  17. PSI/TM-Coffee: a web server for fast and accurate multiple sequence alignments of regular and transmembrane proteins using homology extension on reduced databases.

    Science.gov (United States)

    Floden, Evan W; Tommaso, Paolo D; Chatzou, Maria; Magis, Cedrik; Notredame, Cedric; Chang, Jia-Ming

    2016-07-08

    The PSI/TM-Coffee web server performs multiple sequence alignment (MSA) of proteins by combining homology extension with a consistency based alignment approach. Homology extension is performed with Position Specific Iterative (PSI) BLAST searches against a choice of redundant and non-redundant databases. The main novelty of this server is to allow databases of reduced complexity to rapidly perform homology extension. This server also gives the possibility to use transmembrane proteins (TMPs) reference databases to allow even faster homology extension on this important category of proteins. Aside from an MSA, the server also outputs topological prediction of TMPs using the HMMTOP algorithm. Previous benchmarking of the method has shown this approach outperforms the most accurate alignment methods such as MSAProbs, Kalign, PROMALS, MAFFT, ProbCons and PRALINE™. The web server is available at http://tcoffee.crg.cat/tmcoffee. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. Inhibition of Poliovirus-Induced Cleavage of Cellular Protein PCBP2 Reduces the Levels of Viral RNA Replication

    Science.gov (United States)

    Chase, Amanda J.; Daijogo, Sarah

    2014-01-01

    ABSTRACT Due to their small genome size, picornaviruses must utilize host proteins to mediate cap-independent translation and viral RNA replication. The host RNA-binding protein poly(rC) binding protein 2 (PCBP2) is involved in both processes in poliovirus infected cells. It has been shown that the viral proteinase 3CD cleaves PCBP2 and contributes to viral translation inhibition. However, cleaved PCBP2 remains active in viral RNA replication. This would suggest that both cleaved and intact forms of PCBP2 have a role in the viral RNA replication cycle. The picornavirus genome must act as a template for both translation and RNA replication. However, a template that is actively being translated cannot function as a template for RNA replication, suggesting that there is a switch in template usage from translation to RNA replication. We demonstrate that the cleavage of PCBP2 by the poliovirus 3CD proteinase is a necessary step for efficient viral RNA replication and, as such, may be important for mediating a switch in template usage from translation to RNA replication. IMPORTANCE Poliovirus, like all positive-strand RNA viruses that replicate in the cytoplasm of eukaryotic cells, uses its genomic RNA as a template for both viral protein synthesis and RNA replication. Given that these processes cannot occur simultaneously on the same template, poliovirus has evolved a mechanism(s) to facilitate the switch from using templates for translation to using them for RNA synthesis. This study explores one possible scenario for how the virus alters the functions of a host cell RNA binding protein to mediate, in part, this important transition. PMID:24371074

  19. Omega-3 fatty acid docosahexaenoic acid increases SorLA/LR11, a sorting protein with reduced expression in sporadic Alzheimer's disease (AD): relevance to AD prevention.

    Science.gov (United States)

    Ma, Qiu-Lan; Teter, Bruce; Ubeda, Oliver J; Morihara, Takashi; Dhoot, Dilsher; Nyby, Michael D; Tuck, Michael L; Frautschy, Sally A; Cole, Greg M

    2007-12-26

    Environmental and genetic factors, notably ApoE4, contribute to the etiology of late-onset Alzheimer's disease (LOAD). Reduced mRNA and protein for an apolipoprotein E (ApoE) receptor family member, SorLA (LR11) has been found in LOAD but not early-onset AD, suggesting that LR11 loss is not secondary to pathology. LR11 is a neuronal sorting protein that reduces amyloid precursor protein (APP) trafficking to secretases that generate beta-amyloid (Abeta). Genetic polymorphisms that reduce LR11 expression are associated with increased AD risk. However these polymorphisms account for only a fraction of cases with LR11 deficits, suggesting involvement of environmental factors. Because lipoprotein receptors are typically lipid-regulated, we postulated that LR11 is regulated by docosahexaenoic acid (DHA), an essential omega-3 fatty acid related to reduced AD risk and reduced Abeta accumulation. In this study, we report that DHA significantly increases LR11 in multiple systems, including primary rat neurons, aged non-Tg mice and an aged DHA-depleted APPsw AD mouse model. DHA also increased LR11 in a human neuronal line. In vivo elevation of LR11 was also observed with dietary fish oil in young rats with insulin resistance, a model for type II diabetes, another AD risk factor. These data argue that DHA induction of LR11 does not require DHA-depleting diets and is not age dependent. Because reduced LR11 is known to increase Abeta production and may be a significant genetic cause of LOAD, our results indicate that DHA increases in SorLA/LR11 levels may play an important role in preventing LOAD.

  20. Elevated CO2 plus chronic warming reduce nitrogen uptake and levels or activities of nitrogen-uptake and -assimilatory proteins in tomato roots.

    Science.gov (United States)

    Jayawardena, Dileepa M; Heckathorn, Scott A; Bista, Deepesh R; Mishra, Sasmita; Boldt, Jennifer K; Krause, Charles R

    2017-03-01

    Atmospheric CO 2 enrichment is expected to often benefit plant growth, despite causing global warming and nitrogen (N) dilution in plants. Most plants primarily procure N as inorganic nitrate (NO 3 - ) or ammonium (NH 4 + ), using membrane-localized transport proteins in roots, which are key targets for improving N use. Although interactive effects of elevated CO 2 , chronic warming and N form on N relations are expected, these have not been studied. In this study, tomato (Solanum lycopersicum) plants were grown at two levels of CO 2 (400 or 700 ppm) and two temperature regimes (30 or 37°C), with NO 3 - or NH 4 + as the N source. Elevated CO 2 plus chronic warming severely inhibited plant growth, regardless of N form, while individually they had smaller effects on growth. Although %N in roots was similar among all treatments, elevated CO 2 plus warming decreased (1) N-uptake rate by roots, (2) total protein concentration in roots, indicating an inhibition of N assimilation and (3) shoot %N, indicating a potential inhibition of N translocation from roots to shoots. Under elevated CO 2 plus warming, reduced NO 3 - -uptake rate per g root was correlated with a decrease in the concentration of NO 3 - -uptake proteins per g root, reduced NH 4 + uptake was correlated with decreased activity of NH 4 + -uptake proteins and reduced N assimilation was correlated with decreased concentration of N-assimilatory proteins. These results indicate that elevated CO 2 and chronic warming can act synergistically to decrease plant N uptake and assimilation; hence, future global warming may decrease both plant growth and food quality (%N). © 2016 Scandinavian Plant Physiology Society.

  1. Studies of the aggregation of mutant proteins in vitro provide insights into the genetics of amyloid diseases.

    Science.gov (United States)

    Chiti, Fabrizio; Calamai, Martino; Taddei, Niccolo; Stefani, Massimo; Ramponi, Giampietro; Dobson, Christopher M

    2002-12-10

    Protein aggregation and the formation of highly insoluble amyloid structures is associated with a range of debilitating human conditions, which include Alzheimer's disease, Parkinson's disease, and the Creutzfeldt-Jakob disease. Muscle acylphosphatase (AcP) has already provided significant insights into mutational changes that modulate amyloid formation. In the present paper, we have used this system to investigate the effects of mutations that modify the charge state of a protein without affecting significantly the hydrophobicity or secondary structural propensities of the polypeptide chain. A highly significant inverse correlation was found to exist between the rates of aggregation of the protein variants under denaturing conditions and their overall net charge. This result indicates that aggregation is generally favored by mutations that bring the net charge of the protein closer to neutrality. In light of this finding, we have analyzed natural mutations associated with familial forms of amyloid diseases that involve alteration of the net charge of the proteins or protein fragments associated with the diseases. Sixteen mutations have been identified for which the mechanism of action that causes the pathological condition is not yet known or fully understood. Remarkably, 14 of these 16 mutations cause the net charge of the corresponding peptide or protein that converts into amyloid deposits to be reduced. This result suggests that charge has been a key parameter in molecular evolution to ensure the avoidance of protein aggregation and identifies reduction of the net charge as an important determinant in at least some forms of protein deposition diseases.

  2. Heterologous expression of a plastid EF-Tu reduces protein thermal aggregation and enhances CO2 fixation in wheat (Triticum aestivum) following heat stress.

    Science.gov (United States)

    Fu, Jianming; Momcilović, Ivana; Clemente, Thomas E; Nersesian, Natalya; Trick, Harold N; Ristic, Zoran

    2008-10-01

    Heat stress is a major constraint to wheat production and negatively impacts grain quality, causing tremendous economic losses, and may become a more troublesome factor due to global warming. At the cellular level, heat stress causes denaturation and aggregation of proteins and injury to membranes leading to alterations in metabolic fluxes. Protein aggregation is irreversible, and protection of proteins from thermal aggregation is a strategy a cell uses to tolerate heat stress. Here we report on the development of transgenic wheat (Triticum aestivum) events, expressing a maize gene coding for plastidal protein synthesis elongation factor (EF-Tu), which, compared to non-transgenic plants, display reduced thermal aggregation of leaf proteins, reduced heat injury to photosynthetic membranes (thylakoids), and enhanced rate of CO(2) fixation after exposure to heat stress. The results support the concept that EF-Tu ameliorates negative effects of heat stress by acting as a molecular chaperone. This is the first demonstration of the introduction of a plastidal EF-Tu in plants that leads to protection against heat injury and enhanced photosynthesis after heat stress. This is also the first demonstration that a gene other than HSP gene can be used for improvement of heat tolerance and that the improvement is possible in a species that has a complex genome, hexaploid wheat. The results strongly suggest that heat tolerance of wheat, and possibly other crop plants, can be improved by modulating expression of plastidal EF-Tu and/or by selection of genotypes with increased endogenous levels of this protein.

  3. Multigenerational effects of a reduced balanced protein diet during the rearing and laying period of broiler breeders. 1. Performance of the F1 breeder generation.

    Science.gov (United States)

    Lesuisse, J; Li, C; Schallier, S; Clímaco, W L S; Bautil, A; Everaert, N; Buyse, J

    2018-05-01

    Studies on mammals and poultry showed that maternal dietary treatments can alter the offspring performance. However, in contrast to rodent studies, little is known about multigenerational dietary manipulations in broiler breeders. The presented research aimed to investigate the effects of a reduction of 25% in the dietary crude protein (CP) level in the F0 generation on the body composition and reproductive performance of F1 broiler breeders. In the F0 generation, breeders were fed either a control (C) or reduced balanced protein (RP) diet, 25% reduction in crude protein and amino acids. Female F0-progeny of each treatment were fed a C or RP diet, resulting in 4 treatments in the F1 breeder generation: C/C, C/RP, RP/C, and RP/RP. The reproductive performance of breeders fed RP diets was negatively influenced by the dietary CP reduction in the F1 generation (P diets in the F0 generation showed a significantly reduced reproductive capacity compared to their control fed counterparts (P diets in the F1 generation were characterized by higher plasma T3 concentrations (P diets in the F0 generation needed lower feed allocations in the laying phase to maintain a similar body weight. Egg weight was reduced for the C/RP and RP/RP breeders. At 34 wk of age, eggs from C/RP and RP/RP breeders showed a reduced proportional albumen weight, whereas no effects on egg composition were found at 42 wk of age. It was concluded that prenatal protein undernutrition triggered hens to relocate more energy towards growth and maintenance and less towards reproductive capacity.

  4. CSF Tau proteins reduce misdiagnosis of sporadic Creutzfeldt-Jakob disease suspected cases with inconclusive 14-3-3 result.

    Science.gov (United States)

    Leitão, M J; Baldeiras, I; Almeida, M R; Ribeiro, M H; Santos, A C; Ribeiro, M; Tomás, J; Rocha, S; Santana, I; Oliveira, C R

    2016-09-01

    Cerebrospinal fluid (CSF) 14-3-3 protein supports sporadic Creutzfeldt-Jakob (sCJD) diagnosis, but often leads to weak-positive results and lacks standardization. In this study, we explored the added diagnostic value of Total Tau (t-Tau) and phosphorylated Tau (p-Tau) in sCJD diagnosis, particularly in the cases with inconclusive 14-3-3 result. 95 definite sCJD and 287 patients without prion disease (non-CJD) were included in this study. CSF samples were collected in routine clinical diagnosis and analysed for 14-3-3 detection by Western blot (WB). CSF t-Tau and p-Tau were quantified by commercial ELISA kits and PRNP and APOE genotyping assessed by PCR-RFLP. In a regression analysis of the whole cohort, 14-3-3 protein revealed an overall accuracy of 82 % (sensitivity = 96.7 %; specificity = 75.6 %) for sCJD. Regarding 14-3-3 clear positive results, we observed no added value either of t-Tau alone or p-Tau/t-Tau ratio in the model. On the other hand, considering 14-3-3 weak-positive cases, t-Tau protein increased the overall accuracy of 14-3-3 alone from 91 to 94 % and specificity from 74 to 93 % (p < 0.05), with no sensitivity improvement. However, inclusion of p-Tau/t-Tau ratio did not significantly improve the first model (p = 0.0595). Globally, t-Tau protein allowed a further discrimination of 65 % within 14-3-3 inconclusive results. Furthermore, PRNP MV genotype showed a trend to decrease 14-3-3 sensitivity (p = 0.051), but such effect was not seen on t-Tau protein. In light of these results, we suggest that t-Tau protein assay is of significant importance as a second marker in identifying 14-3-3 false-positive results among sCJD probable cases.

  5. Acetone utilization by sulfate-reducing bacteria: draft genome sequence of Desulfococcus biacutus and a proteomic survey of acetone-inducible proteins.

    Science.gov (United States)

    Gutiérrez Acosta, Olga B; Schleheck, David; Schink, Bernhard

    2014-07-11

    The sulfate-reducing bacterium Desulfococcus biacutus is able to utilize acetone for growth by an inducible degradation pathway that involves a novel activation reaction for acetone with CO as a co-substrate. The mechanism, enzyme(s) and gene(s) involved in this acetone activation reaction are of great interest because they represent a novel and yet undefined type of activation reaction under strictly anoxic conditions. In this study, a draft genome sequence of D. biacutus was established. Sequencing, assembly and annotation resulted in 159 contigs with 5,242,029 base pairs and 4773 predicted genes; 4708 were predicted protein-encoding genes, and 3520 of these had a functional prediction. Proteins and genes were identified that are specifically induced during growth with acetone. A thiamine diphosphate-requiring enzyme appeared to be highly induced during growth with acetone and is probably involved in the activation reaction. Moreover, a coenzyme B12- dependent enzyme and proteins that are involved in redox reactions were also induced during growth with acetone. We present for the first time the genome of a sulfate reducer that is able to grow with acetone. The genome information of this organism represents an important tool for the elucidation of a novel reaction mechanism that is employed by a sulfate reducer in acetone activation.

  6. Maternal protein-energy malnutrition during early pregnancy in sheep impacts the fetal ornithine cycle to reduce fetal kidney microvascular development.

    Science.gov (United States)

    Dunford, Louise J; Sinclair, Kevin D; Kwong, Wing Y; Sturrock, Craig; Clifford, Bethan L; Giles, Tom C; Gardner, David S

    2014-11-01

    This paper identifies a common nutritional pathway relating maternal through to fetal protein-energy malnutrition (PEM) and compromised fetal kidney development. Thirty-one twin-bearing sheep were fed either a control (n=15) or low-protein diet (n=16, 17 vs. 8.7 g crude protein/MJ metabolizable energy) from d 0 to 65 gestation (term, ∼ 145 d). Effects on the maternal and fetal nutritional environment were characterized by sampling blood and amniotic fluid. Kidney development was characterized by histology, immunohistochemistry, vascular corrosion casts, and molecular biology. PEM had little measureable effect on maternal and fetal macronutrient balance (glucose, total protein, total amino acids, and lactate were unaffected) or on fetal growth. PEM decreased maternal and fetal urea concentration, which blunted fetal ornithine availability and affected fetal hepatic polyamine production. For the first time in a large animal model, we associated these nutritional effects with reduced micro- but not macrovascular development in the fetal kidney. Maternal PEM specifically impacts the fetal ornithine cycle, affecting cellular polyamine metabolism and microvascular development of the fetal kidney, effects that likely underpin programming of kidney development and function by a maternal low protein diet. © FASEB.

  7. Excess of methyl donor in the perinatal period reduces postnatal leptin secretion in rat and interacts with the effect of protein content in diet.

    Directory of Open Access Journals (Sweden)

    Fanny Giudicelli

    Full Text Available Methionine, folic acid, betaine and choline interact in the one-carbon metabolism which provides methyl groups for methylation reactions. An optimal intake of these nutrients during pregnancy is required for successful completion of fetal development and evidence is growing that they could be involved in metabolic long-term programming. However, the biological pathways involved in the action of these nutrients are still poorly known. This study investigated the interaction between methyl donors and protein content in maternal diet during the preconceptual, pregnancy and lactation periods and the consequences on the rat offspring in the short and long term. Methyl donor supplementation reduced leptin secretion in offspring, whereas insulin levels were mostly affected by protein restriction. The joint effect of protein restriction and methyl donor excess strongly impaired postnatal growth in both gender and long term weight gain in male offspring only, without affecting food intake. In addition, rats born from protein restricted and methyl donor supplemented dams gained less weight when fed a hypercaloric diet. Methylation of the leptin gene promoter in adipose tissue was increased in methyl donor supplemented groups but not affected by protein restriction only. These results suggest that maternal methyl donor supplementation may influence energy homeostasis in a gender-dependent manner, without affecting food intake. Moreover, we showed that macronutrients and micronutrients in maternal diet interact to influence the programming of the offspring.

  8. Antimicrobial treatment reduces intestinal microflora and improves protein digestive capacity without changes in villous structure in weanling pigs

    DEFF Research Database (Denmark)

    Thymann, Thomas; Sørensen, Kristina U.; Hedemann, Mette S.

    2007-01-01

    The immediate post-weaning period is often associated with gut malfunction and diarrhoea for young pigs. Administration of antimicrobials remains an effective way to control weaning diarrhoea but it remains unclear how they affect gut physiology and microbiology although this is a prerequisite fo...... that the beneficial effects of antimicrobials are mediated not only through reduction in intestinal bacteria] load, but also through a stimulation of protein digestive function and goblet cell density....

  9. Immunization with Brucella VirB proteins reduces organ colonization in mice through a Th1-type immune response and elicits a similar immune response in dogs.

