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Sample records for adh activity increased

  1. Increased Variation in Adh Enzyme Activity in Drosophila Mutation-Accumulation Experiment Is Not Due to Transposable Elements at the Adh Structural Gene

    PubMed Central

    Aquadro, C. F.; Tachida, H.; Langley, C. H.; Harada, K.; Mukai, T.

    1990-01-01

    We present here a molecular analysis of the region surrounding the structural gene encoding alcohol dehydrogenase (Adh) in 47 lines of Drosophila melanogaster that have each accumulated mutations for 300 generations. While these lines show a significant increase in variation of alcohol dehydrogenase enzyme activity compared to control lines, we found no restriction map variation in a 13-kb region including the complete Adh structural gene and roughly 5 kb of both 5' and 3' sequences. Thus, the rapid accumulation of ADH activity variation after 28,200 allele generations does not appear to have been due to the mobilization of transposable elements into or out of the Adh structural gene region. PMID:1963870

  2. Ethanol-Induced ADH Activity in Zebrafish: Differential Concentration-Dependent Effects on High- Versus Low-Affinity ADH Enzymes.

    PubMed

    Tran, Steven; Nowicki, Magda; Facciol, Amanda; Chatterjee, Diptendu; Gerlai, Robert

    2016-04-01

    Zebrafish express enzymes that metabolize ethanol in a manner comparable to that of mammals, including humans. We previously demonstrated that acute ethanol exposure increases alcohol dehydrogenase (ADH) activity in an inverted U-shaped dose-dependent manner. It was hypothesized that the biphasic dose-response was due to the increased activity of a high-affinity ADH isoform following exposure to low concentrations of ethanol and increased activity of a low-affinity ADH isoform following exposure to higher concentrations of ethanol. To test this hypothesis, we exposed zebrafish to different concentrations of ethanol (0%, 0.25%, 0.5%, and 1.0% v/v) for 30 min and measured the total ADH activity in the zebrafish liver. However, we also repeated this enzyme activity assay using a low concentration of the substrate (ethanol) to determine the activity of high-affinity ADH isoforms. We found that total ADH activity in response to ethanol induces an inverted U-shaped dose-response similar to our previous study. Using a lower substrate level in our enzyme assay targeting high-affinity isozymes, we found a similar dose-response. However, the difference in activity between the high and low substrate assays (high substrate activity - low substrate activity), which provide an index of activity for low-affinity ADH isoforms, revealed no significant effect of ethanol exposure. Our results suggest that the inverted U-shaped dose-response for total ADH activity in response to ethanol is driven primarily by high-affinity isoforms of ADH.

  3. Transient overexpression of adh8a increases allyl alcohol toxicity in zebrafish embryos.

    PubMed

    Klüver, Nils; Ortmann, Julia; Paschke, Heidrun; Renner, Patrick; Ritter, Axel P; Scholz, Stefan

    2014-01-01

    Fish embryos are widely used as an alternative model to study toxicity in vertebrates. Due to their complexity, embryos are believed to more resemble an adult organism than in vitro cellular models. However, concerns have been raised with respect to the embryo's metabolic capacity. We recently identified allyl alcohol, an industrial chemical, to be several orders of magnitude less toxic to zebrafish embryo than to adult zebrafish (embryo LC50 = 478 mg/L vs. fish LC50 = 0.28 mg/L). Reports on mammals have indicated that allyl alcohol requires activation by alcohol dehydrogenases (Adh) to form the highly reactive and toxic metabolite acrolein, which shows similar toxicity in zebrafish embryos and adults. To identify if a limited metabolic capacity of embryos indeed can explain the low allyl alcohol sensitivity of zebrafish embryos, we compared the mRNA expression levels of Adh isoenzymes (adh5, adh8a, adh8b and adhfe1) during embryo development to that in adult fish. The greatest difference between embryo and adult fish was found for adh8a and adh8b expression. Therefore, we hypothesized that these genes might be required for allyl alcohol activation. Microinjection of adh8a, but not adh8b mRNA led to a significant increase of allyl alcohol toxicity in embryos similar to levels reported for adults (LC50 = 0.42 mg/L in adh8a mRNA-injected embryos). Furthermore, GC/MS analysis of adh8a-injected embryos indicated a significant decline of internal allyl alcohol concentrations from 0.23-58 ng/embryo to levels below the limit of detection (< 4.6 µg/L). Injection of neither adh8b nor gfp mRNA had an impact on internal allyl alcohol levels supporting that the increased allyl alcohol toxicity was mediated by an increase in its metabolization. These results underline the necessity to critically consider metabolic activation in the zebrafish embryo. As demonstrated here, mRNA injection is one useful approach to study the role of candidate enzymes involved in

  4. [Effects of H2-blockers on alcohol dehydrogenase (ADH) activity].

    PubMed

    Jelski, Wojciech; Orywal, Karolina; Szmitkowski, Maciej

    2008-12-01

    First-pass metabolism (FPM) of alcohol is demonstrated by lower blood alcohol concentrations after oral than intravenous administration of the same dose. FPM occurs predominantly in the stomach and has been attributed to class IV of alcohol dehydrogenase (ADH) isoenzyme localizated in the gastric mucosa. A number of factors that influence on gastric ADH activity and thereby modulate FPM have been identified. These include age, sex, ethnicity, concentrations and amounts of alcohol consumed and drugs. Several H2-receptor antagonists, including cimetidine and ranitidine, inhibit gastric ADH activity and reduce FPM, resulting in higher blood alcohol concentrations after H2-blockers administration.

  5. Ethanol-induced alcohol dehydrogenase E (AdhE) potentiates pneumolysin in Streptococcus pneumoniae.

    PubMed

    Luong, Truc Thanh; Kim, Eun-Hye; Bak, Jong Phil; Nguyen, Cuong Thach; Choi, Sangdun; Briles, David E; Pyo, Suhkneung; Rhee, Dong-Kwon

    2015-01-01

    Alcohol impairs the host immune system, rendering the host more vulnerable to infection. Therefore, alcoholics are at increased risk of acquiring serious bacterial infections caused by Streptococcus pneumoniae, including pneumonia. Nevertheless, how alcohol affects pneumococcal virulence remains unclear. Here, we showed that the S. pneumoniae type 2 D39 strain is ethanol tolerant and that alcohol upregulates alcohol dehydrogenase E (AdhE) and potentiates pneumolysin (Ply). Hemolytic activity, colonization, and virulence of S. pneumoniae, as well as host cell myeloperoxidase activity, proinflammatory cytokine secretion, and inflammation, were significantly attenuated in adhE mutant bacteria (ΔadhE strain) compared to D39 wild-type bacteria. Therefore, AdhE might act as a pneumococcal virulence factor. Moreover, in the presence of ethanol, S. pneumoniae AdhE produced acetaldehyde and NADH, which subsequently led Rex (redox-sensing transcriptional repressor) to dissociate from the adhE promoter. An increase in AdhE level under the ethanol condition conferred an increase in Ply and H2O2 levels. Consistently, S. pneumoniae D39 caused higher cytotoxicity to RAW 264.7 cells than the ΔadhE strain under the ethanol stress condition, and ethanol-fed mice (alcoholic mice) were more susceptible to infection with the D39 wild-type bacteria than with the ΔadhE strain. Taken together, these data indicate that AdhE increases Ply under the ethanol stress condition, thus potentiating pneumococcal virulence.

  6. Temperature and water loss affect ADH activity and gene expression in grape berry during postharvest dehydration.

    PubMed

    Cirilli, Marco; Bellincontro, Andrea; De Santis, Diana; Botondi, Rinaldo; Colao, Maria Chiara; Muleo, Rosario; Mencarelli, Fabio

    2012-05-01

    Clusters of Aleatico wine grape were picked at 18°Brix and placed at 10, 20, or 30°C, 45% relative humidity (RH) and 1.5m/s of air flow to dehydrate the berries up to 40% of loss of initial fresh weight. Sampling was done at 0%, 10%, 20%, 30%, and 40% weight loss (wl). ADH (alcohol dehydrogenase) gene expression, enzyme activity, and related metabolites were analysed. At 10°C, acetaldehyde increased rapidly and then declined, while ethanol continued to rise. At 20°C, acetaldehyde and ethanol increased significantly with the same pattern and declined at 40%wl. At 30°C, acetaldehyde did not increase but ethanol increased rapidly already at 10%wl. At the latter temperature, a significant increase in acetic acid and ethyl acetate occurred, while at 10°C their values were low. At 30°C, the ADH activity (ethanol to acetaldehyde direction), increased rapidly but acetaldehyde did not rise because of its oxidation to acetic acid, which increased together with ethyl acetate. At 10°C, the ADH activity increased at 20%wl and continued to rise even at 40%wl, meaning that ethanol oxidation was delayed. At 20°C, the behaviour was intermediate to the other temperatures. The relative expression of the VvAdh2 gene was the highest at 10°C already at 10%wl in a synchrony with the ADH activity, indicating a rapid response likely due to low temperature. The expression subsequently declined. At 20 and 30°C, the expression was lower and increased slightly during dehydration in combination with the ADH activity. This imbalance between gene expression and ADH activity at 10°C, as well as the unexpected expression of the carotenoid cleavage dioxygenase 1 (CCD1) gene, opens the discussion on the stress sensitivity and transcription event during postharvest dehydration, and the importance of carefully monitoring temperature during dehydration.

  7. Adh1 and Adh1/4 knockout mice as possible rodent models for presymptomatic Parkinson's disease.

    PubMed

    Anvret, Anna; Ran, Caroline; Westerlund, Marie; Gellhaar, Sandra; Lindqvist, Eva; Pernold, Karin; Lundströmer, Karin; Duester, Gregg; Felder, Michael R; Galter, Dagmar; Belin, Andrea Carmine

    2012-02-01

    Alcohol dehydrogenases (ADH) catalyze the reversible metabolism of many types of alcohols and aldehydes to prevent the possible toxic accumulation of these compounds. ADHs are of interest in Parkinson's disease (PD) since these compounds can be harmful to dopamine (DA) neurons. Genetic variants in ADH1C and ADH4 have been found to associate with PD and lack of Adh4 gene activity in a mouse model has recently been reported to induce changes in the DA system. Adh1 knockout (Adh1-/-) and Adh1/4 double knockout (Adh1/4-/-) mice were investigated for possible changes in DA system related activity, biochemical parameters and olfactory function compared to wild-type (WT) mice. Locomotor activity was tested at ∼7 (adult) and >15 months of age to mimic the late onset of PD. Adh1-/- and Adh1/4-/- mice displayed a significantly higher spontaneous locomotor activity than WT littermates. Both apomorphine and d-amphetamine increased total distance activity in Adh1-/- mice at both age intervals and in Adh1/4-/- mice at 7 months of age compared to WT mice. No significant changes were found regarding olfactory function, however biochemical data showed decreased 3,4-dihydroxyphenylacetic acid (DOPAC)/DA ratios in the olfactory bulb and decreased homovanillic acid (HVA)/DA ratios in the olfactory bulb, frontal cortex and striatum of Adh1/4-/- mice compared to WT mice. Our results suggest that lack of Adh1 alone or Adh1 and Adh4 together lead to changes in DA system related behavior, and that these knockout mice might be possible rodent models to study presymptomatic PD.

  8. Opposing--activating or inhibitory--effects of cimetidine and daidzein on human ADH1C activity depending on substrates and solvents.

    PubMed

    Kollock, Ronny; Glatt, Hansruedi

    2012-01-01

    Toxification of benzylic alcohols (e.g. hydroxymethylpyrenes) by sulfotransferases is efficiently competed by alcohol dehydrogenases (ADHs). We are interested in drugs and food constituents affecting this detoxification. Daidzein and cimetidine were reported to inhibit ADH1C-mediated ethanol oxidation. Surprisingly, we found that both modulators enhance the oxidation of 4-hydroxymethylpyrene by ADH1C. This activation was seen with either delivering solvents used, dimethylsulfoxide or acetonitrile. Addition of dimethylsulfoxide, but not acetonitrile, converted daidzein and cimetidine from inhibitors to activators of the ADH1C-mediated oxidation of the other substrate studied, ethanol (added in water). Other human ADH forms (ADH2, 3, 4) were inhibited by both agents independently of the substrate and the corresponding solvent used. Kinetic constants for the various reactions are presented. ADH1C was unique in its complex substrate-dependent interaction with daidzein/cimetidine and solvents.

  9. Locus Adh of Drosophila melanogaster under selection for delayed senescence

    SciTech Connect

    Khaustova, N.D.

    1995-05-01

    Dynamics of the Adh activity and frequencies of alleles Adh{sup F} and Adh{sup S} were analyzed under selection for delayed senescence. The experiments were performed on Drosophila melanogaster. Lines Adh{sup S}cn and Adh{sup F}vg and experimental populations cn` and vg`, selected for an increased duration of reproductive period (late oviposition) were used. Analysis of fertility, longevity, viability and resistance to starvation showed that selection for late oviposition resulted in delayed senescence of flies of the experimental populations. Genetic structure of population vg` changed considerably with regard to the Adh locus. This was confirmed by parameters of activity, thermostability, and electrophoretic mobility of the enzyme isolated from flies after 30 generations of selection. Analysis of frequencies of the Adh alleles showed that in both selected populations, which initially had different genetic composition, accumulated allele Adh{sup S}, which encodes the isozyme that is less active but more resistant to inactivation. Genetic mechanism of delayed senescence in Drosophila is assumed to involve selection at vitally important enzyme loci, including Adh. 18 refs., 2 tabs., 4 figs.

  10. Modeling Parkinson's disease genetics: altered function of the dopamine system in Adh4 knockout mice.

    PubMed

    Belin, Andrea Carmine; Westerlund, Marie; Anvret, Anna; Lindqvist, Eva; Pernold, Karin; Ogren, Sven Ove; Duester, Gregg; Galter, Dagmar

    2011-03-01

    Class IV alcohol dehydrogenase (ADH4) efficiently reduces aldehydes produced during lipid peroxidation, and may thus serve to protect from toxic effects of aldehydes e.g. on neurons. We hypothesized that ADH4 dysfunction may increase risk for Parkinson's disease (PD) and previously reported association of an ADH4 allele with PD. We found that a promoter polymorphism in this allele induced a 25-30% reduction of transcriptional activity. Based on these findings, we have now investigated whether Adh4 homo- (Adh4-/-) or heterozygous (Adh4+/-) knockout mice display any dopamine system-related changes in behavior, biochemical parameters or olfaction compared to wild-type mice. The spontaneous locomotor activity was found to be similar in the three groups, whereas administration of d-amphetamine or apomorphine induced a significant increase in horizontal activity in the Adh4-/- mice compared to wild-type mice. We measured levels of monoamines and their metabolites in striatum, frontal cortex and substantia nigra and found increased levels of dopamine and DOPAC in substantia nigra of Adh4-/- mice. Investigation of olfactory function revealed a reduced sense of smell in Adh4-/- mice accompanied by alterations in dopamine metabolite levels in the olfactory bulb. Taken together, our results suggest that lack of Adh4 gene activity induces changes in the function of the dopamine system, findings which are compatible with a role of loss-of-function mutations in ADH4 as possible risk factors for PD.

  11. Cloning and functional analysis of adhS gene encoding quinoprotein alcohol dehydrogenase subunit III from Acetobacter pasteurianus SKU1108.

    PubMed

    Masud, Uraiwan; Matsushita, Kazunobu; Theeragool, Gunjana

    2010-03-31

    The adhS gene which encodes the smallest subunit, subunit III, of quinoprotein alcohol dehydrogenase (PQQ-ADH) from Acetobacter pasteurianus SKU1108 has been cloned and characterized. The role of this subunit on the function of PQQ-ADH was investigated by construction of adhS gene disruptant and mutants. The adhS gene disruptant completely lost its PQQ-ADH activity and acetate-producing ability but retained acetic acid toleration. In contrast, this disruptant grew well, even better than the wild type, in the ethanol containing medium even though its PQQ-ADH activity and ethanol oxidizing ability was completely lost, while NAD(+)-dependent ADH (NAD(+)-ADH) was induced. Heme staining and immunoblot analysis of both membrane and soluble fractions with anti-ADH subunit III suggested that ethanol did not affect the adhS gene expression but induced PQQ-ADH activity. Over-expressed adhS did not enhance acetic acid production in both the wild type and the adhS disruptant. In addition, deletion analysis of upstream region of adhS gene suggested that its tentative promoter(s) might be located at around 118-268 bp upstream from an initiation codon. Random mutagenesis of adhS gene revealed that complete loss of PQQ-ADH activity and ethanol oxidizing ability were observed in the mutants' lack of the 140 and 73 amino acid residues at the C-terminal, whereas the lack of 22 amino acid residues at the C-terminal affected neither the PQQ-ADH activity nor ethanol oxidizing ability. In addition, some amino acid substitutions such as Leu18Gln, Ala26Val, Val36Ile, Val54Ile, Gly55Asp, Val70Ala and Val107Ala did not show any affect on PQQ-ADH activity and ethanol oxidizing ability. Interestingly, alteration of Thr104Lys led to a complete loss of ethanol oxidizing ability. However, point mutation at the possible promoter region also exhibited low PQQ-ADH activity and ethanol oxidizing ability. This result suggests that 104Thr might be involved in molecular coupling with subunit I in order

  12. Expression pattern, ethanol-metabolizing activities, and cellular localization of alcohol and aldehyde dehydrogenases in human large bowel: association of the functional polymorphisms of ADH and ALDH genes with hemorrhoids and colorectal cancer.

    PubMed

    Chiang, Chien-Ping; Jao, Shu-Wen; Lee, Shiao-Pieng; Chen, Pei-Chi; Chung, Chia-Chi; Lee, Shou-Lun; Nieh, Shin; Yin, Shih-Jiun

    2012-02-01

    Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are principal enzymes responsible for metabolism of ethanol. Functional polymorphisms of ADH1B, ADH1C, and ALDH2 genes occur among racial populations. The goal of this study was to systematically determine the functional expressions and cellular localization of ADHs and ALDHs in human rectal mucosa, the lesions of adenocarcinoma and hemorrhoid, and the genetic association of allelic variations of ADH and ALDH with large bowel disorders. Twenty-one surgical specimens of rectal adenocarcinoma and the adjacent normal mucosa, including 16 paired tissues of rectal tumor, normal mucosae of rectum and sigmoid colon from the same individuals, and 18 surgical mixed hemorrhoid specimens and leukocyte DNA samples from 103 colorectal cancer patients, 67 hemorrhoid patients, and 545 control subjects recruited in previous study, were investigated. The isozyme/allozyme expression patterns of ADH and ALDH were identified by isoelectric focusing and the activities were assayed spectrophotometrically. The protein contents of ADH/ALDH isozymes were determined by immunoblotting using the corresponding purified class-specific antibodies; the cellular activity and protein localizations were detected by immunohistochemistry and histochemistry, respectively. Genotypes of ADH1B, ADH1C, and ALDH2 were determined by polymerase chain reaction-restriction fragment length polymorphisms. At 33mM ethanol, pH 7.5, the activity of ADH1C*1/1 phenotypes exhibited 87% higher than that of the ADH1C*1/*2 phenotypes in normal rectal mucosa. The activity of ALDH2-active phenotypes of rectal mucosa was 33% greater than ALDH2-inactive phenotypes at 200μM acetaldehyde. The protein contents in normal rectal mucosa were in the following order: ADH1>ALDH2>ADH3≈ALDH1A1, whereas those of ADH2, ADH4, and ALDH3A1 were fairly low. Both activity and content of ADH1 were significantly decreased in rectal tumors, whereas the ALDH activity remained

  13. The diagnostic value of alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) measurement in the sera of gastric cancer patients.

    PubMed

    Jelski, Wojciech; Orywal, Karolina; Laniewska, Magdalena; Szmitkowski, Maciej

    2010-12-01

    Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are present in gastric cancer cells (GC). Moreover, the activity of total ADH and class IV isoenzymes is significantly higher in cancer tissue than in healthy mucosa. The activity of these enzymes in cancer cells is probably reflected in the sera and could thus be helpful for diagnostics of gastric cancer. The aim of this study was to investigate a potential role of ADH and ALDH as tumor markers for gastric cancer. We defined diagnostic sensitivity, specificity, predictive value for positive and negative results, and receiver-operating characteristics (ROC) curve for tested enzymes. Serum samples were taken from 168 patients with gastric cancer before treatment and from 168 control subjects. Total ADH activity and class III and IV isoenzymes were measured by photometric but ALDH activity and ADH I and II by the fluorometric method, with class-specific fluorogenic substrates. There was significant increase in the activity of ADH IV isoenzyme and ADH total in the sera of gastric cancer patients compared to the control. The diagnostic sensitivity for ADH IV was 73%, specificity 79%, positive and negative predictive values were 81 and 72% respectively. Area under ROC curve for ADH IV was 0.67. The results suggest a potential role for ADH IV as marker of gastric cancer.

  14. Effects of glucose, ethanol and acetic acid on regulation of ADH2 gene from Lachancea fermentati

    PubMed Central

    Yaacob, Norhayati; Salleh, Abu Bakar; Abdul Rahman, Nor Aini

    2016-01-01

    Background. Not all yeast alcohol dehydrogenase 2 (ADH2) are repressed by glucose, as reported in Saccharomyces cerevisiae. Pichia stipitis ADH2 is regulated by oxygen instead of glucose, whereas Kluyveromyces marxianus ADH2 is regulated by neither glucose nor ethanol. For this reason, ADH2 regulation of yeasts may be species dependent, leading to a different type of expression and fermentation efficiency. Lachancea fermentati is a highly efficient ethanol producer, fast-growing cells and adapted to fermentation-related stresses such as ethanol and organic acid, but the metabolic information regarding the regulation of glucose and ethanol production is still lacking. Methods. Our investigation started with the stimulation of ADH2 activity from S. cerevisiae and L. fermentati by glucose and ethanol induction in a glucose-repressed medium. The study also embarked on the retrospective analysis of ADH2 genomic and protein level through direct sequencing and sites identification. Based on the sequence generated, we demonstrated ADH2 gene expression highlighting the conserved NAD(P)-binding domain in the context of glucose fermentation and ethanol production. Results. An increase of ADH2 activity was observed in starved L. fermentati (LfeADH2) and S. cerevisiae (SceADH2) in response to 2% (w/v) glucose induction. These suggest that in the presence of glucose, ADH2 activity was activated instead of being repressed. An induction of 0.5% (v/v) ethanol also increased LfeADH2 activity, promoting ethanol resistance, whereas accumulating acetic acid at a later stage of fermentation stimulated ADH2 activity and enhanced glucose consumption rates. The lack in upper stream activating sequence (UAS) and TATA elements hindered the possibility of Adr1 binding to LfeADH2. Transcription factors such as SP1 and RAP1 observed in LfeADH2 sequence have been implicated in the regulation of many genes including ADH2. In glucose fermentation, L. fermentati exhibited a bell-shaped ADH2

  15. Adh enhances Actinobacillus pleuropneumoniae pathogenicity by binding to OR5M11 and activating p38 which induces apoptosis of PAMs and IL-8 release.

    PubMed

    Wang, Lei; Qin, Wanhai; Zhang, Jing; Bao, Chuntong; Zhang, Hu; Che, Yanyi; Sun, Changjiang; Gu, Jingmin; Feng, Xin; Du, Chongtao; Han, Wenyu; Richard, Paul Langford; Lei, Liancheng

    2016-04-05

    Members of the Trimeric Autotransporter Adhesin (TAA) family play a crucial role in the adhesion of Gram-negative pathogens to host cells, but the immunopathogenesis of TAAs remains unknown. Our previous studies demonstrated that Adh from Actinobacillus pleuropneumoniae (A. pleuropneumoniae) is required for full bacterial pathogenicity. Alveolar macrophages are the first line of defense against respiratory infections. This study compared the interactions between porcine alveolar macrophages (PAMs) and wild-type A. pleuropneumoniae (5b WT) or an Adh-deletion strain (5b ΔAdh) via gene microarray, immunoprecipitation and other technologies. We found that Adh was shown to interact with the PAMs membrane protein OR5M11, an olfactory receptor, resulting in the high-level secretion of IL-8 by activation of p38 MAPK signaling pathway. Subsequently, PAMs apoptosis via the activation of the Fax and Bax signaling pathways was observed, followed by activation of caspases 8, 9, and 3. The immunological pathogenic roles of Adh were also confirmed in both murine and piglets infectious models in vivo. These results identify a novel immunological strategy for TAAs to boost the pathogenicity of A. pleuropneumoniae. Together, these datas reveal the high versatility of the Adh protein as a virulence factor and provide novel insight into the immunological pathogenic role of TAAs.

  16. The diagnostic value of alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) measurement in the sera of patients with brain tumor

    PubMed Central

    Laniewska-Dunaj, Magdalena; Orywal, Karolina; Kochanowicz, Jan; Rutkowski, Robert; Szmitkowski, Maciej

    2017-01-01

    Introduction Alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) exist in the brain. Alcohol dehydrogenase and ALDH are also present in brain tumor cells. Moreover, the activity of class I isoenzymes was significantly higher in cancer than healthy brain cells. The activity of these enzymes in tumor tissue is reflected in the serum and could thus be helpful for diagnostics of brain neoplasms. The aim of this study was to investigate the potential role of ADH and ALDH as markers for brain tumors. Material and methods Serum samples were taken for routine biochemical investigation from 115 patients suffering from brain tumors (65 glioblastomas, 50 meningiomas). For the measurement of the activity of class I and II ADH isoenzymes and ALDH activity, fluorometric methods were used. The total ADH activity and activity of class III and IV isoenzymes were measured by the photometric method. Results There was a significant increase in the activity of ADH I isoenzyme and ADH total in the sera of brain tumor patients compared to the controls. The diagnostic sensitivity for ADH I was 78%, specificity 85%, and positive and negative predictive values were 86% and 76% respectively. The sensitivity and specificity of ADH I increased with the stage of the carcinoma. Area under receiver-operating characteristic curve for ADH I was 0.71. Conclusions The results suggest a potential role for ADH I as a marker for brain tumor. PMID:28261287

  17. A New View of Alcohol Metabolism and Alcoholism—Role of the High-Km Class III Alcohol Dehydrogenase (ADH3)

    PubMed Central

    Haseba, Takeshi; Ohno, Youkichi

    2010-01-01

    The conventional view is that alcohol metabolism is carried out by ADH1 (Class I) in the liver. However, it has been suggested that another pathway plays an important role in alcohol metabolism, especially when the level of blood ethanol is high or when drinking is chronic. Over the past three decades, vigorous attempts to identify the enzyme responsible for the non-ADH1 pathway have focused on the microsomal ethanol oxidizing system (MEOS) and catalase, but have failed to clarify their roles in systemic alcohol metabolism. Recently, using ADH3-null mutant mice, we demonstrated that ADH3 (Class III), which has a high Km and is a ubiquitous enzyme of ancient origin, contributes to systemic alcohol metabolism in a dose-dependent manner, thereby diminishing acute alcohol intoxication. Although the activity of ADH3 toward ethanol is usually low in vitro due to its very high Km, the catalytic efficiency (kcat/Km) is markedly enhanced when the solution hydrophobicity of the reaction medium increases. Activation of ADH3 by increasing hydrophobicity should also occur in liver cells; a cytoplasmic solution of mouse liver cells was shown to be much more hydrophobic than a buffer solution when using Nile red as a hydrophobicity probe. When various doses of ethanol are administered to mice, liver ADH3 activity is dynamically regulated through induction or kinetic activation, while ADH1 activity is markedly lower at high doses (3–5 g/kg). These data suggest that ADH3 plays a dynamic role in alcohol metabolism, either collaborating with ADH1 or compensating for the reduced role of ADH1. A complex two-ADH model that ascribes total liver ADH activity to both ADH1 and ADH3 explains the dose-dependent changes in the pharmacokinetic parameters (β, CLT, AUC) of blood ethanol very well, suggesting that alcohol metabolism in mice is primarily governed by these two ADHs. In patients with alcoholic liver disease, liver ADH3 activity increases, while ADH1 activity decreases, as alcohol

  18. Ethanol formation in adh0 mutants reveals the existence of a novel acetaldehyde-reducing activity in Saccharomyces cerevisiae.

    PubMed Central

    Drewke, C; Thielen, J; Ciriacy, M

    1990-01-01

    A strain of Saccharomyces cerevisiae has been constructed which is deficient in the four alcohol dehydrogenase (ADH) isozymes known at present. This strain (adh0), being irreversibly mutated in the genes ADH1, ADH3, and ADH4 and carrying a point mutation in the gene ADH2 coding for the glucose-repressible isozyme ADHII, still produces up to one third of the theoretical maximum yield of ethanol in a homofermentative conversion of glucose to ethanol. Analysis of the glucose metabolism of adh0 cells shows that the lack of all known ADH isozymes results in the formation of glycerol as a major fermentation product, accompanied by a significant production of acetaldehyde and acetate. Treatment of glucose-growing adh0 cells with the respiratory-chain inhibitor antimycin A leads to an immediate cessation of ethanol production, demonstrating that ethanol production in adh0 cells is dependent on mitochondrial electron transport. Reduction of acetaldehyde to ethanol in isolated mitochondria could also be demonstrated. This reduction is apparently linked to the oxidation of acetaldehyde to acetate. Preliminary data suggest that this novel type of ethanol formation in S. cerevisiae is associated with the inner mitochondrial membrane. Images PMID:2193925

  19. ADH (Antidiuretic Hormone) Test

    MedlinePlus

    ... stored in the posterior pituitary gland at the base of the brain. ADH helps regulate water balance ... of ADH (vasopressin). Several blood and urine osmolality measurements are performed at timed intervals before and after ...

  20. Alcohol dehydrogenase gene ADH3 activates glucose alcoholic fermentation in genetically engineered Dekkera bruxellensis yeast.

    PubMed

    Schifferdecker, Anna Judith; Siurkus, Juozas; Andersen, Mikael Rørdam; Joerck-Ramberg, Dorte; Ling, Zhihao; Zhou, Nerve; Blevins, James E; Sibirny, Andriy A; Piškur, Jure; Ishchuk, Olena P

    2016-04-01

    Dekkera bruxellensis is a non-conventional Crabtree-positive yeast with a good ethanol production capability. Compared to Saccharomyces cerevisiae, its tolerance to acidic pH and its utilization of alternative carbon sources make it a promising organism for producing biofuel. In this study, we developed an auxotrophic transformation system and an expression vector, which enabled the manipulation of D. bruxellensis, thereby improving its fermentative performance. Its gene ADH3, coding for alcohol dehydrogenase, was cloned and overexpressed under the control of the strong and constitutive promoter TEF1. Our recombinant D. bruxellensis strain displayed 1.4 and 1.7 times faster specific glucose consumption rate during aerobic and anaerobic glucose fermentations, respectively; it yielded 1.2 times and 1.5 times more ethanol than did the parental strain under aerobic and anaerobic conditions, respectively. The overexpression of ADH3 in D. bruxellensis also reduced the inhibition of fermentation by anaerobiosis, the "Custer effect". Thus, the fermentative capacity of D. bruxellensis could be further improved by metabolic engineering.

  1. ADH5 — EDRN Public Portal

    Cancer.gov

    ADH5 is a member of the alcohol dehydrogenase family. This protein forms a homodimer. ADH5 is ineffective in oxidizing ethanol, but exhibits high activity for oxidation of long-chain primary alcohols and for oxidation of S-hydroxymethyl-glutathione, a spontaneous adduct between formaldehyde and glutathione. There are several non-transcribed pseuodogenes related to this gene.

  2. The Relationship between CmADHs and the Diversity of Volatile Organic Compounds of Three Aroma Types of Melon (Cucumis melo)

    PubMed Central

    Chen, Hao; Cao, Songxiao; Jin, Yazhong; Tang, Yufan; Qi, Hongyan

    2016-01-01

    Alcohol dehydrogenase (ADH) plays an important role in aroma volatile compounds synthesis of plants. In this paper, we tried to explore the relationship between CmADHs and the volatile organic compounds (VOCs) in oriental melon. Three different aroma types of melon were used as materials. The principle component analysis of three types of melon fruit was conducted. We also measured the CmADHs expression level and enzymatic activities of ADH and alcohol acyl-transferase (AAT) on different stages of fruit ripening. An incubation experiment was carried out to investigate the effect of substrates and inhibitor (4-MP, 4-methylpyrazole) on CmADHs expression, ADH activity, and the main compounds of oriental melon. The results illustrated that ethyl acetate, hexyl acetate (E,Z)-3,6-nonadien-1-ol and 2-ethyl-2hexen-1-ol were the four principal volatile compounds of these three types of melon. AAT activity was increasing with fruit ripening, and the AAT activity in CH were the highest, whereas ADH activity peaked on 32 DAP, 2 days before maturation, and the ADH activity in CB and CG were higher than that in CH. The expression pattern of 11 CmADH genes from 24 to 36 day after pollination (DAP) was found to vary in three melon varieties. CmADH4 was only expressed in CG and the expression levels of CmADH3 and CmADH12 in CH and CB were much higher than that in CG, and they both peaked 2 days before fruit ripening. Ethanol and 4-MP decreased the reductase activity of ADH, the expression of most CmADHs and ethyl acetate or hexyl acetate contents of CB, except for 0.1 mM 4-MP, while aldehyde improved the two acetate ester contents. In addition, we found a positive correlation between the expression of CmADH3 and CmADH12 and the key volatile compound of CB. The relationship between CmADHs and VOCs synthesis of oriental melon was discussed. PMID:27445845

  3. Characterization of alcohol dehydrogenase (ADH12) from Haloarcula marismortui, an extreme halophile from the Dead Sea.

    PubMed

    Timpson, Leanne M; Alsafadi, Diya; Mac Donnchadha, Cillín; Liddell, Susan; Sharkey, Michael A; Paradisi, Francesca

    2012-01-01

    Haloarchaeal alcohol dehydrogenases are of increasing interest as biocatalysts in the field of white biotechnology. In this study, the gene adh12 from the extreme halophile Haloarcula marismortui (HmADH12), encoding a 384 residue protein, was cloned into two vectors: pRV1 and pTA963. The resulting constructs were used to transform host strains Haloferax volcanii (DS70) and (H1209), respectively. Overexpressed His-tagged recombinant HmADH12 was purified by immobilized metal-affinity chromatography (IMAC). The His-tagged protein was visualized by SDS-PAGE, with a subunit molecular mass of 41.6 kDa, and its identity was confirmed by mass spectrometry. Purified HmADH12 catalyzed the interconversion between alcohols and aldehydes and ketones, being optimally active in the presence of 2 M KCl. It was thermoactive, with maximum activity registered at 60°C. The NADP(H) dependent enzyme was haloalkaliphilic for the oxidative reaction with optimum activity at pH 10.0. It favored a slightly acidic pH of 6.0 for catalysis of the reductive reaction. HmADH12 was significantly more tolerant than mesophilic ADHs to selected organic solvents, making it a much more suitable biocatalyst for industrial application.

  4. POZ domain transcription factor, FBI-1, represses transcription of ADH5/FDH by interacting with the zinc finger and interfering with DNA binding activity of Sp1.

    PubMed

    Lee, Dong-Kee; Suh, Dongchul; Edenberg, Howard J; Hur, Man-Wook

    2002-07-26

    The POZ domain is a protein-protein interaction motif that is found in many transcription factors, which are important for development, oncogenesis, apoptosis, and transcription repression. We cloned the POZ domain transcription factor, FBI-1, that recognizes the cis-element (bp -38 to -22) located just upstream of the core Sp1 binding sites (bp -22 to +22) of the ADH5/FDH minimal promoter (bp -38 to +61) in vitro and in vivo, as revealed by electrophoretic mobility shift assay and chromatin immunoprecipitation assay. The ADH5/FDH minimal promoter is potently repressed by the FBI-1. Glutathione S-transferase fusion protein pull-down showed that the POZ domains of FBI-1, Plzf, and Bcl-6 directly interact with the zinc finger DNA binding domain of Sp1. DNase I footprinting assays showed that the interaction prevents binding of Sp1 to the GC boxes of the ADH5/FDH promoter. Gal4-POZ domain fusions targeted proximal to the GC boxes repress transcription of the Gal4 upstream activator sequence-Sp1-adenovirus major late promoter. Our data suggest that POZ domain represses transcription by interacting with Sp1 zinc fingers and by interfering with the DNA binding activity of Sp1.

  5. Ectopic ADH secretion

    MedlinePlus

    ... ADH. Often, there are no symptoms from a low sodium level. When symptoms do occur, they may include ... Lab tests that can confirm and help diagnose low sodium include: Comprehensive metabolic panel (includes blood sodium) Osmolality ...

  6. Molecular Characterization and Transcriptional Analysis of adhE2, the Gene Encoding the NADH-Dependent Aldehyde/Alcohol Dehydrogenase Responsible for Butanol Production in Alcohologenic Cultures of Clostridium acetobutylicum ATCC 824

    PubMed Central

    Fontaine, Lisa; Meynial-Salles, Isabelle; Girbal, Laurence; Yang, Xinghong; Croux, Christian; Soucaille, Philippe

    2002-01-01

    The adhE2 gene of Clostridium acetobutylicum ATCC 824, coding for an aldehyde/alcohol dehydrogenase (AADH), was characterized from molecular and biochemical points of view. The 2,577-bp adhE2 codes for a 94.4-kDa protein. adhE2 is expressed, as a monocistronic operon, in alcohologenic cultures and not in solventogenic cultures. Primer extension analysis identified two transcriptional start sites 160 and 215 bp upstream of the adhE2 start codon. The expression of adhE2 from a plasmid in the DG1 mutant of C. acetobutylicum, a mutant cured of the pSOL1 megaplasmid, restored butanol production and provided elevated activities of NADH-dependent butyraldehyde and butanol dehydrogenases. The recombinant AdhE2 protein expressed in E. coli as a Strep-tag fusion protein and purified to homogeneity also demonstrated NADH-dependent butyraldehyde and butanol dehydrogenase activities. This is the second AADH identified in C. acetobutylicum ATCC 824, and to our knowledge this is the first example of a bacterium with two AADHs. It is noteworthy that the two corresponding genes, adhE and adhE2, are carried by the pSOL1 megaplasmid of C. acetobutylicum ATCC 824. PMID:11790753

  7. Effects of endogenous antidiuretic hormone (ADH) on macrophage phagocytosis

    SciTech Connect

    Fernandez-Repollet, E.; Opava-Stitzer, S.; Tiffany, S.; Schwartz, A.

    1983-07-01

    Although several studies have indicated that antidiuretic hormone (ADH) enhances the phagocytic function of the reticuloendothelial system (RES) in shock syndromes, it remains unknown what influence ADH exerts upon the individual phagocytic components of this system. The present investigation was designed to evaluate the effects of endogenous ADH on the phagocytic activity of peritoneal macrophage cells. As a phagocytic stimuli, fluorescent methacrylate microbeads were injected intraperitoneally into Brattleboro (ADH deficient) and normal Long Evans rats in the presence and absence of exogenous ADH. Peritoneal cells were harvested 19-22 hr after the administration of the microbeads and the percent phagocytosis was determined in macrophage cells using a fluorescence-activated cell sorter (FACS II). Our results indicate that the percentage of peritoneal macrophages ingesting the fluorescent methacrylate microbeads was significantly reduced in the absence of ADH (Brattleboro rats: 5.4 +/- 0.6% versus Long Evans rats: 16.8 +/- 2.3%; p less than 0.001). In addition, our data demonstrate that exogenous administration of ADH significantly enhanced macrophage phagocytosis in Brattleboro (14.7 +/- 2.2%) and normal Long Evans (49.6 +/- 4.5%) rats. These data suggest, for the first time, that endogenous ADH might play a modulatory role in the phagocytic activity of a specific component of the RES, namely, the macrophage cell.

  8. [Changes in kidney function and the cortisol and ADH levels after peritoneal dialysis with 5% glucose in dogs].

    PubMed

    Nachev, N; Bratanova, Ts; Pavlov, D

    1975-01-01

    The authors made peritoneal dialisis with 5% of glucose (7 ml/kg of body weight) in 11 dogs under the conditions of an acute experiments. They examined cortiosl and ADH activity, hematocrite and plasma protein in the samples of blood, obtained on the 20th and 50th minute. ADH was titrated biologicaly by a new method, proposed by Nacev. The results were compared with the changes in the circulatory and renal indices, obtained at the same procedure in the preceding investigations. There was an increase in the cortisol and ADH activity, which could be explained by the total hypovolemia, induced by peritoneal dialisis. The increase of the cortisol level is described as a separate link in a more complex mechanism, assuring metabolic homeostasis.

  9. Genetic Variation in the Expression of ADH in DROSOPHILA MELANOGASTER

    PubMed Central

    Maroni, G.; Laurie-Ahlberg, C. C.; Adams, D. A.; Wilton, A. N.

    1982-01-01

    Several chromosomes derived from natural populations have been identified that affect the expression of alcohol dehydrogenase (ADH). Second chromosomes, which also carry the structural gene Adh, show a great deal of polymorphism of genetic elements that determine how much enzyme protein accumulates. The level of enzyme was measured in third instar larvae, 6-to-8-day-old males and in larval fat bodies and alimentary canals. In general, activities in the different organs and stages are highly correlated with one another. One line was found, however, in which the ADH level in the fat body is more than twice the level one would expect on the basis of the activity in alimentary canal. We have also found evidence of third-chromosome elements that affect the level of ADH. PMID:6816669

  10. The influence of Adh function on ethanol preference and tolerance in adult Drosophila melanogaster.

    PubMed

    Ogueta, Maite; Cibik, Osman; Eltrop, Rouven; Schneider, Andrea; Scholz, Henrike

    2010-11-01

    Preference determines behavioral choices such as choosing among food sources and mates. One preference-affecting chemical is ethanol, which guides insects to fermenting fruits or leaves. Here, we show that adult Drosophila melanogaster prefer food containing up to 5% ethanol over food without ethanol and avoid food with high levels (23%) of ethanol. Although female and male flies behaved differently at ethanol-containing food sources, there was no sexual dimorphism in the preference for food containing modest ethanol levels. We also investigated whether Drosophila preference, sensitivity and tolerance to ethanol was related to the activity of alcohol dehydrogenase (Adh), the primary ethanol-metabolizing enzyme in D. melanogaster. Impaired Adh function reduced ethanol preference in both D. melanogaster and a related species, D. sechellia. Adh-impaired flies also displayed reduced aversion to high ethanol concentrations, increased sensitivity to the effects of ethanol on postural control, and negative tolerance/sensitization (i.e., a reduction of the increased resistance to ethanol's effects that normally occurs upon repeated exposure). These data strongly indicate a linkage between ethanol-induced behavior and ethanol metabolism in adult fruit flies: Adh deficiency resulted in reduced preference to low ethanol concentrations and reduced aversion to high ones, despite recovery from ethanol being strongly impaired.

  11. Role of cardiac volume receptors in the control of ADH release during acute simulated weightlessness in man

    NASA Technical Reports Server (NTRS)

    Convertino, V. A.; Benjamin, B. A.; Keil, L. C.; Sandler, H.

    1984-01-01

    Hemodynamic responses and antidiuretic hormone (ADH) were measured during body position changes, designed to induce central blood volume shifts in ten cardiac and one heart-lung transplant recipients, to assess the contribution of cardiac volume receptors in the control of ADH release during the initial acute phase of exposure to weightlessness. Each subject underwent 15 min of a sitting-control period (C) followed by 30 min of 6 deg headdown tilt (T) and 30 min of resumed sitting (S). Venous blood samples and cardiac dimensions were taken at 0 and 15 min of C; 5, 15, and 30 min of T; and 5, 15, and 30 min of S. Blood samples were analyzed for hematocrit, plasma osmolality, plasma renin activity (PRA), and ADH. Heart rate and blood pressure were recorded every two min. Plasma osmolality was not altered by posture changes. Mean left ventricular end-diastolic volume increased (P less than 0.05) from 90 ml in C to 106 ml in T and returned to 87 ml in S. Plasma ADH was reduced by 20 percent (P less than 0.05) with T, and returned to control levels with S. These responses were similar in six normal cardiac-innervated control subjects. These data may suggest that cardiac volume receptors are not the primary mechanism for the control of ADH release during acute central volume shifts in man.

  12. Effect of hypovolemia, infusion, and oral rehydration on plasma electrolytes, ADH, renin activity, and +G/z/ tolerance

    NASA Technical Reports Server (NTRS)

    Greenleaf, J. E.; Brock, P. J.; Haines, R. F.; Rositano, S. A.; Montgomery, L. D.; Keil, L. C.

    1977-01-01

    Effects on plasma volume, electrolyte shifts, and +G(z) tolerance induced by: (1) blood withdrawal; (2) blood infusion; and (3) oral fluid intake, were determined at 0.5 G/min in centrifugation tests of six ambulatory male patients, aged 21 to 27 yrs. Hypovolemia induced by withdrawal of 400 ml blood, blood infusion followed by repeated centrifugation, effects of consuming an isotonic drink (0.9% NaCl) to achieve oral rehydration, and donning of red adaptation goggles were studied for effects on acceleration tolerance, pre-acceleration and post-acceleration plasma renin activity (PRA) and plasma vasopressin levels. No significant changes in post-acceleration PRA compared to pre-acceleration PRA were found, and administration of oral rehydration is found as effective as blood replacement in counteracting hypovolemic effects.

  13. Coexpression of Lactobacillus brevis ADH with GDH or G6PDH in Arxula adeninivorans for the synthesis of 1-(R)-phenylethanol.

    PubMed

    Rauter, Marion; Prokoph, Alexandra; Kasprzak, Jakub; Becker, Karin; Baronian, Keith; Bode, Rüdiger; Kunze, Gotthard; Vorbrodt, H- Matthias

    2015-06-01

    The yeast Arxula adeninivorans was used for the overexpression of an ADH gene of Lactobacillus brevis coding for (R)-specific alcohol dehydrogenase (LbADH) to synthesise enantiomerically pure 1-(R)-phenylethanol. Glucose dehydrogenase gene from Bacillus megaterium (BmGDH) or glucose 6-phosphate dehydrogenase of Bacillus pumilus (BpG6PDH) were coexpressed in Arxula to regenerate the cofactor NADPH by oxidising glucose or glucose 6-phosphate. The yeast strain expressing LbADH and BpG6PDH produced 5200 U l(-1) ADH and 370 U l(-1) G6PDH activity, whereas the strain expressing LbADH and BmGDH produced 2700 U l(-1) ADH and 170 U l(-1) GDH activity. However, the crude extract of both strains reduced 40 mM acetophenone to pure 1-(R)-phenylethanol with an enantiomeric excess (ee) of >99 % in 60 min without detectable by-products. An increase in yield was achieved using immobilised crude extracts (IEs), Triton X-100 permeabilised cells (PCs) and permeabilised immobilised cells (PICs) with PICs being most stable with GDH regeneration over 52 cycles. Even though the activity and synthesis rate of 1-(R)-phenylethanol with the BpG6PDH and LbADH coexpressing strain was higher, the BmGDH-LbADH strain was more stable over successive reaction cycles. This, combined with its higher total turnover number (TTN) of 391 mol product per mole NADP(+), makes it the preferred strain for continuous reaction systems. The initial non-optimised semi-continuous reaction produced 9.74 g l(-1) day(-1) or 406 g kg(-1) dry cell weight (dcw) day(-1) isolated 1-(R)-phenylethanol with an ee of 100 % and a TTN of 206 mol product per mole NADP(+). In conclusion, A. adeninivorans is a promising host for LbADH and BpG6PDH or BmGDH production and offers a simple method for the production of enantiomerically pure alcohols.

  14. Metabolite Profiling of adh1 Mutant Response to Cold Stress in Arabidopsis

    PubMed Central

    Song, Yuan; Liu, Lijun; Wei, Yunzhu; Li, Gaopeng; Yue, Xiule; An, Lizhe

    2017-01-01

    As a result of global warming, vegetation suffers from repeated freeze-thaw cycles caused by more frequent short-term low temperatures induced by hail, snow, or night frost. Therefore, short-term freezing stress of plants should be investigated particularly in light of the current climatic conditions. Alcohol dehydrogenase (ADH) plays a central role in the metabolism of alcohols and aldehydes and it is a key enzyme in anaerobic fermentation. ADH1 responds to plant growth and environmental stress; however, the function of ADH1 in the response to short-term freezing stress remains unknown. Using real-time quantitative fluorescence PCR, the expression level of ADH1 was analyzed at low temperature (4°C). The lethal temperature was calculated based on the electrolyte leakage tests for both ADH1 deletion mutants (adh1) and wild type (WT) plants. To further investigate the relationship between ADH1 and cold tolerance in plants, low-Mr polar metabolite analyses of Arabidopsis adh1 and WT were performed at cold temperatures using gas chromatography-mass spectrometry. This investigation focused on freezing treatments (cold acclimation group: −6°C for 2 h with prior 4°C for 7 d, cold shock group: −6°C for 2 h without cold acclimation) and recovery (23°C for 24 h) with respect to seedling growth at optimum temperature. The experimental results revealed a significant increase in ADH1 expression during low temperature treatment (4°C) and at a higher lethal temperature in adh1 compared to that in the WT. Retention time indices and specific mass fragments were used to monitor 263 variables and annotate 78 identified metabolites. From these analyses, differences in the degree of metabolite accumulation between adh1 and WT were detected, including soluble sugars (e.g., sucrose) and amino acids (e.g., asparagine). In addition, the correlation-based network analysis highlighted some metabolites, e.g., melibiose, fumaric acid, succinic acid, glycolic acid, and xylose, which

  15. Metabolite Profiling of adh1 Mutant Response to Cold Stress in Arabidopsis.

    PubMed

    Song, Yuan; Liu, Lijun; Wei, Yunzhu; Li, Gaopeng; Yue, Xiule; An, Lizhe

    2016-01-01

    As a result of global warming, vegetation suffers from repeated freeze-thaw cycles caused by more frequent short-term low temperatures induced by hail, snow, or night frost. Therefore, short-term freezing stress of plants should be investigated particularly in light of the current climatic conditions. Alcohol dehydrogenase (ADH) plays a central role in the metabolism of alcohols and aldehydes and it is a key enzyme in anaerobic fermentation. ADH1 responds to plant growth and environmental stress; however, the function of ADH1 in the response to short-term freezing stress remains unknown. Using real-time quantitative fluorescence PCR, the expression level of ADH1 was analyzed at low temperature (4°C). The lethal temperature was calculated based on the electrolyte leakage tests for both ADH1 deletion mutants (adh1) and wild type (WT) plants. To further investigate the relationship between ADH1 and cold tolerance in plants, low-Mr polar metabolite analyses of Arabidopsis adh1 and WT were performed at cold temperatures using gas chromatography-mass spectrometry. This investigation focused on freezing treatments (cold acclimation group: -6°C for 2 h with prior 4°C for 7 d, cold shock group: -6°C for 2 h without cold acclimation) and recovery (23°C for 24 h) with respect to seedling growth at optimum temperature. The experimental results revealed a significant increase in ADH1 expression during low temperature treatment (4°C) and at a higher lethal temperature in adh1 compared to that in the WT. Retention time indices and specific mass fragments were used to monitor 263 variables and annotate 78 identified metabolites. From these analyses, differences in the degree of metabolite accumulation between adh1 and WT were detected, including soluble sugars (e.g., sucrose) and amino acids (e.g., asparagine). In addition, the correlation-based network analysis highlighted some metabolites, e.g., melibiose, fumaric acid, succinic acid, glycolic acid, and xylose, which

  16. Molecular cloning of alcohol dehydrogenase genes of the yeast Pichia stipitis and identification of the fermentative ADH.

    PubMed

    Passoth, V; Schäfer, B; Liebel, B; Weierstall, T; Klinner, U

    1998-10-01

    Two Pichia stipitis ADH genes (PsADH1 and PsADH2) were isolated by complementation of a Saccharomyces cerevisiae Adh(-)-mutant. The genes enabled the transformants to grow in the presence of antimycin A on glucose, to use ethanol as sole carbon source and made them sensitive to allylalcohol. The sequences of the genes showed similarities of 70-77% to sequences of ADH genes of Candida albicans, Kluyveromyces lactis, K. marxianus, and S. cerevisiae and about 60% homology to those of Schizosaccharomyces pombe and Aspergillus flavus. Southern hybridization experiments suggested that P. stipitis has only these two ADH genes. Both genes are located on the largest chromosome of P. stipitis. PsADH2 encodes for the ADH activity that is responsible for ethanol formation at oxygen limitation. The gene is regulated at the transcriptional level. Moreover, also in cells grown on ethanol, only PsADH2 transcript was found. PsADH1 transcript was detected under aerobic conditions on fermentable carbon sources.

  17. Ethanol tolerance and membrane fatty acid adaptation in adh multiple and null mutants of Kluyveromyces lactis.

    PubMed

    Heipieper, H J; Isken, S; Saliola, M

    2000-11-01

    The effects of ethanol and 1-octanol on growth and fatty acid composition of different strains of Kluyveromyces lactis containing a mutation in the four different alcohol dehydrogenase (KlADH) genes were investigated. In the presence of ethanol and 1-octanol K. lactis reduced the fluidity of its lipids by decreasing the unsaturation index (UI) of its membrane fatty acids. In this way, a direct correlation between nonlethal ethanol concentrations and the decrease in the UI could be observed. At concentrations which totally inhibited cell growth no reaction occurred. These adaptive modifications of the fatty acid pattern of K. lactis to ethanol contrasted with those reported for Saccharomyces cerevisiae and Schizosaccharomyces pombe. Whereas these two yeasts increased the fluidity of their membrane lipids in the presence of ethanol, K. lactis reduced the fluidity (UI) of its lipids. Among the different isogenic adh negative strains tested, the strain containing no ADH (adh0) and that containing only KlADH1 were the most alcohol-sensitive. The strain with only KlADH2 showed nearly the same tolerance as reference strain CBS 2359/152 containing all four ADH genes. This suggests that the KlADH2 product could play an important role in the adaptation/detoxification reactions of K. lactis to high ethanol concentrations.

  18. The inhibitory effect of the cerebellar fastigial stimulation on ADH secretion.

    PubMed

    Hata, N; Miura, M

    1974-11-01

    1. Both cardiovascular and antidiuretic hormone (ADH) responses to some neural inputs were examined in paralysed anaesthetized cats.2. Carotid occlusion elicited cardiovascular responses and increased ADH secretion. When the electrical stimulation of discrete loci of the cerebellar fastigial nucleus (fastigial pressor area) was superimposed on carotid occlusion, cardiovascular responses were further facilitated, while ADH secretion was inhibited.3. The fastigial stimulation alone elicited facilitory cardiovascular responses composed of hypertension and tachycardia, and the fastigial pressor response (FPR), but did not evoke any consistent ADH response.4. These facts indicate that cerebellar modulation of ADH secretion occurs not directly via the hypothalamo-hypophysial system but through the lower brain stem to which both carotid sinus nerves and outflows from the fastigial pressor area project.5. We conclude that the fastigial pressor area is specific for not only cardiovascular and other autonomic responses but pituitary hormonal response.

  19. A distinct type of alcohol dehydrogenase, adh4+, complements ethanol fermentation in an adh1-deficient strain of Schizosaccharomyces pombe.

    PubMed

    Sakurai, Masao; Tohda, Hideki; Kumagai, Hiromichi; Giga-Hama, Yuko

    2004-03-01

    In the fission yeast Schizosaccharomyces pombe, only one alcohol dehydrogenase gene, adh1(+), has been identified. To elucidate the influence of adh1(+) on ethanol fermentation, we constructed the adh1 null strain (delta adh1). The delta adh1 cells still produced ethanol and grew fermentatively as the wild-type cells. Both DNA microarray and RT-PCR analysis demonstrated that this ethanol production is caused by the enhanced expression of a Saccharomyces cerevisiae ADH4-like gene product (SPAC5H10.06C named adh4(+)). Since the strain lacking both adh1 and adh4 genes (delta adh1 delta adh4) showed non-fermentative retarded growth, only these two ADHs produce ethanol for fermentative growth. This is the first observation that a S. cerevisiae ADH4-like alcohol dehydrogenase functions in yeast ethanol fermentation.

  20. Effects of ADH2 overexpression in Saccharomyces bayanus during alcoholic fermentation.

    PubMed

    Maestre, Oscar; García-Martínez, Teresa; Peinado, Rafael A; Mauricio, Juan C

    2008-02-01

    The effect of overexpression of the gene ADH2 on metabolic and biological activity in Saccharomyces bayanus V5 during alcoholic fermentation has been evaluated. This gene is known to encode alcohol dehydrogenase II (ADH II). During the biological aging of sherry wines, where yeasts have to grow on ethanol owing to the absence of glucose, this isoenzyme plays a prominent role by converting the ethanol into acetaldehyde and producing NADH in the process. Overexpression of the gene ADH2 during alcoholic fermentation has no effect on the proteomic profile or the net production of some metabolites associated with glycolysis and alcoholic fermentation such as ethanol, acetaldehyde, and glycerol. However, it affects indirectly glucose and ammonium uptakes, cell growth, and intracellular redox potential, which lead to an altered metabolome. The increased contents in acetoin, acetic acid, and L-proline present in the fermentation medium under these conditions can be ascribed to detoxification by removal of excess acetaldehyde and the need to restore and maintain the intracellular redox potential balance.

  1. Assessing and Increasing Physical Activity

    ERIC Educational Resources Information Center

    Van Camp, Carole M.; Hayes, Lynda B.

    2012-01-01

    Increasing physical activity is a crucial component of any comprehensive approach to combat the growing obesity epidemic. This review summarizes recent behavioral research on the measurement of physical activity and interventions aimed at increasing physical activity and provides directions for future research.

  2. A genetic analysis of Adh1 regulation

    SciTech Connect

    Freeling, M.

    1992-01-01

    The overall goal of our research proposal is to understand the meaning of the various cis-acting sites responsible for AdH1 expression in the entire maize plant. Progress is reported in the following areas: Studies on the TATA box and analysis of revertants of the Adh1-3F1124 allele; screening for more different mutants that affect Adh1 expression differentially; studies on cis-acting sequences required for root-specific Adh1 expression; refinement of the use of the particle gun; and functional analysis of a non- glycolytic anaerobic protein.