    Science.gov (United States)

    Pollak, Cora N; Wanke, María Magdalena; Estein, Silvia M; Delpino, M Victoria; Monachesi, Norma E; Comercio, Elida A; Fossati, Carlos A; Baldi, Pablo C

    2015-03-01

    VirB proteins from Brucella spp. constitute the type IV secretion system, a key virulence factor mediating the intracellular survival of these bacteria. Here, we assessed whether a Th1-type immune response against VirB proteins may protect mice from Brucella infection and whether this response can be induced in the dog, a natural host for Brucella. Splenocytes from mice immunized with VirB7 or VirB9 responded to their respective antigens with significant and specific production of gamma interferon (IFN-γ), whereas interleukin-4 (IL-4) was not detected. Thirty days after an intraperitoneal challenge with live Brucella abortus, the spleen load of bacteria was almost 1 log lower in mice immunized with VirB proteins than in unvaccinated animals. As colonization reduction seemed to correlate with a Th1-type immune response against VirB proteins, we decided to assess whether such a response could be elicited in the dog. Peripheral blood mononuclear cells (PBMCs) from dogs immunized with VirB proteins (three subcutaneous doses in QuilA adjuvant) produced significantly higher levels of IFN-γ than cells from control animals upon in vitro stimulation with VirB proteins. A skin test to assess specific delayed-type hypersensitivity was positive in 4 out of 5 dogs immunized with either VirB7 or VirB9. As both proteins are predicted to locate in the outer membrane of Brucella organisms, the ability of anti-VirB antibodies to mediate complement-dependent bacteriolysis of B. canis was assessed in vitro. Sera from dogs immunized with either VirB7 or VirB9, but not from those receiving phosphate-buffered saline (PBS), produced significant bacteriolysis. These results suggest that VirB-specific responses that reduce organ colonization by Brucella in mice can be also elicited in dogs. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  10. Inhibition of Poly(A)-binding protein with a synthetic RNA mimic reduces pain sensitization in mice.

    Science.gov (United States)

    Barragán-Iglesias, Paulino; Lou, Tzu-Fang; Bhat, Vandita D; Megat, Salim; Burton, Michael D; Price, Theodore J; Campbell, Zachary T

    2018-01-02

    Nociceptors rely on cap-dependent translation to rapidly induce protein synthesis in response to pro-inflammatory signals. Comparatively little is known regarding the role of the regulatory factors bound to the 3' end of mRNA in nociceptor sensitization. Poly(A)-binding protein (PABP) stimulates translation initiation by bridging the Poly(A) tail to the eukaryotic initiation factor 4F complex associated with the mRNA cap. Here, we use unbiased assessment of PABP binding specificity to generate a chemically modified RNA-based competitive inhibitor of PABP. The resulting RNA mimic, which we designated as the Poly(A) SPOT-ON, is more stable than unmodified RNA and binds PABP with high affinity and selectivity in vitro. We show that injection of the Poly(A) SPOT-ON at the site of an injury can attenuate behavioral response to pain. Collectively, these results suggest that PABP is integral for nociceptive plasticity. The general strategy described here provides a broad new source of mechanism-based inhibitors for RNA-binding proteins and is applicable for in vivo studies.

  11. The LMNA mutation p.Arg321Ter associated with dilated cardiomyopathy leads to reduced expression and a skewed ratio of lamin A and lamin C proteins

    Energy Technology Data Exchange (ETDEWEB)

    Al-Saaidi, Rasha [Research Unit for Molecular Medicine, Aarhus University and Aarhus University Hospital, Aarhus (Denmark); Rasmussen, Torsten B. [Department of Cardiology, Aarhus University Hospital, Aarhus (Denmark); Palmfeldt, Johan [Research Unit for Molecular Medicine, Aarhus University and Aarhus University Hospital, Aarhus (Denmark); Nissen, Peter H. [Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus (Denmark); Beqqali, Abdelaziz [Heart Failure Research Center, Academic Medical Center, Amsterdam (Netherlands); Hansen, Jakob [Department of Forensic Medicine, Bioanalytical Unit, University of Aarhus (Denmark); Pinto, Yigal M. [Heart Failure Research Center, Academic Medical Center, Amsterdam (Netherlands); Boesen, Thomas [Department of Molecular Biology and Genetics, University of Aarhus (Denmark); Mogensen, Jens [Department of Cardiology, Odense University Hospital, Odense (Denmark); Bross, Peter, E-mail: peter.bross@ki.au.dk [Research Unit for Molecular Medicine, Aarhus University and Aarhus University Hospital, Aarhus (Denmark)

    2013-11-15

    Dilated cardiomyopathy (DCM) is a disease of the heart muscle characterized by cardiac chamber enlargement and reduced systolic function of the left ventricle. Mutations in the LMNA gene represent the most frequent known genetic cause of DCM associated with disease of the conduction systems. The LMNA gene generates two major transcripts encoding the nuclear lamina major components lamin A and lamin C by alternative splicing. Both haploinsuffiency and dominant negative effects have been proposed as disease mechanism for premature termination codon (PTC) mutations in LMNA. These mechanisms however are still not clearly established. In this study, we used a representative LMNA nonsense mutation, p.Arg321Ter, to shed light on the molecular disease mechanisms. Cultured fibroblasts from three DCM patients carrying this mutation were analyzed. Quantitative reverse transcriptase PCR and sequencing of these PCR products indicated that transcripts from the mutant allele were degraded by the nonsense-mediated mRNA decay (NMD) mechanism. The fact that no truncated mutant protein was detectable in western blot (WB) analysis strengthens the notion that the mutant transcript is efficiently degraded. Furthermore, WB analysis showed that the expression of lamin C protein was reduced by the expected approximately 50%. Clearly decreased lamin A and lamin C levels were also observed by immunofluorescence microscopy analysis. However, results from both WB and nano-liquid chromatography/mass spectrometry demonstrated that the levels of lamin A protein were more reduced suggesting an effect on expression of lamin A from the wild type allele. PCR analysis of the ratio of lamin A to lamin C transcripts showed unchanged relative amounts of lamin A transcript suggesting that the effect on the wild type allele was operative at the protein level. Immunofluorescence microscopy analysis showed no abnormal nuclear morphology of patient fibroblast cells. Based on these data, we propose that

  12. The HCM-linked W792R mutation in cardiac myosin-binding protein C reduces C6 FnIII domain stability.

    Science.gov (United States)

    Smelter, Dan F; de Lange, Willem J; Cai, Wenxuan; Ge, Ying; Ralphe, J Carter

    2018-06-01

    haploinsufficiency. NEW & NOTEWORTHY This study is one of the first to describe a disease mechanism for a missense mutation in cardiac myosin-binding protein C linked to hypertrophic cardiomyopathy. The mutation decreases stability of the fibronectin type III domain and results in substantially reduced mutant protein expression dissonant to transcript abundance.

  13. Wheat bran reduces concentrations of digestible, metabolizable, and net energy in diets fed to pigs, but energy values in wheat bran determined by the difference procedure are not different from values estimated from a linear regression procedure.

    Science.gov (United States)

    Jaworski, N W; Liu, D W; Li, D F; Stein, H H

    2016-07-01

    . The DE, ME, and NE of wheat bran determined using the difference procedure were 2,168, 2,117, and 896 kcal/kg, respectively, and these values were within the 95% confidence interval of the DE (2,285 kcal/kg), ME (2,217 kcal/kg), and NE (961 kcal/kg) estimated by linear regression. In conclusion, increasing the inclusion of wheat bran in a corn-soybean meal based diet reduced energy and nutrient digestibility and heat production as well as DE, ME, and NE of diets, but values for DE, ME, and NE for wheat bran determined using the difference procedure were not different from values determined using linear regression.

  14. Evacuation of the NET vacuum chamber

    International Nuclear Information System (INIS)

    Muller, R.A.

    1987-01-01

    Parametric calculations of the evacuation process were carried out for the NET-vacuum chamber involving two blanket designs. The results show that with an acceptable vacuum pumping capacity the required start vacuum conditions can be realized within reasonable time. The two blanket concepts do not differ remarkably in their evacuation behaviour. The remaining large pressure differences between the different locations of the vacuum chamber can be reduced if approximately 30% of the total gas flow is extracted from the heads of the blanket replacement ports

  15. Evacuation of the NET vacuum chamber

    International Nuclear Information System (INIS)

    Mueller, R.

    1986-01-01

    Parametric calculations of the evacuation process were carried out for the NET-vacuum chamber involving two blanket designs. The results show that with an acceptable vacuum pumping capacity the required start vacuum conditions can be realized within reasonable time. The two blanket concepts do not differ remarkably in their evacuation behaviour. The remaining large pressure differences between the different locations of the vacuum chamber can be reduced if approximately 30% of the total gas flow is extracted from the heads of the blanket replacement ports. (author)

  16. Population preference of net texture prior to bed net trial in Kala-Azar-endemic areas.

    Directory of Open Access Journals (Sweden)

    Murari L Das

    Full Text Available Prior to a community-based efficacy trial of long-lasting insecticidal nets (LLINs in the prevention of visceral leishmaniasis (VL; also called kala-azar, a pilot study on preference of tools was held in endemic areas of India and Nepal in September 2005.LLINs made of polyester and polyethylene were distributed to 60 participants, who used the nets sequentially for 7 d. Acceptability and preference were evaluated via indirect indicators through questionnaires at three defined time points before and after use of the LLINs and through focus group discussions (FGDs. In the latter, preferences for color and size were also assessed. Untreated bed nets were owned by 87% of the households prior to the study. All users liked textures of both LLIN types after 7 d of use, but had a slight preference for those made of polyester if they were to recommend a LLIN to relatives or friends (p<0.05, mainly because of their relatively greater softness in comparison to polyethylene LLINs. Users reported that both net types reduced mosquito bites and number of insects, including sand fly (bhusana; genus Phlebotomus, inside the house. Side effects were minor and disappeared quickly.The large-scale intervention trial considered the preferences of the study population to decide on the best tool of intervention--light-blue, rectangular, polyester LLINs of different sizes.

  17. Absence of Non-histone Protein Complexes at Natural Chromosomal Pause Sites Results in Reduced Replication Pausing in Aging Yeast Cells

    Directory of Open Access Journals (Sweden)

    Marleny Cabral

    2016-11-01

    Full Text Available There is substantial evidence that genomic instability increases during aging. Replication pausing (and stalling at difficult-to-replicate chromosomal sites may induce genomic instability. Interestingly, in aging yeast cells, we observed reduced replication pausing at various natural replication pause sites (RPSs in ribosomal DNA (rDNA and non-rDNA locations (e.g., silent replication origins and tRNA genes. The reduced pausing occurs independent of the DNA helicase Rrm3p, which facilitates replication past these non-histone protein-complex-bound RPSs, and is independent of the deacetylase Sir2p. Conditions of caloric restriction (CR, which extend life span, also cause reduced replication pausing at the 5S rDNA and at tRNA genes. In aged and CR cells, the RPSs are less occupied by their specific non-histone protein complexes (e.g., the preinitiation complex TFIIIC, likely because members of these complexes have primarily cytosolic localization. These conditions may lead to reduced replication pausing and may lower replication stress at these sites during aging.

  18. A high protein moderate carbohydrate diet fed at discrete meals reduces early progression of N-methyl-N-nitrosourea-induced breast tumorigenesis in rats

    Directory of Open Access Journals (Sweden)

    Singletary Keith W

    2010-01-01

    Full Text Available Abstract Breast cancer is the most prevalent cancer in American women. Dietary factors are thought to have a strong influence on breast cancer incidence. This study utilized a meal-feeding protocol with female Sprague-Dawley rats to evaluate effects of two ratios of carbohydrate:protein on promotion and early progression of breast tissue carcinomas. Mammary tumors were induced by N-methyl-N-nitrosourea (MNU at 52 d of age. Post-induction, animals were assigned to consume either a low protein high carbohydrate diet (LPHC; 15% and 60% of energy, respectively or a high protein moderate carbohydrate diet (HPMC; 35% and 40% of energy, respectively for 10 wk. Animals were fed 3 meals/day to mimic human absorption and metabolism patterns. The rate of palpable tumor incidence was reduced in HPMC relative to LPHC (12.9 ± 1.4%/wk vs. 18.2 ± 1.3%/wk. At 3 wk, post-prandial serum insulin was larger in the LPHC relative to HPMC (+136.4 ± 33.1 pmol/L vs. +38.1 ± 23.4 pmol/L, while at 10 wk there was a trend for post-prandial IGF-I to be increased in HPMC (P = 0.055. There were no differences in tumor latency, tumor surface area, or cumulative tumor mass between diet groups. The present study provides evidence that reducing the dietary carbohydrate:protein ratio attenuates the development of mammary tumors. These findings are consistent with reduced post-prandial insulin release potentially diminishing the proliferative environment required for breast cancer tumors to progress.

  19. Propofol reduced myocardial contraction of vertebrates partly by mediating the cyclic AMP-dependent protein kinase phosphorylation pathway

    International Nuclear Information System (INIS)

    Sun, Xiaotong; Zhang, Xinyu; Bo, Qiyu; Meng, Tao; Lei, Zhen; Li, Jingxin; Hou, Yonghao; Yu, Xiaoqian; Yu, Jingui

    2016-01-01

    Propofol inhibits myocardial contraction in a dose dependent manner. The present study is designed to examine the effect of propofol on PKA mediated myocardial contraction in the absence of adrenoreceptor agonist. The contraction of isolated rat heart was measured in the presence or absence of PKA inhibitor H89 or propofol, using a pressure transducer. The levels of cAMP and PKA kinase activity were detected by ELISA. The mRNA and total protein or phosphorylation level of PKA and downstream proteins were tested in the presence or absence of PKA inhibitor H89 or propofol, using RT-PCR, QPCR and western blotting. The phosphorylation level of PKA was examined thoroughly using immunofluorescence and PKA activity non-radioactive detection kit. Propofol induced a dose-dependent negative contractile response on the rat heart. The inhibitory effect of high concentration propofol (50 μM) with 45% decease of control could be partly reversed by the PKA inhibitor H89 (10 μM) and the depressant effect of propofol decreased from 45% to 10%. PKA kinase activity was inhibited by propofol in a dose-dependent manner. Propofol also induced a decrease in phosphorylation of PKA, which was also inhibited by H89, but did not alter the production of cAMP and the mRNA levels of PKA. The downstream proteins of PKA, PLN and RyR2 were phosphorylated to a lesser extent with propofol or H89 than control. These results demonstrated that propofol induced a negative myocardial contractile response partly by mediating the PKA phosphorylation pathway.

  20. Reduced expression of granule proteins during extended survival of eosinophils in splenocyte culture with GM-CSF.

    Science.gov (United States)

    Ryu, Seul Hye; Na, Hye Young; Sohn, Moah; Han, Sun Murray; Choi, Wanho; In, Hyunju; Hong, Sookyung; Jeon, Hyejin; Seo, Jun-Young; Ahn, Jongcheol; Park, Chae Gyu

    2016-05-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multifaceted hematopoietic cytokine and the culture of mouse bone marrow with GM-CSF produces a variety of myeloid cells including granulocytes, macrophages, and dendritic cells. In the present study, we cultured mouse splenocytes with GM-CSF and examined the changes in hematopoietic cell populations over a week. Most of the splenic hematopoietic cells disappeared significantly from culture within 6days with or without the presence of GM-CSF. Among the splenic granulocyte populations, only eosinophils fully survived throughout the culture with GM-CSF for more than a week. During 10days of culture with GM-CSF, splenic eosinophils maintained their morphology as well as most of their surface molecules at high levels, including CCR3 and Siglec F. Meanwhile, the expression of mRNAs encoding major basic protein-1 (MBP-1) and eosinophil peroxidase (EPO), two major eosinophil-derived granule proteins, was diminished significantly from the cultured eosinophils. EPO assays also revealed that eosinophils in culture for more than 5days retained 30% or less EPO activity compared to those in uncultured splenocytes. In contrast, culture of splenocytes with GM-CSF did not change the capacity of eosinophils to migrate in response to eotaxin-1. Our results indicate that mouse splenic eosinophils are effectively cultured for lengthy periods while their expression of eosinophil-derived granule proteins is specifically suppressed. The relevance of these findings to eosinophilic inflammatory response is discussed. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  1. Haploinsufficiency of the retinoblastoma protein gene reduces diet-induced obesity, insulin resistance, and hepatosteatosis in mice

    DEFF Research Database (Denmark)

    Mercader, Josep; Ribot, Joan; Murano, Incoronata

    2009-01-01

    Brown adipose tissue activity dissipates energy as heat, and there is evidence that lack of the retinoblastoma protein (pRb) may favor the development of the brown adipocyte phenotype in adipose cells. In this work we assessed the impact of germ-line haploinsufficiency of the pRb gene (Rb) on the...... first evidence that partial deficiency in the Rb gene protects against the development of obesity and associated metabolic disturbances. Key words: brown adipose tissue, white adipose tissue, energy metabolism, genetic animal model....

  2. MATT: Multi Agents Testing Tool Based Nets within Nets

    Directory of Open Access Journals (Sweden)

    Sara Kerraoui

    2016-12-01

    As part of this effort, we propose a model based testing approach for multi agent systems based on such a model called Reference net, where a tool, which aims to providing a uniform and automated approach is developed. The feasibility and the advantage of the proposed approach are shown through a short case study.

  3. Implementing NetScaler VPX

    CERN Document Server

    Sandbu, Marius

    2014-01-01

    An easy-to-follow guide with detailed step-by step-instructions on how to implement the different key components in NetScaler, with real-world examples and sample scenarios.If you are a Citrix or network administrator who needs to implement NetScaler in your virtual environment to gain an insight on its functionality, this book is ideal for you. A basic understanding of networking and familiarity with some of the different Citrix products such as XenApp or XenDesktop is a prerequisite.

  4. Net4Care PHMR Library

    DEFF Research Database (Denmark)

    2014-01-01

    The Net4Care PHMR library contains a) A GreenCDA approach for constructing a data object representing a PHMR document: SimpleClinicalDocument, and b) A Builder which can produce a XML document representing a valid Danish PHMR (following the MedCom profile) document from the SimpleClinicalDocument......The Net4Care PHMR library contains a) A GreenCDA approach for constructing a data object representing a PHMR document: SimpleClinicalDocument, and b) A Builder which can produce a XML document representing a valid Danish PHMR (following the MedCom profile) document from the Simple...

  5. Coloured Petri Nets and the Invariant Method

    DEFF Research Database (Denmark)

    Jensen, Kurt

    1981-01-01

    processes to be described by a common subnet, without losing the ability to distinguish between them. Our generalization, called coloured Petri nets, is heavily influenced by predicate transition-nets introduced by H.J. Genrich and K. Lautenbach. Moreover our paper shows how the invariant-method, introduced...... for Petri nets by K. Lautenbach, can be generalized to coloured Petri nets....

  6. Efficacy of sweet whey containing final dips in reducing protein oxidation in retail-cut cubed beefsteak

    Science.gov (United States)

    Oxidative degradation results in extensive deterioration of shelf-life and quality of retail-cut muscle foods. Use of antioxidants, especially the ones of natural origin, can markedly reduce this process without adverse health consequences to the consumer. Sweet whey originating from Cheddar (CW) an...