  3. Characterization of the temperate bacteriophage phi adh and plasmid transduction in Lactobacillus acidophilus ADH.

    PubMed

    Raya, R R; Kleeman, E G; Luchansky, J B; Klaenhammer, T R

    1989-09-01

    Lactobacillus acidophilus ADH is lysogenic and harbors an inducible prophage, phi adh. Bacteriophage were detected in cell lysates induced by treatment with mitomycin C or UV light. Electron microscopy of lysates revealed phage particles with a hexagonal head (62 nm) and a long, noncontractile, flexible tail (398 nm) ending in at last five short fibers. Phage phi adh was classified within Bradley's B1 phage group and the Siphoviridae family. The phi adh genome is a linear double-stranded DNA molecule of 41.7 kilobase pairs with cohesive ends: a physical map of the phi adh genome was constructed. A prophage-cured derivative of strain ADH, designated NCK102, was isolated from cells that survived UV exposure. NCK102 did not exhibit mitomycin C-induced lysis, but broth cultures lysed upon addition of phage. Phage phi adh produced clear plaques on NCK102 in media containing 10 mM CaCl2 at pH values between 5.2 and 5.5. A relysogenized derivative (NCK103) of NCK102 was isolated that exhibited mitomycin C-induced lysis and superinfection immunity to phage phi adh. Hybridization experiments showed that the phi adh genome was present in the ADH and NCK103 chromosomes, but absent in NCK102. These results demonstrated classic lytic and lysogenic cycles of replication for the temperate phage phi adh induced from L. acidophilus ADH. Phage phi adh also mediates transduction of plasmid DNA. Transductants of strain ADH containing pC194, pGK12, pGB354, and pVA797 were detected at frequencies in the range of 3.6 x 10(-8) to 8.3 x 10(-10) per PFU. Rearrangements or deletions were not detected in these plasmids as a consequence of transduction. This is the first description of plasmid transduction in the genus Lactobacillus.

  4. Replication Study of ESCC Susceptibility Genetic Polymorphisms Locating in the ADH1B-ADH1C-ADH7 Cluster Identified by GWAS

    PubMed Central

    Xu, Xiaoling; Pan, Wenting; Ge, Yunxia; Zhou, Changchun; Liu, Chao; Gao, Jia; Yang, Ming; Mao, Weimin

    2014-01-01

    China was one of the countries with highest esophageal squamous cell carcinoma (ESCC) incidence and mortality worldwide. Alcohol drinking has been identified as a major environmental risk-factor related to ESCC. The alcohol dehydrogenase (ADH) family are major enzymes involved in the alcohol-metabolizing pathways, including alcohol dehydrogenase 1B (ADH1B) and ADH1C. Interestingly, ADH1B and ADH1C genes locate tandemly with ADH7 in a genomic segment as a gene cluster, and are all polymorphic. Several ESCC susceptibility single nucleotide polymorphisms (SNPs) of the ADH1B-ADH1C-ADH7 cluster have been identified previously through a genome-wide association study (GWAS). In the study, we examined the association between five ADH1B-ADH1C-ADH7 cluster SNPs (rs1042026, rs17033, rs1614972, rs1789903 and rs17028973) and risk of developing ESCC. Genotypes were determined in two independent case-control sets from two regions of China. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. Our data demonstrated that these ADH1B-ADH1C-ADH7 cluster SNPs confer susceptibility to ESCC in these two case-control sets, which were consistent to results of the previous GWAS. PMID:24722735

  5. Replication study of ESCC susceptibility genetic polymorphisms locating in the ADH1B-ADH1C-ADH7 cluster identified by GWAS.

    PubMed

    Wang, Jiwen; Wei, Jinyu; Xu, Xiaoling; Pan, Wenting; Ge, Yunxia; Zhou, Changchun; Liu, Chao; Gao, Jia; Yang, Ming; Mao, Weimin

    2014-01-01

    China was one of the countries with highest esophageal squamous cell carcinoma (ESCC) incidence and mortality worldwide. Alcohol drinking has been identified as a major environmental risk-factor related to ESCC. The alcohol dehydrogenase (ADH) family are major enzymes involved in the alcohol-metabolizing pathways, including alcohol dehydrogenase 1B (ADH1B) and ADH1C. Interestingly, ADH1B and ADH1C genes locate tandemly with ADH7 in a genomic segment as a gene cluster, and are all polymorphic. Several ESCC susceptibility single nucleotide polymorphisms (SNPs) of the ADH1B-ADH1C-ADH7 cluster have been identified previously through a genome-wide association study (GWAS). In the study, we examined the association between five ADH1B-ADH1C-ADH7 cluster SNPs (rs1042026, rs17033, rs1614972, rs1789903 and rs17028973) and risk of developing ESCC. Genotypes were determined in two independent case-control sets from two regions of China. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. Our data demonstrated that these ADH1B-ADH1C-ADH7 cluster SNPs confer susceptibility to ESCC in these two case-control sets, which were consistent to results of the previous GWAS.

  6. Increased Spreading Activation in Depression

    ERIC Educational Resources Information Center

    Foster, Paul S.; Yung, Raegan C.; Branch, Kaylei K.; Stringer, Kristi; Ferguson, Brad J.; Sullivan, William; Drago, Valeria

    2011-01-01

    The dopaminergic system is implicated in depressive disorders and research has also shown that dopamine constricts lexical/semantic networks by reducing spreading activation. Hence, depression, which is linked to reductions of dopamine, may be associated with increased spreading activation. However, research has generally found no effects of…

  7. The ADH7 Promoter of Saccharomyces cerevisiae is Vanillin-Inducible and Enables mRNA Translation Under Severe Vanillin Stress.

    PubMed

    Nguyen, Trinh T M; Iwaki, Aya; Izawa, Shingo

    2015-01-01

    Vanillin is one of the major phenolic aldehyde compounds derived from lignocellulosic biomass and acts as a potent fermentation inhibitor to repress the growth and fermentative ability of yeast. Vanillin can be reduced to its less toxic form, vanillyl alcohol, by the yeast NADPH-dependent medium chain alcohol dehydrogenases, Adh6 and Adh7. However, there is little information available regarding the regulation of their gene expression upon severe vanillin stress, which has been shown to repress the bulk translation activity in yeast cells. Therefore, in this study, we investigated expression patterns of the ADH6 and ADH7 genes in the presence of high concentrations of vanillin. We found that although both genes were transcriptionally upregulated by vanillin stress, they showed different protein expression patterns in response to vanillin. Expression of Adh6 was constitutive and gradually decreased under vanillin stress, whereas expression of Adh7 was inducible, and, importantly, occurred under severe vanillin stress. The null mutants of ADH6 or ADH7 genes were hypersensitive to vanillin and reduced vanillin less efficiently than the wild type, confirming the importance of Adh6 and Adh7 in vanillin detoxification. Additionally, we demonstrate that the ADH7 promoter is vanillin-inducible and enables effective protein synthesis even under severe vanillin stress, and it may be useful for the improvement of vanillin-tolerance and biofuel production efficiency via modification of yeast gene expression in the presence of high concentrations of vanillin.

  8. Elimination of hydrogenase active site assembly blocks H2 production and increases ethanol yield in Clostridium thermocellum

    SciTech Connect

    Biswas, Ranjita; Zheng, Tianyong; Olson, Daniel G.; Lynd, Lee R.; Guss, Adam M.

    2015-02-01

    The native ability of Clostridium thermocellum to rapidly consume cellulose and produce ethanol makes it a leading candidate for a consolidated bioprocessing (CBP) biofuel production strategy. C. thermocellum also synthesizes lactate, formate, acetate, H2, and amino acids that compete with ethanol production for carbon and electrons. Elimination of H2 production could redirect carbon flux towards ethanol production by making more electrons available for acetyl-CoA reduction to ethanol. C. thermocellum encodes four hydrogenases and rather than delete each individually, we targeted a hydrogenase maturase gene (hydG), involved in converting the three [FeFe] hydrogenase apoenzymes into holoenzymes. Further deletion of the [NiFe] hydrogenase (ech) resulted in a mutant that functionally lacks all four hydrogenases. H2 production in hydG ech was undetectable and ethanol yield increased nearly 2-fold compared to wild type. Interestingly, mutant growth improved upon the addition of acetate, which led to increased expression of genes related to sulfate metabolism, suggesting these mutants may use sulfate as a terminal electron acceptor to balance redox reactions. Genomic analysis of hydG revealed a mutation in adhE, resulting in a strain with both NADH- and NADPH-dependent alcohol dehydrogenase activities. While this same adhE mutation is found in ethanol tolerant C. thermocellum strain E50C, hydG and hydG ech are not more ethanol tolerant than wild type, illustrating the complicated interactions between redox balancing and ethanol tolerance in C. thermocellum. The dramatic increase in ethanol production here suggests that targeting protein post-translational modification is a promising new approach for inactivation of multiple enzymes simultaneously for metabolic engineering.

  9. Elimination of hydrogenase active site assembly blocks H2 production and increases ethanol yield in Clostridium thermocellum

    DOE PAGES

    Biswas, Ranjita; Zheng, Tianyong; Olson, Daniel G.; ...

    2015-02-01

    The native ability of Clostridium thermocellum to rapidly consume cellulose and produce ethanol makes it a leading candidate for a consolidated bioprocessing (CBP) biofuel production strategy. C. thermocellum also synthesizes lactate, formate, acetate, H2, and amino acids that compete with ethanol production for carbon and electrons. Elimination of H2 production could redirect carbon flux towards ethanol production by making more electrons available for acetyl-CoA reduction to ethanol. C. thermocellum encodes four hydrogenases and rather than delete each individually, we targeted a hydrogenase maturase gene (hydG), involved in converting the three [FeFe] hydrogenase apoenzymes into holoenzymes. Further deletion of the [NiFe]more » hydrogenase (ech) resulted in a mutant that functionally lacks all four hydrogenases. H2 production in hydG ech was undetectable and ethanol yield increased nearly 2-fold compared to wild type. Interestingly, mutant growth improved upon the addition of acetate, which led to increased expression of genes related to sulfate metabolism, suggesting these mutants may use sulfate as a terminal electron acceptor to balance redox reactions. Genomic analysis of hydG revealed a mutation in adhE, resulting in a strain with both NADH- and NADPH-dependent alcohol dehydrogenase activities. While this same adhE mutation is found in ethanol tolerant C. thermocellum strain E50C, hydG and hydG ech are not more ethanol tolerant than wild type, illustrating the complicated interactions between redox balancing and ethanol tolerance in C. thermocellum. The dramatic increase in ethanol production here suggests that targeting protein post-translational modification is a promising new approach for inactivation of multiple enzymes simultaneously for metabolic engineering.« less

  10. Alcohol dehydrogenase AdhA plays a role in ethanol tolerance in model cyanobacterium Synechocystis sp. PCC 6803.

    PubMed

    Vidal, Rebeca

    2017-02-03

    The protein AdhA from the cyanobacterium Synechocystis sp. PCC 6803 (hereafter Synechocystis) has been previously reported to show alcohol dehydrogenase activity towards ethanol and both NAD and NADP. This protein is currently being used in genetically modified strains of Synechocystis capable of synthesizing ethanol showing the highest ethanol productivities. In the present work, mutant strains of Synechocystis lacking AdhA have been constructed and tested for tolerance to ethanol. The lack of AdhA in the wild-type strain reduces survival to externally added ethanol at lethal concentration of 4% (v/v). On the other hand, the lack of AdhA in an ethanologenic strain diminishes tolerance of cells to internally produced ethanol. It is also shown that light-activated heterotrophic growth (LAHG) of the wild-type strain is impaired in the mutant strain lacking AdhA (∆adhA strain). Photoautotrophic, mixotrophic, and photoheterotrophic growth are not affected in the mutant strain. Based on phenotypic characterization of ∆adhA mutants, the possible physiological function of AdhA in Synechocystis is discussed.

  11. Functional relevance of human adh polymorphism.

    PubMed

    Eriksson, C J; Fukunaga, T; Sarkola, T; Chen, W J; Chen, C C; Ju, J M; Cheng, A T; Yamamoto, H; Kohlenberg-Müller, K; Kimura, M; Murayama, M; Matsushita, S; Kashima, H; Higuchi, S; Carr, L; Viljoen, D; Brooke, L; Stewart, T; Foroud, T; Su, J; Li, T K; Whitfield, J B

    2001-05-01

    This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were C. J. Peter Eriksson and Tatsushige Fukunaga. The presentations were (1) 4-Methylpyrazole as a tool in the investigation of the role of ADH in the actions of alcohol in humans, by Taisto Sarkola and C. J. Peter Eriksson; (2) ADH2 polymorphism and flushing in Asian populations, by Wei J. Chen, C. C. Chen, J. M. Ju, and Andrew T. A. Cheng; (3) Role of ADH3 genotypes in the acute effects of alcohol in a Finnish population, by Hidetaka Yamamoto, Kathrin Kohlenberg-Müller, and C. J. Peter Eriksson; (4) Clinical characteristics and disease course of alcoholics with different ADH2 genotypes, by Mitsuru Kimura, Masanobu Murayama, Sachio Matsushita, Haruo Kashima, and Susumu Higuchi; (5) ADH2 polymorphism, alcohol drinking, and birth defects, by Lucinda Carr, D. Viljoen, L. Brooke, T. Stewart, T. Foroud, J. Su, and Ting-Kai Li; and (6) ADH genotypes and alcohol use in Europeans, by John B. Whitfield.

  12. Alcohol Dehydrogenase and Pyruvate Decarboxylase Activity in Leaves and Roots of Eastern Cottonwood (Populus deltoides Bartr.) and Soybean (Glycine max L.) 1

    PubMed Central

    Kimmerer, Thomas W.

    1987-01-01

    Pyruvate decarboxylase (PDC, EC 4.1.1.1) and alcohol dehydrogenase (ADH, EC 1.1.1.1) are responsible for the anaerobic production of acetaldehyde and ethanol in higher plants. In developing soybean embryos, ADH activity increased upon imbibition and then declined exponentially with development, and was undetectable in leaves by 30 days after imbibition. PDC was not detectable in soybean leaves. In contrast, ADH activity remained high in developing cottonwood seedlings, with no decline in activity during development. ADH activity in the first fully expanded leaf of cottonwood was 230 micromoles NADH oxidized per minute per gram dry weight, and increased with leaf age. Maximal PDC activity of cottonwood leaves was 10 micromoles NADH oxidized per minute per gram dry weight. ADH activity in cottonwood roots was induced by anaerobic stress, increasing from 58 to 205 micromoles NADH oxidized per minute per gram dry weight in intact plants in 48 hours, and from 38 to 246 micromoles NADH oxidized per minute per gram dry weight in detached roots in 48 hours. Leaf ADH activity increased by 10 to 20% on exposure to anaerobic conditions. Crude leaf enzyme extracts with high ADH activity reduced little or no NADH when other aldehydes, such as trans-2-hexenal, were provided as substrate. ADH and PDC are constitutive enzyme in cottonwood leaves, but their metabolic role is not known. PMID:16665586

  13. Overexpression of ADH1 and HXT1 genes in the yeast Saccharomyces cerevisiae improves the fermentative efficiency during tequila elaboration.

    PubMed

    Gutiérrez-Lomelí, Melesio; Torres-Guzmán, Juan Carlos; González-Hernández, Gloria Angélica; Cira-Chávez, Luis Alberto; Pelayo-Ortiz, Carlos; Ramírez-Córdova, Jose de Jesús

    2008-05-01

    This work assessed the effect of the overexpression of ADH1 and HXT1 genes in the Saccharomyces cerevisiae AR5 strain during fermentation of Agave tequilana Weber blue variety must. Both genes were cloned individually and simultaneously into a yeast centromere plasmid. Two transformant strains overexpressing ADH1 and HXT1 individually and one strain overexpressing both genes were randomly selected and named A1, A3 and A5 respectively. Overexpression effect on growth and ethanol production of the A1, A3 and A5 strains was evaluated in fermentative conditions in A. tequilana Weber blue variety must and YPD medium. During growth in YPD and Agave media, all the recombinant strains showed lower cell mass formation than the wild type AR5 strain. Adh enzymatic activity in the recombinant strains A1 and A5 cultivated in A. tequilana and YPD medium was higher than in the wild type. The overexpression of both genes individually and simultaneously had no significant effect on ethanol formation; however, the fermentative efficiency of the A5 strain increased from 80.33% to 84.57% and 89.40% to 94.29% in YPD and Agave medium respectively.

  14. Recombinant industrial brewing yeast strains with ADH2 interruption using self-cloning GSH1+CUP1 cassette.

    PubMed

    Wang, Zhao-Yue; Wang, Jin-Jing; Liu, Xi-Feng; He, Xiu-Ping; Zhang, Bo-Run

    2009-06-01

    A self-cloning module for gene knock-out and knock-in in industrial brewing yeast strain was constructed that contains copper resistance and gamma-glutamylcysteine synthetase gene cassette, flanked by alcohol dehydrogenase II gene (ADH2) of Saccharomyces cerevisiae. The module was used to obtain recombined strains RY1 and RY2 by targeting the ADH2 locus of host Y1. RY1 and RY2 were genetically stable. PCR and enzyme activity analysis of RY1 and RY2 cells showed that one copy of ADH2 was deleted by GSH1+CUP1 insertion, and an additional copy of wild type was still present. The fermentation ability of the recombinants was not changed after genetic modification, and a high level of glutathione (GSH) was secreted, resulting from GSH1 overexpression, which codes for gamma-glutamylcysteine synthetase. A pilot-scale brewing test for RY1 and RY2 indicated that acetaldehyde content in fermenting liquor decreased by 21-22%, GSH content increased by 20-22% compared with the host, the antioxidizability of the recombinants was improved, and the sensorial evaluation was also better than that of the host. No heterologous DNA was harbored in the recombinants; therefore, they could be applied in the beer industry in terms of their biosafety.

  15. Increase in composite binder activity

    NASA Astrophysics Data System (ADS)

    Fediuk, R.; Smoliakov, A.; Stoyushko, N.

    2016-11-01

    The binder of portland cement (51-59 wt.%), fly ash of thermal power stations (3644 wt.%), limestone crushing waste (4-9 wt.%) and dry hyper plasticizer (0.2 wt.%) has been created. It can be used in the building materials industry for production of high-strength concrete. The composite binder is obtained by co-milling of the components in vario-planetary mill to a specific surface area of 550-600 m2/kg. The technical result is the possibility of obtaining a composite binder with significant replacement of cement with industrial waste, cost-effective and superior to portland cement for construction and technical properties, increased activity. This allows producing concrete for walling with a compressive strength of 100 MPa, while using more than 50% of industrial waste.

  16. Rare ADH Variant Constellations are Specific for Alcohol Dependence

    PubMed Central

    Zuo, Lingjun; Zhang, Heping; Malison, Robert T.; Li, Chiang-Shan R.; Zhang, Xiang-Yang; Wang, Fei; Lu, Lingeng; Lu, Lin; Wang, Xiaoping; Krystal, John H.; Zhang, Fengyu; Deng, Hong-Wen; Luo, Xingguang

    2013-01-01

    Aims: Some of the well-known functional alcohol dehydrogenase (ADH) gene variants (e.g. ADH1B*2, ADH1B*3 and ADH1C*2) that significantly affect the risk of alcohol dependence are rare variants in most populations. In the present study, we comprehensively examined the associations between rare ADH variants [minor allele frequency (MAF) <0.05] and alcohol dependence, with several other neuropsychiatric and neurological disorders as reference. Methods: A total of 49,358 subjects in 22 independent cohorts with 11 different neuropsychiatric and neurological disorders were analyzed, including 3 cohorts with alcohol dependence. The entire ADH gene cluster (ADH7–ADH1C–ADH1B–ADH1A–ADH6–ADH4–ADH5 at Chr4) was imputed in all samples using the same reference panels that included whole-genome sequencing data. We stringently cleaned the phenotype and genotype data to obtain a total of 870 single nucleotide polymorphisms with 0< MAF <0.05 for association analysis. Results: We found that a rare variant constellation across the entire ADH gene cluster was significantly associated with alcohol dependence in European-Americans (Fp1: simulated global P = 0.045), European-Australians (Fp5: global P = 0.027; collapsing: P = 0.038) and African-Americans (Fp5: global P = 0.050; collapsing: P = 0.038), but not with any other neuropsychiatric disease. Association signals in this region came principally from ADH6, ADH7, ADH1B and ADH1C. In particular, a rare ADH6 variant constellation showed a replicable association with alcohol dependence across these three independent cohorts. No individual rare variants were statistically significantly associated with any disease examined after group- and region-wide correction for multiple comparisons. Conclusion: We conclude that rare ADH variants are specific for alcohol dependence. The ADH gene cluster may harbor a causal variant(s) for alcohol dependence. PMID:23019235

  17. Increasing opportunities for physical activity.

    PubMed

    Buckley, Sue

    2007-07-01

    Being physically active can have a number of benefits - having fun, meeting with friends, keeping healthy and experiencing success. For children with Down syndrome the foundations need to be laid early if they are to keep active in school, teenage and adult years and parents ask for more help in this area from professionals.

  18. Inhibition of alcohol dehydrogenase after 2-propanol exposure in different geographic races of Drosophila mojavensis: lack of evidence for selection at the Adh-2 locus.

    PubMed

    Pfeiler, Edward; Reed, Laura K; Markow, Therese A

    2005-03-15

    High frequencies of the fast allele of alcohol dehydrogenase-2 (Adh-2F) are found in populations of Drosophila mojavensis that inhabit the Baja California peninsula (race BII) whereas the slow allele (Adh-2S) predominates at most other localities within the species' geographic range. Race BII flies utilize necrotic tissue of pitaya agria cactus (Stenocereus gummosus) which contains high levels of 2-propanol, whereas flies from most other localities utilize different cactus hosts in which 2-propanol levels are low. To test if 2-propanol acts as a selective force on Adh-2 genotype, or whether some other yet undetermined genetic factor is responsible, mature males of D. mojavensis lines derived from the Grand Canyon (race A) and Santa Catalina Island (race C), each with individuals homozygous for Adh-2F and Adh-2S, were exposed to 2-propanol for 24 h and ADH-2 specific activity was then determined on each genotype. Flies from five other localities homozygous for either the fast or slow allele also were examined. Results for all reported races of D. mojavensis were obtained. 2-propanol exposure inhibited ADH-2 specific activity in both genotypes from all localities, but inhibition was significantly less in two populations of race BII flies homozygous for Adh-2F. When F/F and S/S genotypes in flies from the same locality were compared, both genotypes showed high 2-propanol inhibition that was not statistically different, indicating that the F/F genotype alone does not provide a benefit against the inhibitory effects of 2-propanol. ADH-1 activity in female ovaries was inhibited less by 2-propanol than ADH-2. These results do not support the hypothesis that 2-propanol acts as a selective factor favoring the Adh-2F allele.

  19. Increasing Youth Physical Activity with Activity Calendars

    ERIC Educational Resources Information Center

    Eckler, Seth

    2016-01-01

    Physical educators often struggle with ways to get their students to be active beyond the school day. One strategy to accomplish this is the use of physical activity calendars (PACs). The purpose of this article is to support the use of PACs and give practical advice for creating effective PACs.

  20. ADH single nucleotide polymorphism associations with alcohol metabolism in vivo

    PubMed Central

    Birley, Andrew J.; James, Michael R.; Dickson, Peter A.; Montgomery, Grant W.; Heath, Andrew C.; Martin, Nicholas G.; Whitfield, John B.

    2009-01-01

    We have previously found that variation in alcohol metabolism in Europeans is linked to the chromosome 4q region containing the ADH gene family. We have now typed 103 single nucleotide polymorphisms (SNPs) across this region to test for allelic associations with variation in blood and breath alcohol concentrations after an alcohol challenge. In vivo alcohol metabolism was modelled with three parameters that identified the absorption and rise of alcohol concentration following ingestion, and the rate of elimination. Alleles of ADH7 SNPs were associated with the early stages of alcohol metabolism, with additional effects in the ADH1A, ADH1B and ADH4 regions. Rate of elimination was associated with SNPs in the intragenic region between ADH7 and ADH1C, and across ADH1C and ADH1B. SNPs affecting alcohol metabolism did not correspond to those reported to affect alcohol dependence or alcohol-related disease. The combined SNP associations with early- and late-stage metabolism only account for approximately 20% of the total genetic variance linked to the ADH region, and most of the variance for in vivo alcohol metabolism linked to this region is yet to be explained. PMID:19193628

  1. Genome-wide responses to carbonyl electrophiles in Bacillus subtilis: control of the thiol-dependent formaldehyde dehydrogenase AdhA and cysteine proteinase YraA by the MerR-family regulator YraB (AdhR).

    PubMed

    Nguyen, Thi Thu Huyen; Eiamphungporn, Warawan; Mäder, Ulrike; Liebeke, Manuel; Lalk, Michael; Hecker, Michael; Helmann, John D; Antelmann, Haike

    2009-02-01

    Quinones and alpha,beta-unsaturated carbonyls are naturally occurring electrophiles that target cysteine residues via thiol-(S)-alkylation. We analysed the global expression profile of Bacillus subtilis to the toxic carbonyls methylglyoxal (MG) and formaldehyde (FA). Both carbonyl compounds cause a stress response characteristic for thiol-reactive electrophiles as revealed by the induction of the Spx, CtsR, CymR, PerR, ArsR, CzrA, CsoR and SigmaD regulons. MG and FA triggered also a SOS response which indicates DNA damage. Protection against FA is mediated by both the hxlAB operon, encoding the ribulose monophosphate pathway for FA fixation, and a thiol-dependent formaldehyde dehydrogenase (AdhA) and DJ-1/PfpI-family cysteine proteinase (YraA). The adhA-yraA operon and the yraC gene, encoding a gamma-carboxymuconolactone decarboxylase, are positively regulated by the MerR-family regulator, YraB(AdhR). AdhR binds specifically to its target promoters which contain a 7-4-7 inverted repeat (CTTAAAG-N4-CTTTAAG) between the -35 and -10 elements. Activation of adhA-yraA transcription by AdhR requires the conserved Cys52 residue in vivo. We speculate that AdhR is redox-regulated via thiol-(S)-alkylation by aldehydes and that AdhA and YraA are specifically involved in reduction of aldehydes and degradation or repair of damaged thiol-containing proteins respectively.

  2. A 5-hydroxymethyl furfural reducing enzyme encoded by the Saccharomyces cerevisiae ADH6 gene conveys HMF tolerance.

    PubMed

    Petersson, Anneli; Almeida, João R M; Modig, Tobias; Karhumaa, Kaisa; Hahn-Hägerdal, Bärbel; Gorwa-Grauslund, Marie F; Lidén, Gunnar

    2006-04-30

    The fermentation of lignocellulose hydrolysates by Saccharomyces cerevisiae for fuel ethanol production is inhibited by 5-hydroxymethyl furfural (HMF), a furan derivative which is formed during the hydrolysis of lignocellulosic materials. The inhibition can be avoided if the yeast strain used in the fermentation has the ability to reduce HMF to 5-hydroxymethylfurfuryl alcohol. To enable the identification of enzyme(s) responsible for HMF conversion in S. cerevisiae, microarray analyses of two strains with different abilities to convert HMF were performed. Based on the expression data, a subset of 15 reductase genes was chosen to be further examined using an overexpression strain collection. Three candidate genes were cloned from two different strains, TMB3000 and the laboratory strain CEN.PK 113-5D, and overexpressed using a strong promoter in the strain CEN.PK 113-5D. Strains overexpressing ADH6 had increased HMF conversion activity in cell-free crude extracts with both NADPH and NADH as co-factors. In vitro activities were recorded of 8 mU/mg with NADH as co-factor and as high as 1200 mU/mg for the NADPH-coupled reduction. Yeast strains overexpressing ADH6 also had a substantially higher in vivo conversion rate of HMF in both aerobic and anaerobic cultures, showing that the overexpression indeed conveyed the desired increased reduction capacity.

  3. Interactions between ADH and prostaglandins in isolated erythrocyte-perfused rat kidney

    SciTech Connect

    Lieberthal, W.; Vasilevsky, M.L.; Valeri, C.R.; Levinsky, N.G.

    1987-02-01

    Interactions between antidiuretic hormone (ADH) and renal prostaglandins in the regulation of sodium reabsorption and urinary concentrating ability were studied in isolated erythrocyte-perfused rat kidneys (IEPK). In this model, hemodynamic characteristics are comparable to those found in vivo, and tubular morphology is preserved throughout the period of perfusion. (Deamino)-D-arginine vasopressin (dDAVP) markedly reduced fractional sodium excretion (FE/sub Na/) in the IEPK. After indomethacin, FE/sub Na/ fell still further. In the absence of dDAVP indomethacin had no effect on sodium excretion. dDAVP increased urine osmolality in the IEPK. When prostaglandin synthesis was blocked with indomethacin, urinary osmolality increased further. In isolated kidneys perfused without erythrocytes (IPK), dDAVP decreased FE/sub Na/ from 14.5 +/- 1.8% to 9.6 +/- 1.2%. dDAVP increased urine osmolality only modestly in the IPK and indomethacin did not increase concentrating ability further. Thus the IEPK (unlike the IPK) can excrete markedly hypertonic urine in response to ADH. ADH also enhances tubular reabsorption of sodium in the IEPK. Prostaglandins inhibit both these actions of ADH but do not directly affect sodium excretion in the absence of the hormone. Prostaglandius were measured by radioimmunoassay.

  4. Opossum alcohol dehydrogenases: Sequences, structures, phylogeny and evolution: evidence for the tandem location of ADH genes on opossum chromosome 5.

    PubMed

    Holmes, Roger S

    2009-03-16

    BLAT (BLAST-Like Alignment Tool) analyses and interrogations of the recently published opossum genome were undertaken using previously reported rat ADH amino acid sequences. Evidence is presented for six opossum ADH genes localized on chromosome 5 and organized in a comparable ADH gene cluster to that reported for human and rat ADH genes. The predicted amino acid sequences and secondary structures for the opossum ADH subunits and the intron-exon boundaries for opossum ADH genes showed a high degree of similarity with other mammalian ADHs, and four opossum ADH classes were identified, namely ADH1, ADH3, ADH6 and ADH4 (for which three genes were observed: ADH4A, ADH4B and ADH4C). Previous biochemical analyses of opossum ADHs have reported the tissue distribution and properties for these enzymes: ADH1, the major liver enzyme; ADH3, widely distributed in opossum tissues with similar kinetic properties to mammalian class 3 ADHs; and ADH4, for which several forms were localized in extrahepatic tissues, especially in the digestive system and in the eye. These ADHs are likely to perform similar functions to those reported for other mammalian ADHs in the metabolism of ingested and endogenous alcohols and aldehydes. Phylogenetic analyses examined opossum, human, rat, chicken and cod ADHs, and supported the proposed designation of opossum ADHs as class I (ADH1), class III (ADH3), class IV (ADH4A, ADH4B and ADH4C) and class VI (ADH6). Percentage substitution rates were examined for ADHs during vertebrate evolution which indicated that ADH3 is evolving at a much slower rate to that of the other ADH classes.

  5. Genetic polymorphisms of ADH1B, ADH1C and ALDH2, alcohol consumption, and the risk of gastric cancer: the Japan Public Health Center-based prospective study.

    PubMed

    Hidaka, Akihisa; Sasazuki, Shizuka; Matsuo, Keitaro; Ito, Hidemi; Sawada, Norie; Shimazu, Taichi; Yamaji, Taiki; Iwasaki, Motoki; Inoue, Manami; Tsugane, Shoichiro

    2015-02-01

    The association between alcohol consumption, genetic polymorphisms of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) and gastric cancer risk is not completely understood. We investigated the association between ADH1B (rs1229984), ADH1C (rs698) and ALDH2 (rs671) polymorphisms, alcohol consumption and the risk of gastric cancer among Japanese subjects in a population-based, nested, case-control study (1990-2004). Among 36 745 subjects who answered the baseline questionnaire and provided blood samples, 457 new gastric cancer cases matched to 457 controls were used in the analysis. The odds ratios (OR) and corresponding 95% confidence intervals (CI) were calculated using logistic regression models. No association was observed between alcohol consumption, ADH1B (rs1229984), ADH1C (rs698) and ALDH2 (rs671) polymorphisms and gastric cancer risk. However, considering gene-environmental interaction, ADH1C G allele carriers who drink ≥150 g/week of ethanol had a 2.5-fold increased risk of gastric cancer (OR = 2.54, 95% CI = 1.05-6.17) relative to AA genotype carriers who drink 0 to <150 g/week (P for interaction = 0.02). ALDH2 A allele carriers who drink ≥150 g/week also had an increased risk (OR = 2.08, 95% CI = 1.05-4.12) relative to GG genotype carriers who drink 0 to < 150 g/week (P for interaction = 0.08). To find the relation between alcohol consumption and gastric cancer risk, it is important to consider both alcohol consumption level and ADH1C and ALDH2 polymorphisms.

  6. Hemodynamic and ADH responses to central blood volume shifts in cardiac-denervated humans

    NASA Technical Reports Server (NTRS)

    Convertino, V. A.; Thompson, C. A.; Benjamin, B. A.; Keil, L. C.; Savin, W. M.; Gordon, E. P.; Haskell, W. L.; Schroeder, J. S.; Sandler, H.

    1990-01-01

    Hemodynamic responses and antidiuretic hormone (ADH) were measured during body position changes designed to induce blood volume shifts in ten cardiac transplant recipients to assess the contribution of cardiac and vascular volume receptors in the control of ADH secretion. Each subject underwent 15 min of a control period in the seated posture, then assumed a lying posture for 30 min at 6 deg head down tilt (HDT) followed by 20 min of seated recovery. Venous blood samples and cardiac dimensions (echocardiography) were taken at 0 and 15 min before HDT, 5, 15, and 30 min of HDT, and 5, 15, and 30 min of seated recovery. Blood samples were analyzed for hematocrit, plasma osmolality, plasma renin activity (PRA), and ADH. Resting plasma volume (PV) was measured by Evans blue dye and percent changes in PV during posture changes were calculated from changes in hematocrit. Heart rate (HR) and blood pressure (BP) were recorded every 2 min. Results indicate that cardiac volume receptors are not the only mechanism for the control of ADH release during acute blood volume shifts in man.

  7. Evaluation of the Saccharomyces cerevisiae ADH2 promoter for protein synthesis.

    PubMed

    Lee, K Michael; DaSilva, Nancy A

    2005-04-30

    The Saccharomyces cerevisiae ADH2 promoter (P(ADH2)) is repressed several hundred-fold in the presence of glucose; transcription is initiated once the glucose in the medium is exhausted. The promoter can thus be utilized for effective regulation of recombinant gene expression in S. cerevisiae without the addition of an inducer. To evaluate this promoter in the absence of plasmid copy number and stability variations, the P(ADH2)-lacZ cassette was integrated into the yeast chromosomes. The effects of medium composition, glucose concentration and cultivation time on promoter derepression and expression level were investigated. Maximum protein activity was obtained after 48 h of growth in complex YPD medium containing 1% glucose. The widely used S. cerevisiae GAL1 and CUP1 promoters both require the addition of an inducer [galactose and copper(II) ion, respectively] before regulated genes will be expressed. The strengths of these three different promoters were compared for cells containing one copy of an integrated lacZ gene under their control. The ADH2 promoter was superior for all induction strategies investigated.

  8. Exergames: Increasing Physical Activity through Effective Instruction

    ERIC Educational Resources Information Center

    Rudella, Jennifer L.; Butz, Jennifer V.

    2015-01-01

    Due to the growing obesity epidemic in the United States, educators must consider new ways to increase physical activity in an effort to address obesity. There are a variety of ways educators can increase physical activity in the classroom, and exergames--video games that require physical movement in order to play--are a modern-day approach to…

  9. Suppression of ADH during water immersion in normal man. [antidiuretic hormone

    NASA Technical Reports Server (NTRS)

    Epstein, M.; Pins, D. S.; Miller, M.

    1975-01-01

    A study was undertaken to ascertain whether diuresis induced by immersion is medicated by an inhibition of ADH. Immersion resulted in a progressive decrease in ADH excretion from 80.1 + or - 7 (SEM) to 37.3 + or - 6.3 microU/min (P less than 0.025). Cessation of immersion was associated with a marked increase in ADH from 37.3 + or - 6.3 microU/min to 176.6 + or - 72.6 microU/min during the recovery hour (P less than 0.05). Concomitant with these changes, urine osmolality decreased significantly beginning as early as the initial hour of immersion from 1044 + or - 36 to 542 + or - 66 mosmol/kg H2O during the final hour of immersion (P less than 0.001). These findings are consistent with the earlier suggestion that suppression of ADH release contributes to enhanced free water clearance in hydrated subjects undergoing immersion.

  10. Combination of ADH1B*2/ALDH2*2 polymorphisms alters acetaldehyde-derived DNA damage in the blood of Japanese alcoholics.

    PubMed

    Yukawa, Yoshiyuki; Muto, Manabu; Hori, Kimiko; Nagayoshi, Haruna; Yokoyama, Akira; Chiba, Tsutomu; Matsuda, Tomonari

    2012-09-01

    The acetaldehyde associated with alcoholic beverages is an evident carcinogen for the esophagus. Genetic polymorphisms of the alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2) genes are associated with the risk of esophageal cancer. However, the exact mechanism via which these genetic polymorphisms affect esophageal carcinogenesis has not been elucidated. ADH1B*2 is involved in overproduction of acetaldehyde due to increased ethanol metabolism into acetaldehyde, and ALDH2*2 is involved in accumulation of acetaldehyde due to the deficiency of acetaldehyde metabolism. Acetaldehyde can interact with DNA and form DNA adducts, resulting in DNA damage. N(2)-ethylidene-2'-deoxyguanosine (N(2)-ethylidene-dG) is the most abundant DNA adduct derived from acetaldehyde. Therefore, we quantified N(2)-ethylidene-dG levels in blood samples from 66 Japanese alcoholic patients using liquid chromatography/electrospray tandem mass spectrometry, and investigated the relationship between N(2)-ethylidene-dG levels and ADH1B and ALDH2 genotypes. The median N(2)-ethylidene-dG levels (25th percentile, 75th percentile) in patients with ADH1B*1/*1 plus ALDH2*1/*1, ADH1B*2 carrier plus ALDH2*1/*1, ADH1B*1/*1 plus ALDH2*1/*2, and ADH1B*2 carrier plus ALDH2*1/*2 were 2.14 (0.97, 2.37)/10(7) bases, 2.38 (1.18, 2.98)/10(7) bases, 5.38 (3.19, 6.52)/10(7) bases, and 21.04 (12.75, 34.80)/10(7) bases, respectively. In the ALDH2*1/*2 group, N(2)-ethylidene-dG levels were significantly higher in ADH1B*2 carriers than in the ADH1B*1/*1 group (P < 0.01). N(2)-ethylidene-dG levels were significantly higher in the ALDH2*1/*2 group than in the ALDH2*1/*1 group, regardless of ADH1B genotype (ADH1B*1/*1, P < 0.05; ADH1B*2 carriers, P < 0.01) N(2)-ethylidene-dG levels in blood DNA of the alcoholics was remarkably higher in individuals with a combination of the ADH1B*2 and ALDH2*2 alleles. These results provide a new perspective on the carcinogenicity of the acetaldehyde associated with

  11. Cloning of the Arabidopsis and Rice Formaldehyde Dehydrogenase Genes: Implications for the Origin of Plant Adh Enzymes

    PubMed Central

    Dolferus, R.; Osterman, J. C.; Peacock, W. J.; Dennis, E. S.

    1997-01-01

    This article reports the cloning of the genes encoding the Arabidopsis and rice class III ADH enzymes, members of the alcohol dehydrogenase or medium chain reductase/dehydrogenase superfamily of proteins with glutathione-dependent formaldehyde dehydrogenase activity (GSH-FDH). Both genes contain eight introns in exactly the same positions, and these positions are conserved in plant ethanol-active Adh genes (class P). These data provide further evidence that plant class P genes have evolved from class III genes by gene duplication and acquisition of new substrate specificities. The position of introns and similarities in the nucleic acid and amino acid sequences of the different classes of ADH enzymes in plants and humans suggest that plant and animal class III enzymes diverged before they duplicated to give rise to plant and animal ethanol-active ADH enzymes. Plant class P ADH enzymes have gained substrate specificities and evolved promoters with different expression properties, in keeping with their metabolic function as part of the alcohol fermentation pathway. PMID:9215914

  12. Regulation of nitrogen metabolism, starch utilisation and the beta-hbd-adh1 gene cluster in Clostridium acetobutylicum.

    PubMed

    Woods, D R; Reid, S J

    1995-10-01

    The successful genetic manipulation of Clostridium acetobutylicum for the increased production of solvents will depend on an understanding of gene structure and regulation in the bacterium. The glutamine synthetase (glnA) gene is regulated by antisense RNA, transcribed from a downstream promoter, in the opposite direction to the glnA gene. An open reading frame (ORF) was detected downstream of the glnA gene, which has sequence homology to response regulators with anti-termination activity and may be involved in sensing nitrogen conditions. The expression of the linked beta-hbd, adh1 and fixB genes was investigated throughout the bacterial growth cycle by RNA hybridisation techniques. The adh1 gene was independently expressed as a 2.4-kb transcript which peaked at 12 h, immediately prior to the solventogenic phase. The beta-hbd and fixB genes were transcribed throughout the acidogenic and solventogenic phases. A regulator gene, regA, which complements a Bacillus subtilis ccpA mutant, has been identified and sequenced from C. acetobutylicum P262. The regA gene repressed the degradation of starch by an uncharacterised C. acetobutylicum gene, and may therefore play a role in the utilisation of carbohydrate substrates in this organism.

  13. The metabolic enzyme AdhE controls the virulence of Escherichia coli O157:H7

    PubMed Central

    Beckham, Katherine S H; Connolly, James P R; Ritchie, Jennifer M; Wang, Dai; Gawthorne, Jayde A; Tahoun, Amin; Gally, David L; Burgess, Karl; Burchmore, Richard J; Smith, Brian O; Beatson, Scott A; Byron, Olwyn; Wolfe, Alan J; Douce, Gillian R; Roe, Andrew J

    2014-01-01

    Classical studies have focused on the role that individual regulators play in controlling virulence gene expression. An emerging theme, however, is that bacterial metabolism also plays a key role in this process. Our previous work identified a series of proteins that were implicated in the regulation of virulence. One of these proteins was AdhE, a bi-functional acetaldehyde-CoA dehydrogenase and alcohol dehydrogenase. Deletion of its gene (adhE) resulted in elevated levels of extracellular acetate and a stark pleiotropic phenotype: strong suppression of the Type Three Secretion System (T3SS) and overexpression of non-functional flagella. Correspondingly, the adhE mutant bound poorly to host cells and was unable to swim. Furthermore, the mutant was significantly less virulent than its parent when tested in vivo, which supports the hypothesis that attachment and motility are central to the colonization process. The molecular basis by which AdhE affects virulence gene regulation was found to be multifactorial, involving acetate-stimulated transcription of flagella expression and post-transcriptional regulation of the T3SS through Hfq. Our study reveals fascinating insights into the links between bacterial physiology, the expression of virulence genes, and the underlying molecular mechanism mechanisms by which these processes are regulated. PMID:24846743

  14. Evidence for a role for AtMYB2 in the induction of the Arabidopsis alcohol dehydrogenase gene (ADH1) by low oxygen.

    PubMed Central

    Hoeren, F U; Dolferus, R; Wu, Y; Peacock, W J; Dennis, E S

    1998-01-01

    The transcription factor AtMYB2 binds to two sequence motifs in the promoter of the Arabidopsis ADH1 gene. The binding to the GT-motif (5'-TGGTTT-3') is essential for induction of ADH1 by low oxygen, while binding to the second motif, MBS-2, is not essential for induction. We show that AtMYB2 is induced by hypoxia with kinetics compatible with a role in the regulation of ADH1. Like ADH1, AtMYB2 has root-limited expression. When driven by a constitutive promoter, AtMYB2 is able to transactivate ADH1 expression in transient assays in both Arabidopsis and Nicotiana plumbaginifolia protoplasts, and in particle bombardment of Pisum sativum leaves. Mutation of the GT-motif abolished binding of AtMYB2 and caused loss of activity of the ADH1 promoter in both transient assays and transgenic Arabidopsis plants. These results are consistent with AtMYB2 being a key regulatory factor in the induction of the ADH1 promoter by low oxygen. PMID:9611167

  15. T-shaped trichome-specific expression of monoterpene synthase ADH2 using promoter-β-GUS fusion in transgenic Artemisia annua L.

    PubMed

    Fu, Xueqing; Shi, Pu; Shen, Qian; Jiang, Weimin; Tang, Yueli; Lv, Zongyou; Yan, Tingxiang; Li, Ling; Wang, Guofeng; Sun, Xiaofen; Tang, Kexuan

    2016-11-01

    Artemisinin, a sesquiterpene lactone isolated from Artemisia annua L. (sweet wormwood), is extensively used in the treatment of malaria. In order to better understand the metabolism of terpenes in A. annua and the influence of terpene synthases on artemisinin yield, the expression pattern of a monoterpene alcohol dehydrogenase (ADH2) has been studied using transgenic plants expressing promoter-β-glucuronidase (GUS) fusion. ADH2 played a major role in monoterpenoid biosynthesis including carveol, borneol, and artemisia ketone through in vitro biochemical analysis. In this study, the ADH2 promoter was cloned by the genome walking method. A number of putative cis-acting elements were predicted in promoter region, suggesting that the ADH2 is driven by a complex regulation mechanism. ADH2 gene was highly expressed in old leaves, whereas the artemisinin biosynthetic genes were mainly expressed in bud and young leaves. The expression of ADH2 gene increased quickly during leaf development, revealed by qRT-PCR. GUS expression analysis in different tissues of transgenic A. annua demonstrates that ADH2 expression is exclusively located to T-shaped trichome, not glandular secretory trichome.

  16. Protective effects of the alcohol dehydrogenase-ADH1B*3 allele on attention and behavior problems in adolescents exposed to alcohol during pregnancy.

    PubMed

    Dodge, Neil C; Jacobson, Joseph L; Jacobson, Sandra W

    2014-01-01

    Alcohol dehydrogenase is a critical enzyme in the metabolism of alcohol. Expression of three alleles at the ADH1B locus results in enzymes that differ in turnover rate and affinity for alcohol. The ADH1B*3 allele, which appears to be unique to individuals of African descent, is associated with more rapid alcohol metabolism than the more prevalent ADH1B*1 allele. It has been previously demonstrated that the presence of at least one maternal ADH1B*3 allele confers a protective effect against alcohol teratogenicity in infants and children. This study was conducted to determine whether the presence of the ADH1B*3 allele in the mother or child continues to be protective in alcohol-exposed individuals during adolescence. 186 adolescents and 167 mothers participating in a 14-year follow-up of the Detroit Longitudinal Cohort were genotyped for ADH1B alleles. Behavioral reports were obtained from classroom teachers. Frequencies of the ADH1B*3 allele were 17.6% in the mothers and 21.0% in the adolescents, which are consistent with the 15-20% expected for African Americans. Prenatal alcohol exposure was associated with increased attention problems and externalizing behaviors in adolescents born to mothers with two ADH1B*1 alleles but not in those whose mothers had at least one ADH1B*3 allele. A similar pattern was seen in relation to the presence or absence of an ADH1B*3 allele in the adolescent, which may have reflected the presence/absence of the maternal variant. This study is the first to demonstrate that the protective effects of the maternal ADH1B*3 allele continue to be evident during adolescence. These persistent individual differences in vulnerability of offspring to the behavioral effects of fetal alcohol exposure are likely attributable to more rapid metabolism of alcohol that the ADH1B*3 variant confers on the mother, leading to a reduction of the peak blood alcohol concentration to which the fetus is exposed during each drinking episode.

  17. Increased Ribozyme Activity in Crowded Solutions*

    PubMed Central

    Desai, Ravi; Kilburn, Duncan; Lee, Hui-Ting; Woodson, Sarah A.

    2014-01-01

    Noncoding RNAs must function in the crowded environment of the cell. Previous small-angle x-ray scattering experiments showed that molecular crowders stabilize the structure of the Azoarcus group I ribozyme, allowing the ribozyme to fold at low physiological Mg2+ concentrations. Here, we used an RNA cleavage assay to show that the PEG and Ficoll crowder molecules increased the biochemical activity of the ribozyme, whereas sucrose did not. Crowding lowered the Mg2+ threshold at which activity was detected and increased total RNA cleavage at high Mg2+ concentrations sufficient to fold the RNA in crowded or dilute solution. After correcting for solution viscosity, the observed reaction rate was proportional to the fraction of active ribozyme. We conclude that molecular crowders stabilize the native ribozyme and favor the active structure relative to compact inactive folding intermediates. PMID:24337582

  18. Enantiomeric recognition of racemic 4-aryl-1,4-dihydropyridine derivatives via chiralpak AD-H stationary phases.

    PubMed

    Dai, Zhi; Pittman, Charles U; Li, Tingyu

    2012-10-01

    The chromatographic chiral resolution of two new series of racemic 4-substituted-1,4-dihydropyridine derivatives was studied on a commercial Chiralpak AD-H column. Analytes without 5,5-dimethyl substituents (1-15) are more efficiently resolved than analytes with 5,5-dimethyl groups (16-30). The AD-H column discriminated between enantiomers through both hydrogen bonding attractions and π-π interactions. This interpretation is in accord with plots of the logarithm of separation factors, log(α), versus σ (Hammett-Swain substituent parameter) and σ(+) (Brown substituent constant) plots. By elucidating the effects of the remote substituents on these chiral separations, it was shown that the influence of π-π interaction forces increase when steric bulk effects act to decrease the hydrogen bonding attractive forces on the AD-H column.

  19. Sequence variation of alcohol dehydrogenase (Adh) paralogs in cactophilic Drosophila.

    PubMed Central

    Matzkin, Luciano M; Eanes, Walter F

    2003-01-01

    This study focuses on the population genetics of alcohol dehydrogenase (Adh) in cactophilic Drosophila. Drosophila mojavensis and D. arizonae utilize cactus hosts, and each host contains a characteristic mixture of alcohol compounds. In these Drosophila species there are two functional Adh loci, an adult form (Adh-2) and a larval and ovarian form (Adh-1). Overall, the greater level of variation segregating in D. arizonae than in D. mojavensis suggests a larger population size for D. arizonae. There are markedly different patterns of variation between the paralogs across both species. A 16-bp intron haplotype segregates in both species at Adh-2, apparently the product of an ancient gene conversion event between the paralogs, which suggests that there is selection for the maintenance of the intron structure possibly for the maintenance of pre-mRNA structure. We observe a pattern of variation consistent with adaptive protein evolution in the D. mojavensis lineage at Adh-1, suggesting that the cactus host shift that occurred in the divergence of D. mojavensis from D. arizonae had an effect on the evolution of the larval expressed paralog. Contrary to previous work we estimate a recent time for both the divergence of D. mojavensis and D. arizonae (2.4 +/- 0.7 MY) and the age of the gene duplication (3.95 +/- 0.45 MY). PMID:12586706

  20. Prospective Multicenter Phase II Trial of Systemic ADH-1 in Combination With Melphalan via Isolated Limb Infusion in Patients With Advanced Extremity Melanoma

    PubMed Central

    Beasley, Georgia M.; Riboh, Jonathan C.; Augustine, Christina K.; Zager, Jonathan S.; Hochwald, Steven N.; Grobmyer, Stephen R.; Peterson, Bercedis; Royal, Richard; Ross, Merrick I.; Tyler, Douglas S.

    2011-01-01

    Purpose Isolated limb infusion (ILI) with melphalan (M-ILI) dosing corrected for ideal body weight (IBW) is a well-tolerated treatment for patients with in-transit melanoma with a 29% complete response rate. ADH-1 is a cyclic pentapeptide that disrupts N-cadherin adhesion complexes. In a preclinical animal model, systemic ADH-1 given with regional melphalan demonstrated synergistic antitumor activity, and in a phase I trial with M-ILI it had minimal toxicity. Patients and Methods Patients with American Joint Committee on Cancer (AJCC) stage IIIB or IIIC extremity melanoma were treated with 4,000 mg of ADH-1, administered systemically on days 1 and 8, and with M-ILI corrected for IBW on day 1. Drug pharmacokinetics and N-cadherin immunohistochemical staining were performed on pretreatment tumor. The primary end point was response at 12 weeks determined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Results In all, 45 patients were enrolled over 15 months at four institutions. In-field responses included 17 patients with complete responses (CRs; 38%), 10 with partial responses (22%), six with stable disease (13%), eight with progressive disease (18%), and four (9%) who were not evaluable. Median duration of in-field response among the 17 CRs was 5 months, and median time to in-field progression among 41 evaluable patients was 4.6 months (95% CI, 4.0 to 7.1 months). N-cadherin was detected in 20 (69%) of 29 tumor samples. Grade 4 toxicities included creatinine phosphokinase increase (four patients), arterial injury (one), neutropenia (one), and pneumonitis (one). Conclusion To the best of our knowledge, this phase II trial is the first prospective multicenter ILI trial and the first to incorporate a targeted agent in an attempt to augment antitumor responses to regional chemotherapy. Although targeting N-cadherin may improve melanoma sensitivity to chemotherapy, no difference in response to treatment was seen in this study. PMID:21343562

  1. Isolation and DNA sequence of ADH3, a nuclear gene encoding the mitochondrial isozyme of alcohol dehydrogenase in Saccharomyces cerevisiae.

    PubMed Central

    Young, E T; Pilgrim, D

    1985-01-01

    The Saccharomyces cerevisiae nuclear gene, ADH3, that encodes the mitochondrial alcohol dehydrogenase isozyme ADH III was cloned by virtue of its nucleotide homology to ADH1 and ADH2. Both chromosomal and plasmid-encoded ADH III isozymes were repressed by glucose and migrated heterogeneously on nondenaturing gels. Nucleotide sequence analysis indicated 73 and 74% identity for ADH3 with ADH1 and ADH2, respectively. The amino acid identity between the predicted ADH III polypeptide and ADH I and ADH II was 79 and 80%, respectively. The open reading frame encoding ADH III has a highly basic 27-amino-acid amino-terminal extension relative to ADH I and ADH II. The nucleotide sequence of the presumed leader peptide has a high degree of identity with the untranslated leader regions of ADH1 and ADH2 mRNAs. A strain containing a null allele of ADH3 did not have a detectably altered phenotype. The cloned gene integrated at the ADH3 locus, indicating that this is the structural gene for ADH III. Images PMID:2943982

  2. Differential interactions of promoter elements in stress responses of the Arabidopsis Adh gene.

    PubMed Central

    Dolferus, R; Jacobs, M; Peacock, W J; Dennis, E S

    1994-01-01

    The Adh (alcohol dehydrogenase, EC 1.1.1.1.) gene from Arabidopsis thaliana (L.) Heynh. can be induced by dehydration and cold, as well as by hypoxia. A 1-kb promoter fragment (CADH: -964 to +53) is sufficient to confer the stress induction and tissue-specific developmental expression characteristics of the Adh gene to a beta-glucuronidase reporter gene. Deletion mapping of the 5' end and site-specific mutagenesis identified four regions of the promoter essential for expression under the three stress conditions. Some sequence elements are important for response to all three stress treatments, whereas others are stress specific. The most critical region essential for expression of the Arabidopsis Adh promoter under all three environmental stresses (region IV: -172 to -141) contains sequences homologous to the GT motif (-160 to -152) and the GC motif (-147 to -144) of the maize Adh1 anaerobic responsive element. Region III (-235 to -172) contains two regions shown by R.J. Ferl and B.H. Laughner ([1989] Plant Mol Biol 12: 357-366) to bind regulatory proteins; mutation of the G-box-1 region (5'-CCACGTGG-3', -216 to -209) does not affect expression under uninduced or hypoxic conditions, but significantly reduces induction by cold stress and, to a lesser extent, by dehydration stress. Mutation of the other G-box-like sequence (G-box-2: 5'-CCAAGTGG-3', -193 to -182) does not change hypoxic response and affects cold and dehydration stress only slightly. G-box-2 mutations also promote high levels of expression under uninduced conditions. Deletion of region I (-964 to -510) results in increased expression under uninduced and all stress conditions, suggesting that this region contains a repressor binding site. Region II (-510 to -384) contains a positive regulatory element and is necessary for high expression levels under all treatments. PMID:7972489

  3. Genetic polymorphisms of ADH1B, ADH1C and ALDH2 in Turkish alcoholics: lack of association with alcoholism and alcoholic cirrhosis.

    PubMed

    Vatansever, Sezgin; Tekin, Fatih; Salman, Esin; Altintoprak, Ender; Coskunol, Hakan; Akarca, Ulus Salih

    2015-05-17

    No data exists regarding the alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) gene polymorphisms in Turkish alcoholic cirrhotics. We studied the polymorphisms of ADH1B, ADH1C and ALDH2 genes in alcoholic cirrhotics and compared the results with non-cirrhotic alcoholics and healthy volunteers. Overall, 237 subjects were included for the study: 156 alcoholic patients (78 cirrhotics, 78 non-cirrhotic alcoholics) and 81 healthy volunteers. Three different single-nucleotide-polymorphism genotyping methods were used. ADH1C genotyping was performed using a polymerase chain reaction-restriction fragment length polymorphism method. The identified ADH1C genotypes were named according to the presence or absence of the enzyme restriction sites. ADH1B (Arg47Hys) genotyping was performed using the allele specific primer extension method, and ALDH2 (Glu487Lys) genotyping was performed by a multiplex polymerase chain reaction using two allele-specific primer pairs. For ADH1B, the frequency of allele *1 in the cirrhotics, non-cirrhotic alcoholics and healthy volunteers was 97.4%, 94.9% and 99.4%, respectively. For ADH1C, the frequency of allele *1 in the cirrhotics, non-cirrhotic alcoholics and healthy volunteers was 47%, 36.3% and 45%, respectively. There was no statistical difference between the groups for ADH1B and ADH1C (p>0.05). All alcoholic and non-alcoholic subjects (100%) had the allele *1 for ALDH2. The obtained results for ADH1B, ADH1C, and ALDH gene polymorphisms in the present study are similar to the results of Caucasian studies. ADH1B and ADH1C genetic variations are not related to the development of alcoholism or susceptibility to alcoholic cirrhosis. ALDH2 gene has no genetic variation in the Turkish population.

  4. Crystal structure of the vertebrate NADP(H)-dependent alcohol dehydrogenase (ADH8).

    PubMed

    Rosell, Albert; Valencia, Eva; Parés, Xavier; Fita, Ignacio; Farrés, Jaume; Ochoa, Wendy F

    2003-06-27

    The amphibian enzyme ADH8, previously named class IV-like, is the only known vertebrate alcohol dehydrogenase (ADH) with specificity towards NADP(H). The three-dimensional structures of ADH8 and of the binary complex ADH8-NADP(+) have been now determined and refined to resolutions of 2.2A and 1.8A, respectively. The coenzyme and substrate specificity of ADH8, that has 50-65% sequence identity with vertebrate NAD(H)-dependent ADHs, suggest a role in aldehyde reduction probably as a retinal reductase. The large volume of the substrate-binding pocket can explain both the high catalytic efficiency of ADH8 with retinoids and the high K(m) value for ethanol. Preference of NADP(H) appears to be achieved by the presence in ADH8 of the triad Gly223-Thr224-His225 and the recruitment of conserved Lys228, which define a binding pocket for the terminal phosphate group of the cofactor. NADP(H) binds to ADH8 in an extended conformation that superimposes well with the NAD(H) molecules found in NAD(H)-dependent ADH complexes. No additional reshaping of the dinucleotide-binding site is observed which explains why NAD(H) can also be used as a cofactor by ADH8. The structural features support the classification of ADH8 as an independent ADH class.