  7. NetMOD Version 2.0 Parameters

    Energy Technology Data Exchange (ETDEWEB)

    Merchant, Bion J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-08-01

    NetMOD ( Net work M onitoring for O ptimal D etection) is a Java-based software package for conducting simulation of seismic, hydroacoustic and infrasonic networks. Network simulations have long been used to study network resilience to station outages and to determine where additional stations are needed to reduce monitoring thresholds. NetMOD makes use of geophysical models to determine the source characteristics, signal attenuation along the path between the source and station, and the performance and noise properties of the station. These geophysical models are combined to simulate the relative amplitudes of signal and noise that are observed at each of the stations. From these signal-to-noise ratios (SNR), the probability of detection can be computed given a detection threshold. This document describes the parameters that are used to configure the NetMOD tool and the input and output parameters that make up the simulation definitions.

  8. Human SGT interacts with Bag-6/Bat-3/Scythe and cells with reduced levels of either protein display persistence of few misaligned chromosomes and mitotic arrest

    International Nuclear Information System (INIS)

    Winnefeld, Marc; Grewenig, Annabel; Schnoelzer, Martina; Spring, Herbert; Knoch, Tobias A.; Gan, Eugene C.; Rommelaere, Jean; Cziepluch, Celina

    2006-01-01

    The human small glutamine-rich TPR-containing protein (hSGT) is essential for cell division since RNA-interference-mediated strong reduction of hSGT protein levels causes mitotic arrest (M. Winnefeld, J. Rommelaere, and C. Cziepluch, The human small glutamine-rich TPR-containing protein is required for progress through cell division, Exp. Cell Res. 293 (2004), 43-57). Analysis of HeLa cells expressing a histone 2A-YFP fusion protein revealed the continuous presence of few mislocalized chromosomes close to the spindle poles as possible cause for hSGT depletion-dependent prometaphase arrest. Cells unable to rescue these mislocalized chromosomes into the metaphase plate died at this stage through apoptosis. In order to address hSGT function at the molecular level, mass spectrometry analysis of proteins which co-immunoprecipitated with Flag-tagged hSGT was performed. Thereby, Hsp70 and Bag-6/Bat-3/Scythe were identified as novel hSGT interaction partners while interaction with Hsc70 was confirmed. Results obtained with truncated versions of the hSGT protein revealed that Bag-6/Bat-3/Scythe and Hsp70 or Hsc70 were independently able to form complexes with hSGT. Interaction of hSGT with Hsc70, Hsp70 or Bag-6/Bat-3/Scythe was demonstrated in prometaphase, thereby suggesting a possible role for complexes containing hSGT and distinct (co)-chaperones during mitosis. Finally, cells from populations with reduced levels of Bag-6/Bat-3/Scythe also displayed persistence of mislocalized chromosomes and mitotic arrest, which strongly indicated that hSGT-Bag-6/Bat-3/Scythe complexes could be directly or indirectly required for complete chromosome congression

  9. Cyanide-induced death of dopaminergic cells is mediated by uncoupling protein-2 up-regulation and reduced Bcl-2 expression

    International Nuclear Information System (INIS)

    Zhang, X.; Li, L.; Zhang, L.; Borowitz, J.L.; Isom, G.E.

    2009-01-01

    Cyanide is a potent inhibitor of mitochondrial oxidative metabolism and produces mitochondria-mediated death of dopaminergic neurons and sublethal intoxications that are associated with a Parkinson-like syndrome. Cyanide toxicity is enhanced when mitochondrial uncoupling is stimulated following up-regulation of uncoupling protein-2 (UCP-2). In this study, the role of a pro-survival protein, Bcl-2, in cyanide-mediated cell death was determined in a rat dopaminergic immortalized mesencephalic cell line (N27 cells). Following pharmacological up-regulation of UCP-2 by treatment with Wy14,643, cyanide reduced cellular Bcl-2 expression by increasing proteasomal degradation of the protein. The increased turnover of Bcl-2 was mediated by an increase of oxidative stress following UCP-2 up-regulation. The oxidative stress involved depletion of mitochondrial glutathione (mtGSH) and increased H 2 O 2 generation. Repletion of mtGSH by loading cells with glutathione ethyl ester reduced H 2 O 2 generation and in turn blocked the cyanide-induced decrease of Bcl-2. To determine if UCP-2 mediated the response, RNAi knock down was conducted. The RNAi decreased cyanide-induced depletion of mtGSH, reduced H 2 O 2 accumulation, and inhibited down-regulation of Bcl-2, thus blocking cell death. To confirm the role of Bcl-2 down-regulation in the cell death, it was shown that over-expression of Bcl-2 by cDNA transfection attenuated the enhancement of cyanide toxicity after UCP-2 up-regulation. It was concluded that UCP-2 up-regulation sensitizes cells to cyanide by increasing cellular oxidative stress, leading to an increase of Bcl-2 degradation. Then the reduced Bcl-2 levels sensitize the cells to cyanide-mediated cell death.

  10. Mutations in ribosomal protein L3 and 23S ribosomal RNA at the peptidyl transferase centre are associated with reduced susceptibility to tiamulin in Brachyspira spp. isolates.

    Science.gov (United States)

    Pringle, Märit; Poehlsgaard, Jacob; Vester, Birte; Long, Katherine S

    2004-12-01

    The pleuromutilin antibiotic tiamulin binds to the ribosomal peptidyl transferase centre. Three groups of Brachyspira spp. isolates with reduced tiamulin susceptibility were analysed to define resistance mechanisms to the drug. Mutations were identified in genes encoding ribosomal protein L3 and 23S rRNA at positions proximal to the peptidyl transferase centre. In two groups of laboratory-selected mutants, mutations were found at nucleotide positions 2032, 2055, 2447, 2499, 2504 and 2572 of 23S rRNA (Escherichia coli numbering) and at amino acid positions 148 and 149 of ribosomal protein L3 (Brachyspira pilosicoli numbering). In a third group of clinical B. hyodysenteriae isolates, only a single mutation at amino acid 148 of ribosomal protein L3 was detected. Chemical footprinting experiments show a reduced binding of tiamulin to ribosomal subunits from mutants with decreased susceptibility to the drug. This reduction in drug binding is likely the resistance mechanism for these strains. Hence, the identified mutations located near the tiamulin binding site are predicted to be responsible for the resistance phenotype. The positions of the mutated residues relative to the bound drug advocate a model where the mutations affect tiamulin binding indirectly through perturbation of nucleotide U2504.

  11. Selective effects of charge on G protein activation by FSH-receptor residues 551-555 and 650-653.

    Science.gov (United States)

    Grasso, P; Deziel, M R; Reichert, L E

    1995-01-01

    Two cytosolic regions of the rat testicular FSH receptor (FSHR), residues 533-555 and 645-653, have been identified as G protein-coupling domains. We localized the activity in these domains to their C-terminal sequences, residues 551-555 (KIAKR, net charge +3) and 650-653 (RKSH, net charge +3), and examined the effects of charge on G protein activation by the C-terminal peptides, using synthetic analogs containing additions, through alanine (A) linkages, of arginine (R, +), histidine (H, +) or both. RA-KIAKR (net charge +4) mimicked the effect of FSHR-(551-555) on guanine nucleotide exchange in rat testis membranes, but reduced its ability to inhibit FSH-stimulated estradiol biosynthesis in cultured rat Sertoli cells. Further increasing net charge by the addition of H (HARA-KIAKR, net charge +5) increased guanosine 5'-triphosphate (GTP) binding, but eliminated FSHR-(551-555) effects on FSH-stimulated steroidogenesis. HA-RKSH (net charge +4) significantly inhibited guanine nucleotide exchange in rat testis membranes, but stimulated basal and potentiated FSH-induced estradiol biosynthesis in cultured rat Sertoli cells. Addition of two H residues (HAHA-RKSH, net charge +5) restored GTP binding and further potentiated basal and FSH-stimulated steroidogenesis. These results suggest that positive charges in G protein-coupling domains of the FSHR play a role in modulating G protein activation and postbinding effects of FSH, such as steroidogenesis.

  12. Reduced dimensionality (3,2)D NMR experiments and their automated analysis: implications to high-throughput structural studies on proteins.

    Science.gov (United States)

    Reddy, Jithender G; Kumar, Dinesh; Hosur, Ramakrishna V

    2015-02-01

    Protein NMR spectroscopy has expanded dramatically over the last decade into a powerful tool for the study of their structure, dynamics, and interactions. The primary requirement for all such investigations is sequence-specific resonance assignment. The demand now is to obtain this information as rapidly as possible and in all types of protein systems, stable/unstable, soluble/insoluble, small/big, structured/unstructured, and so on. In this context, we introduce here two reduced dimensionality experiments – (3,2)D-hNCOcanH and (3,2)D-hNcoCAnH – which enhance the previously described 2D NMR-based assignment methods quite significantly. Both the experiments can be recorded in just about 2-3 h each and hence would be of immense value for high-throughput structural proteomics and drug discovery research. The applicability of the method has been demonstrated using alpha-helical bovine apo calbindin-D9k P43M mutant (75 aa) protein. Automated assignment of this data using AUTOBA has been presented, which enhances the utility of these experiments. The backbone resonance assignments so derived are utilized to estimate secondary structures and the backbone fold using Web-based algorithms. Taken together, we believe that the method and the protocol proposed here can be used for routine high-throughput structural studies of proteins. Copyright © 2014 John Wiley & Sons, Ltd.

  13. Inhibition of lectin-like oxidized low-density lipoprotein receptor-1 reduces cardiac fibroblast proliferation by suppressing GATA Binding Protein 4

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Bin; Liu, Ning-Ning; Liu, Wei-Hua; Zhang, Shuang-Wei; Zhang, Jing-Zhi; Li, Ai-Qun [Department of Cardiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou (China); Guangzhou Institute of Cardiovascular Disease, Guangzhou (China); Liu, Shi-Ming, E-mail: gzliushiming@126.com [Department of Cardiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou (China); Guangzhou Institute of Cardiovascular Disease, Guangzhou (China)

    2016-07-08

    Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and GATA Binding Protein 4 (GATA4) are important for the growth of cardiac fibroblasts (CFs). When deregulated, LOX-1 and GATA4 can cause cardiac remodeling. In the present study, we found novel evidence that GATA4 was required for the LOX-1 regulation of CF proliferation. The inhibition of LOX-1 by RNA interference LOX-1 lentivirus resulted in the loss of PI3K/Akt activation and GATA4 protein expression. The overexpression of LOX-1 by lentivirus rescued CF proliferation, PI3K/Akt activation, and GATA4 protein expression. Moreover, GATA4 overexpression enhanced CF proliferation with LOX-1 inhibition. We also found that the inhibition of PI3K/Akt activation by LY294002, a PI3K inhibitor, reduced cell proliferation and protein level of GATA4. In summary, GATA4 may play an important role in the LOX-1 and PI3K/Akt regulation of CF proliferation. -- Highlights: •GATA4 is regulated by LOX-1 signaling in CFs. •GATA4 is involved in LOX-1 regulating CF proliferation. •GATA4 is regulated by PI3K/Akt signaling in CFs.

  14. Regulation of autophagy by AMP-activated protein kinase/ sirtuin 1 pathway reduces spinal cord neurons damage

    Directory of Open Access Journals (Sweden)

    Peng Yan

    2017-09-01

    Full Text Available Objective(s: AMP-activated protein kinase/sirtuin 1 (AMPK/SIRT1 signaling pathway has been proved to be involved in the regulation of autophagy in various models. The aim of this study was to evaluate the effect of AMPK/SIRT1 pathway on autophagy after spinal cord injury (SCI. Materials and Methods:The SCI model was established in rats in vivo and the primary spinal cord neurons were subjected to mechanical injury (MI in vitro. The apoptosis in spinal cord tissue and neurons was assessed by TUNEL staining and Hoechst 33342 staining, respectively. The autophagy-related proteins levels were detected by Western blot. The activation of AMPK/SIRT1 pathway was determined by Western blot and immunohistochemical staining. Results: We found that the apoptosis of spinal cord tissue and cell damage of spinal cord neurons was obvious after the trauma. The ratio of LC3II/LC3I and level of p62 were first increased significantly and then decreased after the trauma in vivo and in vitro, indicating the defect in autophagy. The levels of p-AMPK and SIRT1 were increased obviously after the trauma in vivo and in vitro. Further activation of the AMPK/SIRT1 pathway by pretreatment with resveratrol, a confirmed activator of the AMPK/SIRT1 pathway, alleviated the cell damage and promoted the autophagy flux via downregulation of p62 in spinal cord neurons at 24 hr after MI. Conclusion: Our results demonstrate that regulation of autophagy by AMPK/SIRT1 pathway can restrain spinal cord neurons damage, which may be a potential intervention of SCI.

  15. Regulation of autophagy by AMP-activated protein kinase/sirtuin 1 pathway reduces spinal cord neurons damage.

    Science.gov (United States)

    Yan, Peng; Bai, Liangjie; Lu, Wei; Gao, Yuzhong; Bi, Yunlong; Lv, Gang

    2017-09-01

    AMP-activated protein kinase/sirtuin 1 (AMPK/SIRT1) signaling pathway has been proved to be involved in the regulation of autophagy in various models. The aim of this study was to evaluate the effect of AMPK/SIRT1 pathway on autophagy after spinal cord injury (SCI). The SCI model was established in rats in vivo and the primary spinal cord neurons were subjected to mechanical injury (MI) in vitro . The apoptosis in spinal cord tissue and neurons was assessed by TUNEL staining and Hoechst 33342 staining, respectively. The autophagy-related proteins levels were detected by Western blot. The activation of AMPK/SIRT1 pathway was determined by Western blot and immunohistochemical staining. We found that the apoptosis of spinal cord tissue and cell damage of spinal cord neurons was obvious after the trauma. The ratio of LC3II/LC3I and level of p62 were first increased significantly and then decreased after the trauma in vivo and in vitro , indicating the defect in autophagy. The levels of p-AMPK and SIRT1 were increased obviously after the trauma in vivo and in vitro . Further activation of the AMPK/SIRT1 pathway by pretreatment with resveratrol, a confirmed activator of the AMPK/SIRT1 pathway, alleviated the cell damage and promoted the autophagy flux via downregulation of p62 in spinal cord neurons at 24 hr after MI. Our results demonstrate that regulation of autophagy by AMPK/SIRT1 pathway can restrain spinal cord neurons damage, which may be a potential intervention of SCI.

  16. D.NET case study

    International Development Research Centre (IDRC) Digital Library (Canada)

    lremy

    The mission was defined to build, “A society where information and ... innovative ideas and projects around different themes (using ICT), and piloting them to test .... like D.Net with several projects that had moved beyond their pilot phase.

  17. Petri Nets in Cryptographic Protocols

    DEFF Research Database (Denmark)

    Crazzolara, Federico; Winskel, Glynn

    2001-01-01

    A process language for security protocols is presented together with a semantics in terms of sets of events. The denotation of process is a set of events, and as each event specifies a set of pre and postconditions, this denotation can be viewed as a Petri net. By means of an example we illustrate...

  18. Complexity metrics for workflow nets

    NARCIS (Netherlands)

    Lassen, K.B.; Aalst, van der W.M.P.

    2009-01-01

    Process modeling languages such as EPCs, BPMN, flow charts, UML activity diagrams, Petri nets, etc., are used to model business processes and to configure process-aware information systems. It is known that users have problems understanding these diagrams. In fact, even process engineers and system

  19. Reference Guide Microsoft.NET

    NARCIS (Netherlands)

    Zee M van der; Verspaij GJ; Rosbergen S; IMP; NMD

    2003-01-01

    Met behulp van het rapport kunnen ontwikkelaars, beheerders en betrokken managers bij ICT projecten meer inzicht krijgen in de .NET technologie en een goede keuze maken in de inzetbaarheid van deze technologie. Het rapport geeft de bevindingen en conclusies van een verkennende studie naar het

  20. Complexity Metrics for Workflow Nets

    DEFF Research Database (Denmark)

    Lassen, Kristian Bisgaard; van der Aalst, Wil M.P.

    2009-01-01

    Process modeling languages such as EPCs, BPMN, flow charts, UML activity diagrams, Petri nets, etc.\\ are used to model business processes and to configure process-aware information systems. It is known that users have problems understanding these diagrams. In fact, even process engineers and system...

  1. Communicating with the Net Generation

    Science.gov (United States)

    2011-03-11

    resource investment is necessary to sustain a high quality all-volunteer force. 9 Leadership Technique for the Net Generation Army Regulation 600...Generations at Work, Millenials at Work, http://www.generationsatwork. com /articles_millennials_at_work.php (accessed November 21, 2010). 31 Thomas

  2. Net Neutrality in the Netherlands

    NARCIS (Netherlands)

    van Eijk, N.

    2014-01-01

    The Netherlands is among the first countries that have put specific net neutrality standards in place. The decision to implement specific regulation was influenced by at least three factors. The first was the prevailing social and academic debate, partly due to developments in the United States. The

  3. Surgery for GEP-NETs

    DEFF Research Database (Denmark)

    Knigge, Ulrich; Hansen, Carsten Palnæs

    2012-01-01

    Surgery is the only treatment that may cure the patient with gastroentero-pancreatic (GEP) neuroendocrine tumours (NET) and neuroendocrine carcinomas (NEC) and should always be considered as first line treatment if R0/R1 resection can be achieved. The surgical and interventional procedures for GEP...

  4. Net4Care PHMR Tutorial

    DEFF Research Database (Denmark)

    Christensen, Henrik Bærbak

    Goal To demonstrate how to use the Net4Care PHMR builder module to a) Create a SimpleClinicalDocument instance and populate it with relevant administrative and medical information to form a tele medical report of a set of measurements, b) Use the provided DanishPHMRBuilder to generate a correctly...