  5. Interaction of vitamin A supplementation level with ADH1C genotype on intramuscular fat in beef steers.

    PubMed

    Krone, K G; Ward, A K; Madder, K M; Hendrick, S; McKinnon, J J; Buchanan, F C

    2016-03-01

    Previously, the single nucleotide polymorphism in alcohol dehydrogenase (ADH1C c.-64T>C) was shown to have an association with intramuscular fat (IMF) in the longissimus thoracis (LT) muscle when vitamin A was limited in finishing rations of beef steers. The purpose of this study was to determine the optimum vitamin A supplementation level, in combination with ADH1C genotype, to increase IMF of the LT muscle. In total, 45 TT genotype, 45 CT and 27 CC Black Angus crossbred steers were backgrounded on a commercial ration containing 3360 IU vitamin A/kg dry matter (DM). During finishing, the steers were randomly assigned to one of three vitamin A treatments at 25%, 50% and 75% of the National Research Council recommendation of 2200 IU/kg DM. Treatments were administered via an oral bolus. Carcass quality was evaluated and a sample from the LT muscle was collected for analysis of IMF. A treatment×genotype interaction (P=0.04) was observed for IMF; TT steers on the 75% treatment had higher IMF relative to CT and CC steers on the same treatment. Western blot analysis showed that TT steers had higher (P=0.02) ADH1C protein expression in hepatic tissue. Previously, TT steers exhibited increased IMF when fed limited vitamin A. In the current study, the lack of variation in IMF between treatments and genotypes at the lower vitamin A treatment levels was likely due to the majority of the steers grading Canada AAA (USDA Choice). However, the western blot data supports that TT steers are expected to have higher IMF deposition, due to an increased production of ADH1C. The interaction between ADH1C genotype and vitamin A supplementation level has the potential for use in marker-assisted management programs to target niche markets based on increased marbling.

  6. Enhanced H2 gas production from bagasse using adhE inactivated Klebsiella oxytoca HP1 by sequential dark-photo fermentations.

    PubMed

    Wu, Xiaobing; Li, Qianyi; Dieudonne, Mutangana; Cong, Yibo; Zhou, Juan; Long, Minnan

    2010-12-01

    Sequential dark-photo fermentations (SDPF) was used for hydrogen production from bagasse, an acetaldehyde dehydrogenase (adhE) gene inactivated Klebsiella oxytoca HP1 (DeltaadhE HP1) mutant was used to reduce the alcohol content in dark fermentation (DF) broths and to further enhance the hydrogen yield during the photo fermentation (PF) stage. Compared with that of the wild strain, the ethanol concentration in DF broths of DeltaadhE HP1 decreased 69.4%, which resulted in a hydrogen yield in the PF stage and the total hydrogen yield over the two steps increased by 54.7% and 23.5%, respectively. The culture conditions for hydrogen production from acid pretreated bagasse by SDPF were optimized as culture temperature 37.5 degrees C, initial pH 7.0, and cellulase loading 20 FPA/g in the DF stage, with initial pH 6.5, temperature 30 degrees C and photo intensity 5,000 lux in the PF stage. Under optimum conditions, by using DeltaadhE HP1 and wild type strain, the H(2) yields were 107.8+/-5.3 mL H(2)/g-bagasse, 96.2+/-4.4 mL H(2)/g-bagasse in DF and 54.3+/-2.2 mL H(2)/g-bagasse, 35.1+/-2.0 mL H(2)/g-bagasse in PF, respectively. The special hydrogen production rate (SHPR) were 5.51+/-0.34 mL H(2)/g-bagasseh, 4.95+/-0.22 mL H(2)/g-bagasseh in DF and 0.93+/-0.12 mL H(2)/g-bagasseh, 0.59+/-0.07 mL H(2)/g-bagasseh in PF, respectively. The total hydrogen yield from bagasse over two steps was 162.1+/-7.5 mL H(2)/g-bagasse by using DeltaadhE HP1, which was 50.4% higher than that from dark fermentation only. These results indicate that reducing ethanol content during dark fermentation by using an adhE inactivated strain can significantly enhance hydrogen production from bagasse in the SDPF system. This work also proved that SDPF was an effective way to improve hydrogen production from bagasse.

  7. Exercise Sandals Increase Lower Extremity Electromyographic Activity During Functional Activities

    PubMed Central

    Hirth, Christopher J.; Guskiewicz, Kevin M.

    2003-01-01

    Objective: Anecdotal evidence suggests that use of Exercise Sandals results in a number of positive clinical outcomes. However, little research has been conducted to determine their efficacy objectively. Our purposes were to determine the effect of Exercise Sandals on lower leg electromyography (EMG) during activities in the Exercise Sandals and to compare EMG associated with Exercise Sandals with traditional lower extremity rehabilitation exercises. Design and Setting: Two within-subjects, repeated-measures designs were used to identify differences in lower extremity EMG: (1) between activities with and without Exercise Sandals and (2) between Exercise Sandals activities and traditional rehabilitation activities. All data were collected in the Sports Medicine Research Laboratory. Subjects: Eighteen subjects involved in rehabilitation using Exercise Sandals for at least 2 weeks within the year before data collection. Measurements: Mean EMG amplitudes from the tibialis anterior, peroneus longus, soleus, and lateral gastrocnemius muscles were measured during single-leg stance, side stepping, and “high knees,” all performed with and without the Exercise Sandals, as well as single-leg stance on a foam surface and T-band kicks in the sagittal and frontal planes. Results: Exercise Sandals increased lower leg EMG activity, particularly in the ankle invertors and evertors. Also, activities involving the Exercise Sandals resulted in EMG activity similar to or exceeding that associated with traditional ankle-rehabilitation exercises. Conclusions: These results, coupled with the fact that Exercise Sandals are used in a functional closed kinetic chain manner, suggest that they are an effective means of increasing lower extremity muscle activity. PMID:14608427

  8. School Programs to Increase Physical Activity

    ERIC Educational Resources Information Center

    Lee, Amelia; Solmon, Melinda

    2007-01-01

    A quality physical education program is at the heart of any plan to promote lifelong participation in physical activity, but it has become evident at many schools that physical education specialists alone cannot address the physical activity needs of children. This is why a series of studies were conducted to develop strategies for the…

  9. Genetic variants in or near ADH1B and ADH1C affect susceptibility to alcohol dependence in a British and Irish population.

    PubMed

    Way, Michael; McQuillin, Andrew; Saini, Jit; Ruparelia, Kush; Lydall, Gregory J; Guerrini, Irene; Ball, David; Smith, Iain; Quadri, Giorgia; Thomson, Allan D; Kasiakogia-Worlley, Katherine; Cherian, Raquin; Gunwardena, Priyanthi; Rao, Harish; Kottalgi, Girija; Patel, Shamir; Hillman, Audrey; Douglas, Ewen; Qureshi, Sherhzad Y; Reynolds, Gerry; Jauhar, Sameer; O'Kane, Aideen; Dedman, Alex; Sharp, Sally; Kandaswamy, Radhika; Dar, Karim; Curtis, David; Morgan, Marsha Y; Gurling, Hugh M D

    2015-05-01

    Certain single nucleotide polymorphisms (SNPs) in genes encoding alcohol dehydrogenase (ADH) enzymes confer a significant protective effect against alcohol dependence syndrome (ADS) in East Asian populations. Recently, attention has focused on the role of these SNPs in determining ADS risk in European populations. To further elucidate these associations, SNPs of interest in ADH1B, ADH1C and the ADH1B/1C intergenic region were genotyped in a British and Irish population (ADS cases n = 1076: controls n = 1027) to assess their relative contribution to ADS risk. A highly significant, protective association was observed between the minor allele of rs1229984 in ADH1B and ADS risk [allelic P = 8.4 × 10(-6) , odds ratio (OR) = 0.26, 95 percent confidence interval, 0.14, 0.49]. Significant associations were also observed between ADS risk and the ADH1B/1C intergenic variant, rs1789891 [allelic P = 7.2 × 10(-5) , OR = 1.4 (1.2, 1.6)] and three non-synonymous SNPs rs698, rs1693482 and rs283413 in ADH1C. However, these associations were not completely independent; thus, while the ADH1B rs1229984 minor allele association was independent of those of the intergenic variant rs1789891 and the three ADH1C variants, the three ADH1C variants were not individually independent. In conclusion, the rare ADH1B rs1229984 mutation provides significant protection against ADS in this British and Irish population; other variants in the ADH gene cluster also alter ADS risk, although the strong linkage disequilibrium between SNPs at this location precluded clear identification of the variant(s) driving the associations.

  10. Ethylene-responsive transcription factors interact with promoters of ADH and PDC involved in persimmon (Diospyros kaki) fruit de-astringency.

    PubMed

    Min, Ting; Yin, Xue-ren; Shi, Yan-na; Luo, Zheng-rong; Yao, Yun-cong; Grierson, Donald; Ferguson, Ian B; Chen, Kun-song

    2012-11-01

    The persimmon fruit is a particularly good model for studying fruit response to hypoxia, in particular, the hypoxia-response ERF (HRE) genes. An anaerobic environment reduces fruit astringency by converting soluble condensed tannins (SCTs) into an insoluble form. Although the physiology of de-astringency has been widely studied, its molecular control is poorly understood. Both CO(2) and ethylene treatments efficiently removed the astringency from 'Mopan' persimmon fruit, as indicated by a decrease in SCTs. Acetaldehyde, the putative agent for causing de-astringency, accumulated during these treatments, as did activities of the key enzymes of acetaldehyde synthesis, alcohol dehydrogenase (ADH), and pyruvate decarboxylase (PDC). Eight DkADH and DkPDC genes were isolated, and three candidates for a role in de-astringency, DkADH1, DkPDC1, and DkPDC2, were characterized by transcriptional analysis in different tissues. The significance of these specific isoforms was confirmed by principal component analysis. Transient expression in leaf tissue showed that DkPDC2 decreased SCTs. Interactions of six hypoxia-responsive ERF genes and target promoters were tested in transient assays. The results indicated that two hypoxia-responsive ERF genes, DkERF9 and DkERF10, were involved in separately regulating the DkPDC2 and DkADH1 promoters. It is proposed that a DkERF-DkADH/DkPDC cascade is involved in regulating persimmon de-astringency.

  11. Increased ABCA1 activity protects against atherosclerosis.

    PubMed

    Singaraja, Roshni R; Fievet, Catherine; Castro, Graciela; James, Erick R; Hennuyer, Nathalie; Clee, Susanne M; Bissada, Nagat; Choy, Jonathan C; Fruchart, Jean-Charles; McManus, Bruce M; Staels, Bart; Hayden, Michael R

    2002-07-01

    The ABC transporter ABCA1 plays a key role in the first steps of the reverse cholesterol transport pathway by mediating lipid efflux from macrophages. Previously, it was demonstrated that human ABCA1 overexpression in vivo in transgenic mice results in a mild elevation of plasma HDL levels and increased efflux of cholesterol from macrophages. In this study, we determined the effect of overexpression of ABCA1 on atherosclerosis development. Human ABCA1 transgenic mice (BAC(+)) were crossed with ApoE(-/-) mice, a strain that spontaneously develop atherosclerotic lesions. BAC(+)ApoE(-/-) mice developed dramatically smaller, less-complex lesions as compared with their ApoE(-/-) counterparts. In addition, there was increased efflux of cholesterol from macrophages isolated from the BAC(+)ApoE(-/-) mice. Although the increase in plasma HDL cholesterol levels was small, HDL particles from BAC(+)ApoE(-/-) mice were significantly better acceptors of cholesterol. Lipid analysis of HDL particles from BAC(+)ApoE(-/-) mice revealed an increase in phospholipid levels, which was correlated significantly with their ability to enhance cholesterol efflux.

  12. A new regulatory element mediates ethanol repression of KlADH3, a Kluyveromyces lactis gene coding for a mitochondrial alcohol dehydrogenase.

    PubMed

    Saliola, Michele; Getuli, Claudia; Mazzoni, Cristina; Fantozzi, Ivana; Falcone, Claudio

    2007-08-01

    KlADH3 is a Kluyveromyces lactis alcohol dehydrogenase gene induced in the presence of all respiratory carbon sources except ethanol, which specifically represses this gene. Deletion analysis of the KlADH3 promoter revealed the presence of both positive and negative elements. However, by site-directed mutagenesis and gel retardation experiments, we identified a 15-bp element responsible for the transcriptional repression of this gene by ethanol. In particular, this element showed putative sites required for the sequential binding of ethanol-induced factors responsible for the repressed conditions, and the binding of additional factors relieved repression. In addition, we showed that the ethanol element was required for in vivo repression of KlAdh3 activity.

  13. Characterization of the Saccharomyces cerevisiae YMR318C (ADH6) gene product as a broad specificity NADPH-dependent alcohol dehydrogenase: relevance in aldehyde reduction.

    PubMed Central

    Larroy, Carol; Fernández, M Rosario; González, Eva; Parés, Xavier; Biosca, Josep A

    2002-01-01

    YMR318C represents an open reading frame from Saccharomyces cerevisiae with unknown function. It possesses a conserved sequence motif, the zinc-containing alcohol dehydrogenase (ADH) signature, specific to the medium-chain zinc-containing ADHs. In the present study, the YMR318C gene product has been purified to homogeneity from overexpressing yeast cells, and found to be a homodimeric ADH, composed of 40 kDa subunits and with a pI of 5.0-5.4. The enzyme was strictly specific for NADPH and was active with a wide variety of substrates, including aliphatic (linear and branched-chain) and aromatic primary alcohols and aldehydes. Aldehydes were processed with a 50-fold higher catalytic efficiency than that for the corresponding alcohols. The highest k(cat)/K(m) values were found with pentanal>veratraldehyde > hexanal > 3-methylbutanal >cinnamaldehyde. Taking into consideration the substrate specificity and sequence characteristics of the YMR318C gene product, we have proposed this gene to be called ADH6. The disruption of ADH6 was not lethal for the yeast under laboratory conditions. Although S. cerevisiae is considered a non lignin-degrading organism, the catalytic activity of ADHVI can direct veratraldehyde and anisaldehyde, arising from the oxidation of lignocellulose by fungal lignin peroxidases, to the lignin biodegradation pathway. ADHVI is the only S. cerevisiae enzyme able to significantly reduce veratraldehyde in vivo, and its overexpression allowed yeast to grow under toxic concentrations of this aldehyde. The enzyme may also be involved in the synthesis of fusel alcohols. To our knowledge this is the first NADPH-dependent medium-chain ADH to be characterized in S. cerevisiae. PMID:11742541

  14. Spaceflight exposure effects on transcription, activity, and localization of alcohol dehydrogenase in the roots of Arabidopsis thaliana

    NASA Technical Reports Server (NTRS)

    Porterfield, D. M.; Matthews, S. W.; Daugherty, C. J.; Musgrave, M. E.

    1997-01-01

    Although considerable research and speculation have been directed toward understanding a plant's perception of gravity and the resulting gravitropic responses, little is known about the role of gravity-dependent physical processes in normal physiological function. These studies were conducted to determine whether the roots of plants exposed to spaceflight conditions may be experiencing hypoxia. Arabidopsis thaliana (L.) Heynh. plants were grown in agar medium during 6 or 11 d of spaceflight exposure on shuttle missions STS-54 (CHROMEX-03) and STS-68 (CHROMEX-05), respectively. The analysis included measurement of agar redox potential and root alcohol dehydrogenase (ADH) activity, localization, and expression. ADH activity increased by 89% as a result of spaceflight exposure for both CHROMEX-03 and -05 experiments, and ADH RNase protection assays revealed a 136% increase in ADH mRNA. The increase in ADH activity associated with the spaceflight roots was realized by a 28% decrease in oxygen availability in a ground-based study; however, no reduction in redox potential was observed in measurements of the spaceflight bulk agar. Spaceflight exposure appears to effect a hypoxic response in the roots of agar-grown plants that may be caused by changes in gravity-mediated fluid and/or gas behavior.

  15. Spaceflight exposure effects on transcription, activity, and localization of alcohol dehydrogenase in the roots of Arabidopsis thaliana.

    PubMed Central

    Porterfield, D M; Matthews, S W; Daugherty, C J; Musgrave, M E

    1997-01-01

    Although considerable research and speculation have been directed toward understanding a plant's perception of gravity and the resulting gravitropic responses, little is known about the role of gravity-dependent physical processes in normal physiological function. These studies were conducted to determine whether the roots of plants exposed to spaceflight conditions may be experiencing hypoxia. Arabidopsis thaliana (L.) Heynh. plants were grown in agar medium during 6 or 11 d of spaceflight exposure on shuttle missions STS-54 (CHROMEX-03) and STS-68 (CHROMEX-05), respectively. The analysis included measurement of agar redox potential and root alcohol dehydrogenase (ADH) activity, localization, and expression. ADH activity increased by 89% as a result of spaceflight exposure for both CHROMEX-03 and -05 experiments, and ADH RNase protection assays revealed a 136% increase in ADH mRNA. The increase in ADH activity associated with the spaceflight roots was realized by a 28% decrease in oxygen availability in a ground-based study; however, no reduction in redox potential was observed in measurements of the spaceflight bulk agar. Spaceflight exposure appears to effect a hypoxic response in the roots of agar-grown plants that may be caused by changes in gravity-mediated fluid and/or gas behavior. PMID:9085569

  16. Purification of acetaldehyde dehydrogenase and alcohol dehydrogenases from Thermoanaerobacter ethanolicus 39E and characterization of the secondary-alcohol dehydrogenase (2 degrees Adh) as a bifunctional alcohol dehydrogenase--acetyl-CoA reductive thioesterase.

    PubMed

    Burdette, D; Zeikus, J G

    1994-08-15

    The purification and characterization of three enzymes involved in ethanol formation from acetyl-CoA in Thermoanaerobacter ethanolicus 39E (formerly Clostridium thermohydrosulfuricum 39E) is described. The secondary-alcohol dehydrogenase (2 degrees Adh) was determined to be a homotetramer of 40 kDa subunits (SDS/PAGE) with a molecular mass of 160 kDa. The 2 degrees Adh had a lower catalytic efficiency for the oxidation of 1 degree alcohols, including ethanol, than for the oxidation of secondary (2 degrees) alcohols or the reduction of ketones or aldehydes. This enzyme possesses a significant acetyl-CoA reductive thioesterase activity as determined by NADPH oxidation, thiol formation and ethanol production. The primary-alcohol dehydrogenase (1 degree Adh) was determined to be a homotetramer of 41.5 kDa (SDS/PAGE) subunits with a molecular mass of 170 kDa. The 1 degree Adh used both NAD(H) and NADP(H) and displayed higher catalytic efficiencies for NADP(+)-dependent ethanol oxidation and NADH-dependent acetaldehyde (identical to ethanal) reduction than for NADPH-dependent acetaldehyde reduction or NAD(+)-dependent ethanol oxidation. The NAD(H)-linked acetaldehyde dehydrogenase was a homotetramer (360 kDa) of identical subunits (100 kDa) that readily catalysed thioester cleavage and condensation. The 1 degree Adh was expressed at 5-20% of the level of the 2 degrees Adh throughout the growth cycle on glucose. The results suggest that the 2 degrees Adh primarily functions in ethanol production from acetyl-CoA and acetaldehyde, whereas the 1 degree Adh functions in ethanol consumption for nicotinamide-cofactor recycling.

  17. Purification of acetaldehyde dehydrogenase and alcohol dehydrogenases from Thermoanaerobacter ethanolicus 39E and characterization of the secondary-alcohol dehydrogenase (2 degrees Adh) as a bifunctional alcohol dehydrogenase--acetyl-CoA reductive thioesterase.

    PubMed Central

    Burdette, D; Zeikus, J G

    1994-01-01

    The purification and characterization of three enzymes involved in ethanol formation from acetyl-CoA in Thermoanaerobacter ethanolicus 39E (formerly Clostridium thermohydrosulfuricum 39E) is described. The secondary-alcohol dehydrogenase (2 degrees Adh) was determined to be a homotetramer of 40 kDa subunits (SDS/PAGE) with a molecular mass of 160 kDa. The 2 degrees Adh had a lower catalytic efficiency for the oxidation of 1 degree alcohols, including ethanol, than for the oxidation of secondary (2 degrees) alcohols or the reduction of ketones or aldehydes. This enzyme possesses a significant acetyl-CoA reductive thioesterase activity as determined by NADPH oxidation, thiol formation and ethanol production. The primary-alcohol dehydrogenase (1 degree Adh) was determined to be a homotetramer of 41.5 kDa (SDS/PAGE) subunits with a molecular mass of 170 kDa. The 1 degree Adh used both NAD(H) and NADP(H) and displayed higher catalytic efficiencies for NADP(+)-dependent ethanol oxidation and NADH-dependent acetaldehyde (identical to ethanal) reduction than for NADPH-dependent acetaldehyde reduction or NAD(+)-dependent ethanol oxidation. The NAD(H)-linked acetaldehyde dehydrogenase was a homotetramer (360 kDa) of identical subunits (100 kDa) that readily catalysed thioester cleavage and condensation. The 1 degree Adh was expressed at 5-20% of the level of the 2 degrees Adh throughout the growth cycle on glucose. The results suggest that the 2 degrees Adh primarily functions in ethanol production from acetyl-CoA and acetaldehyde, whereas the 1 degree Adh functions in ethanol consumption for nicotinamide-cofactor recycling. Images Figure 1 PMID:8068002

  18. Genetic and Cytogenetic Analysis of the ADH Region in DROSOPHILA MELANOGASTER

    PubMed Central

    O'Donnell, Janis; Mandel, Howard C.; Krauss, Marc; Sofer, William

    1977-01-01

    Eighteen Adh-negative mutations were selected with 1-pentyn-3-ol after feeding of formaldehyde. Twelve of the 18 were shown by cytological and genetic analysis to be deletions. Cytological examination of the deletions allowed us to localize the Adh gene to a region including bands 35B3–5 on the left arm of chromosome 2. The deletions were also used to order known visible loci located near Adh.—The vital loci near Adh were also investigated. A total of 109 lethal mutations were generated with EMS and 33 of these, localized within a region defined by the overlap of two of the deletions, were found to belong to 13 complementation groups. If one includes three other loci known to belong there (el, Adh and Sco), a total of 16 complementation groups have been identified in the region close to Adh. PMID:408228

  19. How Active Are Your Students? Increasing Physical Activity in Schools

    ERIC Educational Resources Information Center

    Avery, Marybell; Brandt, Janet

    2010-01-01

    The U. S. Department of Health and Human Services recommends that youth engage in at least 60 minutes of physical activity each day, most of which should be either moderate- or vigorous-intensity aerobic physical activity. Half of this amount (30 minutes) should be achieved during the school day. NASPE provides guidance in the form of a…

  20. A genetic analysis of Adh1 regulation. Progress report, June 1991--February 1992

    SciTech Connect

    Freeling, M.

    1992-03-01

    The overall goal of our research proposal is to understand the meaning of the various cis-acting sites responsible for AdH1 expression in the entire maize plant. Progress is reported in the following areas: Studies on the TATA box and analysis of revertants of the Adh1-3F1124 allele; screening for more different mutants that affect Adh1 expression differentially; studies on cis-acting sequences required for root-specific Adh1 expression; refinement of the use of the particle gun; and functional analysis of a non- glycolytic anaerobic protein.

  1. ADH and ALDH polymorphisms among Alaska Natives entering treatment for alcoholism.

    PubMed

    Segal, B

    1999-01-01

    The alcohol dehydrogenase (ADHs) and aldehyde dehydrogenases (ALDHs) involved in alcohol metabolism are polymorphic. Different alleles encode subunits of the enzymes that are related to differences in alcohol metabolism with different ethnic groups. This study examined the allele frequencies at the ADH1, ADH2, ADH3 and ALDH2 loci in Alaska Natives entering treatment for alcoholism to determine if allele frequencies at these loci differ among five distinct Alaska Native groups: Yupik and Inupiat Eskimos, Athabascan, Tlingit and Aleut. It was found that all persons were homozygous for the ADH1*1, ADH2*1 and ALDH2*1 alleles. Variations, however, were found for the allele distribution of the ADH3 genotype. Comparison with a general population sample found no differences in allele distributions for ADHs and ALDH2*1, but differences were found when comparisons were made with four Asian Groups. The study's findings suggest that the Alaska Natives are not protected from the risk of alcoholism in the same way that Asians who possess the ALDH2*2 genotype are considered to have a negative risk factor. Nor, does there appear to be any generalized differences between Alaska Native alcoholics and members of the general population with respect to the ALDH and ADH polymorphisms studied herein.

  2. Structure, Expression, Chromosomal Location and Product of the Gene Encoding Adh2 in Petunia

    PubMed Central

    Gregerson, R. G.; Cameron, L.; McLean, M.; Dennis, P.; Strommer, J.

    1993-01-01

    In most higher plants the genes encoding alcohol dehydrogenase comprise a small gene family, usually with two members. The Adh1 gene of Petunia has been cloned and analyzed, but a second identifiable gene was not recovered from any of three genomic libraries. We have therefore employed the polymerase chain reaction to obtain the major portion of a second Adh gene. From sequence, mapping and northern data we conclude this gene encodes ADH2, the major anaerobically inducible Adh gene of Petunia. The availability of both Adh1 and Adh2 from Petunia has permitted us to compare their structures and patterns of expression to those of the well-studied Adh genes of maize, of which one is highly expressed developmentally, while both are induced in response to hypoxia. Despite their evolutionary distance, evidenced by deduced amino acid sequence as well as taxonomic classification, the pairs of genes are regulated in strikingly similar ways in maize and Petunia. Our findings suggest a significant biological basis for the regulatory strategy employed by these distant species for differential expression of multiple Adh genes. PMID:8096485

  3. Metabolic process engineering of Clostridium tyrobutyricum Δack-adhE2 for enhanced n-butanol production from glucose: effects of methyl viologen on NADH availability, flux distribution, and fermentation kinetics.

    PubMed

    Du, Yinming; Jiang, Wenyan; Yu, Mingrui; Tang, I-Ching; Yang, Shang-Tian

    2015-04-01

    Butanol biosynthesis through aldehyde/alcohol dehydrogenase (adhE2) is usually limited by NADH availability, resulting in low butanol titer, yield, and productivity. To alleviate this limitation and improve n-butanol production by Clostridium tyrobutyricum Δack-adhE2 overexpressing adhE2, the NADH availability was increased by using methyl viologen (MV) as an artificial electron carrier to divert electrons from ferredoxin normally used for H2 production. In the batch fermentation with the addition of 500 μM MV, H2 , acetate, and butyrate production was reduced by more than 80-90%, while butanol production increased more than 40% to 14.5 g/L. Metabolic flux analysis revealed that butanol production increased in the fermentation with MV because of increased NADH availability as a result of reduced H2 production. Furthermore, continuous butanol production of ∼55 g/L with a high yield of ∼0.33 g/g glucose and extremely low ethanol, acetate, and butyrate production was obtained in fed-batch fermentation with gas stripping for in situ butanol recovery. This study demonstrated a stable and reliable process for high-yield and high-titer n-butanol production by metabolically engineered C. tyrobutyricum by applying MV as an electron carrier to increase butanol biosynthesis.

  4. The interplay between alcohol consumption, oral hygiene, ALDH2 and ADH1B in the risk of head and neck cancer.

    PubMed

    Tsai, Sen-Tien; Wong, Tung-Yiu; Ou, Chun-Yen; Fang, Sheen-Yie; Chen, Ken-Chung; Hsiao, Jenn-Ren; Huang, Cheng-Chih; Lee, Wei-Ting; Lo, Hung-I; Huang, Jehn-Shyun; Wu, Jiunn-Liang; Yen, Chia-Jui; Hsueh, Wei-Ting; Wu, Yuan-Hua; Yang, Ming-Wei; Lin, Forn-Chia; Chang, Jang-Yang; Chang, Kwang-Yu; Wu, Shang-Yin; Liao, Hsiao-Chen; Lin, Chen-Lin; Wang, Yi-Hui; Weng, Ya-Ling; Yang, Han-Chien; Chang, Jeffrey S

    2014-11-15

    Alcohol consumption is an established risk factor for head and neck cancer (HNC). The major carcinogen from alcohol is acetaldehyde, which may be produced by humans or by oral microorganisms through the metabolism of ethanol. To account for the different sources of acetaldehyde production, the current study examined the interplay between alcohol consumption, oral hygiene (as a proxy measure for the growth of oral microorganisms), and alcohol-metabolizing genes (ADH1B and ALDH2) in the risk of HNC. We found that both the fast (*2/*2) and the slow (*1/*1+ *1/*2) ADH1B genotypes increased the risk of HNC due to alcohol consumption, and this association differed according to the slow/non-functional ALDH2 genotypes (*1/*2+ *2/*2) or poor oral hygiene. In persons with the fast ADH1B genotype, the HNC risk associated with alcohol drinking was increased for those with the slow/non-functional ALDH2 genotypes. For those with the slow ADH1B genotypes, oral hygiene appeared to play an important role; the highest magnitude of an increased HNC risk in alcohol drinkers occurred among those with the worst oral hygiene. This is the first study to show that the association between alcohol drinking and HNC risk may be modified by the interplay between genetic polymorphisms of ADH1B and ALDH2 and oral hygiene. Although it is important to promote abstinence from or reduction of alcohol drinking to decrease the occurrence of HNC, improving oral hygiene practices may provide additional benefit.

  5. The Older Woman: Increased Psychosocial Benefits from Physical Activity.

    ERIC Educational Resources Information Center

    Wakat, Diane; Odom, Sarah

    1982-01-01

    Older women who participate in physical activity programs find physical benefits in the improvement of cardiovascular and musculoskeletal systems. The psychosocial benefits which result from physical activity include an increase in self-esteem, increased social contacts, a counteraction to depression, and improved stress management. Suggestions…

  6. Best Practices and Recommendations for Increasing Physical Activity in Youth

    ERIC Educational Resources Information Center

    Erwin, Heather; Beets, Michael W.; Centeio, Erin; Morrow, James R., Jr.

    2014-01-01

    Many efforts to increase the physical activity levels of Americans have been introduced and implemented over the past 20 years. National Physical Activity Guidelines have been established, and the National Physical Activity Plan (NPAP) is now in place, which includes a specific sector dedicated to education. This article addresses the Education…

  7. School-Based Health Promotion Initiative Increases Children's Physical Activity

    ERIC Educational Resources Information Center

    Cluss, Patricia; Lorigan, Devin; Kinsky, Suzanne; Nikolajski, Cara; McDermott, Anne; Bhat, Kiran B.

    2016-01-01

    Background: Childhood obesity increases health risk, and modest physical activity can impact that risk. Schools have an opportunity to help children become more active. Purpose: This study implemented a program offering extra school-day activity opportunities in a rural school district where 37% of students were obese or overweight in 2005 and…

  8. Acute and chronic ethanol exposure differentially alters alcohol dehydrogenase and aldehyde dehydrogenase activity in the zebrafish liver.

    PubMed

    Tran, Steven; Nowicki, Magda; Chatterjee, Diptendu; Gerlai, Robert

    2015-01-02

    Chronic ethanol exposure paradigms have been successfully used in the past to induce behavioral and central nervous system related changes in zebrafish. However, it is currently unknown whether chronic ethanol exposure alters ethanol metabolism in adult zebrafish. In the current study we examine the effect of acute ethanol exposure on adult zebrafish behavioral responses, as well as alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activity in the liver. We then examine how two different chronic ethanol exposure paradigms (continuous and repeated ethanol exposure) alter behavioral responses and liver enzyme activity during a subsequent acute ethanol challenge. Acute ethanol exposure increased locomotor activity in a dose-dependent manner. ADH activity was shown to exhibit an inverted U-shaped curve and ALDH activity was decreased by ethanol exposure at all doses. During the acute ethanol challenge, animals that were continuously housed in ethanol exhibited a significantly reduced locomotor response and increased ADH activity, however, ALDH activity did not change. Zebrafish that were repeatedly exposed to ethanol demonstrated a small but significant attenuation of the locomotor response during the acute ethanol challenge but ADH and ALDH activity was similar to controls. Overall, we identified two different chronic ethanol exposure paradigms that differentially alter behavioral and physiological responses in zebrafish. We speculate that these two paradigms may allow dissociation of central nervous system-related and liver enzyme-dependent ethanol induced changes in zebrafish.

  9. Technology to promote and increase physical activity in heart failure.

    PubMed

    Franklin, Nina C

    2015-01-01

    Regular physical activity is firmly recommended as part of a multifaceted approach to heart failure (HF) self-management. Unfortunately, research indicates that most patients are less likely to engage in and adhere to such activities. The widespread use of information and communication technology tools and resources offers an innovative and potentially beneficial avenue for increasing physical activity levels in HF patients. This article presents specific ways in which advances in information and communication technologies, including Internet- and mobile-based communications, social media platforms, and self-monitoring health devices, can serve as a means to broadly promote increasing levels of physical activity to improve health outcomes in the HF population.

  10. SPINK1, ADH2, and ALDH2 gene variants and alcoholic chronic pancreatitis in Japan.

    PubMed

    Shimosegawa, Tooru; Kume, Kiyoshi; Masamune, Atsushi

    2008-03-01

    The serine protease inhibitor Kazal type 1 (SPINK1) is a potent antiprotease and an important inactivation factor of intrapancreatic trypsin activity. Loss of function by the SPINK1 mutations leads to decreased inhibitory capacity. The significance of SPINK1 mutations in alcoholic chronic pancreatitis (CP) in Japan and its functional role remain unclear. The aim of the present study was to clarify the incidence of SPINK1, alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2) variants in CP patients in Japan. One hundred and 86 patients with CP, and 527 healthy volunteers were enrolled. Mutational analyses were performed by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. Serum pancreatic secretory trypsin inhibitor (PSTI) level was measured by radioimmunoassay. The frequencies of N34S and IVS3 + 2T > C in the SPINK1 gene were significantly higher in patients with non-alcoholic CP (12.9% and 8.6%, respectively) than in normal subjects (0.37% and 0%). In total, 18 of 93 (19.4%) patients with non-alcoholic CP had at least one SPINK1 mutation. Concerning alcoholic CP, we found IVS3 + 2T > C in a small number of patients (3.9%). Serum PSTI concentration was decreased in patients with the IVS3 + 2T > C mutation. The frequency of the ADH2*2 allele in the alcoholic CP group was significantly higher than that in alcoholics without pancreatitis. The frequency of the ALDH2*2 allele was significantly low in patients with alcoholic CP compared with healthy controls. In conclusion, SPINK1 mutations were associated with non-alcoholic CP. Furthermore, we revealed the amount of wild-type PSTI was decreased in patients with IVS3 + 2T > C mutation. Variants of alcohol-metabolizing enzymes appeared in the relation to alcoholic CP.

  11. Asbestos exposure increases human bronchial epithelial cell fibrinolytic activity.

    PubMed

    Gross, T J; Cobb, S M; Gruenert, D C; Peterson, M W

    1993-03-01

    Chronic exposure to asbestos fibers results in fibrotic lung disease. The distal pulmonary epithelium is an early target of asbestos-mediated injury. Local plasmin activity may be important in modulating endoluminal inflammatory responses in the lung. We studied the effects of asbestos exposure on cell-mediated plasma clot lysis as a marker of pericellular plasminogen activation. Exposing human bronchial epithelial (HBE) cells to 100 micrograms/ml of asbestos fibers for 24 h resulted in increased plasma clot lysis. Fibrinolytic activity was augmented in a dose-dependent fashion, was not due to secreted protease, and occurred only when there was direct contact between the plasma clot and the epithelial monolayer. Further analysis showed that asbestos exposure increased HBE cell-associated urokinase-type plasminogen activator (uPA) activity in a time-dependent manner. The increased cell-associated PA activity could be removed by acid washing. The increase in PA activity following asbestos exposure required new protein synthesis because it was abrogated by treatment with either cycloheximide or actinomycin D. Therefore, asbestos exposure increases epithelial-mediated fibrinolysis by augmenting expression of uPA activity at the cell surface by mechanisms that require new RNA and protein synthesis. These observations suggest a novel mechanism whereby exposure of the distal epithelium to inhaled particulates may result in a chronic inflammatory response that culminates in the development of fibrotic lung disease.

  12. Increased sternocleidomastoid, but not trapezius, muscle activity in response to increased chewing load.

    PubMed

    Häggman-Henrikson, Birgitta; Nordh, Erik; Eriksson, Per-Olof

    2013-10-01

    Previous findings, during chewing, that boluses of larger size and harder texture result in larger amplitudes of both mandibular and head-neck movements suggest a relationship between increased chewing load and incremental recruitment of jaw and neck muscles. The present report evaluated jaw (masseter and digastric) and neck [sternocleidomastoid (SCM) and trapezius] muscle activity during the chewing of test foods of different sizes and textures by 10 healthy subjects. Muscle activity was recorded by surface electromyography and simultaneous mandibular and head movements were recorded using an optoelectronic technique. Each subject performed continuous jaw-opening/jaw-closing movements whilst chewing small and large boluses of chewing gum and rubber silicone (Optosil). For jaw opening/jaw closing without a bolus, SCM activity was recorded for jaw opening concomitantly with digastric activity. During chewing, SCM activity was recorded for jaw closing concomitantly with masseter activity. Trapezius activity was present in some, but not all, cycles. For the masseter and SCM muscles, higher activity was seen with larger test foods, suggesting increased demand and recruitment of these muscles in response to an increased chewing load. This result reinforces the previous notion of a close functional connection between the jaw and the neck motor systems in jaw actions and has scientific and clinical significance for studying jaw function and dysfunction.

  13. Temporal expression of the human alcohol dehydrogenase gene family during liver development correlates with differential promoter activation by hepatocyte nuclear factor 1, CCAAT/enhancer-binding protein alpha, liver activator protein, and D-element-binding protein.

    PubMed Central

    van Ooij, C; Snyder, R C; Paeper, B W; Duester, G

    1992-01-01

    The human class I alcohol dehydrogenase (ADH) gene family consists of ADH1, ADH2, and ADH3, which are sequentially activated in early fetal, late fetal, and postnatal liver, respectively. Analysis of ADH promoters revealed differential activation by several factors previously shown to control liver transcription. In cotransfection assays, the ADH1 promoter, but not the ADH2 or ADH3 promoter, was shown to respond to hepatocyte nuclear factor 1 (HNF-1), which has previously been shown to regulate transcription in early liver development. The ADH2 promoter, but not the ADH1 or ADH3 promoter, was shown to respond to CCAAT/enhancer-binding protein alpha (C/EBP alpha), a transcription factor particularly active during late fetal liver and early postnatal liver development. The ADH1, ADH2, and ADH3 promoters all responded to the liver transcription factors liver activator protein (LAP) and D-element-binding protein (DBP), which are most active in postnatal liver. For all three promoters, the activation by LAP or DBP was higher than that seen by HNF-1 or C/EBP alpha, and a significant synergism between C/EBP alpha and LAP was noticed for the ADH2 and ADH3 promoters when both factors were simultaneously cotransfected. A hierarchy of ADH promoter responsiveness to C/EBP alpha and LAP homo- and heterodimers is suggested. In all three ADH genes, LAP bound to the same four sites previously reported for C/EBP alpha (i.e., -160, -120, -40, and -20 bp), but DBP bound strongly only to the site located at -40 bp relative to the transcriptional start. Mutational analysis of ADH2 indicated that the -40 bp element accounts for most of the promoter regulation by the bZIP factors analyzed. These studies suggest that HNF-1 and C/EBP alpha help establish ADH gene family transcription in fetal liver and that LAP and DBP help maintain high-level ADH gene family transcription in postnatal liver. Images PMID:1620113

  14. Use of a modified alcohol dehydrogenase, ADH1, promoter in construction of diacetyl non-producing brewer's yeast.

    PubMed

    Onnela, M L; Suihko, M L; Penttilä, M; Keränen, S

    1996-08-20

    The bacterial gene, encoding alpha-acetolactate decarboxylase (alpha-ALDC), was expressed in a bottom-fermenting brewer's yeast under the control of a modified Saccharomyces cerevisiae alcohol dehydrogenase (ADH1) promoter which lacks the upstream regions from -800 bp to -1500 bp. In pilot scale brewing conditions, the level of alpha-ALDC produced was high enough to reduce the concentration of diacetyl so that lagering was not required. alpha-ALDC active brewer's yeast strains were also shown to be suitable for high gravity brewing.

  15. Mechanism of pyruvate dehydrogenase activation by increased cardiac work.

    PubMed

    Kobayashi, K; Neely, J R

    1983-06-01

    The effects of increased cardiac work, pyruvate and insulin on the state of pyruvate dehydrogenase (PDH) activation and rate of pyruvate decarboxylation was studied in the isolated perfused rat heart. At low levels of cardiac work, 61% of PDH was present in the active form when glucose was the only substrate provided. The actual rate of pyruvate decarboxylation was only 5% of the available capacity calculated from the percent of active PDH. Under this condition, the rate of pyruvate decarboxylation was restricted by the slow rate of pyruvate production from glycolysis. Increasing cardiac work accelerated glycolysis, but production of pyruvate remained rate limiting for pyruvate oxidation and only 40% of the maximal active PDH capacity was used. Addition of insulin along with glucose reduced the percent of active PDH to 16% of the total at low cardiac work. This effect of insulin was associated with increased mitochondria NADH/NAD and acetyl CoA/CoA ratios. With both glucose and insulin the calculated maximum capacity of active PDH was about the same as measured rates of pyruvate oxidation indicating that pyruvate oxidation was limited by the activation state of PDH. In this case, raising the level of cardiac work increased the active PDH to 85% and although pyruvate oxidation was accelerated, measured flux through PDH was only 73% of the maximal activity of active PDH. With pyruvate as added exogenous substrate, PDH was 82% of active at low cardiac work probably due to pyruvate inhibition of PDH kinase. In this case, the measured rate of pyruvate oxidation was 64% of the capacity of active PDH. However, increased cardiac work still caused further activation of PDH to 96% active. Thus, actual rates of pyruvate oxidation in the intact tissue were determined by (1) the supply of pyruvate in hearts receiving glucose alone, (2) by the percent of active PDH in hearts receiving both glucose and insulin at low work and (3) by end-product inhibition in hearts receiving

  16. Mineral exploration, Mahd adh Dhahab District, Kingdom of Saudi Arabia

    USGS Publications Warehouse

    Worl, Ronald G.

    1978-01-01

    Mahd adh Dhahab is the largest of numerous ancient gold mines scattered through the Precambrian shield of Saudi Arabia and the only one with recent production. During the period 1939-54, 765,768 fine ounces of gold and 1,002,029 ounces of silver were produced from the mines by the Saudi Arabian Mining Syndicate. Ore minerals at Mahd adh Dhahab include free gold and silver, tellurides, sphalerite, and chalcopyrite in and associated with a system of north-trending quartz veins and quartz veinlet stockworks. Pyrite is a common sulfide gangue mineral. Country rocks are a north dipping sequence of pyroclastic and transported pyroclastic rocks of the Hulayfah Group that are locally highly silicified and potassium-feldspathized. The prime target for this exploration program was a north-trending zone of quartz veins and breccias, faults, alteration, and metalization approximately 400 m wide and 1000 m long. The ancient and recent mine workings are located in the northern part of this zone. Although the quartz veins and alteration cut all lithologies, the major metalization is confined to the intersection of veins and agglomerate. Ten holes were diamond drilled to explore geochemical, geological, and geophysical targets in the area. A significant new zone of metalization was discovered 700 m south of the ancient and recent mine workings and within the same major zone of quartz veins, alteration, and faults. Metalization in this southern mineralized zone is at the intersection of the quartz veins and a distinctive and highly altered agglomerate. The total zone of vein and agglomerate intercept is potentially metalized and comprises a block of ground 40 m thick and 400 m wide along the strike of the agglomerate and projected downdip 250 m. Tonnage of this block is 17.2 million tons. The explored zone, approximately 25 percent of the potentially metalized rock, has a potential resource of 1.1 million tons containing 27 g/t gold and 73 g/t silver.

  17. Building a better mousetrap (exergame) to increase youth physical activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    While exergames have been demonstrated to induce moderate levels of physical activity (PA) if played as designed, there is conflicting evidence on use of exergaming leading to increased habitual PA. Exergames have increased PA in some home and school studies, but not others. Exergames have been us...

  18. Identification of a G‐Protein Subunit‐α11 Gain‐of‐Function Mutation, Val340Met, in a Family With Autosomal Dominant Hypocalcemia Type 2 (ADH2)

    PubMed Central

    Piret, Sian E; Gorvin, Caroline M; Pagnamenta, Alistair T; Howles, Sarah A; Cranston, Treena; Rust, Nigel; Nesbit, M Andrew; Glaser, Ben; Taylor, Jenny C; Buchs, Andreas E; Hannan, Fadil M

    2016-01-01

    ABSTRACT Autosomal dominant hypocalcemia (ADH) is characterized by hypocalcemia, inappropriately low serum parathyroid hormone concentrations and hypercalciuria. ADH is genetically heterogeneous with ADH type 1 (ADH1), the predominant form, being caused by germline gain‐of‐function mutations of the G‐protein coupled calcium‐sensing receptor (CaSR), and ADH2 caused by germline gain‐of‐function mutations of G‐protein subunit α‐11 (Gα11). To date Gα11 mutations causing ADH2 have been reported in only five probands. We investigated a multigenerational nonconsanguineous family, from Iran, with ADH and keratoconus which are not known to be associated, for causative mutations by whole‐exome sequencing in two individuals with hypoparathyroidism, of whom one also had keratoconus, followed by cosegregation analysis of variants. This identified a novel heterozygous germline Val340Met Gα11 mutation in both individuals, and this was also present in the other two relatives with hypocalcemia that were tested. Three‐dimensional modeling revealed the Val340Met mutation to likely alter the conformation of the C‐terminal α5 helix, which may affect G‐protein coupled receptor binding and G‐protein activation. In vitro functional expression of wild‐type (Val340) and mutant (Met340) Gα11 proteins in HEK293 cells stably expressing the CaSR, demonstrated that the intracellular calcium responses following stimulation with extracellular calcium, of the mutant Met340 Gα11 led to a leftward shift of the concentration‐response curve with a significantly (p < 0.0001) reduced mean half‐maximal concentration (EC50) value of 2.44 mM (95% CI, 2.31 to 2.77 mM) when compared to the wild‐type EC50 of 3.14 mM (95% CI, 3.03 to 3.26 mM), consistent with a gain‐of‐function mutation. A novel His403Gln variant in transforming growth factor, beta‐induced (TGFBI), that may be causing keratoconus was also identified, indicating likely digenic

  19. [Increase of physical activity by improvement of the nutritional status].

    PubMed

    Torún, B

    1989-09-01

    Physical activity is affected by nutritional modifications and, in turn, influences growth, cognition, social behavior, work performance and other functions. Studies in preschool children showed that: 1. A decrease in energy intake during four to seven days reduced the time allocated to energy-demanding activities and increased sedentary activities. 2. Children with mild weight deficit were more sedentary than well-nourished counterparts. 3. Children became more active when nutritional status improved. 4. A 10% reduction in energy intake reduced total energy expenditure by 15% without affecting weight gain nor basal metabolism. Studies of men working in non-mechanized agriculture showed that: 1. Dietary improvements led to faster salaried work, reduction of napping time and greater physical activity after work. 2. An increase in energy intake increased total daily energy expenditure, tending to maintain energy balance and relatively stable body weight within the cyclic variations of the agricultural year. 3. Food supplementation did not necessarily improve productivity. Other labor incentives without dietary improvements increased energy expenditure during working hours, which resulted in weight loss. In conclusion, good health and nutrition provide the biological basis for adequate physical activity that may improve cognitive development, social interactions, economic productivity and the quality of life of an individual or a population, but other incentives are required for the optimal expression of that biologic potential.

  20. Steric vs. electronic effects in the Lactobacillus brevis ADH-catalyzed bioreduction of ketones.

    PubMed

    Rodríguez, Cristina; Borzęcka, Wioleta; Sattler, Johann H; Kroutil, Wolfgang; Lavandera, Iván; Gotor, Vicente

    2014-01-28

    Lactobacillus brevis ADH (LBADH) is an alcohol dehydrogenase that is commonly employed to reduce alkyl or aryl ketones usually bearing a methyl, an ethyl or a chloromethyl as a small ketone substituent to the corresponding (R)-alcohols. Herein we have tested a series of 24 acetophenone derivatives differing in their size and electronic properties for their reduction employing LBADH. After plotting the relative activity against the measured substrate volumes we observed that apart from the substrate size other effects must be responsible for the activity obtained. Compared to acetophenone (100% relative activity), other small substrates such as propiophenone, α,α,α-trifluoroacetophenone, α-hydroxyacetophenone, and benzoylacetonitrile had relative activities lower than 30%, while medium-sized ketones such as α-bromo-, α,α-dichloro-, and α,α-dibromoacetophenone presented relative activities between 70% and 550%. Moreover, the comparison between the enzymatic activity and the obtained final conversions using an excess or just 2.5 equiv. of the hydrogen donor 2-propanol, denoted again deviations between them. These data supported that these hydrogen transfer (HT) transformations are mainly thermodynamically controlled. For instance, bulky α-halogenated derivatives could be quantitatively reduced by LBADH even employing 2.5 equiv. of 2-propanol independently of their kinetic values. Finally, we found good correlations between the IR absorption band of the carbonyl groups and the degrees of conversion obtained in these HT processes, making this simple method a convenient tool to predict the success of these transformations.

  1. Increasing physical activity of children during school recess.

    PubMed

    Hayes, Lynda B; Van Camp, Carole M

    2015-09-01

    Physical activity is crucial for children's health. Fitbit accelerometers were used to measure steps of 6 elementary students during recess. The intervention included reinforcement, self-monitoring, goal setting, and feedback. Steps taken during the intervention phase (M = 1,956 steps) were 47% higher than in baseline (M = 1,326 steps), and the percentage of recess spent in moderate-to-vigorous physical activity was higher during intervention (M = 25%) than in baseline (M = 4%). These methods successfully increased steps during recess and could be used to increase steps in other settings.

  2. Characterization of polymorphisms of genes ADH2, ADH3, ALDH2 and CYP2E1 and relationship to the alcoholism in a Colombian population

    PubMed Central

    Méndez, Claudia

    2015-01-01

    Objective: Identify and characterize polymorphisms of genes ADH2, ADH3, ALDH2 and CYP2E1 in a Colombian population residing in the city of Bogotá and determine its possible relationship to the alcoholism. Methods: ADH2, ADH3, ALDH2, and CYP2E1 genotypes a population of 148 individuals with non-problematic alcohol and 65 individuals with alcoholism were determined with TaqMan probes and PCR-RFLP. DNA was obtained from peripheral blood white cells. Results: Significant difference was found in family history of alcoholism and use of other psychoactive substances to compare alcoholics with controls. When allelic frequencies for each category (gender) were considered, frequency of A2 allele carriers in ADH2 was found higher in male patients than controls. In women, the relative frequency for c1 allele in CYP2E1 was lower in controls than alcoholics. The ALDH2 locus is monomorphic. No significant differences in allele distributions of the loci examined to compare two populations were observed, however when stratifying the same trend was found that these differences tended to be significant. Conclusions: This study allows us to conclude the positive association between family history of alcoholism and alcoholism suggesting that there is a favourable hereditary predisposition. Since substance dependence requires interaction of multiple genes, the combination of genotypes ADH2 * 2, CYP2E1 * 1 combined with genotype homozygous ALDH2 * 1 found in this study could be leading to the population to a potential risk to alcoholism. PMID:26848198

  3. The Complete Sequence of 340 kb of DNA around the Rice Adh1–Adh2 Region Reveals Interrupted Colinearity with Maize Chromosome 4

    PubMed Central

    Tarchini, Renato; Biddle, Phyllis; Wineland, Robin; Tingey, Scott; Rafalski, Antoni

    2000-01-01

    A 2.3-centimorgan (cM) segment of rice chromosome 11 consisting of 340 kb of DNA sequence around the alcohol dehydrogenase Adh1 and Adh2 loci was completely sequenced, revealing the presence of 33 putative genes, including several apparently involved in disease resistance. Fourteen of the genes were confirmed by identifying the corresponding transcripts. Five genes, spanning 1.9 cM of the region, cross-hybridized with maize genomic DNA and were genetically mapped in maize, revealing a stretch of colinearity with maize chromosome 4. The Adh1 gene marked one significant interruption. This gene mapped to maize chromosome 1, indicating a possible translocation of Adh1 after the evolutionary divergence leading to maize and sorghum. Several other genes, most notably genes similar to known disease resistance genes, showed no cross-hybridization with maize genomic DNA, suggesting sequence divergence or absence of these sequences in maize, which is in contrast to several other well-conserved genes, including Adh1 and Adh2. These findings indicate that the use of rice as the model system for other cereals may sometimes be complicated by the presence of rapidly evolving gene families and microtranslocations. Seven retrotransposons and eight transposons were identified in this rice segment, including a Tc1/Mariner–like element, which is new to rice. In contrast to maize, retroelements are less frequent in rice. Only 14.4% of this genome segment consist of retroelements. Miniature inverted repeat transposable elements were found to be the most frequently occurring class of repetitive elements, accounting for 18.8% of the total repetitive DNA. PMID:10715324

  4. Local school policies increase physical activity in Norwegian secondary schools

    PubMed Central

    Haug, Ellen; Torsheim, Torbjørn; Samdal, Oddrun

    2010-01-01

    SUMMARY The implementation of school policies to support the adoption of physical activity is one of the main strategies recommended to increase physical activity levels among this age group. However, documentation of the effect of such policies is so far limited. The purpose of this study was to explore policy-related practices to support physical activity in Norwegian secondary schools and their association with recess physical activity. Emphasis was given to examine the association between policies and physical activity, over and beyond, individual level interests and environmental factors and to examine cross-level interaction effects. This cross-sectional study was based on a nationally representative sample of Norwegian secondary schools and grade 8 students who participated in the Health Behaviour in School-aged Children (HBSC) 2005/06 study. The final sample comprised 68 schools and 1347 students. Data were collected through questionnaires. The results showed that schools with a written policy for physical activity and schools offering organized non-curricular physical activity several times a week had a higher proportion of students reporting daily participation in recess physical activity. Multilevel logistic regression analysis demonstrated a cross-level main effect of the policy index after controlling for sex, socio-economic status, individual-level interests and the physical environment. A significant contribution of adding the policy index to the prediction of recess physical activity above that provided by the individual-level interests and the physical environment was demonstrated. The results are encouraging and give scientific support to policy documents recommending the implementation of school policies to increase physical activity. PMID:19884244

  5. Using the Web to Increase Physical Activity in College Students

    ERIC Educational Resources Information Center

    Magoc, Dejan; Tomaka, Joe; Bridges-Arzaga, Amber

    2011-01-01

    Objectives: To evaluate the effectiveness of a theoretically based and Web-delivered intervention using common course technology for increasing physical activity in a college student sample. Methods: One hundred four students randomly participated in either a Web-based intervention involving 7 theory-based learning lessons or a control group that…

  6. Increased proteasome activity determines human embryonic stem cell identity

    PubMed Central

    Vilchez, David; Boyer, Leah; Morantte, Ianessa; Lutz, Margaret; Merkwirth, Carsten; Joyce, Derek; Spencer, Brian; Page, Lesley; Masliah, Eliezer; Berggren, W. Travis; Gage, Fred H.; Dillin, Andrew

    2016-01-01

    Embryonic stem cells are able to replicate continuously in the absence of senescence and, therefore, are immortal in culture1,2. While genome stability is central for survival of stem cells; proteome stability may play an equally important role in stem cell identity and function. Additionally, with the asymmetric divisions invoked by stem cells, the passage of damaged proteins to daughter cells could potentially destroy the resulting lineage of cells. We hypothesized that stem cells have an increased proteostasis ability compared to their differentiated counterparts and asked whether proteasome activity differed among human embryonic stem cells (hESCs). Notably, hESC populations exhibit a high proteasome activity that is correlated with increased levels of the 19S proteasome subunit PSMD11/RPN-63–5 and a corresponding increased assembly of the 26S/30S proteasome. Ectopic expression of PSMD11 is sufficient to increase proteasome assembly and activity. Proteasome inhibition affects pluripotency of hESCs inducing differentiation towards specific cell lineages. FOXO4, an insulin/IGF-1 responsive transcription factor associated with long lifespan in invertebrates6,7, regulates proteasome activity by modulating the expression of PSMD11 in hESCs. Our results establish a novel regulation of proteostasis in hESCs that links longevity and stress resistance in invertebrates with hESC function and identity. PMID:22972301

  7. Texting to increase adolescent physical activity: Feasibility assessment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Feasibility trials assess whether a behavior change program warrants a definite trial evaluation. This paper reports the feasibility of an intervention consisting of Self Determination Theory-informed text messages, pedometers, and goal prompts to increase adolescent physical activity. A 4-group ran...

  8. Reduced Frontal Activation with Increasing 2nd Language Proficiency

    ERIC Educational Resources Information Center

    Stein, Maria; Federspiel, Andrea; Koenig, Thomas; Wirth, Miranka; Lehmann, Christoph; Wiest, Roland; Strik, Werner; Brandeis, Daniel; Dierks, Thomas

    2009-01-01

    The factors influencing the degree of separation or overlap in the neuronal networks responsible for the processing of first and second language are still subject to investigation. This longitudinal study investigates how increasing second language proficiency influences activation differences during lexico-semantic processing of first and second…

  9. Games for increasing physical activity: Mechanisms for change

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A small conference was held in Houston, TX, in May 2014, to address how to enhance exergames to increase physical activity. Several leading researchers were asked to address specific topics. Attendees came from across the globe. This Games for Health Journal Special Issue is devoted to sharing the a...