  5. Probing the Selectivity and Protein•Protein Interactions of a Non-Reducing Fungal Polyketide Synthase Using Mechanism-Based Crosslinkers

    Science.gov (United States)

    Bruegger, Joel; Haushalter, Bob; Vagstad, Anna; Shakya, Gaurav; Mih, Nathan; Townsend, Craig A.; Burkart, Michael D.; Tsai, Shiou-Chuan

    2013-01-01

    SUMMARY Protein•protein interactions, which often involve interactions between an acyl carrier protein (ACP) and its partner enzymes, are important for coordinating polyketide biosynthesis. However, the nature of such interactions is not well understood, especially in the fungal non-reducing polyketide synthases (NR-PKSs) that biosynthesize toxic and pharmaceutically important polyketides. Here, we employ a mechanism-based crosslinker to successfully probe ACP and ketosynthase (KS) domain interactions in NR-PKSs. We found that crosslinking efficiency is closely correlated with the strength of ACP•KS interactions, and that KS demonstrates strong starter unit selectivity. We further identified positively charged surface residues by KS mutagenesis, which mediate key interactions with the negatively-charged ACP surface. Such complementary/matching contact pairs can serve as “adapter surfaces” for future efforts to generate new polyketides using NR-PKSs. PMID:23993461

  6. Integration of multi-omics data of a genome-reduced bacterium: Prevalence of post-transcriptional regulation and its correlation with protein abundances

    Science.gov (United States)

    Chen, Wei-Hua; van Noort, Vera; Lluch-Senar, Maria; Hennrich, Marco L.; H. Wodke, Judith A.; Yus, Eva; Alibés, Andreu; Roma, Guglielmo; Mende, Daniel R.; Pesavento, Christina; Typas, Athanasios; Gavin, Anne-Claude; Serrano, Luis; Bork, Peer

    2016-01-01

    We developed a comprehensive resource for the genome-reduced bacterium Mycoplasma pneumoniae comprising 1748 consistently generated ‘-omics’ data sets, and used it to quantify the power of antisense non-coding RNAs (ncRNAs), lysine acetylation, and protein phosphorylation in predicting protein abundance (11%, 24% and 8%, respectively). These factors taken together are four times more predictive of the proteome abundance than of mRNA abundance. In bacteria, post-translational modifications (PTMs) and ncRNA transcription were both found to increase with decreasing genomic GC-content and genome size. Thus, the evolutionary forces constraining genome size and GC-content modify the relative contributions of the different regulatory layers to proteome homeostasis, and impact more genomic and genetic features than previously appreciated. Indeed, these scaling principles will enable us to develop more informed approaches when engineering minimal synthetic genomes. PMID:26773059

  7. Efficacy of humidity retention bags for the reduced adsorption and improved cleaning of tissue proteins including prion-associated amyloid to surgical stainless steel surfaces.

    Science.gov (United States)

    Secker, T J; Pinchin, H E; Hervé, R C; Keevil, C W

    2015-01-01

    Increasing drying time adversely affects attachment of tissue proteins and prion-associated amyloid to surgical stainless steel, and reduces the efficacy of commercial cleaning chemistries. This study tested the efficacy of commercial humidity retention bags to reduce biofouling on surgical stainless steel and to improve subsequent cleaning. Surgical stainless steel surfaces were contaminated with ME7-infected brain homogenates and left to dry for 15 to 1,440 min either in air, in dry polythene bags or within humidity retention bags. Residual contamination pre/post cleaning was analysed using Thioflavin T/SYPRO Ruby dual staining and microscope analysis. An increase in biofouling was observed with increased drying time in air or in sealed dry bags. Humidity retention bags kept both protein and prion-associated amyloid minimal across the drying times both pre- and post-cleaning. Therefore, humidity bags demonstrate a cheap, easy to implement solution to improve surgical instrument reprocessing and to potentially reduce associated hospital acquired infections.

  8. Tissue protein metabolism in parasitized animals

    International Nuclear Information System (INIS)

    Symons, L.E.A.; Steel, J.W.; Jones, W.O.

    1981-01-01

    The effects of gastrointestinal nematode infection of mammals, particularly of the small intestine of the sheep, on protein metabolism of skeletal muscle, liver, the gastrointestinal tract and wool are described. These changes have been integrated to explain poor growth and production in the sheep heavily infected with Trichostrongylus colubriformis. The rates of both synthesis and catabolism of muscle protein are depressed, but nitrogen is lost from this tissue because the depression of synthesis exceeds that of catabolism. Anorexia is the major cause of these changes. Although the effect on liver protein synthesis is unclear, it is probable that the leakage of plasma proteins into the gastrointestinal tract stimulates an early increase in the rate of synthesis of these proteins, but this eventually declines and is insufficient to correct developing hypoalbuminaemia. Changes in the intestinal tract are complex. Exogenous nitrogen is reduced by anorexia, but the flow of nitrogen through the tract from abomasum to faeces is above normal because of the increase of endogenous protein from leakage of plasma protein and, presumably, from exfoliated epithelial cells. There is evidence that protein metabolism of intestinal tissue, particularly in the uninfected distal two-thirds, is increased. Synthesis of wool protein is decreased. As the result of anorexia, intestinal loss of endogenous protein and an increased rate of intestinal protein metabolism there is a net movement of amino nitrogen from muscle, liver and possibly skin to the intestine of the heavily infected sheep. Thus, the availability of amino nitrogen for growth and wool production is reduced. (author)

  9. Numerical study on the hydrodynamic characteristics of biofouled full-scale net cage

    Science.gov (United States)

    Bi, Chun-wei; Zhao, Yun-peng; Dong, Guo-hai

    2015-06-01

    The effect of biofouling on the hydrodynamic characteristics of the net cage is of particular interest as biofouled nettings can significantly reduce flow of well-oxygenated water reaching the stocked fish. For computational efficiency, the porous-media fluid model is proposed to simulate flow through the biofouled plane net and full-scale net cage. The porous coefficients of the porous-media fluid model can be determined from the quadratic-function relationship between the hydrodynamic forces on a plane net and the flow velocity using the least squares method. In this study, drag forces on and flow fields around five plane nets with different levels of biofouling are calculated by use of the proposed model. The numerical results are compared with the experimental data of Swift et al. (2006) and the effectiveness of the numerical model is presented. On that basis, flow through full-scale net cages with the same level of biofouling as the tested plane nets are modeled. The flow fields inside and around biofouled net cages are analyzed and the drag force acting on a net cage is estimated by a control volume analysis method. According to the numerical results, empirical formulas of reduction in flow velocity and load on a net cage are derived as function of drag coefficient of the corresponding biofouled netting.

  10. Use of a Spreadsheet to Calculate the Net Charge of Peptides and Proteins as a Function of pH: An Alternative to Using "Canned" Programs to Estimate the Isoelectric Point of These Important Biomolecules

    Science.gov (United States)

    Sims, Paul A.

    2010-01-01

    An approach is presented that utilizes a spreadsheet to allow students to explore different means of calculating and visualizing how the charge on peptides and proteins varies as a function of pH. In particular, the concept of isoelectric point is developed to allow students to compare the results of their spreadsheet calculations with those of…

  11. Reduced expression of mitochondrial electron transport chain proteins from hibernating hearts relative to ischemic preconditioned hearts in the second window of protection.

    Science.gov (United States)

    Cabrera, Jesús A; Butterick, Tammy A; Long, Eric K; Ziemba, Elizabeth A; Anderson, Lorraine B; Duffy, Cayla M; Sluiter, Willem; Duncker, Dirk J; Zhang, Jianyi; Chen, Yingjie; Ward, Herbert B; Kelly, Rosemary F; McFalls, Edward O

    2013-07-01

    Although protection against necrosis has been observed in both hibernating (HIB) and ischemic preconditioned hearts in the second window of protection (SWOP), a comparison of the mitochondrial proteome between the two entities has not been previously performed. Anesthetized swine underwent instrumentation with a fixed constrictor around the LAD artery and were followed for 12 weeks (HIB; N=7). A second group of anesthetized swine underwent ischemic preconditioning by inflating a balloon within the LAD artery 10 times for 2 min, each separated by 2 min reperfusion and were sacrificed 24h later (SWOP; N=7). Myocardial blood flow and high-energy nucleotides were obtained in the LAD region and normalized to remote regions. Post-sacrifice, protein content as measured with iTRAQ was compared in isolated mitochondria from the LAD area of a Sham heart. Basal regional blood flow in the LAD region when normalized to the remote region was 0.86±0.04 in HIB and 1.02±0.02 in SWOP tissue (Pregional blood flows in HIB hearts, ATP content in the LAD region, when normalized to the remote region was similar in HIB versus SWOP (1.06±0.06 and 1.02±0.05 respectively; NS) as was the transmural phosphocreatine (PCr) to ATP ratio (2.1±0.2 and 2.2±0.2 respectively; NS). Using iTRAQ, 64 common proteins were identified in HIB and SWOP hearts. Compared with SWOP, the relative abundance of mitochondrial proteins involved with electron transport chain (ETC) were reduced in HIB including NADH dehydrogenase, Cytochrome c reductase and oxidase, ATP synthase, and nicotinamide nucleotide transhydrogenase. Within chronically HIB heart tissue with reduced blood flow, the relative abundance of mitochondrial ETC proteins is decreased when compared with SWOP tissue. These data support the concept that HIB heart tissue subjected to chronically reduced blood flow is associated with a down-regulation in the expression of key mitochondrial proteins involved in electron transport. Published by Elsevier

  12. Intermittent fasting reduces body fat but exacerbates hepatic insulin resistance in young rats regardless of high protein and fat diets.

    Science.gov (United States)

    Park, Sunmin; Yoo, Kyung Min; Hyun, Joo Suk; Kang, Suna

    2017-02-01

    Intermittent fasting (IMF) is a relatively new dietary approach to weight management, although the efficacy and adverse effects have not been full elucidated and the optimal diets for IMF are unknown. We tested the hypothesis that a one-meal-per-day intermittent fasting with high fat (HF) or protein (HP) diets can modify energy, lipid, and glucose metabolism in normal young male Sprague-Dawley rats with diet-induced obesity or overweight. Male rats aged 5 weeks received either HF (40% fat) or HP (26% protein) diets ad libitum (AL) or for 3 h at the beginning of the dark cycle (IMF) for 5 weeks. Epidydimal fat pads and fat deposits in the leg and abdomen were lower with HP and IMF. Energy expenditure at the beginning of the dark cycle, especially from fat oxidation, was higher with IMF than AL, possibly due to greater activity levels. Brown fat content was higher with IMF. Serum ghrelin levels were higher in HP-IMF than other groups, and accordingly, cumulative food intake was also higher in HP-IMF than HF-IMF. HF-IMF exhibited higher area under the curve (AUC) of serum glucose at the first part (0-40 min) during oral glucose tolerance test, whereas AUC of serum insulin levels in both parts were higher in IMF and HF. During intraperitoneal insulin tolerance test, serum glucose levels were higher with IMF than AL. Consistently, hepatic insulin signaling (GLUT2, pAkt) was attenuated and PEPCK expression was higher with IMF and HF than other groups, and HOMA-IR revealed significantly impaired attenuated insulin sensitivity in the IMF groups. However, surprisingly, hepatic and skeletal muscle glycogen storage was higher in IMF groups than AL. The higher glycogen storage in the IMF groups was associated with the lower expression of glycogen phosphorylase than the AL groups. In conclusion, IMF especially with HF increased insulin resistance, possibly by attenuating hepatic insulin signaling, and lowered glycogen phosphorylase expression despite decreased fat mass in young

  13. Breakfasts Higher in Protein Increase Postprandial Energy Expenditure, Increase Fat Oxidation, and Reduce Hunger in Overweight Children from 8 to 12 Years of Age.

    Science.gov (United States)

    Baum, Jamie I; Gray, Michelle; Binns, Ashley

    2015-10-01

    Currently 1 in every 3 children aged 2-19 y is overweight or obese. Breakfast is a key component of a healthy diet and has the potential to affect children's health. The objective of this study was to determine whether consumption of a protein-based breakfast (PRO) increases postprandial energy metabolism and substrate oxidation, reduces hunger, and reduces food intake at lunch compared with a carbohydrate-based breakfast (CHO) in normal weight (NW) vs. overweight/obese (OW) children. A randomized, crossover-design study was conducted in NW (n = 16; 33 ± 1 kg) and OW (n = 13; 46 ± 2 kg) children (10 ± 1 y). Participants were served either a PRO [344 kcal, 21% protein (18 g), 52% carbohydrate, and 27% fat] or CHO [327 kcal, 4% protein (3 g), 67% carbohydrate, and 29% fat]. Energy expenditure (EE), substrate oxidation, appetite, and blood glucose were measured over a 4 h period. Four hour postprandial participants were provided with access to a lunch buffet and food intake was recorded. After breakfast, OW children in the PRO group had higher (P fat oxidation over the 4 h period than did the NW children in the CHO and PRO groups. There was no difference in postprandial EE or carbohydrate oxidation between the CHO and PRO groups over the 4 h period; however, fat oxidation was 16% higher (P children. A PRO increases postprandial EE and fat oxidation, reduces hunger, and increases satiety when compared with a carbohydrate-based breakfast. © 2015 American Society for Nutrition.

  14. High-protein diet selectively reduces fat mass and improves glucose tolerance in Western-type diet-induced obese rats

    Science.gov (United States)

    Stengel, Andreas; Goebel-Stengel, Miriam; Wang, Lixin; Hu, Eugenia; Karasawa, Hiroshi; Pisegna, Joseph R.

    2013-01-01

    Obesity is an increasing health problem. Because drug treatments are limited, diets remain popular. High-protein diets (HPD) reduce body weight (BW), although the mechanisms are unclear. We investigated physiological mechanisms altered by switching diet induced obesity (DIO) rats from Western-type diet (WTD) to HPD. Male rats were fed standard (SD) or WTD (45% calories from fat). After developing DIO (50% of rats), they were switched to SD (15% calories from protein) or HPD (52% calories from protein) for up to 4 weeks. Food intake (FI), BW, body composition, glucose tolerance, insulin sensitivity, and intestinal hormone plasma levels were monitored. Rats fed WTD showed an increased FI and had a 25% greater BW gain after 9 wk compared with SD (P Diet-induced obese rats switched from WTD to HPD reduced daily FI by 30% on day 1, which lasted to day 9 (−9%) and decreased BW during the 2-wk period compared with SD/SD (P < 0.05). During these 2 wk, WTD/HPD rats lost 72% more fat mass than WTD/SD (P < 0.05), whereas lean mass was unaltered. WTD/HPD rats had lower blood glucose than WTD/SD at 30 min postglucose gavage (P < 0.05). The increase of pancreatic polypeptide and peptide YY during the 2-h dark-phase feeding was higher in WTD/HPD compared with WTD/SD (P < 0.05). These data indicate that HPD reduces BW in WTD rats, which may be related to decreased FI and the selective reduction of fat mass accompanied by improved glucose tolerance, suggesting relevant benefits of HPD in the treatment of obesity. PMID:23883680

  15. .net

    Directory of Open Access Journals (Sweden)

    Le Comité de Rédaction d' EspacesTemps.net

    2002-06-01

    Full Text Available EspacesTemps lance aujourd'hui deux objets différents : un site internet et, sur ce site, Le Journal . Il s'agit donc de bien plus, et, au fond, de tout autre chose qu'un simple outil de communication destiné à informer nos lecteurs de nos parutions. Ce n'est pas non plus la « mise en ligne » de nos numéros-papier. L'internet nous donne au contraire l'occasion de réaliser, dans de meilleures conditions, ce que nous avons tenté de faire depuis quelques ...

  16. Caught in the Net: Perineuronal Nets and Addiction

    Directory of Open Access Journals (Sweden)

    Megan Slaker

    2016-01-01

    Full Text Available Exposure to drugs of abuse induces plasticity in the brain and creates persistent drug-related memories. These changes in plasticity and persistent drug memories are believed to produce aberrant motivation and reinforcement contributing to addiction. Most studies have explored the effect drugs of abuse have on pre- and postsynaptic cells and astrocytes; however, more recently, attention has shifted to explore the effect these drugs have on the extracellular matrix (ECM. Within the ECM are unique structures arranged in a net-like manner, surrounding a subset of neurons called perineuronal nets (PNNs. This review focuses on drug-induced changes in PNNs, the molecules that regulate PNNs, and the expression of PNNs within brain circuitry mediating motivation, reward, and reinforcement as it pertains to addiction.

  17. Krill protein hydrolysate reduces plasma triacylglycerol level with concurrent increase in plasma bile acid level and hepatic fatty acid catabolism in high-fat fed mice

    Directory of Open Access Journals (Sweden)

    Marie S. Ramsvik

    2013-11-01

    Full Text Available Background: Krill powder, consisting of both lipids and proteins, has been reported to modulate hepatic lipid catabolism in animals. Fish protein hydrolysate diets have also been reported to affect lipid metabolism and to elevate bile acid (BA level in plasma. BA interacts with a number of nuclear receptors and thus affects a variety of signaling pathways, including very low density lipoprotein (VLDL secretion. The aim of the present study was to investigate whether a krill protein hydrolysate (KPH could affect lipid and BA metabolism in mice. Method: C57BL/6 mice were fed a high-fat (21%, w/w diet containing 20% crude protein (w/w as casein (control group or KPH for 6 weeks. Lipids and fatty acid composition were measured from plasma, enzyme activity and gene expression were analyzed from liver samples, and BA was measured from plasma. Results: The effect of dietary treatment with KPH resulted in reduced levels of plasma triacylglycerols (TAG and non-esterified fatty acids (NEFAs. The KPH treated mice had also a marked increased plasma BA concentration. The increased plasma BA level was associated with induction of genes related to membrane canalicular exporter proteins (Abcc2, Abcb4 and to BA exporters to blood (Abcc3 and Abcc4. Of note, we observed a 2-fold increased nuclear farnesoid X receptor (Fxr mRNA levels in the liver of mice fed KPH. We also observed increased activity of the nuclear peroxiosme proliferator-activated receptor alpha (PPARα target gene carnitine plamitoyltransferase 2 (CPT-2. Conclusion: The KPH diet showed to influence lipid and BA metabolism in high-fat fed mice. Moreover, increased mitochondrial fatty acid oxidation and elevation of BA concentration may regulate the plasma level of TAGs and NEFAs.

  18. Army Net Zero Prove Out. Net Zero Energy Best Practices

    Science.gov (United States)

    2014-11-18

    recovery and cogeneration opportunities, offsetting the remaining demand with the production of renewable energy from onsite sources so that the Net...implementing energy recovery and cogeneration opportunities, and then offsetting the remaining demand with the production of renewable energy from on-site...they impact overall energy performance. The use of energy modeling in the design stage provides insights that can contribute to more effective design

  19. Net alkalinity and net acidity 2: Practical considerations

    Science.gov (United States)

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

    2005-01-01

    The pH, alkalinity, and acidity of mine drainage and associated waters can be misinterpreted because of the chemical instability of samples and possible misunderstandings of standard analytical method results. Synthetic and field samples of mine drainage having various initial pH values and concentrations of dissolved metals and alkalinity were titrated by several methods, and the results were compared to alkalinity and acidity calculated based on dissolved solutes. The pH, alkalinity, and acidity were compared between fresh, unoxidized and aged, oxidized samples. Data for Pennsylvania coal mine drainage indicates that the pH of fresh samples was predominantly acidic (pH 2.5-4) or near neutral (pH 6-7); ??? 25% of the samples had pH values between 5 and 6. Following oxidation, no samples had pH values between 5 and 6. The Standard Method Alkalinity titration is constrained to yield values >0. Most calculated and measured alkalinities for samples with positive alkalinities were in close agreement. However, for low-pH samples, the calculated alkalinity can be negative due to negative contributions by dissolved metals that may oxidize and hydrolyze. The Standard Method hot peroxide treatment titration for acidity determination (Hot Acidity) accurately indicates the potential for pH to decrease to acidic values after complete degassing of CO2 and oxidation of Fe and Mn, and it indicates either the excess alkalinity or that required for neutralization of the sample. The Hot Acidity directly measures net acidity (= -net alkalinity). Samples that had near-neutral pH after oxidation had negative Hot Acidity; samples that had pH mine drainage treatment can lead to systems with insufficient Alkalinity to neutralize metal and H+ acidity and is not recommended. The use of net alkalinity = -Hot Acidity titration is recommended for the planning of mine drainage treatment. The use of net alkalinity = (Alkalinitymeasured - Aciditycalculated) is recommended with some cautions

  20. Reduced basal autophagy and impaired mitochondrial dynamics due to loss of Parkinson's disease-associated protein DJ-1.