  10. Hypocholesterolemia in chronic anemias with increased erythropoietic activity.

    PubMed

    Shalev, Hanna; Kapelushnik, Joseph; Moser, Asher; Knobler, Hilla; Tamary, Hannah

    2007-03-01

    Hypocholesterolemia of unknown etiology has been previously described in various chronic anemias. Few small studies also suggested that those patients have a lower incidence of atherosclerotic events. The aim of our study was to determine the extent of hypocholesterolemia in various types of anemias. We studied 59 patients with chronic anemias associated with high-erythropoietic activity (thalassemia intermedia, congenital dyserythropoietic anemia type I, congenital spherocytosis), 8 patients with low-erythropoietic activity anemias (acquired aplastic anemia, Fanconi anemia, and Diamond Blackfan anemia), and 20 healthy controls. Mean serum cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, hemoglobin, serum ferritin, soluble transferrin receptor (STR), and serum erythropoietin levels were determined in each patient. All patients with chronic anemia and increased erythropoietic activity had hypocholesterolemia, whereas none of those with low erythropoietic activity was hypocholesterolemic. Mean serum cholesterol, HDL cholesterol, and LDL cholesterol levels were found to be significantly lower in the high-erythropoietic activity group (80+/-19 mg/dl; 31+/-10 mg/dl; 35+/-14 mg/dl, respectively) compared with the control group (P<0.001; 0.001; 0.001, respectively) and the low-erythropoietic activity group (P<0.001; 0.001; 0.01, respectively). Significant inverse correlation (R2=0.507) was observed between serum cholesterol and STR levels, which in the absence of iron deficiency reflect bone marrow activity. Taken together, our results imply that hypocholesterolemia accompanies anemias with high-erythropoietic activity. We suggest that the high-erythropoitic activity-associated hypocholesterolemia is due to increased cholesterol requirements by the proliferating erythoid cells. Further studies are needed to elucidate the exact mechanism and the possible clinical consequences of this phenomenon.

  11. Increased matriptase zymogen activation in inflammatory skin disorders

    PubMed Central

    Chen, Cheng-Jueng; Wu, Bai-Yao; Tsao, Pai-In; Chen, Chi-Yung; Wu, Mei-Hsuan; Chan, Yee Lam E.; Lee, Herng-Sheng; Johnson, Michael D.; Eckert, Richard L.; Chen, Ya-Wen; Chou, Fengpai; Lin, Chen-Yong

    2011-01-01

    Matriptase, a type 2 transmembrane serine protease, and its inhibitor hepatocyte growth factor activator inhibitor (HAI)-1 are required for normal epidermal barrier function, and matriptase activity is tightly regulated during this process. We therefore hypothesized that this protease system might be deregulated in skin disease. To test this, we examined the level and activation state of matriptase in examples of 23 human skin disorders. We first examined matriptase and HAI-1 protein distribution in normal epidermis. Matriptase was detected at high levels at cell-cell junctions in the basal layer and spinous layers but was present at minimal levels in the granular layer. HAI-1 was distributed in a similar pattern, except that high-level expression was retained in the granular layer. This pattern of expression was retained in most skin disorders. We next examined the distribution of activated matriptase. Although activated matriptase is not detected in normal epidermis, a dramatic increase is seen in keratinocytes at the site of inflammation in 16 different skin diseases. To gain further evidence that activation is associated with inflammatory stimuli, we challenged HaCaT cells with acidic pH or H2O2 and observed matriptase activation. These findings suggest that inflammation-associated reactive oxygen species and tissue acidity may enhance matriptase activation in some skin diseases. PMID:21123732

  12. Chromosome 1 replacement increases brain orexins and antidepressive measures without increasing locomotor activity.

    PubMed

    Feng, Pingfu; Hu, Yufen; Vurbic, Drina; Akladious, Afaf; Strohl, Kingman P

    2014-12-01

    Decreased orexin level has been well demonstrated in patients suffering from narcolepsy, depression accompanied with suicide attempt; obstructive sleep apnea and comorbidity were also demonstrated in these diseases. As C57BL/6J (B6) mice are more "depressed" and have lower brain orexins than A/J mice, B6 mice having chromosome 1 replacement (B6A1 mice) might have restored orexin levels and less depressive behavior. We studied the behavior of 4-6 month old B6, A/J and B6A1 mice with forced swim, tail suspension, and locomotor activity tests. The animals were then sacrificed and hypothalamus and medullas dissected from brain tissue. Orexins-A and -B were determined by radioimmunoassay. Compared with A/J mice, B6 mice displayed several signs of depression, including increased immobility, increased locomotors activity, and decreased orexin A and -B levels in both the hypothalamus and medulla. Compared to B6 mice, B6A1 mice exhibited significantly higher levels of orexins-A and -B in both brain regions. B6A1 mice also exhibited antidepressive features in most of measured variables, including decreased locomotor activity, decreased immobility and increased swim in tail suspension test; compared with B6 mice, however. B6A1 mice also reversed immobility in the early phase of the swim test. In summary, B6 mice exhibited depressive attributes compared with A/J mice, including increased locomotor activity, greater immobility, and decreased brain orexins, these were largely reversed in B6A1 mice. We conclude that orexin levels modulate these B6 behaviors, likely due to expression of A/J alleles on Chromosome 1.

  13. Methods of increasing secretion of polypeptides having biological activity

    SciTech Connect

    Merino, Sandra

    2013-10-01

    The present invention relates to methods for producing a secreted polypeptide having biological activity, comprising: (a) transforming a fungal host cell with a fusion protein construct encoding a fusion protein, which comprises: (i) a first polynucleotide encoding a signal peptide; (ii) a second polynucleotide encoding at least a catalytic domain of an endoglucanase or a portion thereof; and (iii) a third polynucleotide encoding at least a catalytic domain of a polypeptide having biological activity; wherein the signal peptide and at least the catalytic domain of the endoglucanase increases secretion of the polypeptide having biological activity compared to the absence of at least the catalytic domain of the endoglucanase; (b) cultivating the transformed fungal host cell under conditions suitable for production of the fusion protein; and (c) recovering the fusion protein, a component thereof, or a combination thereof, having biological activity, from the cultivation medium.

  14. Methods of increasing secretion of polypeptides having biological activity

    DOEpatents

    Merino, Sandra

    2014-10-28

    The present invention relates to methods for producing a secreted polypeptide having biological activity, comprising: (a) transforming a fungal host cell with a fusion protein construct encoding a fusion protein, which comprises: (i) a first polynucleotide encoding a signal peptide; (ii) a second polynucleotide encoding at least a catalytic domain of an endoglucanase or a portion thereof; and (iii) a third polynucleotide encoding at least a catalytic domain of a polypeptide having biological activity; wherein the signal peptide and at least the catalytic domain of the endoglucanase increases secretion of the polypeptide having biological activity compared to the absence of at least the catalytic domain of the endoglucanase; (b) cultivating the transformed fungal host cell under conditions suitable for production of the fusion protein; and (c) recovering the fusion protein, a component thereof, or a combination thereof, having biological activity, from the cultivation medium.

  15. Methods of increasing secretion of polypeptides having biological activity

    DOEpatents

    Merino, Sandra

    2014-05-27

    The present invention relates to methods for producing a secreted polypeptide having biological activity, comprising: (a) transforming a fungal host cell with a fusion protein construct encoding a fusion protein, which comprises: (i) a first polynucleotide encoding a signal peptide; (ii) a second polynucleotide encoding at least a catalytic domain of an endoglucanase or a portion thereof; and (iii) a third polynucleotide encoding at least a catalytic domain of a polypeptide having biological activity; wherein the signal peptide and at least the catalytic domain of the endoglucanase increases secretion of the polypeptide having biological activity compared to the absence of at least the catalytic domain of the endoglucanase; (b) cultivating the transformed fungal host cell under conditions suitable for production of the fusion protein; and (c) recovering the fusion protein, a component thereof, or a combination thereof, having biological activity, from the cultivation medium.

  16. Methods of increasing secretion of polypeptides having biological activity

    SciTech Connect

    Merino, Sandra

    2015-04-14

    The present invention relates to methods for producing a secreted polypeptide having biological activity, comprising: (a) transforming a fungal host cell with a fusion protein construct encoding a fusion protein, which comprises: (i) a first polynucleotide encoding a signal peptide; (ii) a second polynucleotide encoding at least a catalytic domain of an endoglucanase or a portion thereof; and (iii) a third polynucleotide encoding at least a catalytic domain of a polypeptide having biological activity; wherein the signal peptide and at least the catalytic domain of the endoglucanase increases secretion of the polypeptide having biological activity compared to the absence of at least the catalytic domain of the endoglucanase; (b) cultivating the transformed fungal host cell under conditions suitable for production of the fusion protein; and (c) recovering the fusion protein, a component thereof, or a combination thereof, having biological activity, from the cultivation medium.

  17. Plant species richness increases phosphatase activities in an experimental grassland

    NASA Astrophysics Data System (ADS)

    Hacker, Nina; Wilcke, Wolfgang; Oelmann, Yvonne

    2014-05-01

    Plant species richness has been shown to increase aboveground nutrient uptake requiring the mobilization of soil nutrient pools. For phosphorus (P) the underlying mechanisms for increased P release in soil under highly diverse grassland mixtures remain obscure because aboveground P storage and concentrations of inorganic and organic P in soil solution and differently reactive soil P pools are unrelated (Oelmann et al. 2011). The need of plants and soil microorganisms for P can increase the exudation of enzymes hydrolyzing organically bound P (phosphatases) which might represent an important release mechanism of inorganic P in a competitive environment such as highly diverse grassland mixtures. Our objectives were to test the effects of i) plant functional groups (legumes, grasses, non-leguminous tall and small herbs), and of (ii) plant species richness on microbial P (Pmic) and phosphatase activities in soil. In autumn 2013, we measured Pmic and alkaline phosphomonoesterase and phosphodiesterase activities in soil of 80 grassland mixtures comprising different community compositions and species richness (1, 2, 4, 8, 16, 60) in the Jena Experiment. In general, Pmic and enzyme activities were correlated (r = 0.59 and 0.46 for phosphomonoesterase and phosphodiesterase activities, respectively; p

  18. Exercising self-control increases relative left frontal cortical activation.

    PubMed

    Schmeichel, Brandon J; Crowell, Adrienne; Harmon-Jones, Eddie

    2016-02-01

    Self-control refers to the capacity to override or alter a predominant response tendency. The current experiment tested the hypothesis that exercising self-control temporarily increases approach motivation, as revealed by patterns of electrical activity in the prefrontal cortex. Participants completed a writing task that did vs did not require them to exercise self-control. Then they viewed pictures known to evoke positive, negative or neutral affect. We assessed electroencephalographic (EEG) activity while participants viewed the pictures, and participants reported their trait levels of behavioral inhibition system (BIS) and behavioral activation system (BAS) sensitivity at the end of the study. We found that exercising (vs not exercising) self-control increased relative left frontal cortical activity during picture viewing, particularly among individuals with relatively higher BAS than BIS, and particularly during positive picture viewing. A similar but weaker pattern emerged during negative picture viewing. The results suggest that exercising self-control temporarily increases approach motivation, which may help to explain the aftereffects of self-control (i.e. ego depletion).

  19. Metabolism of trans, trans-muconaldehyde, a cytotoxic metabolite of benzene, in mouse liver by alcohol dehydrogenase Adh1 and aldehyde reductase AKR1A4

    SciTech Connect

    Short, Duncan M.; Lyon, Robert; Watson, David G.; Barski, Oleg A.; McGarvie, Gail; Ellis, Elizabeth M. . E-mail: Elizabeth.ellis@strath.ac.uk

    2006-01-15

    The reductive metabolism of trans, trans-muconaldehyde, a cytotoxic metabolite of benzene, was studied in mouse liver. Using an HPLC-based stopped assay, the primary reduced metabolite was identified as 6-hydroxy-trans, trans-2,4-hexadienal (OH/CHO) and the secondary metabolite as 1,6-dihydroxy-trans, trans-2,4-hexadiene (OH/OH). The main enzymes responsible for the highest levels of reductase activity towards trans, trans-muconaldehyde were purified from mouse liver soluble fraction first by Q-sepharose chromatography followed by either blue or red dye affinity chromatography. In mouse liver, trans, trans-muconaldehyde is predominantly reduced by an NADH-dependent enzyme, which was identified as alcohol dehydrogenase (Adh1). Kinetic constants obtained for trans, trans-muconaldehyde with the native Adh1 enzyme showed a V {sub max} of 2141 {+-} 500 nmol/min/mg and a K {sub m} of 11 {+-} 4 {mu}M. This enzyme was inhibited by pyrazole with a K {sub I} of 3.1 {+-} 0.57 {mu}M. Other fractions were found to contain muconaldehyde reductase activity independent of Adh1, and one enzyme was identified as the NADPH-dependent aldehyde reductase AKR1A4. This showed a V {sub max} of 115 nmol/min/mg and a K {sub m} of 15 {+-} 2 {mu}M and was not inhibited by pyrazole.

  20. Increasing Arabian dust activity and the Indian summer monsoon

    NASA Astrophysics Data System (ADS)

    Solmon, F.; Nair, V. S.; Mallet, M.

    2015-07-01

    Over the past decade, aerosol optical depth (AOD) observations based on satellite and ground measurements have shown a significant increase over Arabia and the Arabian Sea, attributed to an intensification of regional dust activity. Recent studies have also suggested that west Asian dust forcing could induce a positive response of Indian monsoon precipitations on a weekly timescale. Using observations and a regional climate model including interactive slab-ocean and dust aerosol schemes, the present study investigates possible climatic links between the increasing June-July-August-September (JJAS) Arabian dust activity and precipitation trends over southern India during the 2000-2009 decade. Meteorological reanalysis and AOD observations suggest that the observed decadal increase of dust activity and a simultaneous intensification of summer precipitation trend over southern India are both linked to a deepening of JJAS surface pressure conditions over the Arabian Sea. In the first part of the study, we analyze the mean climate response to dust radiative forcing over the domain, discussing notably the relative role of Arabian vs. Indo-Pakistani dust regions. In the second part of the study, we show that the model skills in reproducing regional dynamical patterns and southern Indian precipitation trends are significantly improved only when an increasing dust emission trend is imposed on the basis of observations. We conclude that although interannual climate variability might primarily determine the observed regional pattern of increasing dust activity and precipitation during the 2000-2009 decade, the associated dust radiative forcing might in return induce a critical dynamical feedback contributing to enhancing regional moisture convergence and JJAS precipitations over southern India.

  1. Increased antitumor activity of tumor-specific peptide modified thymopentin.

    PubMed

    Lao, Xingzhen; Li, Bin; Liu, Meng; Chen, Jiao; Gao, Xiangdong; Zheng, Heng

    2014-12-01

    Thymopoietin pentapeptide (thymopentin, TP5), an immunomodulatory peptide, has been successfully used as an immune system enhancer for treating immune deficiency, cancer, and infectious diseases. However, poor penetration into tumors remains a key limitation to the efficacy and application of TP5. iRGD (CRGDK/RGPD/EC) has been introduced to certain anticancer agents, and increased specific tumor penetrability of drugs and cell internalization have been observed. In the present study, we fused this iRGD fragment with the C-terminal of TP5 to yield a new product, TP5-iRGD. Cell attachment assay showed that TP5-iRGD exhibits more extensive attachment to the melanoma cell line B16F10 than wild-type TP5. Tumor cell viability assay showed that iRGD conjugation with the TP5 C-terminus increases the basal antiproliferative activity of the pentapeptide against the melanoma cell line B16F10, the human lung cancer cell line H460, and the human breast cancer cell line MCF-7. Subsequent injections of TP5-iRGD inhibited in vivo melanoma progression more efficiently than the native TP5. Murine spleen lymphocyte proliferation assay also showed that TP5-iRGD and the parent pentapeptide feature nearly identical spleen lymphocyte proliferation activities. We built an integrin αvβ3 and TP5-iRGD computational binding model to investigate the mechanism by which TP5-iRGD promotes increased activity further. Conjugation with iRGD promotes binding to integrin αvβ3, thereby increasing the tumor-homing efficiency of the resultant peptide. These experimental and computational observations of increased TP5-iRGD activity help broaden the usage of TP5 and reflect the great application potential of the peptide as an anticancer agent.

  2. Plant diversity increases soil microbial activity and soil carbon storage.

    PubMed

    Lange, Markus; Eisenhauer, Nico; Sierra, Carlos A; Bessler, Holger; Engels, Christoph; Griffiths, Robert I; Mellado-Vázquez, Perla G; Malik, Ashish A; Roy, Jacques; Scheu, Stefan; Steinbeiss, Sibylle; Thomson, Bruce C; Trumbore, Susan E; Gleixner, Gerd

    2015-04-07

    Plant diversity strongly influences ecosystem functions and services, such as soil carbon storage. However, the mechanisms underlying the positive plant diversity effects on soil carbon storage are poorly understood. We explored this relationship using long-term data from a grassland biodiversity experiment (The Jena Experiment) and radiocarbon ((14)C) modelling. Here we show that higher plant diversity increases rhizosphere carbon inputs into the microbial community resulting in both increased microbial activity and carbon storage. Increases in soil carbon were related to the enhanced accumulation of recently fixed carbon in high-diversity plots, while plant diversity had less pronounced effects on the decomposition rate of existing carbon. The present study shows that elevated carbon storage at high plant diversity is a direct function of the soil microbial community, indicating that the increase in carbon storage is mainly limited by the integration of new carbon into soil and less by the decomposition of existing soil carbon.

  3. Active learning increases student performance in science, engineering, and mathematics.

    PubMed

    Freeman, Scott; Eddy, Sarah L; McDonough, Miles; Smith, Michelle K; Okoroafor, Nnadozie; Jordt, Hannah; Wenderoth, Mary Pat

    2014-06-10

    To test the hypothesis that lecturing maximizes learning and course performance, we metaanalyzed 225 studies that reported data on examination scores or failure rates when comparing student performance in undergraduate science, technology, engineering, and mathematics (STEM) courses under traditional lecturing versus active learning. The effect sizes indicate that on average, student performance on examinations and concept inventories increased by 0.47 SDs under active learning (n = 158 studies), and that the odds ratio for failing was 1.95 under traditional lecturing (n = 67 studies). These results indicate that average examination scores improved by about 6% in active learning sections, and that students in classes with traditional lecturing were 1.5 times more likely to fail than were students in classes with active learning. Heterogeneity analyses indicated that both results hold across the STEM disciplines, that active learning increases scores on concept inventories more than on course examinations, and that active learning appears effective across all class sizes--although the greatest effects are in small (n ≤ 50) classes. Trim and fill analyses and fail-safe n calculations suggest that the results are not due to publication bias. The results also appear robust to variation in the methodological rigor of the included studies, based on the quality of controls over student quality and instructor identity. This is the largest and most comprehensive metaanalysis of undergraduate STEM education published to date. The results raise questions about the continued use of traditional lecturing as a control in research studies, and support active learning as the preferred, empirically validated teaching practice in regular classrooms.

  4. Active learning increases student performance in science, engineering, and mathematics

    PubMed Central

    Freeman, Scott; Eddy, Sarah L.; McDonough, Miles; Smith, Michelle K.; Okoroafor, Nnadozie; Jordt, Hannah; Wenderoth, Mary Pat

    2014-01-01

    To test the hypothesis that lecturing maximizes learning and course performance, we metaanalyzed 225 studies that reported data on examination scores or failure rates when comparing student performance in undergraduate science, technology, engineering, and mathematics (STEM) courses under traditional lecturing versus active learning. The effect sizes indicate that on average, student performance on examinations and concept inventories increased by 0.47 SDs under active learning (n = 158 studies), and that the odds ratio for failing was 1.95 under traditional lecturing (n = 67 studies). These results indicate that average examination scores improved by about 6% in active learning sections, and that students in classes with traditional lecturing were 1.5 times more likely to fail than were students in classes with active learning. Heterogeneity analyses indicated that both results hold across the STEM disciplines, that active learning increases scores on concept inventories more than on course examinations, and that active learning appears effective across all class sizes—although the greatest effects are in small (n ≤ 50) classes. Trim and fill analyses and fail-safe n calculations suggest that the results are not due to publication bias. The results also appear robust to variation in the methodological rigor of the included studies, based on the quality of controls over student quality and instructor identity. This is the largest and most comprehensive metaanalysis of undergraduate STEM education published to date. The results raise questions about the continued use of traditional lecturing as a control in research studies, and support active learning as the preferred, empirically validated teaching practice in regular classrooms. PMID:24821756

  5. Self-etching adhesives increase collagenolytic activity in radicular dentin.

    PubMed

    Tay, Franklin R; Pashley, David H; Loushine, Robert J; Weller, R Norman; Monticelli, Francesca; Osorio, Raquel

    2006-09-01

    Endogenous matrix metalloproteinases (MMPs) release from crown dentin and their activation results in degradation of hybrid layers created by dentin adhesives. This study tested the hypothesis that instrumented intraradicular dentin possesses latent collagenolytic activity that is activated by mild self-etching adhesives. Root dentin shavings were produced from 50 cleaned and shaped, saline-irrigated root canals using Gates Glidden drills and rinsed with sodium azide to prevent bacterial growth. Dried dentin powder aliquots were treated with two clinically-relevant MMP inhibitors, 2% chlorhexidine for 10 minutes and 17% EDTA for 1 minute. Additional dentin powder was mixed with Clearfil Liner Bond 2V or Clearfil Tri-S Bond for 1 minute followed by extracting the adhesives with acetone. Dentin powder was also treated with 2% chlorhexidine for 10 minutes before or after adhesive application. Collagenolytic activities of the nine groups were assayed with a fluorometer in 96-well plates, by recording the changes in fluorescence before and after addition of fluorescein-labeled type I collagen. Epoxy resin-embedded powders were examined with TEM for the extent of demineralization. Instrumented, mineralized intraradicular dentin possessed low but detectable collagenolytic activity that was inhibited by chlorhexidine (p < 0.001) and EDTA (p < 0.001). Both adhesives partially demineralized the dentin powder and activated latent MMPs, with 14- to 15-fold increases in collagenolytic activities (p < 0.001) that were significantly (p < 0.001) but incompletely inactivated after 10 min application of chlorhexidine. Mild self-etching adhesives activate latent MMPs without denaturing these enzymes, and may adversely affect the longevity of bonded root canal fillings and posts.

  6. Interactions Increase Forager Availability and Activity in Harvester Ants.

    PubMed

    Pless, Evlyn; Queirolo, Jovel; Pinter-Wollman, Noa; Crow, Sam; Allen, Kelsey; Mathur, Maya B; Gordon, Deborah M

    2015-01-01

    Social insect colonies use interactions among workers to regulate collective behavior. Harvester ant foragers interact in a chamber just inside the nest entrance, here called the 'entrance chamber'. Previous studies of the activation of foragers in red harvester ants show that an outgoing forager inside the nest experiences an increase in brief antennal contacts before it leaves the nest to forage. Here we compare the interaction rate experienced by foragers that left the nest and ants that did not. We found that ants in the entrance chamber that leave the nest to forage experienced more interactions than ants that descend to the deeper nest without foraging. Additionally, we found that the availability of foragers in the entrance chamber is associated with the rate of forager return. An increase in the rate of forager return leads to an increase in the rate at which ants descend to the deeper nest, which then stimulates more ants to ascend into the entrance chamber. Thus a higher rate of forager return leads to more available foragers in the entrance chamber. The highest density of interactions occurs near the nest entrance and the entrances of the tunnels from the entrance chamber to the deeper nest. Local interactions with returning foragers regulate both the activation of waiting foragers and the number of foragers available to be activated.

  7. Changes in baseball batters' brain activity with increased pitch choice.

    PubMed

    Ryu, Kwangmin; Kim, Jingu; Ali, Asif; Kim, Woojong; Radlo, Steven J

    2015-09-01

    In baseball, one factor necessary for batters to decide whether to swing or not depends on what type of pitch is thrown. Oftentimes batters will look for their pitch (i.e., waiting for a fastball). In general, when a pitcher has many types of pitches in his arsenal, batters will have greater difficulty deciding upon the pitch thrown. Little research has been investigated the psychophysiology of a batters decision-making processes. Therefore, the primary purpose of this study was to determine how brain activation changes according to an increase in the number of alternatives (NA) available. A total of 15 male college baseball players participated in this study. The stimuli used in this experiment were video clips of a right-handed pitcher throwing fastball, curve, and slider pitches. The task was to press a button after selecting the fastball as the target stimulus from two pitch choices (fastball and curve), and then from three possibilities (fastball, curve, and slider). Functional and anatomic image scanning magnetic resonance imaging (MRI) runs took 4 and 5[Formula: see text]min, respectively. According to our analysis, the right precentral gyrus, left medial frontal gyrus, and right fusiform gyrus were activated when the NA was one. The supplementary motor areas (SMA) and primary motor cortex were activated when there were two alternatives to choose from and the inferior orbitofrontal gyrus was specifically activated with three alternatives. Contrary to our expectations, the NA was not a critical factor influencing the activation of related decision making areas when the NA was compared against one another. These findings highlight that specific brain areas related to decision making were activated as the NA increased.

  8. Projecting climate-driven increases in North American fire activity

    NASA Astrophysics Data System (ADS)

    Wang, D.; Morton, D. C.; Collatz, G. J.

    2013-12-01

    Climate regulates fire activity through controls on vegetation productivity (fuels), lightning ignitions, and conditions governing fire spread. In many regions of the world, human management also influences the timing, duration, and extent of fire activity. These coupled interactions between human and natural systems make fire a complex component of the Earth system. Satellite data provide valuable information on the spatial and temporal dynamics of recent fire activity, as active fires, burned area, and land cover information can be combined to separate wildfires from intentional burning for agriculture and forestry. Here, we combined satellite-derived burned area data with land cover and climate data to assess fire-climate relationships in North America between 2000-2012. We used the latest versions of the Global Fire Emissions Database (GFED) burned area product and Modern-Era Retrospective Analysis for Research and Applications (MERRA) climate data to develop regional relationships between burned area and potential evaporation (PE), an integrated dryness metric. Logistic regression models were developed to link burned area with PE and individual climate variables during and preceding the fire season, and optimal models were selected based on Akaike Information Criterion (AIC). Overall, our model explained 85% of the variance in burned area since 2000 across North America. Fire-climate relationships from the era of satellite observations provide a blueprint for potential changes in fire activity under scenarios of climate change. We used that blueprint to evaluate potential changes in fire activity over the next 50 years based on twenty models from the Coupled Model Intercomparison Project Phase 5 (CMIP5). All models suggest an increase of PE under low and high emissions scenarios (Representative Concentration Pathways (RCP) 4.5 and 8.5, respectively), with largest increases in projected burned area across the western US and central Canada. Overall, near

  9. ADH1A variation predisposes to personality traits and substance dependence.

    PubMed

    Zuo, Lingjun; Gelernter, Joel; Kranzler, Henry R; Stein, Murray B; Zhang, Huiping; Wei, Feng; Sen, Srijan; Poling, James; Luo, Xingguang

    2010-03-05

    Human personality traits are strong predictors or characteristics of many psychiatric disorders including substance dependence (SD). Recently, significant associations between alcohol dehydrogenase type 1A gene (ADH1A) and SD have been reported, which led us to investigate the impact of ADH1A variation on personality traits and risk of SD. Five hundred fifty-eight subjects with SD [398 European-Americans (EAs) and 160 African-Americans (AAs)], 517 college students (384 EAs and 133 European-origin Hispanics), and 448 healthy subjects (385 EAs, 48 AAs, and 15 European-origin Hispanics) participated. Personality traits were assessed in 247 subjects with SD (179 EAs and 68 AAs), all 517 college students, and 332 healthy subjects (285 EAs, 40 AAs, and 7 European-origin Hispanics). The relationships between ADH1A and personality traits were comprehensively examined using stepwise multivariate analysis of covariance (MANCOVA), and then decomposed by stepwise analysis of covariance (ANCOVA). The relationship between ADH1A and SD was examined using stepwise logistic regression analysis. Admixture effects on analyses were considered. Overall, Agreeableness and Conscientiousness were associated with the diplotypes, haplotypes, genotypes, and/or alleles of ADH1A in three of four phenotype groups including EA SD subjects, healthy subjects, and AA SD subjects (1.7 x 10(-4) ADH1A (0.008 ADH1A variation may contribute to the genetic component of variation in personality traits and SD.

  10. Serotonin increases synaptic activity in olfactory bulb glomeruli.

    PubMed

    Brill, Julia; Shao, Zuoyi; Puche, Adam C; Wachowiak, Matt; Shipley, Michael T

    2016-03-01

    Serotoninergic fibers densely innervate olfactory bulb glomeruli, the first sites of synaptic integration in the olfactory system. Acting through 5HT2A receptors, serotonin (5HT) directly excites external tufted cells (ETCs), key excitatory glomerular neurons, and depolarizes some mitral cells (MCs), the olfactory bulb's main output neurons. We further investigated 5HT action on MCs and determined its effects on the two major classes of glomerular interneurons: GABAergic/dopaminergic short axon cells (SACs) and GABAergic periglomerular cells (PGCs). In SACs, 5HT evoked a depolarizing current mediated by 5HT2C receptors but did not significantly impact spike rate. 5HT had no measurable direct effect in PGCs. Serotonin increased spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) in PGCs and SACs. Increased sEPSCs were mediated by 5HT2A receptors, suggesting that they are primarily due to enhanced excitatory drive from ETCs. Increased sIPSCs resulted from elevated excitatory drive onto GABAergic interneurons and augmented GABA release from SACs. Serotonin-mediated GABA release from SACs was action potential independent and significantly increased miniature IPSC frequency in glomerular neurons. When focally applied to a glomerulus, 5HT increased MC spontaneous firing greater than twofold but did not increase olfactory nerve-evoked responses. Taken together, 5HT modulates glomerular network activity in several ways: 1) it increases ETC-mediated feed-forward excitation onto MCs, SACs, and PGCs; 2) it increases inhibition of glomerular interneurons; 3) it directly triggers action potential-independent GABA release from SACs; and 4) these network actions increase spontaneous MC firing without enhancing responses to suprathreshold sensory input. This may enhance MC sensitivity while maintaining dynamic range.