    Directory of Open Access Journals (Sweden)

    Guido Krebiehl

    2010-02-01

    Full Text Available Mitochondrial dysfunction and degradation takes a central role in current paradigms of neurodegeneration in Parkinson's disease (PD. Loss of DJ-1 function is a rare cause of familial PD. Although a critical role of DJ-1 in oxidative stress response and mitochondrial function has been recognized, the effects on mitochondrial dynamics and downstream consequences remain to be determined.Using DJ-1 loss of function cellular models from knockout (KO mice and human carriers of the E64D mutation in the DJ-1 gene we define a novel role of DJ-1 in the integrity of both cellular organelles, mitochondria and lysosomes. We show that loss of DJ-1 caused impaired mitochondrial respiration, increased intramitochondrial reactive oxygen species, reduced mitochondrial membrane potential and characteristic alterations of mitochondrial shape as shown by quantitative morphology. Importantly, ultrastructural imaging and subsequent detailed lysosomal activity analyses revealed reduced basal autophagic degradation and the accumulation of defective mitochondria in DJ-1 KO cells, that was linked with decreased levels of phospho-activated ERK2.We show that loss of DJ-1 leads to impaired autophagy and accumulation of dysfunctional mitochondria that under physiological conditions would be compensated via lysosomal clearance. Our study provides evidence for a critical role of DJ-1 in mitochondrial homeostasis by connecting basal autophagy and mitochondrial integrity in Parkinson's disease.

  1. Liver Growth Factor (LGF Upregulates Frataxin Protein Expression and Reduces Oxidative Stress in Friedreich’s Ataxia Transgenic Mice

    Directory of Open Access Journals (Sweden)

    Lucía Calatrava-Ferreras

    2016-12-01

    Full Text Available Friedreich’s ataxia (FA is a severe disorder with autosomal recessive inheritance that is caused by the abnormal expansion of GAA repeat in intron 1 of FRDA gen. This alteration leads to a partial silencing of frataxin transcription, causing a multisystem disorder disease that includes neurological and non-neurological damage. Recent studies have proven the effectiveness of neurotrophic factors in a number of neurodegenerative diseases. Therefore, we intend to determine if liver growth factor (LGF, which has a demonstrated antioxidant and neuroprotective capability, could be a useful therapy for FA. To investigate the potential therapeutic activity of LGF we used transgenic mice of the FXNtm1MknTg (FXNYG8Pook strain. In these mice, intraperitoneal administration of LGF (1.6 μg/mouse exerted a neuroprotective effect on neurons of the lumbar spinal cord and improved cardiac hypertrophy. Both events could be the consequence of the increment in frataxin expression induced by LGF in spinal cord (1.34-fold and heart (1.2-fold. LGF also upregulated by 2.6-fold mitochondrial chain complex IV expression in spinal cord, while in skeletal muscle it reduced the relation oxidized glutathione/reduced glutathione. Since LGF partially restores motor coordination, we propose LGF as a novel factor that may be useful in the treatment of FA.

  2. High-temperature short-time pasteurisation of human breastmilk is efficient in retaining protein and reducing the bacterial count.

    Science.gov (United States)

    Klotz, Daniel; Joellenbeck, Mirjam; Winkler, Karl; Kunze, Mirjam; Huzly, Daniela; Hentschel, Roland

    2017-05-01

    Milk banks are advised to use Holder pasteurisation to inactivate the cytomegalovirus, but the process adversely affects the bioactive properties of human breastmilk. This study explored the antibacterial efficacy of an alternative high-temperature short-time (HTST) treatment of human breastmilk and its effect on marker proteins, compared with the Holder method. Breastmilk samples were obtained from 27 mothers with infants in a German neonatal intensive care unit. The samples were either heated to 62°C for five seconds using HTST or processed using Holder pasteurisation, at 63 ± 0.5°C for 30 minutes. Immunoglobulin A, lactoferrin, lysozyme, alkaline phosphatase and bile salt-stimulated lipase concentrations and bacterial colony-forming units/mL were measured before and after heating. HTST-treated samples retained higher rates of immunoglobulin A (95% versus 83%), alkaline phosphatase (6% versus 0%) and bile salt-stimulated lipase (0.8% versus 0.4%) than Holder pasteurisation samples (all p HTST treatment protocol retained some of the bioactive properties of human breastmilk and appeared to have similar antibacterial efficacy to Holder pasteurisation. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  3. Long-term manure amendments reduced soil aggregate stability via redistribution of the glomalin-related soil protein in macroaggregates

    Science.gov (United States)

    Xie, Hongtu; Li, Jianwei; Zhang, Bin; Wang, Lianfeng; Wang, Jingkuan; He, Hongbo; Zhang, Xudong

    2015-01-01

    Glomalin-related soil protein (GRSP) contributes to the formation and maintenance of soil aggregates, it is however remains unclear whether long-term intensive manure amendments alter soil aggregates stability and whether GRSP regulates these changes. Based on a three-decade long fertilization experiment in northeast China, this study examined the impact of long-term manure input on soil organic carbon (SOC), total and easily extractable GRSP (GRSPt and GRSPe) and their respective allocations in four soil aggregates (>2000 μm; 2000–250 μm; 250–53 μm; and soil and SOC in each aggregate generally increased with increasing manure input, GRSPt and GRSPe in each aggregate showed varying changes with manure input. Both GRSP in macroaggregates (2000–250 μm) were significantly higher under low manure input, a pattern consistent with changes in soil aggregate stability. Constituting 38~49% of soil mass, macroaggregates likely contributed to the nonlinear changes of aggregate stability under manure amendments. The regulatory process of GRSP allocations in soil aggregates has important implications for manure management under intensive agriculture. PMID:26423355

  4. p38 Mitogen Activated Protein Kinase (MAPK): A New Therapeutic Target for Reducing the Risk of Adverse Pregnancy Outcomes

    Science.gov (United States)

    Menon, Ramkumar; Papaconstantinou, John

    2016-01-01

    Introduction Spontaneous preterm birth (PTB) and preterm premature rupture of the membranes (pPROM) remain as a major clinical and therapeutic problem for intervention and management. Current strategies, based on our knowledge of pathways of preterm labor, have only been effective, in part, due to major gaps in our existing knowledge of risks and risk specific pathways. Areas covered Recent literature has identified physiologic aging of fetal tissues as a potential mechanistic feature of normal parturition. This process is affected by telomere dependent and p38 mitogen activated protein kinase (MAPK) induced senescence activation. Pregnancy associated risk factors can cause pathologic activation of this pathway that can cause oxidative stress induced p38 MAPK activation leading to senescence and premature aging of fetal tissues. Premature aging is associated with sterile inflammation capable of triggering preterm labor or preterm premature rupture of membranes. Preterm activation of p38MAPK can be considered as a key contributor to adverse pregnancies. Expert Opinion This review considers p38MAPK activation as a potential target for therapeutic interventions to prevent adverse pregnancy outcomes mediated by stress factors. In this review, we propose multiple strategies to prevent p38MAPK activation and its functional effects. PMID:27459026

  5. The Kunitz-protease inhibitor domain in amyloid precursor protein reduces cellular mitochondrial enzymes expression and function.

    Science.gov (United States)

    Chua, Li-Min; Lim, Mei-Li; Wong, Boon-Seng

    2013-08-09

    Mitochondrial dysfunction is a prominent feature of Alzheimer's disease (AD) and this can be contributed by aberrant metabolic enzyme function. But, the mechanism causing this enzymatic impairment is unclear. Amyloid precursor protein (APP) is known to be alternatively spliced to produce three major isoforms in the brain (APP695, APP751, APP770). Both APP770 and APP751 contain the Kunitz Protease Inhibitory (KPI) domain, but the former also contain an extra OX-2 domain. APP695 on the other hand, lacks both domains. In AD, up-regulation of the KPI-containing APP isoforms has been reported. But the functional contribution of this elevation is unclear. In the present study, we have expressed and compared the effect of the non-KPI containing APP695 and the KPI-containing APP751 on mitochondrial function. We found that the KPI-containing APP751 significantly decreased the expression of three major mitochondrial metabolic enzymes; citrate synthase, succinate dehydrogenase and cytochrome c oxidase (COX IV). This reduction lowers the NAD(+)/NADH ratio, COX IV activity and mitochondrial membrane potential. Overall, this study demonstrated that up-regulation of the KPI-containing APP isoforms is likely to contribute to the impairment of metabolic enzymes and mitochondrial function in AD. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Acetoacetate reduces growth and ATP concentration in cancer cell lines which over-express uncoupling protein 2

    Directory of Open Access Journals (Sweden)

    Quadros Edward V

    2009-05-01

    Full Text Available Abstract Background Recent evidence suggests that several human cancers are capable of uncoupling of mitochondrial ATP generation in the presence of intact tricarboxylic acid (TCA enzymes. The goal of the current study was to test the hypothesis that ketone bodies can inhibit cell growth in aggressive cancers and that expression of uncoupling protein 2 is a contributing factor. The proposed mechanism involves inhibition of glycolytic ATP production via a Randle-like cycle while increased uncoupling renders cancers unable to produce compensatory ATP from respiration. Methods Seven aggressive human cancer cell lines, and three control fibroblast lines were grown in vitro in either 10 mM glucose medium (GM, or in glucose plus 10 mM acetoacetate [G+AcA]. The cells were assayed for cell growth, ATP production and expression of UCP2. Results There was a high correlation of cell growth with ATP concentration (r = 0.948 in a continuum across all cell lines. Controls demonstrated normal cell growth and ATP with the lowest density of mitochondrial UCP2 staining while all cancer lines demonstrated proportionally inhibited growth and ATP, and over-expression of UCP2 (p Conclusion Seven human cancer cell lines grown in glucose plus acetoacetate medium showed tightly coupled reduction of growth and ATP concentration. The findings were not observed in control fibroblasts. The observed over-expression of UCP2 in cancer lines, but not in controls, provides a plausible molecular mechanism by which acetoacetate spares normal cells but suppresses growth in cancer lines. The results bear on the hypothesized potential for ketogenic diets as therapeutic strategies.

  7. NetMOD Version 2.0 Mathematical Framework

    Energy Technology Data Exchange (ETDEWEB)

    Merchant, Bion J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Young, Christopher J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Chael, Eric P. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-08-01

    NetMOD ( Net work M onitoring for O ptimal D etection) is a Java-based software package for conducting simulation of seismic, hydroacoustic and infrasonic networks. Network simulations have long been used to study network resilience to station outages and to determine where additional stations are needed to reduce monitoring thresholds. NetMOD makes use of geophysical models to determine the source characteristics, signal attenuation along the path between the source and station, and the performance and noise properties of the station. These geophysical models are combined to simulate the relative amplitudes of signal and noise that are observed at each of the stations. From these signal-to-noise ratios (SNR), the probabilities of signal detection at each station and event detection across the network of stations can be computed given a detection threshold. The purpose of this document is to clearly and comprehensively present the mathematical framework used by NetMOD, the software package developed by Sandia National Laboratories to assess the monitoring capability of ground-based sensor networks. Many of the NetMOD equations used for simulations are inherited from the NetSim network capability assessment package developed in the late 1980s by SAIC (Sereno et al., 1990).

  8. Net alkalinity and net acidity 1: Theoretical considerations

    International Nuclear Information System (INIS)

    Kirby, Carl S.; Cravotta, Charles A.

    2005-01-01

    Net acidity and net alkalinity are widely used, poorly defined, and commonly misunderstood parameters for the characterization of mine drainage. The authors explain theoretical expressions of 3 types of alkalinity (caustic, phenolphthalein, and total) and acidity (mineral, CO 2 , and total). Except for rarely-invoked negative alkalinity, theoretically defined total alkalinity is closely analogous to measured alkalinity and presents few practical interpretation problems. Theoretically defined 'CO 2 -acidity' is closely related to most standard titration methods with an endpoint pH of 8.3 used for determining acidity in mine drainage, but it is unfortunately named because CO 2 is intentionally driven off during titration of mine-drainage samples. Using the proton condition/mass-action approach and employing graphs to illustrate speciation with changes in pH, the authors explore the concept of principal components and how to assign acidity contributions to aqueous species commonly present in mine drainage. Acidity is defined in mine drainage based on aqueous speciation at the sample pH and on the capacity of these species to undergo hydrolysis to pH 8.3. Application of this definition shows that the computed acidity in mgL -1 as CaCO 3 (based on pH and analytical concentrations of dissolved Fe II , Fe III , Mn, and Al in mgL -1 ):acidity calculated =50{1000(10 -pH )+[2(Fe II )+3(Fe III )]/56+2(Mn) /55+3(Al)/27}underestimates contributions from HSO 4 - and H + , but overestimates the acidity due to Fe 3+ and Al 3+ . However, these errors tend to approximately cancel each other. It is demonstrated that 'net alkalinity' is a valid mathematical construction based on theoretical definitions of alkalinity and acidity. Further, it is shown that, for most mine-drainage solutions, a useful net alkalinity value can be derived from: (1) alkalinity and acidity values based on aqueous speciation (2) measured alkalinity minus calculated acidity, or (3) taking the negative of the

  9. Net alkalinity and net acidity 1: Theoretical considerations

    Science.gov (United States)

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

    2005-01-01

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

  10. Les dispositifs du Net art

    OpenAIRE

    Fourmentraux, Jean-Paul

    2010-01-01

    La pratique du Net art radicalise la question du potentiel communicationnel d’un média —Internet— qui constitue tout à la fois le support technique, l’outil créatif et le dispositif social de l’œuvre. Les technologies de l’information et de la communication (TIC) placent en effet l’œuvre d’art au cœur d’une négociation socialement distribuée entre l’artiste et le public. L’article est focalisé sur cette construction collective du Net art et sur ses mises en scènes. Il montre le travail artist...

  11. Complexity Metrics for Workflow Nets

    DEFF Research Database (Denmark)

    Lassen, Kristian Bisgaard; van der Aalst, Wil M.P.

    2009-01-01

    analysts have difficulties grasping the dynamics implied by a process model. Recent empirical studies show that people make numerous errors when modeling complex business processes, e.g., about 20 percent of the EPCs in the SAP reference model have design flaws resulting in potential deadlocks, livelocks......, etc. It seems obvious that the complexity of the model contributes to design errors and a lack of understanding. It is not easy to measure complexity, however. This paper presents three complexity metrics that have been implemented in the process analysis tool ProM. The metrics are defined...... for a subclass of Petri nets named Workflow nets, but the results can easily be applied to other languages. To demonstrate the applicability of these metrics, we have applied our approach and tool to 262 relatively complex Protos models made in the context of various student projects. This allows us to validate...

  12. Reduction of voltage gated sodium channel protein in DRG by vector mediated miRNA reduces pain in rats with painful diabetic neuropathy.

    Science.gov (United States)

    Chattopadhyay, Munmun; Zhou, Zhigang; Hao, Shuanglin; Mata, Marina; Fink, David J

    2012-03-22

    Painful neuropathy is a common complication of diabetes. Previous studies have identified significant increases in the amount of voltage gated sodium channel isoforms Na(V)1.7 and Na(V)1.3 protein in the dorsal root ganglia (DRG) of rats with streptozotocin (STZ)-induced diabetes. We found that gene transfer-mediated release of the inhibitory neurotransmitters enkephalin or gamma amino butyric acid (GABA) from DRG neurons in diabetic animals reduced pain-related behaviors coincident with a reduction in Na(V)1.7 protein levels in DRG in vivo. To further evaluate the role of Na(V)α subunit levels in DRG in the pathogenesis of pain in diabetic neuropathy, we constructed a non-replicating herpes simplex virus (HSV)-based vector expressing a microRNA (miRNA) against Na(V)α subunits. Subcutaneous inoculation of the miRNA-expressing HSV vector into the feet of diabetic rats to transduce DRG resulted in a reduction in Na(V)α subunit levels in DRG neurons, coincident with a reduction in cold allodynia, thermal hyperalgesia and mechanical hyperalgesia. These data support the role of increased Na(V)α protein in DRG in the pathogenesis of pain in diabetic neuropathy, and provide a proof-of-principle demonstration for the development of a novel therapy that could be used to treat intractable pain in patients with diabetic neuropathy.

  13. Peripheral T-Cell Reactivity to Heat Shock Protein 70 and Its Cofactor GrpE from Tropheryma whipplei Is Reduced in Patients with Classical Whipple's Disease.

    Science.gov (United States)

    Trotta, Lucia; Weigt, Kathleen; Schinnerling, Katina; Geelhaar-Karsch, Anika; Oelkers, Gerrit; Biagi, Federico; Corazza, Gino Roberto; Allers, Kristina; Schneider, Thomas; Erben, Ulrike; Moos, Verena

    2017-08-01

    Classical Whipple's disease (CWD) is characterized by the lack of specific Th1 response toward Tropheryma whipplei in genetically predisposed individuals. The cofactor GrpE of heat shock protein 70 (Hsp70) from T. whipplei was previously identified as a B-cell antigen. We tested the capacity of Hsp70 and GrpE to elicit specific proinflammatory T-cell responses. Peripheral mononuclear cells from CWD patients and healthy donors were stimulated with T. whipplei lysate or recombinant GrpE or Hsp70 before levels of CD40L, CD69, perforin, granzyme B, CD107a, and gamma interferon (IFN-γ) were determined in T cells by flow cytometry. Upon stimulation with total bacterial lysate or recombinant GrpE or Hsp70 of T. whipplei , the proportions of activated effector CD4 + T cells, determined as CD40L + IFN-γ + , were significantly lower in patients with CWD than in healthy controls; CD8 + T cells of untreated CWD patients revealed an enhanced activation toward unspecific stimulation and T. whipplei -specific degranulation, although CD69 + IFN-γ + CD8 + T cells were reduced upon stimulation with T. whipplei lysate and recombinant T. whipplei -derived proteins. Hsp70 and its cofactor GrpE are immunogenic in healthy individuals, eliciting effective responses against T. whipplei to control bacterial spreading. The lack of specific T-cell responses against these T. whipplei -derived proteins may contribute to the pathogenesis of CWD. Copyright © 2017 American Society for Microbiology.

  14. dotNet som multimediaplattform

    OpenAIRE

    Johansson, Glenn

    2008-01-01

    As the speed and complexity of computers have increased so have software and the expectations of users. Software development follows a straightforward evolution where complicated tasks are made easier by better tools; this repeats itself as those tasks in turn are automated. Software mechanics that were seen as revolutionary a decade ago are seen as obvious requirements that no multimedia application can be without. dotNet is the next step in line and makes it easier and faster to build softw...

  15. Reduced phosphorylation of brain insulin receptor substrate and Akt proteins in apolipoprotein-E4 targeted replacement mice.

    Science.gov (United States)

    Ong, Qi-Rui; Chan, Elizabeth S; Lim, Mei-Li; Cole, Gregory M; Wong, Boon-Seng

    2014-01-17

    Human ApoE4 accelerates memory decline in ageing and in Alzheimer's disease. Although intranasal insulin can improve cognition, this has little effect in ApoE4 subjects. To understand this ApoE genotype-dependent effect, we examined brain insulin signaling in huApoE3 and huApoE4 targeted replacement (TR) mice. At 32 weeks, lower insulin receptor substrate 1 (IRS1) at S636/639 and Akt phosphorylation at T308 were detected in fasting huApoE4 TR mice as compared to fasting huApoE3 TR mice. These changes in fasting huApoE4 TR mice were linked to lower brain glucose content and have no effect on plasma glucose level. However, at 72 weeks of age, these early changes were accompanied by reduction in IRS2 expression, IRS1 phosphorylation at Y608, Akt phosphorylation at S473, and MAPK (p38 and p44/42) activation in the fasting huApoE4 TR mice. The lower brain glucose was significantly associated with higher brain insulin in the aged huApoE4 TR mice. These results show that ApoE4 reduces brain insulin signaling and glucose level leading to higher insulin content.

  16. NET model coil test possibilities

    International Nuclear Information System (INIS)

    Erb, J.; Gruenhagen, A.; Herz, W.; Jentzsch, K.; Komarek, P.; Lotz, E.; Malang, S.; Maurer, W.; Noether, G.; Ulbricht, A.; Vogt, A.; Zahn, G.; Horvath, I.; Kwasnitza, K.; Marinucci, C.; Pasztor, G.; Sborchia, C.; Weymuth, P.; Peters, A.; Roeterdink, A.

    1987-11-01

    A single full size coil for NET/INTOR represents an investment of the order of 40 MUC (Million Unit Costs). Before such an amount of money or even more for the 16 TF coils is invested as much risks as possible must be eliminated by a comprehensive development programme. In the course of such a programme a coil technology verification test should finally prove the feasibility of NET/INTOR TF coils. This study report is almost exclusively dealing with such a verification test by model coil testing. These coils will be built out of two Nb 3 Sn-conductors based on two concepts already under development and investigation. Two possible coil arrangements are discussed: A cluster facility, where two model coils out of the two Nb 3 TF-conductors are used, and the already tested LCT-coils producing a background field. A solenoid arrangement, where in addition to the two TF model coils another model coil out of a PF-conductor for the central PF-coils of NET/INTOR is used instead of LCT background coils. Technical advantages and disadvantages are worked out in order to compare and judge both facilities. Costs estimates and the time schedules broaden the base for a decision about the realisation of such a facility. (orig.) [de

  17. NET-2 Network Analysis Program

    International Nuclear Information System (INIS)

    Malmberg, A.F.

    1974-01-01

    The NET-2 Network Analysis Program is a general purpose digital computer program which solves the nonlinear time domain response and the linearized small signal frequency domain response of an arbitrary network of interconnected components. NET-2 is capable of handling a variety of components and has been applied to problems in several engineering fields, including electronic circuit design and analysis, missile flight simulation, control systems, heat flow, fluid flow, mechanical systems, structural dynamics, digital logic, communications network design, solid state device physics, fluidic systems, and nuclear vulnerability due to blast, thermal, gamma radiation, neutron damage, and EMP effects. Network components may be selected from a repertoire of built-in models or they may be constructed by the user through appropriate combinations of mathematical, empirical, and topological functions. Higher-level components may be defined by subnetworks composed of any combination of user-defined components and built-in models. The program provides a modeling capability to represent and intermix system components on many levels, e.g., from hole and electron spatial charge distributions in solid state devices through discrete and integrated electronic components to functional system blocks. NET-2 is capable of simultaneous computation in both the time and frequency domain, and has statistical and optimization capability. Network topology may be controlled as a function of the network solution. (U.S.)

  18. Acyclovir Therapy Reduces the CD4+ T Cell Response against the Immunodominant pp65 Protein from Cytomegalovirus in Immune Competent Individuals.

    Directory of Open Access Journals (Sweden)

    Annette Pachnio

    Full Text Available Cytomegalovirus (CMV infects the majority of the global population and leads to the development of a strong virus-specific immune response. The CMV-specific CD4+ and CD8+ T cell immune response can comprise between 10 and 50% of the T cell pool within peripheral blood and there is concern that this may impair immunity to other pathogens. Elderly individuals with the highest magnitude of CMV-specific immune response have been demonstrated to be at increased risk of mortality and there is increasing interest in interventions that may serve to moderate this. Acyclovir is an anti-viral drug with activity against a range of herpes viruses and is used as long term treatment to suppress reactivation of herpes simplex virus. We studied the immune response to CMV in patients who were taking acyclovir to assess if therapy could be used to suppress the CMV-specific immune response. The T cell reactivity against the immunodominant late viral protein pp65 was reduced by 53% in people who were taking acyclovir. This effect was seen within one year of therapy and was observed primarily within the CD4+ response. Acyclovir treatment only modestly influenced the immune response to the IE-1 target protein. These data show that low dose acyclovir treatment has the potential to modulate components of the T cell response to CMV antigen proteins and indicate that anti-viral drugs should be further investigated as a means to reduce the magnitude of CMV-specific immune response and potentially improve overall immune function.

  19. The effects of a reduced balanced protein diet on litter moisture, pododermatitis and feather condition of female broiler breeders over three generations.

    Science.gov (United States)

    Li, C; Lesuisse, J; Schallier, S; Clímaco, W; Wang, Y; Bautil, A; Everaert, N; Buyse, J

    2017-11-02

    Protein content reduction in broiler breeder diets has been increasingly investigated. However, broiler breeders reared on low protein diets are characterized by a deterioration of the feather condition. Furthermore, polydipsia induced by controlled feed intake increases litter moisture and as a consequence pododermatitis. This project aimed to study the litter moisture, pododermatitis and feather condition of breeders fed with a 25% reduced balanced protein (RP) diet during the rearing and laying period over three successive generations. The experiment started with two treatments for the F0 generation: control (C) group fed with standard C diets and RP group fed with RP diets. The female F0-progeny of each treatment was divided into the two dietary treatments as well, resulting in four treatments for the F1 generation: C/C, C/RP, RP/C and RP/RP (breeder feed in F0/F1 generation). The RP diet fed breeders received on average 10% more feed than C diet fed breeders to achieve the same target BW. The female F1-progeny of each treatment were all fed with C diets which resulted in four treatments for the F2 generation: C/C/C, C/RP/C, RP/C/C and RP/RP/C (breeder feed in F0/F1/F2 generation). Litter moisture, footpad and hock dermatitis were recorded at regular intervals throughout the experimental period in all three generations. For the F0 and F1 generation, the pens of breeders receiving C diets had significantly higher litter moisture than the RP diets fed groups (Pdiets had poorer feather condition than those receiving the C diets (Pdiets to broiler breeders improved litter condition and hence reduced FDO whereas impaired feather condition. Furthermore, positive transgenerational effects of the maternal RP diets on the feather condition may be inferred, hence potentially altering the welfare status.

  20. Molecular mechanisms of reduced glutathione transport: role of the MRP/CFTR/ABCC and OATP/SLC21A families of membrane proteins

    International Nuclear Information System (INIS)

    Ballatori, Nazzareno; Hammond, Christine L.; Cunningham, Jennifer B.; Krance, Suzanne M.; Marchan, Rosemarie

    2005-01-01

    The initial step in reduced glutathione (GSH) turnover in all mammalian cells is its transport across the plasma membrane into the extracellular space; however, the mechanisms of GSH transport are not clearly defined. GSH export is required for the delivery of its constituent amino acids to other tissues, detoxification of drugs, metals, and other reactive compounds of both endogenous and exogenous origin, protection against oxidant stress, and secretion of hepatic bile. Recent studies indicate that some members of the multidrug resistance-associated protein (MRP/CFTR or ABCC) family of ATP-binding cassette (ABC) proteins, as well as some members of the organic anion transporting polypeptide (OATP or SLC21A) family of transporters contribute to this process. In particular, five of the 12 members of the MRP/CFTR family appear to mediate GSH export from cells namely, MRP1, MRP2, MRP4, MRP5, and CFTR. Additionally, two members of the OATP family, rat Oatp1 and Oatp2, have been identified as GSH transporters. For the Oatp1 transporter, efflux of GSH may provide the driving force for the uptake of extracellular substrates. In humans, OATP-B and OATP8 do not appear to transport GSH; however, other members of this family have yet to be characterized in regards to GSH transport. In yeast, the ABC proteins Ycf1p and Bpt1p transport GSH from the cytosol into the vacuole, whereas Hgt1p mediates GSH uptake across the plasma membrane. Because transport is a key step in GSH homeostasis and is intimately linked to its biological functions, GSH export proteins are likely to modulate essential cellular functions

  1. Mental performance in 8-year-old children fed reduced protein content formula during the 1st year of life: safety analysis of a randomised clinical trial.

    Science.gov (United States)

    Escribano, J; Luque, V; Canals-Sans, J; Ferré, N; Koletzko, B; Grote, V; Weber, M; Gruszfeld, D; Szott, K; Verduci, E; Riva, E; Brasselle, G; Poncelet, P; Closa-Monasterolo, R

    2016-01-22

    In humans, maximum brain development occurs between the third trimester of gestation and 2 years of life. Nutrition during these critical windows of rapid brain development might be essential for later cognitive functioning and behaviour. In the last few years, trends on protein recommendations during infancy and childhood have tended to be lower than that in the past. It remains to be demonstrated that lower protein intakes among healthy infants, a part of being able to reduce obesity risk, is safe in terms of mental performance achievement. Secondary analyses of the EU CHOP, a clinical trial in which infants from five European countries were randomised to be fed a higher or a lower protein content formula during the 1st year of life. Children were assessed at the age of 8 years with a neuropsychological battery of tests that included assessments of memory (visual and verbal), attention (visual, selective, focused and sustained), visual-perceptual integration, processing speed, visual-motor coordination, verbal fluency and comprehension, impulsivity/inhibition, flexibility/shifting, working memory, reasoning, visual-spatial skills and decision making. Internalising, externalising and total behaviour problems were assessed using the Child Behaviour Checklist 4-18. Adjusted analyses considering factors that could influence neurodevelopment, such as parental education level, maternal smoking, child's gestational age at birth and head circumference, showed no differences between feeding groups in any of the assessed neuropsychological domains and behaviour. In summary, herewith we report on the safety of lower protein content in infant formulae (closer to the content of human milk) according to long-term mental performance.

  2. Laminin-111 protein therapy reduces muscle pathology and improves viability of a mouse model of merosin-deficient congenital muscular dystrophy.

    Science.gov (United States)

    Rooney, Jachinta E; Knapp, Jolie R; Hodges, Bradley L; Wuebbles, Ryan D; Burkin, Dean J

    2012-04-01

    Merosin-deficient congenital muscular dystrophy type 1A (MDC1A) is a lethal muscle-wasting disease that is caused by mutations in the LAMA2 gene, resulting in the loss of laminin-α2 protein. MDC1A patients exhibit severe muscle weakness from birth, are confined to a wheelchair, require ventilator assistance, and have reduced life expectancy. There are currently no effective treatments or cures for MDC1A. Laminin-α2 is required for the formation of heterotrimeric laminin-211 (ie, α2, β1, and γ1) and laminin-221 (ie, α2, β2, and γ1), which are major constituents of skeletal muscle basal lamina. Laminin-111 (ie, α1, β1, and γ1) is the predominant laminin isoform in embryonic skeletal muscle and supports normal skeletal muscle development in laminin-α2-deficient muscle but is absent from adult skeletal muscle. In this study, we determined whether treatment with Engelbreth-Holm-Swarm-derived mouse laminin-111 protein could rescue MDC1A in the dy(W-/-) mouse model. We demonstrate that laminin-111 protein systemically delivered to the muscles of laminin-α2-deficient mice prevents muscle pathology, improves muscle strength, and dramatically increases life expectancy. Laminin-111 also prevented apoptosis in laminin-α2-deficient mouse muscle and primary human MDC1A myogenic cells, which indicates a conserved mechanism of action and cross-reactivity between species. Our results demonstrate that laminin-111 can serve as an effective protein substitution therapy for the treatment of muscular dystrophy in the dy(W-/-) mouse model and establish the potential for its use in the treatment of MDC1A. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  3. Energy balance framework for Net Zero Energy buildings

    Science.gov (United States)

    Approaching a Net Zero Energy (NZE) building goal based on current definitions is flawed for two principal reasons - they only deal with energy quantities required for operations, and they do not establish a threshold, which ensures that buildings are optimized for reduced consum...

  4. Limiting beta of stellarators with no net current

    International Nuclear Information System (INIS)

    Strauss, H.R.; Monticello, D.A.

    1981-01-01

    Using reduced nonlinear MHD equations, we find finite beta, resistive, l = 2 stellarator equilibria with no net current. We then investigate stability to low mode number internal MHD modes, and find beta limits comparable to tokamaks. Low shear equilibria appear to be substantially more stable than high shear

  5. Net foreign asset (com)position : Does financial development matter?

    NARCIS (Netherlands)

    Vermeulen, Robert; de Haan, Jakob

    We investigate the relationship between a country's domestic financial development and the (composition of its) net foreign asset position using a pooled mean group estimator and data for 50 countries for the 1970-2007 period. The results show that financial development reduces a country's long-run

  6. The Uniframe .Net Web Service Discovery Service

    National Research Council Canada - National Science Library

    Berbeco, Robert W

    2003-01-01

    Microsoft .NET allows the creation of distributed systems in a seamless manner Within NET small, discrete applications, referred to as Web services, are utilized to connect to each other or larger applications...

  7. Long Term RadNet Quality Data

    Data.gov (United States)

    U.S. Environmental Protection Agency — This RadNet Quality Data Asset includes all data since initiation and when ERAMS was expanded to become RadNet, name changed to reflect new mission. This includes...

  8. Special Section on Coloured Petri Nets

    DEFF Research Database (Denmark)

    1998-01-01

    Special section on coloured Petri nets, their basic concepts, analysis methods, tool support and industrial applications.......Special section on coloured Petri nets, their basic concepts, analysis methods, tool support and industrial applications....

  9. Peptides of presenilin-1 bind the amyloid precursor protein ectodomain and offer a novel and specific therapeutic approach to reduce ß-amyloid in Alzheimer's disease.

    Science.gov (United States)

    Dewji, Nazneen N; Singer, S Jonathan; Masliah, Eliezer; Rockenstein, Edward; Kim, Mihyun; Harber, Martha; Horwood, Taylor

    2015-01-01

    β-Amyloid (Aβ) accumulation in the brain is widely accepted to be critical to the development of Alzheimer's disease (AD). Current efforts at reducing toxic Aβ40 or 42 have largely focused on modulating γ-secretase activity to produce shorter, less toxic Aβ, while attempting to spare other secretase functions. In this paper we provide data that offer the potential for a new approach for the treatment of AD. The method is based on our previous findings that the production of Aβ from the interaction between the β-amyloid precursor protein (APP) and Presenilin (PS), as part of the γ-secretase complex, in cell culture is largely inhibited if the entire water-soluble NH2-terminal domain of PS is first added to the culture. Here we demonstrate that two small, non-overlapping water-soluble peptides from the PS-1 NH2-terminal domain can substantially and specifically inhibit the production of total Aβ as well as Aβ40 and 42 in vitro and in vivo in the brains of APP transgenic mice. These results suggest that the inhibitory activity of the entire amino terminal domain of PS-1 on Aβ production is largely focused in a few smaller sequences within that domain. Using biolayer interferometry and confocal microscopy we provide evidence that peptides effective in reducing Aβ give a strong, specific and biologically relevant binding with the purified ectodomain of APP 695. Finally, we demonstrate that the reduction of Aβ by the peptides does not affect the catalytic activities of β- or γ-secretase, or the level of APP. P4 and P8 are the first reported protein site-specific small peptides to reduce Aβ production in model systems of AD. These peptides and their derivatives offer new potential drug candidates for the treatment of AD.

  10. Peptides of presenilin-1 bind the amyloid precursor protein ectodomain and offer a novel and specific therapeutic approach to reduce ß-amyloid in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Nazneen N Dewji

    Full Text Available β-Amyloid (Aβ accumulation in the brain is widely accepted to be critical to the development of Alzheimer's disease (AD. Current efforts at reducing toxic Aβ40 or 42 have largely focused on modulating γ-secretase activity to produce shorter, less toxic Aβ, while attempting to spare other secretase functions. In this paper we provide data that offer the potential for a new approach for the treatment of AD. The method is based on our previous findings that the production of Aβ from the interaction between the β-amyloid precursor protein (APP and Presenilin (PS, as part of the γ-secretase complex, in cell culture is largely inhibited if the entire water-soluble NH2-terminal domain of PS is first added to the culture. Here we demonstrate that two small, non-overlapping water-soluble peptides from the PS-1 NH2-terminal domain can substantially and specifically inhibit the production of total Aβ as well as Aβ40 and 42 in vitro and in vivo in the brains of APP transgenic mice. These results suggest that the inhibitory activity of the entire amino terminal domain of PS-1 on Aβ production is largely focused in a few smaller sequences within that domain. Using biolayer interferometry and confocal microscopy we provide evidence that peptides effective in reducing Aβ give a strong, specific and biologically relevant binding with the purified ectodomain of APP 695. Finally, we demonstrate that the reduction of Aβ by the peptides does not affect the catalytic activities of β- or γ-secretase, or the level of APP. P4 and P8 are the first reported protein site-specific small peptides to reduce Aβ production in model systems of AD. These peptides and their derivatives offer new potential drug candidates for the treatment of AD.

  11. Proteína e energia na dieta de jundiás criados em tanques-rede Protein and energy in diet for catsfish raised in net cages

    Directory of Open Access Journals (Sweden)

    Jakeline Marcela Azambuja de Freitas

    2011-12-01

    Full Text Available Objetivou-se com este trabalho avaliar a influência de dois níveis de energia digestível (3.250 e 3.500 kcal kg-1 em combinação a três níveis de proteína bruta (25, 30 e 35% sobre o desempenho produtivo de juvenis de jundiá (Rhamdia voulezi. Utilizaram-se 240 juvenis de jundiá com peso inicial de 95,55±6,70 g e 20,43±1,13 cm de comprimento total, distribuídos ao acaso em 24 tanques-rede (370 L cada em delineamento fatorial com seis tratamentos e quatro repetições. O arraçoamento foi realizado quatro vezes ao dia, à vontade. Ao final do período experimental, a análise fatorial de variância evidenciou influência significativa nos parâmetros zootécnicos avaliados. Foram observados melhor ganho de peso e comprimento final médios e menor deposição de gordura visceral nos peixes alimentados com a dieta contendo 30% de proteína bruta e 3.250 kcal de energia digestível kg-1. Portanto, recomendam-se para juvenis de jundiá dietas que contenham no mínimo 30% de proteína bruta e 3.250 kcal de energia digestível kg-1 de ração.The objective of this study was to evaluate the influence of two levels of digestible energy (3250 and 3500 kcal kg-1 in conjunction with three levels of crude protein (25, 30 and 35% on the productive performance of catfish (Rhamdia voulezi juveniles. Two-hundred and forty catfish juveniles with 95.55±6.70 g average weight and 20.43±1.13 cm total length were randomly assigned into twenty-four 370 L-cages, in a factorial arrangement with six treatments and four reptitions. Feeding was performed four times a day, ad libitum. At end of experimental period, the factorial analysis of variance showed significant influence with respect to the different parameters evaluated. The fish fed with diets of 30% crude protein and 3,250 kcal digestible energy kg-1 of diet presented the best results. Therefore, diets with at least 30% crude protein and 3,250 kcal digestible energy kg-1 are recommend for catfish

  12. Reduced egfr, elevated urine protein and low level of personal protective equipment compliance among artisanal small scale gold miners at Bibiani-Ghana: a cross-sectional study.

    Science.gov (United States)

    Afrifa, Justice; Essien-Baidoo, Samuel; Ephraim, Richard K D; Nkrumah, Daniel; Dankyira, Daniel Osei

    2017-06-27

    Mercury is a toxic metal with its effects on human health ranging from acute to chronic in a very short time of exposure. Artisanal and small-scale gold mining (ASGM) is the main source of direct human exposure to mercury. To access the effect of mercury exposure on the renal function and level of personal protective equipment (PPE) compliance among small-scale gold miners in Bibiani District of the Western Region of Ghana METHOD: 110 consenting male gold miners were purposively recruited for this study. A structured questionnaire was used to collect socio-demographic information from the participants. Work place assessment and interviews were conducted. Urine samples were analysed for protein; blood was analysed for mercury and creatinine. Estimated glomerular filtration rate (eGFR) was calculated using the chronic kidney disease-epidemiology collaboration (CKD-EPI) equation. Of the 110 participants, 61(55.5%) exceeded the occupational exposure threshold (blood mercury <5μg/L). Urine protein (41.72±68.34, P<0.0001), serum creatinine (2.24±1.19, P<0.0001) and blood mercury (18.37±10.47, P<0.0001) were significantly elevated among the exposed group compared to the non-exposed group. However, the exposed group had a significantly reduced eGFR (P<0.0001). There was a significant correlation (r=0.7338, p<0.0001) between blood mercury concentration and urine protein concentration. An increase in blood mercury correlated negatively (r = -0.8233, P<0.0001) with eGFR among the exposed group. High urine protein (P< 0.0001) and high serum creatinine (P< 0.0001) were significantly associated with increased mercury exposure. Increased mercury exposure was significantly associated with burning of amalgam (P=0.0196), sucking of excess mercury (P=0.0336), longer work duration (P=0.0314) and low educational background (P=0.0473). Small scale miners at the Bibiani work site are exposed to excess mercury. Proteinuria and reduced eGFR is common in mine workers exposed to excess

  13. Processing of soybean meal and 00-rapeseed meal reduces protein digestibility and pig growth performance but does not affect nitrogen solubilization along the small intestine.

    Science.gov (United States)

    Hulshof, T G; van der Poel, A F B; Hendriks, W H; Bikker, P

    2016-06-01

    An experiment was conducted to determine the effects of processing of soybean meal (SBM) and 00-rapeseed meal (RSM) on N solubilization in chyme, CP digestibility along the small intestine, metabolic load as determined by organ weight, body composition, and growth performance in growing pigs. The SBM and RSM were processed by secondary toasting (at 95°C for 30 min) in the presence of lignosulfonate, resulting in processed SBM (pSBM) and processed RSM (pRSM) as a model for overprocessed protein sources. Fifty-four growing pigs were each fed 1 of the 6 experimental diets. Four of the diets contained SBM, pSBM, RSM, or pRSM as the sole protein source. The remaining 2 experimental diets contained pSBM or pRSM and were supplemented with crystalline AA to the same standardized ileal digestible AA levels as the SBM or RSM diet. Pigs were slaughtered at 40 kg, and organ weights were recorded. The organs plus blood and empty carcass were analyzed for CP content. The small intestine was divided into 3 segments, and chyme samples were taken from the last meter of each segment. Chyme of the SBM, pSBM, RSM, and pRSM diets was centrifuged to separate the soluble and insoluble fractions, and N content was determined in the latter. The amount of insoluble N as a fraction of N in chyme at each small intestinal segment was not affected by processing. Diet type, comprising effects of processing and supplementing crystalline AA, affected ( < 0.05) the G:F and standardized ileal digestibility (SID) of CP. Processing reduced G:F from 0.56 to 0.38 for SBM and 0.49 to 0.40 for RSM, whereas supplementing crystalline AA increased G:F to the level of the SBM and RSM diets. Processing reduced the SID of CP from 87.2% to 69.2% for SBM and 71.0% to 52.2% for RSM. Diet type affected ( < 0.05) the CP content in the empty body, with processing reducing this content from 170 to 144 g/kg empty BW for SBM and 157 to 149 g/kg empty BW for RSM and supplementing crystalline AA restoring this content

  14. NetBeans IDE 8 cookbook

    CERN Document Server

    Salter, David

    2014-01-01

    If you're a Java developer of any level using NetBeans and want to learn how to get the most out of NetBeans, then this book is for you. Learning how to utilize NetBeans will provide a firm foundation for your Java application development.

  15. History-dependent stochastic Petri nets

    NARCIS (Netherlands)

    Schonenberg, H.; Sidorova, N.; Aalst, van der W.M.P.; Hee, van K.M.; Pnueli, A.; Virbitskaite, I.; Voronkov, A.

    2010-01-01

    Stochastic Petri Nets are a useful and well-known tool for performance analysis. However, an implicit assumption in the different types of Stochastic Petri Nets is the Markov property. It is assumed that a choice in the Petri net only depends on the current state and not on earlier choices. For many

  16. Putting Petri nets to work in Industry

    NARCIS (Netherlands)

    Aalst, van der W.M.P.

    1994-01-01

    Petri nets exist for over 30 years. Especially in the last decade Petri nets have been put into practive extensively. Thanks to several useful extensions and the availability of computer tools, Petri nets have become a mature tool for modelling and analysing industrial systems. This paper describes

  17. Aplicació Microsoft .Net : Hotel Spa

    OpenAIRE

    Marquès Palmer, Jordi

    2010-01-01

    Desenvolupament d'una aplicació amb Microsoft .NET, WCF, WPF, Linq2SQL, d'un Hotel Spa. Desarrollo de una aplicación con Microsoft .NET, WCF, WPF, Linq2SQL, de un Hotel Spa. Application development using Microsoft .NET, WCF, WPF, Linq2SQL, for a Spa Hotel.

  18. Delta Semantics Defined By Petri Nets

    DEFF Research Database (Denmark)

    Jensen, Kurt; Kyng, Morten; Madsen, Ole Lehrmann

    and the possibility of using predicates to specify state changes. In this paper a formal semantics for Delta is defined and analysed using Petri nets. Petri nets was chosen because the ideas behind Petri nets and Delta concide on several points. A number of proposals for changes in Delta, which resulted from...

  19. The K-NET - A year after

    International Nuclear Information System (INIS)

    Kinoshita, S.; Ohtani, K.; Katayama, T.

    2001-01-01

    We started to release the K-NET strong-motion data from June 1996 and about one year passed. In this article, we report the development of K-NET and some applications using the K-NET information released on the Internet. (author)

  20. 47 CFR 65.500 - Net income.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Net income. 65.500 Section 65.500... OF RETURN PRESCRIPTION PROCEDURES AND METHODOLOGIES Interexchange Carriers § 65.500 Net income. The net income methodology specified in § 65.450 shall be utilized by all interexchange carriers that are...

  1. 47 CFR 65.450 - Net income.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Net income. 65.450 Section 65.450... OF RETURN PRESCRIPTION PROCEDURES AND METHODOLOGIES Exchange Carriers § 65.450 Net income. (a) Net income shall consist of all revenues derived from the provision of interstate telecommunications services...

  2. INMARSAT-C SafetyNET

    Science.gov (United States)

    Tsunamis 406 EPIRB's National Weather Service Marine Forecasts INMARSAT-C SafetyNET Marine Forecast Offices greater danger near shore or any shallow waters? NATIONAL WEATHER SERVICE PRODUCTS VIA INMARSAT-C SafetyNET Inmarsat-C SafetyNET is an internationally adopted, automated satellite system for promulgating

  3. Ginsenoside F2 reduces hair loss by controlling apoptosis through the sterol regulatory element-binding protein cleavage activating protein and transforming growth factor-β pathways in a dihydrotestosterone-induced mouse model.

    Science.gov (United States)

    Shin, Heon-Sub; Park, Sang-Yong; Hwang, Eun-Son; Lee, Don-Gil; Mavlonov, Gafurjon Turdalievich; Yi, Tae-Hoo

    2014-01-01

    This study was conducted to test whether ginsenoside F2 can reduce hair loss by influencing sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) and the transforming growth factor beta (TGF-β) pathway of apoptosis in dihydrotestosterone (DHT)-treated hair cells and in a DHT-induced hair loss model in mice. Results for ginsenoside F2 were compared with finasteride. DHT inhibits proliferation of hair cells and induces androgenetic alopecia and was shown to activate an apoptosis signal pathway both in vitro and in vivo. The cell-based 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that the proliferation rates of DHT-treated human hair dermal papilla cells (HHDPCs) and HaCaTs increased by 48% in the ginsenoside F2-treated group and by 12% in the finasteride-treated group. Western blot analysis showed that ginsenoside F2 decreased expression of TGF-β2 related factors involved in hair loss. The present study suggested a hair loss related pathway by changing SCAP related apoptosis pathway, which has been known to control cholesterol metabolism. SCAP, sterol regulatory element-binding protein (SREBP) and caspase-12 expression in the ginsenoside F2-treated group were decreased compared to the DHT and finasteride-treated group. C57BL/6 mice were also prepared by injection with DHT and then treated with ginsenoside F2 or finasteride. Hair growth rate, density, thickness measurements and tissue histotological analysis in these groups suggested that ginsenoside F2 suppressed hair cell apoptosis and premature entry to catagen more effectively than finasteride. Our results indicated that ginsenoside F2 decreased the expression of TGF-β2 and SCAP proteins, which have been suggested to be involved in apoptosis and entry into catagen. This study provides evidence those factors in the SCAP pathway could be targets for hair loss prevention drugs.

  4. Overexpression and deletion of phospholipid transfer protein reduce HDL mass and cholesterol efflux capacity but not macrophage reverse cholesterol transport[S

    Science.gov (United States)

    Kuwano, Takashi; Bi, Xin; Cipollari, Eleonora; Yasuda, Tomoyuki; Lagor, William R.; Szapary, Hannah J.; Tohyama, Junichiro; Millar, John S.; Billheimer, Jeffrey T.; Lyssenko, Nicholas N.; Rader, Daniel J.

    2017-01-01

    Phospholipid transfer protein (PLTP) may affect macrophage reverse cholesterol transport (mRCT) through its role in the metabolism of HDL. Ex vivo cholesterol efflux capacity and in vivo mRCT were assessed in PLTP deletion and PLTP overexpression mice. PLTP deletion mice had reduced HDL mass and cholesterol efflux capacity, but unchanged in vivo mRCT. To directly compare the effects of PLTP overexpression and deletion on mRCT, human PLTP was overexpressed in the liver of wild-type animals using an adeno-associated viral (AAV) vector, and control and PLTP deletion animals were injected with AAV-null. PLTP overexpression and deletion reduced plasma HDL mass and cholesterol efflux capacity. Both substantially decreased ABCA1-independent cholesterol efflux, whereas ABCA1-dependent cholesterol efflux remained the same or increased, even though preβ HDL levels were lower. Neither PLTP overexpression nor deletion affected excretion of macrophage-derived radiocholesterol in the in vivo mRCT assay. The ex vivo and in vivo assays were modified to gauge the rate of cholesterol efflux from macrophages to plasma. PLTP activity did not affect this metric. Thus, deviations in PLTP activity from the wild-type level reduce HDL mass and ex vivo cholesterol efflux capacity, but not the rate of macrophage cholesterol efflux to plasma or in vivo mRCT. PMID:28137768

  5. Periodontal therapy reduces plasma levels of interleukin-6, C-reactive protein, and fibrinogen in patients with severe periodontitis and refractory arterial hypertension.

    Science.gov (United States)

    Vidal, Fábio; Figueredo, Carlos Marcelo S; Cordovil, Ivan; Fischer, Ricardo G

    2009-05-01

    Recent epidemiologic studies suggest that inflammation is the link between periodontal diseases and cardiovascular complications. This study aimed to evaluate the effects of non-surgical periodontal treatment on plasma levels of inflammatory markers (interleukin [IL]-6, C-reactive protein [CRP], and fibrinogen) in patients with severe periodontitis and refractory arterial hypertension. Twenty-two patients were examined and randomly divided into two groups. The test group was composed of 11 patients (mean age, 48.9 +/- 3.9 years) who received periodontal treatment, whereas the control group had 11 patients (mean age, 49.7 +/- 6.0 years) whose treatment was delayed for 3 months. Demographic and clinical periodontal data were collected, and blood tests were performed to measure the levels of IL-6, CRP, and fibrinogen at baseline and 3 months later. The clinical results showed that the mean percentages of sites with bleeding on probing, probing depth (PD) 4 to 5 mm, PD > or =6 mm, clinical attachment loss (CAL) 4 to 5 mm, and CAL > or =6 mm were significantly reduced in the test group 3 months after periodontal treatment. There were no significant differences between the data at baseline and 3 months in the control group. Periodontal treatment significantly reduced the blood levels of fibrinogen, CRP, and IL-6 in the test group. Non-surgical periodontal therapy was effective in improving periodontal clinical data and in reducing the plasma levels of IL-6, CRP, and fibrinogen in hypertensive patients with severe periodontitis.

  6. Multigenerational effects of a reduced balanced protein diet during the rearing and laying period of broiler breeders. 2. Zootechnical performance of the F1 broiler offspring.

    Science.gov (United States)

    Lesuisse, J; Schallier, S; Li, C; Bautil, A; Li, B; Leblois, J; Buyse, J; Everaert, N

    2018-05-01

    Several studies in mammals focused on the maternal programming of the metabolism by epigenetic mechanisms, while currently, the consequences of a maternal dietary treatment on the offspring performance of farm animals are of particular interest for commercial purpose. In the present study, we investigated if the zootechnical performance of the progeny was altered by a maternal dietary treatment, being a lower dietary crude protein (CP) of the grandparent and/or parent generation. The multigenerational effects of a reduced maternal CP content were investigated by reducing the dietary CP level by 25% in rearing and laying diets of pure line A breeders. The F0 generation breeders were fed either control (C) or reduced balanced protein (RP) diets. The F1 breeder generation was constructed by dividing the F0 female progeny again over a C or RP diet, resulting in 4 dietary treatments in the F1 generation: C/C, C/RP, RP/C, and RP/RP (letters indicating the diets in, respectively, F0 and F1 generations). The offspring performance was evaluated by a zootechnical and nitrogen retention trial on C and low-protein (LP) broiler diets. For the C broiler diet, the C/RP and RP/RP offspring were characterized by a higher BW from d 35 until d 42 compared to the C/C progeny, whereas the RP/C offspring had an intermediate BW that did not differ from the other groups. A tendency (P = 0.067) towards a better nitrogen retention was observed for the offspring of breeders that received the RP diets in F0 and/or F1 generation compared to the C/C progeny. For the LP broiler diet, the C/RP (P = 0.021) and RP/C (P = 0.001) offspring had a higher BW compared to the C/C progeny during the entire grow-out period. In addition, the C/RP offspring were characterized by a lower FCR from d 28 onwards (P = 0.021). In conclusion, dietary treatments imposed on mother hens can have direct effects on the next generation, as well as indirect effects on multiple generations.

  7. NET 40 Generics Beginner's Guide

    CERN Document Server

    Mukherjee, Sudipta

    2012-01-01

    This is a concise, practical guide that will help you learn Generics in .NET, with lots of real world and fun-to-build examples and clear explanations. It is packed with screenshots to aid your understanding of the process. This book is aimed at beginners in Generics. It assumes some working knowledge of C# , but it isn't mandatory. The following would get the most use out of the book: Newbie C# developers struggling with Generics. Experienced C++ and Java Programmers who are migrating to C# and looking for an alternative to other generic frameworks like STL and JCF would find this book handy.

  8. Drag of Clean and Fouled Net Panels--Measurements and Parameterization of Fouling.

    Directory of Open Access Journals (Sweden)

    Lars Christian Gansel

    Full Text Available Biofouling is a serious problem in marine aquaculture and it has a number of negative impacts including increased forces on aquaculture structures and reduced water exchange across nets. This in turn affects the behavior of fish cages in waves and currents and has an impact on the water volume and quality inside net pens. Even though these negative effects are acknowledged by the research community and governmental institutions, there is limited knowledge about fouling related effects on the flow past nets, and more detailed investigations distinguishing between different fouling types have been called for. This study evaluates the effect of hydroids, an important fouling organism in Norwegian aquaculture, on the forces acting on net panels. Drag forces on clean and fouled nets were measured in a flume tank, and net solidity including effect of fouling were determined using image analysis. The relationship between net solidity and drag was assessed, and it was found that a solidity increase due to hydroids caused less additional drag than a similar increase caused by change in clean net parameters. For solidities tested in this study, the difference in drag force increase could be as high as 43% between fouled and clean nets with same solidity. The relationship between solidity and drag force is well described by exponential functions for clean as well as for fouled nets. A method is proposed to parameterize the effect of fouling in terms of an increase in net solidity. This allows existing numerical methods developed for clean nets to be used to model the effects of biofouling on nets. Measurements with other types of fouling can be added to build a database on effects of the accumulation of different fouling organisms on aquaculture nets.

  9. Towards a Standard for Modular Petri Nets

    DEFF Research Database (Denmark)

    Kindler, Ekkart; Petrucci, Laure

    2009-01-01

    concepts could or should be subject to import and export in high-level Petri nets. In this paper, we formalise a minimal version of modular high-level Petri nets, which is based on the concepts of modular PNML. This shows that modular PNML can be formalised once a specific version of Petri net is fixed....... Moreover, we present and discuss some more advanced features of modular Petri nets that could be included in the standard. This way, we provide a formal foundation and a basis for a discussion of features to be included in the upcoming standard of a module concept for Petri nets in general and for high-level...

  10. Increased Expression of Cytotoxic T-Lymphocyte-Associated Protein 4 by T Cells, Induced by B7 in Sera, Reduces Adaptive Immunity in Patients With Acute Liver Failure

    DEFF Research Database (Denmark)

    Khamri, Wafa; Abeles, Robin D; Hou, Tie Zheng

    2017-01-01

    , hepatic sinusoidal endothelial cells, and biliary epithelial cells from healthy or diseased liver tissues. We also measured levels of soluble B7 serum samples from patients and controls, and mice with acetaminophen-induced liver injury using enzyme-linked immunosorbent assays. RESULTS: Peripheral blood...... mice with acetaminophen-induced liver injury contained high levels of soluble B7 compared to sera from mice without liver injury. Plasma exchange reduced circulating levels of soluble B7 in patients with ALF and expression of CTLA4 on T cells. CONCLUSIONS: Peripheral CD4+ T cells from patients with ALF......BACKGROUND & AIMS: Patients with acute liver failure (ALF) have defects in innate immune responses to microbes (immune paresis) and are susceptible to sepsis. Cytotoxic T-lymphocyte-associated protein 4 (CTLA4), which interacts with the membrane receptor B7 (also called CD80 and CD86...

  11. The rice dwarf virus P2 protein interacts with ent-kaurene oxidases in vivo, leading to reduced biosynthesis of gibberellins and rice dwarf symptoms.

    Science.gov (United States)

    Zhu, Shifeng; Gao, Feng; Cao, Xuesong; Chen, Mao; Ye, Gongyin; Wei, Chunhong; Li, Yi

    2005-12-01

    The mechanisms of viral diseases are a major focus of biology. Despite intensive investigations, how a plant virus interacts with host factors to cause diseases remains poorly understood. The Rice dwarf virus (RDV), a member of the genus Phytoreovirus, causes dwarfed growth phenotypes in infected rice (Oryza sativa) plants. The outer capsid protein P2 is essential during RDV infection of insects and thus influences transmission of RDV by the insect vector. However, its role during RDV infection within the rice host is unknown. By yeast two-hybrid and coimmunoprecipitation assays, we report that P2 of RDV interacts with ent-kaurene oxidases, which play a key role in the biosynthesis of plant growth hormones gibberellins, in infected plants. Furthermore, the expression of ent-kaurene oxidases was reduced in the infected plants. The level of endogenous GA1 (a major active gibberellin in rice vegetative tissues) in the RDV-infected plants was lower than that in healthy plants. Exogenous application of GA3 to RDV-infected rice plants restored the normal growth phenotypes. These results provide evidence that the P2 protein of RDV interferes with the function of a cellular factor, through direct physical interactions, that is important for the biosynthesis of a growth hormone leading to symptom expression. In addition, the interaction between P2 and rice ent-kaurene oxidase-like proteins may decrease phytoalexin biosynthesis and make plants more competent for virus replication. Moreover, P2 may provide a novel tool to investigate the regulation of GA metabolism for plant growth and development.

  12. The Rice Dwarf Virus P2 Protein Interacts with ent-Kaurene Oxidases in Vivo, Leading to Reduced Biosynthesis of Gibberellins and Rice Dwarf Symptoms1

    Science.gov (United States)

    Zhu, Shifeng; Gao, Feng; Cao, Xuesong; Chen, Mao; Ye, Gongyin; Wei, Chunhong; Li, Yi

    2005-01-01

    The mechanisms of viral diseases are a major focus of biology. Despite intensive investigations, how a plant virus interacts with host factors to cause diseases remains poorly understood. The Rice dwarf virus (RDV), a member of the genus Phytoreovirus, causes dwarfed growth phenotypes in infected rice (Oryza sativa) plants. The outer capsid protein P2 is essential during RDV infection of insects and thus influences transmission of RDV by the insect vector. However, its role during RDV infection within the rice host is unknown. By yeast two-hybrid and coimmunoprecipitation assays, we report that P2 of RDV interacts with ent-kaurene oxidases, which play a key role in the biosynthesis of plant growth hormones gibberellins, in infected plants. Furthermore, the expression of ent-kaurene oxidases was reduced in the infected plants. The level of endogenous GA1 (a major active gibberellin in rice vegetative tissues) in the RDV-infected plants was lower than that in healthy plants. Exogenous application of GA3 to RDV-infected rice plants restored the normal growth phenotypes. These results provide evidence that the P2 protein of RDV interferes with the function of a cellular factor, through direct physical interactions, that is important for the biosynthesis of a growth hormone leading to symptom expression. In addition, the interaction between P2 and rice ent-kaurene oxidase-like proteins may decrease phytoalexin biosynthesis and make plants more competent for virus replication. Moreover, P2 may provide a novel tool to investigate the regulation of GA metabolism for plant growth and development. PMID:16299167

  13. Dietary Mung Bean Protein Reduces Hepatic Steatosis, Fibrosis, and Inflammation in Male Mice with Diet-Induced, Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Watanabe, Hitoshi; Inaba, Yuka; Kimura, Kumi; Asahara, Shun-Ichiro; Kido, Yoshiaki; Matsumoto, Michihiro; Motoyama, Takayasu; Tachibana, Nobuhiko; Kaneko, Shuichi; Kohno, Mitsutaka; Inoue, Hiroshi

    2017-01-01

    As the prevalence of nonalcoholic fatty liver disease (NAFLD), including steatosis and nonalcoholic steatohepatitis, is increasing, novel dietary approaches are required for the prevention and treatment of NAFLD. We evaluated the potential of mung bean protein isolate (MuPI) to prevent NAFLD progression. In Expts. 1 and 2, the hepatic triglyceride (TG) concentration was compared between 8-wk-old male mice fed a high-fat diet (61% of energy from fat) containing casein, MuPI, and soy protein isolate and an MuPI-constituent amino acid mixture as a source of amino acids (18% of energy) for 4 wk. In Expt. 3, hepatic fatty acid synthase (Fasn) expression was evaluated in 8-wk-old male Fasn-promoter-reporter mice fed a casein- or MuPI-containing high-fat diet for 20 wk. In Expt. 4, hepatic fibrosis was examined in 8-wk-old male mice fed an atherogenic diet (61% of energy from fat, containing 1.3 g cholesterol/100 g diet) containing casein or MuPI (18% of energy) as a protein source for 20 wk. In the high fat-diet mice, the hepatic TG concentration in the MuPI group decreased by 66% and 47% in Expt. 1 compared with the casein group (P hepatic TG concentration were lower in the MuPI group than in those fed casein (P hepatic fibrosis was not induced in the MuPI group, whereas it developed overtly in the casein group. MuPI potently reduced hepatic lipid accumulation in mice and may be a potential foodstuff to prevent NAFLD onset and progression. © 2017 American Society for Nutrition.

  14. Near net shape of powder metallurgy rhenium parts

    International Nuclear Information System (INIS)

    Leonhardt, T.; Downs, J.

    2001-01-01

    In this paper, a description of the stages of processing necessary to produce a near-net shape (NNS) powder metallurgy (PM) rhenium component through the use of cold isostatic pressing (CIP) to form a complex shape will be explained. This method was primarily developed for the production of the 440 N and 490 N liquid apogee engine combustion chambers used in satellite positioning systems. The CIP to NNS process has been used in the manufacture and production of other rhenium aerospace components as well. Cold isostatic pressing (CIP) to a near net shape utilizing a one or two-part mandrel greatly reduces the quantity of rhenium required to produce the component, and also significantly reduces the number of secondary machining operations necessary to complete the manufacturing process. Further, the developments in near-net shape powder metallurgy rhenium manufacturing techniques have generated significant savings in the area of both time and budget. Overall, cost declined by as much as 35 % for the quantity of rhenium chambers, and manufacturing time was decreased by 30-40 %. The quantity of rhenium metal powder used to produce a rhenium chamber was reduced by approximately 70 %, with a subsequent reduction of nearly 50 % in secondary machining operation schedules. Thus, it is apparent that the overall savings provided by the production of near-net shape powder metallurgy rhenium components will be more than merely another aspect of any project involving high temperature applications, it will constitute significant benefit. (author)

  15. Hepatocyte SLAMF3 reduced specifically the multidrugs resistance protein MRP-1 and increases HCC cells sensitization to anti-cancer drugs.

    Science.gov (United States)

    Fouquet, Grégory; Debuysscher, Véronique; Ouled-Haddou, Hakim; Eugenio, Mélanie Simoes; Demey, Baptiste; Singh, Amrathlal Rabbind; Ossart, Christèle; Al Bagami, Mohammed; Regimbeau, Jean-Marc; Nguyen-Khac, Eric; Naassila, Mickael; Marcq, Ingrid; Bouhlal, Hicham

    2016-05-31

    Multidrug resistance MDR proteins (MRPs) are members of the C family of a group of proteins named ATP binding cassette (ABC) transporters. MRPs can transport drugs including anticancer drugs, nucleoside analogs, antimetabolites and tyrosine kinase inhibitors. Drugs used in HCC therapy, such as tyrosine kinase inhibitor sorafenib, are substrates of uptake and/or efflux transporters. Variable expression of MRPs at the plasma membrane of tumor cells may contribute to drug resistance and subsequent clinical response. Recently, we reported that the hepatocyte SLAMF3 expression (Signaling Lymphocytic Activation Molecule Family member 3) was reduced in tumor cells from hepatocellular carcinoma (HCC) compared to its high expression in adjacent tissues. In the present study, we make a strong correlation between induced SLAMF3 overexpression and the specific loss of MRP-1 expression and its functionalities as a drugs resistance transporter. No changes were observed on expression of ABCG2 and MDR. More importantly, we highlight a strong inverse correlation between MRP-1 and SLAMF3 expression in patients with HCC. We propose that the SLAMF3 overexpression in cancerous cells could represent a potential therapeutic strategy to improve the drugs sensibility of resistant cells and thus control the therapeutic failure in HCC patients.

  16. C1qTNF-related protein 1 improve insulin resistance by reducing phosphorylation of serine 1101 in insulin receptor substrate 1.

    Science.gov (United States)

    Xin, Yaping; Zhang, Dongming; Fu, Yanqin; Wang, Chongxian; Li, Qingju; Tian, Chenguang; Zhang, Suhe; Lyu, Xiaodong

    2017-08-30

    C1qTNF-related protein 1 (CTRP1) is independently associated with type 2 diabetes. However, the relationship between CTRP1 and insulin resistance is still not established. This study aimed to explore the role of CTRP1 under the situation of insulin resistance in adipose tissue. Plasma CTRP1 level was investigated in type 2 diabetic subjects (n = 35) and non-diabetic subjects (n = 35). The relationship between CTRP1 and phosphorylation of multi insulin receptor substrate 1 (IRS-1) serine (Ser) sites was further explored. Our data showed that Plasma CTRP1 was higher and negative correlation with insulin resistance in diabetic subjects (r = -0.283, p = 0.018). Glucose utilisation test revealed that the glucose utilisation rate of mature adipocytes was improved by CTRP1 in the presence of insulin. CTRP1 was not only related to IRS-1 protein, but also negatively correlated with IRS-1 Ser1101 phosphorylation (r = -0.398, p = 0.031). Furthermore, Phosphorylation levels of IRS-1 Ser1101 were significantly lower after incubation with 40 ng/mL CTRP1 in mature adipocytes than those with no intervention (p insulin resistance by reducing the phosphorylation of IRS-1 Ser1101, induced in the situation of insulin resistance as a feedback adipokine.

  17. Improvement of reduced serum cartilage oligomeric matrix protein levels in systemic juvenile idiopathic arthritis patients treated with the anti-interleukin-6 receptor monoclonal antibody tocilizumab.

    Science.gov (United States)

    Nakajima, Shoko; Naruto, Takuya; Miyamae, Takako; Imagawa, Tomoyuki; Mori, Masaaki; Nishimaki, Shigeru; Yokota, Shumpei

    2009-01-01

    In this study, we determined serum cartilage oligomeric matrix protein (COMP) levels in systemic juvenile idiopathic arthritis (sJIA) patients during both the active and the remission phases to investigate how the growth cartilage turnover changed under tocilizumab treatment. Specimens were collected from 201 healthy children under 16 years of age with no growth impairment, and paired sera were collected from 11 sJIA patients treated with tocilizumab. Disease activity was assessed from white blood cell count, erythrocyte sedimentation rate, C-reactive protein, and ferritin, and the COMP concentration was determined by sandwich enzyme-linked immunosorbent assay. Serum COMP concentrations were found independent of age, and the mean value in healthy children was 17.74+/-5.6 U/L. The mean serum COMP in sJIA patients during the active phase was 10.75+/-3.9 U/L, lower than that of healthy children. The mean serum COMP in the remission phase (14.89+/-3.9 U/L) was significantly higher than that in the active period (P<0.05). These results suggested that in sJIA patients, a reduced serum COMP concentration is a useful marker of active disease and growth impairment, and that the growth cartilage turnover suppressed during the active phase is improved in the remission phase under tocilizumab treatment.

  18. Melatonin-Mediated Intracellular Insulin during 2-Deoxy-d-glucose Treatment Is Reduced through Autophagy and EDC3 Protein in Insulinoma INS-1E Cells

    Directory of Open Access Journals (Sweden)

    Han Sung Kim

    2016-01-01

    Full Text Available 2-DG triggers glucose deprivation without altering other nutrients or metabolic pathways and then activates autophagy via activation of AMPK and endoplasmic reticulum (ER stress. We investigated whether 2-DG reduced intracellular insulin increased by melatonin via autophagy/EDC3 in insulinoma INS-1E cells. p-AMPK and GRP78/BiP level were significantly increased by 2-DG in the presence/absence of melatonin, but IRE1α level was reduced in 2-DG treatment. Levels of p85α, p110, p-Akt (Ser473, Thr308, and p-mTOR (Ser2481 were also significantly reduced by 2-DG in the presence/absence of melatonin. Mn-SOD increased with 2-DG plus melatonin compared to groups treated with/without melatonin alone. Bcl-2 was decreased and Bax increased with 2-DG plus melatonin. LC3II level increased with 2-DG treatment in the presence/absence of melatonin. Intracellular insulin production increased in melatonin plus 2-DG but reduced in treatment with 2-DG with/without melatonin. EDC3 was increased by 2-DG in the presence/absence of melatonin. Rapamycin, an mTOR inhibitor, increased GRP78/BiP and EDC3 levels in a dose-dependent manner and subsequently resulted in a decrease in intracellular production of insulin. These results suggest that melatonin-mediated insulin synthesis during 2-DG treatment involves autophagy and EDC3 protein in rat insulinoma INS-1E cells and subsequently results in a decrease in intracellular production of insulin.

  19. A dietary pattern including nopal, chia seed, soy protein, and oat reduces serum triglycerides and glucose intolerance in patients with metabolic syndrome.

    Science.gov (United States)

    Guevara-Cruz, Martha; Tovar, Armando R; Aguilar-Salinas, Carlos A; Medina-Vera, Isabel; Gil-Zenteno, Lidia; Hernández-Viveros, Isaac; López-Romero, Patricia; Ordaz-Nava, Guillermo; Canizales-Quinteros, Samuel; Guillen Pineda, Luz E; Torres, Nimbe

    2012-01-01

    Metabolic syndrome (MetS) is a health problem throughout the world and is associated with cardiovascular disease and diabetes. Thus, the purpose of the present work was to evaluate the effects of a dietary pattern (DP; soy protein, nopal, chia seed, and oat) on the biochemical variables of MetS, the AUC for glucose and insulin, glucose intolerance (GI), the relationship of the presence of certain polymorphisms related to MetS, and the response to the DP. In this randomized trial, the participants consumed their habitual diet but reduced by 500 kcal for 2 wk. They were then assigned to the placebo (P; n = 35) or DP (n = 32) group and consumed the reduced energy diet plus the P or DP beverage (235 kcal) minus the energy provided by these for 2 mo. All participants had decreases in body weight (BW), BMI, and waist circumference during the 2-mo treatment (P < 0.0001); however, only the DP group had decreases in serum TG, C-reactive protein (CRP), and AUC for insulin and GI after a glucose tolerance test. Interestingly, participants in the DP group with MetS and the ABCA1 R230C variant had a greater decrease in BW and an increase in serum adiponectin concentration after 2 mo of dietary treatment than those with the ABCA1 R230R variant. The results from this study suggest that lifestyle interventions involving specific DP for the treatment of MetS could be more effective if local foods and genetic variations of the population are considered.

  20. Central and peripheral administration of antisense oligonucleotide targeting amyloid-β protein precursor improves learning and memory and reduces neuroinflammatory cytokines in Tg2576 (AβPPswe) mice.

    Science.gov (United States)

    Farr, Susan A; Erickson, Michelle A; Niehoff, Michael L; Banks, William A; Morley, John E

    2014-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disease. Currently, there are no therapies to stop or reverse the symptoms of AD. We have developed an antisense oligonucleotide (OL-1) against the amyloid-β protein precursor (AβPP) that can decrease AβPP expression and amyloid-β protein (Aβ) production. This antisense rapidly crosses the blood-brain barrier, reverses learning and memory impairments, reduces oxidative stress, and restores brain-to-blood efflux of Aβ in SAMP8 mice. Here, we examined the effects of this AβPP antisense in the Tg2576 mouse model of AD. We administered the OL-1 antisense into the lateral ventricle 3 times at 2week intervals. Seventy-two hours after the third injection, we tested learning and memory in T-maze foot shock avoidance. In the second study, we injected the mice with OL-1 antisense 3 times at 2-week intervals via the tail vein. Seventy-two hours later, we tested learning and memory T-maze, novel object recognition, and elevated plus maze. At the end of behavioral testing, brain tissue was collected. OL-1 antisense administered centrally improved acquisition and retention of T-maze foot shock avoidance. OL-1 antisense administered via tail vein improved learning and memory in both T-maze foot shock avoidance and novel object-place recognition. In the elevated plus maze, the mice which received OL-1 antisense spent less time in the open arms and had fewer entries into the open arms indicating reduced disinhibitation. Biochemical analyses reveal significant reduction of AβPP signal and a reduction of measures of neuroinflammation. The current findings support the therapeutic potential of OL-1 AβPP antisense.