  11. Increased AICD generation does not result in increased nuclear translocation or activation of target gene transcription

    SciTech Connect

    Waldron, Elaine; Isbert, Simone; Kern, Andreas; Jaeger, Sebastian; Martin, Anne M.; Hebert, Sebastien S.; Behl, Christian; Weggen, Sascha; De Strooper, Bart; Pietrzik, Claus U.

    2008-08-01

    A sequence of amyloid precursor protein (APP) cleavages culminates in the sequential release of the APP intracellular domain (AICD) and the amyloid {beta} peptide (A{beta}) and/or p3 fragment. One of the environmental factors favouring the accumulation of AICD appears to be a rise in intracellular pH. Here we further identified the metabolism and subcellular localization of artificially expressed constructs under such conditions. We also co-examined the mechanistic lead up to the AICD accumulation and explored possible significances for its increased expression. We found that most of the AICD generated under pH neutralized conditions is likely cleaved from C83. While the AICD surplus was unable to further activate transcription of a luciferase reporter via a Gal4-DNA-binding domain, it failed entirely via the endogenous promoter regions of proposed target genes, APP and KAI1. The lack of a specific transactivation potential was also demonstrated by the unchanged levels of target gene mRNA. However, rather than translocating to the nucleus, the AICD surplus remains membrane tethered or free in the cytosol where it interacts with Fe65. Therefore we provide strong evidence that an increase in AICD generation does not directly promote gene activation of previously proposed target 0011gen.

  12. A ketogenic diet increases succinic dehydrogenase activity in aging cardiomyocytes.

    PubMed

    Balietti, Marta; Fattoretti, Patrizia; Giorgetti, Belinda; Casoli, Tiziana; Di Stefano, Giuseppina; Solazzi, Moreno; Platano, Daniela; Aicardi, Giorgio; Bertoni-Freddari, Carlo

    2009-08-01

    Impairment of energy metabolism and an increase of reactive oxygen species (ROS) production seem to play a major role in age-related apoptotic loss of cardiomyocytes. Succinic dehydrogenase (SDH) is an important marker of the mitochondrial capability to provide an adequate amount of ATP. Moreover, because of its unique redox properties, SDH activity contributes to maintain the reduced state of the ubiquinone pool. Recent reports have shown that ketone body intake improves cardiac metabolic efficiency and exerts a cardioprotective antioxidant action, we therefore performed a cytochemical investigation of SDH activity in cardiomyocytes of late-adult (19-month-old) rats fed for 8 weeks with a medium-chain triglycerides ketogenic diet (MCT-KD). Young, age-matched and old animals fed with a standard chow were used as controls. The overall area of the precipitates (PA) from SDH activity and the area of the SDH-positive mitochondria (MA) were measured. The percent ratios PA/MA and MA/total myocardial tissue area (MA/TA) were the parameters taken into account. We found that PA/MA was significantly higher in young control rats and in MCT-KD-fed rats versus late-adult and old control rats and in young control versus MCT-KD-fed rats. MA/TA of MCT-KD-fed rats was significantly higher versus age-matched and old control rats and tended to be higher versus young control rats; this parameter was significantly higher in young versus old control rats. Thus, MCT-KD intake partially recovers age-related decrease of SDH activity and increases the myocardial area occupied by metabolically active mitochondria. These effects might counteract metabolic alterations leading to apoptosis-induced myocardial atrophy and failure during aging.

  13. Alcohol and aldehyde dehydrogenase from Saccharomyces cerevisiae: specific activity and influence on the production of acetic acid, ethanol and higher alcohols in the first 48 h of fermentation of grape must.

    PubMed

    Millán, C; Mauricio, J C; Ortega, J M

    1990-01-01

    The changes in the specific activity of alcohol dehydrogenase (ADH-I and ADH-II) and aldehyde dehydrogenases [AIDH-NADP+ and AIDH-NAD(P)+] from Saccharomyces cerevisiae during the first 48 h of fermentation of grape must were investigated. The biosynthesis of ADH-I and AIDH-NADP+ took place basically during the adaptation of the yeasts to the must (first 4 h), while that of ADH-II occurred immediately after exponential growth (after 12 h). From the products produced by the yeast, only the specific rate of production of ethanol was found to be directly related to the specific activity of ADH-I.

  14. Betaine increases the butyrylcholinesterase activity in rat plasma.

    PubMed

    Šišková, K; Dubničková, M; Pašková, Ľ; Rajdl, D; Ďuračková, Z; Muchová, J; Pauliková, I; Racek, J

    2016-01-01

    The physiological function of butyrylcholinesterase (EC 3.1.1.8, BChE) is not clearly understood, but a role was suggested in the fat utilization process, resulting in positive correlation between plasma triglyceride (TG) levels and BChE activity. Consequently we tested the hypothesis that regular intake of betaine, a natural compound intervening in the liver TG metabolism could influence the BChE activity. The BChE activity was estimated spectrophotometrically in plasma of rats fed with betaine enriched standard (B) or high-fat diet (HFB). The results confirmed decreased TG plasma levels after betaine treatment independently on the type of diet (0.15+/-0.03 (B) vs. 0.27+/-0.08 (control) mmol/l; p=0.003 and 0.13+/-0.03 (HFB) vs. 0.27+/-0.08 (control) mmol/l; p=0.005). The BChE activity increased significantly with betaine administration, however the change was more distinct in the HFB group (0.84+/-0.34 (HFB) vs. 0.22+/-0.04 (control) O.D./min/mg; p<0.001 and 0.41+/-0.11 (B) vs. 0.22+/-0.04 (control) O.D./min/mg; p=0.001). In conclusion, betaine intake led to elevated BChE activity in plasma and this effect was potentiated by the HF diet. Since betaine is in general used as a supplement in the treatment of liver diseases accompanied by TG overload, its impact on the BChE activity in the role of the liver function marker should be taken into account.

  15. Obstruction increases activation in the right inferior frontal gyrus.

    PubMed

    Liu, Tao; Saito, Hirofumi; Oi, Misato

    2016-01-01

    The right inferior frontal gyrus (IFG) is involved in intention understanding during interpersonal interactions. To examine how prior experience of cooperation and competition affects one's right IFG activation in the subsequent interaction, using near-infrared spectroscopy (NIRS) we simultaneously measured paired participants' bilateral IFG activations during a turn-taking game. Participant pairs were assigned to either one of two roles: a Builder taking the initial move to copy a target disk-pattern on monitor and the Partner taking the second move to aid in (cooperation) or to obstruct (competition) the Builder. The experiment consisted of two sessions. One participant (B-P) played as a Builder (B-) in session 1 and changed the role to the Partner (-P) in session 2, and vice versa for the paired participant (P-B). NIRS data in competition demonstrated that the Builder (B-) being obstructed in session 1 showed higher right IFG activation when (s)he took a role of obstructor (-P) in session 2 (the obstructed effect), whereas "the cooperated effect" was not revealed in cooperation. These results suggest that prior experience of being obstructed may facilitate understanding of the Builder and/or the obstructor's tactical move, thereby increasing his/her right IFG activation when one is meant to obstruct in subsequent competitions.

  16. Both novelty and expertise increase action observation network activity

    PubMed Central

    Liew, Sook-Lei; Sheng, Tong; Margetis, John L.; Aziz-Zadeh, Lisa

    2013-01-01

    Our experiences with others affect how we perceive their actions. In particular, activity in bilateral premotor and parietal cortices during action observation, collectively known as the action observation network (AON), is modulated by one's expertise with the observed actions or individuals. However, conflicting reports suggest that AON activity is greatest both for familiar and unfamiliar actions. The current study examines the effects of different types and amounts of experience (e.g., visual, interpersonal, personal) on AON activation. fMRI was used to scan 16 healthy participants without prior experience with individuals with amputations (novices), 11 experienced occupational therapists (OTs) who had varying amounts of experience with individuals with amputations, and one individual born with below-elbow residual limbs (participant CJ), as they viewed video clips of goal-matched actions performed by an individual with residual limbs and by an individual with hands. Participants were given increased visual exposure to actions performed by both effectors midway through the scanning procedure. Novices demonstrated a large AON response to the initial viewing of an individual with residual limbs compared to one with hands, but this signal was attenuated after they received visual exposure to both effectors. In contrast, OTs, who had moderate familiarity with residual limbs, demonstrated a lower AON response upon initial viewing—similar to novices after they received visual exposure. At the other extreme, CJ, who has extreme familiarity with residual limbs both visually and motorically, shows a largely increased left-lateralized AON response, exceeding that of novices and experienced OTs, when viewing the residual limb compared to hand actions. These results suggest that a nuanced model of AON engagement is needed to explain how cases of both extreme experience (CJ) and extreme novelty (novices) can result in the greatest AON activity. PMID:24062656

  17. Flavone deglycosylation increases their anti-inflammatory activity and absorption

    PubMed Central

    Hostetler, Gregory; Riedl, Ken; Cardenas, Horacio; Diosa-Toro, Mayra; Arango, Daniel; Schwartz, Steven; Doseff, Andrea I.

    2014-01-01

    Scope Flavones have reported anti-inflammatory activities, but the ability of flavone-rich foods to reduce inflammation is unclear. Here, we report the effect of flavone glycosylation in the regulation of inflammatory mediators in vitro and the absorption of dietary flavones in vivo. Methods and results The anti-inflammatory activities of celery extracts, some rich in flavone aglycones and others rich in flavone glycosides, were tested on the inflammatory mediators tumor necrosis factor α (TNF-α) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in lipopolysaccharide-stimulated macrophages. Pure flavone aglycones and aglycone-rich extracts effectively reduced TNF-α production and inhibited the transcriptional activity of NF-κB, while glycoside-rich extracts showed no significant effects. Deglycosylation of flavones increased cellular uptake and cytoplasmic localization as shown by high-performance liquid chromatography (HPLC) and microscopy using the flavonoid fluorescent dye diphenyl-boric acid 2-aminoethyl ester (DPBA). Celery diets with different glycoside or aglycone contents were formulated and absorption was evaluated in mice fed with 5 or 10% celery diets. Relative absorption in vivo was significantly higher in mice fed with aglycone-rich diets as determined by HPLC-MS/MS (where MS/MS is tandem mass spectrometry). Conclusion These results demonstrate that deglycosylation increases absorption of dietary flavones in vivo and modulates inflammation by reducing TNF-α and NF-κB, suggesting the potential use of functional foods rich in flavones for the treatment and prevention of inflammatory diseases. PMID:22351119

  18. [Increased fibrinolytic activity during cardiopulmonary bypass is caused by activated protein C system].

    PubMed

    Gando, S; Tedo, I; Masio, H; Goda, Y; Kawahigashi, H

    1994-06-01

    To examine the hypothesis that activated protein C system during cardiopulmonary bypass surgery may increase fibrinolytic activity during cardiopulmonary bypass, protein C activity, protein C antigen and thrombomodulin of sixteen patients undergoing elective cardiopulmonary bypass surgery were investigated after induction of anesthesia, before and after cardiopulmonary bypass, and at the end of operation. Protein C activity decreased and thrombomodulin increased significantly after the cardiopulmonary bypass. There were no significant correlations of thrombomodulin with protein C activity and protein C antigen. In conclusion, we have demonstrated that protein C system is activated and circulating thrombomodulin appears in the systemic circulation during cardiopulmonary bypass surgery and this enhanced activation of protein C system is possibly related to the reported increase of fibrinolytic activity during cardiopulmonary bypass.

  19. Dopamine Receptor Activation Increases HIV Entry into Primary Human Macrophages

    PubMed Central

    Gaskill, Peter J.; Yano, Hideaki H.; Kalpana, Ganjam V.; Javitch, Jonathan A.; Berman, Joan W.

    2014-01-01

    Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers. PMID:25268786

  20. Increased serum cortisol binding in chronic active hepatitis

    SciTech Connect

    Orbach, O.; Schussler, G.C.

    1989-01-01

    A high serum cortisol concentration, apparently due to increased cortisol-binding globulin (CBG), was found in a patient (index case) with chronic active hepatitis (CAH). We therefore performed further studies to determine whether increased cortisol binding is generally associated with CAH. Serum samples were obtained from 15 hospitalized patients with long-term liver function test elevations but no evidence of cirrhosis, 15 normal subjects without a history of hepatitis, four healthy pregnant women, and 10 alcoholic patients with stigmata of cirrhosis. Serum cortisol binding was measured by an adaptation of a previously described charcoal uptake method. Thyroxine-binding globulin (TBG) and sex hormone-binding globulin were determined by radioimmunoassays. Charcoal uptake of 125I cortisol from sera of normal subjects and additional patients with CAH revealed that increased serum cortisol binding by a saturable site, presumably CBG, was associated with CAH. Cortisol binding was significantly correlated with immunoassayable TBG, suggesting that in CAH, similar mechanisms may be responsible for increasing the serum concentrations of CBG and TBG.

  1. Cytokinin activity increases stomatal density and transpiration rate in tomato

    PubMed Central

    Farber, Mika; Attia, Ziv; Weiss, David

    2016-01-01

    Previous studies on cytokinin (CK) and drought have suggested that the hormone has positive and negative effects on plant adaptation to restrictive conditions. This study examined the effect of CK on transpiration, stomatal activity, and response to drought in tomato (Solanum lycopersicum) plants. Transgenic tomato plants overexpressing the Arabidopsis thaliana CK-degrading enzyme CK oxidase/dehydrogenase 3 (CKX3) maintained higher leaf water status under drought conditions due to reduced whole-plant transpiration. The reduced transpiration could be attributed to smaller leaf area and reduced stomatal density. CKX3-overexpressing plants contained fewer and larger pavement cells and fewer stomata per leaf area than wild-type plants. In addition, wild-type leaves treated with CK exhibited enhanced transpiration and had more pavement cells and increased numbers of stomata per leaf area than untreated leaves. Manipulation of CK levels did not affect stomatal movement or abscisic acid-induced stomatal closure. Moreover, we found no correlation between stomatal aperture and the activity of the CK-induced promoter Two-Component Signaling Sensor (TCS) in guard cells. Previous studies have shown that drought reduces CK levels, and we propose this to be a mechanism of adaptation to water deficiency: the reduced CK levels suppress growth and reduce stomatal density, both of which reduce transpiration, thereby increasing tolerance to prolonged drought conditions. PMID:27811005

  2. Prescribed Active Learning Increases Performance in Introductory Biology

    PubMed Central

    O'Connor, Eileen; Parks, John W.; Cunningham, Matthew; Hurley, David; Haak, David; Dirks, Clarissa; Wenderoth, Mary Pat

    2007-01-01

    We tested five course designs that varied in the structure of daily and weekly active-learning exercises in an attempt to lower the traditionally high failure rate in a gateway course for biology majors. Students were given daily multiple-choice questions and answered with electronic response devices (clickers) or cards. Card responses were ungraded; clicker responses were graded for right/wrong answers or participation. Weekly practice exams were done as an individual or as part of a study group. Compared with previous versions of the same course taught by the same instructor, students in the new course designs performed better: There were significantly lower failure rates, higher total exam points, and higher scores on an identical midterm. Attendance was higher in the clicker versus cards section; attendance and course grade were positively correlated. Students did better on clicker questions if they were graded for right/wrong answers versus participation, although this improvement did not translate into increased scores on exams. In this course, achievement increases when students get regular practice via prescribed (graded) active-learning exercises. PMID:17548875

  3. Obesity-induced increases in sympathetic nerve activity: sex matters.

    PubMed

    Brooks, Virginia L; Shi, Zhigang; Holwerda, Seth W; Fadel, Paul J

    2015-01-01

    Abundant evidence obtained largely from male human and animal subjects indicates that obesity increases sympathetic nerve activity (SNA), which contributes to hypertension development. However, recent studies that included women reported that the strong relationships between muscle SNA and waist circumference or body mass index (BMI) found in men are not present in overweight and obese women. A similar sex difference in the association between adiposity and hypertension development has been identified in animal models of obesity. In this brief review, we consider two possible mechanisms for this sex difference. First, visceral adiposity, leptin, insulin, and angiotensin II have been identified as potential culprits in obesity-induced sympathoexcitation in males. We explore if these factors wield the same impact in females. Second, we consider if sex differences in vascular reactivity to sympathetic activation contribute. Our survey of the literature suggests that premenopausal females may be able to resist obesity-induced sympathoexcitation and hypertension in part due to differences in adipose disposition as well as its muted inflammatory response and reduced production of pressor versus depressor components of the renin-angiotensin system. In addition, vascular responsiveness to increased SNA may be reduced. However, more importantly, we identify the urgent need for further study, not only of sex differences per se, but also of the mechanisms that may mediate these differences. This information is required not only to refine treatment options for obese premenopausal women but also to potentially reveal new therapeutic avenues in obese men and women.

  4. Cytokinin activity increases stomatal density and transpiration rate in tomato.

    PubMed

    Farber, Mika; Attia, Ziv; Weiss, David

    2016-12-01

    Previous studies on cytokinin (CK) and drought have suggested that the hormone has positive and negative effects on plant adaptation to restrictive conditions. This study examined the effect of CK on transpiration, stomatal activity, and response to drought in tomato (Solanum lycopersicum) plants. Transgenic tomato plants overexpressing the Arabidopsis thaliana CK-degrading enzyme CK oxidase/dehydrogenase 3 (CKX3) maintained higher leaf water status under drought conditions due to reduced whole-plant transpiration. The reduced transpiration could be attributed to smaller leaf area and reduced stomatal density. CKX3-overexpressing plants contained fewer and larger pavement cells and fewer stomata per leaf area than wild-type plants. In addition, wild-type leaves treated with CK exhibited enhanced transpiration and had more pavement cells and increased numbers of stomata per leaf area than untreated leaves. Manipulation of CK levels did not affect stomatal movement or abscisic acid-induced stomatal closure. Moreover, we found no correlation between stomatal aperture and the activity of the CK-induced promoter Two-Component Signaling Sensor (TCS) in guard cells. Previous studies have shown that drought reduces CK levels, and we propose this to be a mechanism of adaptation to water deficiency: the reduced CK levels suppress growth and reduce stomatal density, both of which reduce transpiration, thereby increasing tolerance to prolonged drought conditions.

  5. Geometric complexity is increased in in vitro activated platelets.

    PubMed

    Bianciardi, Giorgio

    2015-06-01

    This article investigates the use of computerized fractal analysis for objective characterization of the complexity of platelets in vitro stimulated by low level thrombin (0.02 U mL(-1) ), collected from healthy individuals and observed by means of transmission electron microscopy. Platelet boundaries were extracted by means of automatically image analysis. Local fractal dimension was evaluated by the box-counting technique (measure of geometric complexity of the platelet outline). The results showed that the platelet boundary is fractal when observed by transmission electron microscopy and that, after an in vitro platelet activation test, the shape of platelets present increased geometric complexity in comparison to the no stimulated platelets (P < 0.001), with 100% correct classification. Computerized fractal analysis of platelet shape by transmission electron microscopy can provide accurate, quantitative, data to study platelet activation. The results may play important roles in the evaluation of the platelets status in pathological conditions, like as atherosclerosis and diabetes mellitus, where in in vivo activated platelets have been described.

  6. NOX Activity Is Increased in Mild Cognitive Impairment

    PubMed Central

    Gupta, Sunita; Parrino, Taryn E.; Knight, Alecia G.; Ebenezer, Philip J.; Weidner, Adam M.; LeVine, Harry; Keller, Jeffrey N.; Markesbery, William R.

    2010-01-01

    Abstract This study was undertaken to investigate the profile of NADPH oxidase (NOX) in the clinical progression of Alzheimer's disease (AD). Specifically, NOX activity and expression of the regulatory subunit p47phox and the catalytic subunit gp91phox was evaluated in affected (superior and middle temporal gyri) and unaffected (cerebellum) brain regions from a longitudinally followed group of patients. This group included both control and late-stage AD subjects, and also subjects with preclinical AD and with amnestic mild cognitive impairment (MCI) to evaluate the profile of NOX in the earliest stages of dementia. Data show significant elevations in NOX activity and expression in the temporal gyri of MCI patients as compared with controls, but not in preclinical or late-stage AD samples, and not in the cerebellum. Immunohistochemical evaluations of NOX expression indicate that whereas microglia express high levels of gp91phox, moderate levels of gp91phox also are expressed in neurons. Finally, in vitro experiments showed that NOX inhibition blunted the ability of oligomeric amyloid beta peptides to injure cultured neurons. Collectively, these data show that NOX expression and activity are upregulated specifically in a vulnerable brain region of MCI patients, and suggest that increases in NOX-associated redox pathways in neurons might participate in the early pathogenesis of AD. Antioxid. Redox Signal. 12, 1371–1382. PMID:19929442

  7. Increased nitrite reductase activity of fetal versus adult ovine hemoglobin

    PubMed Central

    Blood, Arlin B.; Tiso, Mauro; Verma, Shilpa T.; Lo, Jennifer; Joshi, Mahesh S.; Azarov, Ivan; Longo, Lawrence D.; Gladwin, Mark T.; Kim-Shapiro, Daniel B.; Power, Gordon G.

    2009-01-01

    Growing evidence indicates that nitrite, NO2−, serves as a circulating reservoir of nitric oxide (NO) bioactivity that is activated during physiological and pathological hypoxia. One of the intravascular mechanisms for nitrite conversion to NO is a chemical nitrite reductase activity of deoxyhemoglobin. The rate of NO production from this reaction is increased when hemoglobin is in the R conformation. Because the mammalian fetus exists in a low-oxygen environment compared with the adult and is exposed to episodes of severe ischemia during the normal birthing process, and because fetal hemoglobin assumes the R conformation more readily than adult hemoglobin, we hypothesized that nitrite reduction to NO may be enhanced in the fetal circulation. We found that the reaction was faster for fetal than maternal hemoglobin or blood and that the reactions were fastest at 50–80% oxygen saturation, consistent with an R-state catalysis that is predominant for fetal hemoglobin. Nitrite concentrations were similar in blood taken from chronically instrumented normoxic ewes and their fetuses but were elevated in response to chronic hypoxia. The findings suggest an augmented nitrite reductase activity of fetal hemoglobin and that the production of nitrite may participate in the regulation of vascular NO homeostasis in the fetus. PMID:19028797

  8. The Potential for Pocket Parks to Increase Physical Activity

    PubMed Central

    Cohen, Deborah A.; Marsh, Terry; Williamson, Stephanie; Han, Bing; Derose, Kathryn Pitkin; Golinelli, Daniella; McKenzie, Thomas L.

    2014-01-01

    Purpose To assess the use of new pocket parks in low-income neighborhoods. Setting Los Angeles Subjects Parks users and residents living within ½ mile of 3 pocket parks and 15 neighborhood parks Intervention The creation of pocket parks Design Quasi-experimental post-only comparison Measures We used the System of Observing Play and Recreation in Communities (SOPARC) to measure park use and park-based physical activity and surveyed park users and residents about their park use. Analysis We surveyed 392 and 432 household members within one-half mile of the 3 pocket parks before and after park construction, respectively, as well as 71 pocket park users and compared them to 992 neighborhood park users and 342 residents living within ½ mile of other neighborhood parks. We compared pocket park use to playground area use in the larger neighborhood parks. We used descriptive statistics and Generalized Estimating Equations for the analysis. Results Overall, pocket park use compared favorably in promoting moderate-to-vigorous physical activity with that of existing playground space in nearby parks and they were cost-effective at $0.73/MET hour gained. Pocket park visitors walked an average of 0.25 miles to get there. Conclusions Pocket parks, when perceived as attractive and safe destinations, may increase physical activity by encouraging families with children to walk there. Additional strategies and programs may be needed to encourage more residents to use the parks. PMID:24380461

  9. Effect of increasing the choice of active options on children’s physical activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objectives: To determine whether increasing the choice of physical activity options increases the duration and intensity of children’s physical activity. Design: This cross-sectional laboratory study included gender (male, female) and choice group [single toy (no choice), three toys (low choice...

  10. Phylogenetic analysis of the nuclear alcohol dehydrogenase (Adh) gene family in Carex section Acrocystis (Cyperaceae) and combined analyses of Adh and nuclear ribosomal ITS and ETS sequences for inferring species relationships.

    PubMed

    Roalson, Eric H; Friar, Elizabeth A

    2004-12-01

    We analyzed sequence variation for the alcohol dehydrogenase (Adh) gene family in Carex section Acrocystis (Cyperaceae) to reconstruct Adh gene trees for Acrocystis species and to characterize the structure of the Adh gene family in Carex. Two Adh loci were included with ITS and ETS sequences in a combined Bayesian inference analysis of Carex section Acrocystis to gain a better understanding of species relationships in the section. In addition, we comment on how the results presented here contribute to our knowledge of the birth-death process of the Adh gene family in angiosperms. It appears that the structure of the Adh gene family in Carex is complex with possibly six loci present in the gene family. Additionally, variation among Acrocystis species within loci is quite low, and there is little phylogenetic resolution in the individual datasets. Bayesian inference analysis of the combined ITS, ETS, Adh1, and Adh2 datasets resulted in a moderately well-supported phylogenetic hypothesis of relationships in the section which is discussed in relation to previous hypotheses of relationships.

  11. Cellulosic Ethanol Production by Recombinant Cellulolytic Bacteria Harbouring pdc and adh II Genes of Zymomonas mobilis

    PubMed Central

    Piriya, P. Sobana; Vasan, P. Thirumalai; Padma, V. S.; Vidhyadevi, U.; Archana, K.; Vennison, S. John

    2012-01-01

    The ethanol fermenting genes such as pyruvate decarboxylase (pdc) and alcohol dehydrogenase II (adh II) were cloned from Zymomonas mobilis and transformed into three different cellulolytic bacteria, namely Enterobacter cloacae JV, Proteus mirabilis JV and Erwinia chrysanthemi and their cellulosic ethanol production capability was studied. Recombinant E. cloacae JV was found to produce 4.5% and 3.5% (v/v) ethanol, respectively, when CMC and 4% NaOH pretreated bagasse were used as substrates, whereas recombinant P. mirabilis and E. chrysanthemi with the same substrates could only produce 4%, 3.5%, 1%, and 1.5 % of ethanol, respectively. The recombinant E. cloacae strain produced twofold higher percentage of ethanol than the wild type. The recombinant E. cloacae strain could be improved further by increasing its ethanol tolerance capability through media optimization and also by combining multigene cellulase expression for enhancing ethanol production from various types of lignocellulosic biomass so that it can be used for industrial level ethanol production. PMID:22919503

  12. Use of active video games to increase physical activity in children: a (virtual) reality?

    PubMed

    Foley, Louise; Maddison, Ralph

    2010-02-01

    There has been increased research interest in the use of active video games (in which players physically interact with images onscreen) as a means to promote physical activity in children. The aim of this review was to assess active video games as a means of increasing energy expenditure and physical activity behavior in children. Studies were obtained from computerized searches of multiple electronic bibliographic databases. The last search was conducted in December 2008. Eleven studies focused on the quantification of the energy cost associated with playing active video games, and eight studies focused on the utility of active video games as an intervention to increase physical activity in children. Compared with traditional nonactive video games, active video games elicited greater energy expenditure, which was similar in intensity to mild to moderate intensity physical activity. The intervention studies indicate that active video games may have the potential to increase free-living physical activity and improve body composition in children; however, methodological limitations prevent definitive conclusions. Future research should focus on larger, methodologically sound intervention trials to provide definitive answers as to whether this technology is effective in promoting long-term physical activity in children.

  13. NIMS Observes Increased Activity at Loki Patera, Io

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Loki Patera, historically the most active and persistent hot spot on Io, is located on the hemisphere of Io always facing Jupiter. Loki Patera was the site of two plumes during the Voyager encounters, which were not seen during the early orbits of Galileo. Ground-based observers reported Loki Patera to be unusually dim during this time, marking a period of low volcanic activity.

    On 21 February 1997, during Galileo's sixth orbit, the Near Infrared Mapping Spectrometer (NIMS) on the Galileo spacecraft observed Io in daylight from a range of approximately 703,000 km (440,000 miles). The image on the left shows Io at a wavelength of 2.95 microns. Loki Patera is seen to be relatively quiescent (at longer wavelengths which are more sensitive to thermal emission, Loki Patera is more noticeable).

    A few weeks later, on March 12th 1997, ground based observers using the Infra-Red Telescope Facility (IRTF) on Mauna Kea, Hawaii, observed an intense brightening in the Loki region, so much that Loki was contributing 75% of Io's in-eclipse flux for this hemisphere. A large eruption was taking place! Other ground-based observations through March, April and May tracked the course of the activity and confirmed its location at Loki Patera.

    On 4 April 1997, NIMS again observed Io during the seventh orbit from a range of 556,000 km (348,000 miles), with Loki Patera positioned in darkness, close to the limb. The image on the right shows the increase in activity at Loki Patera, again at 2.95 microns. A preliminary single temperature fit to NIMS orbit seven Loki Patera hot spot data yields a temperature of 500 K and an area of over 800 square kilometers. That the image is so bright at this wavelength is an indication of the areal extent of the activity. It is also probable that some part of the volcanic material being erupted or exposed is at considerably higher temperatures than that of the 500 K single-temperature fit.

    Io is under observation by ground-based observers under

  14. Increased microglial catalase activity in multiple sclerosis grey matter.

    PubMed

    Gray, Elizabeth; Kemp, Kevin; Hares, Kelly; Redondo, Julianna; Rice, Claire; Scolding, Neil; Wilkins, Alastair

    2014-04-22

    Chronic demyelination, on-going inflammation, axonal loss and grey matter neuronal injury are likely pathological processes that contribute to disease progression in multiple sclerosis (MS). Although the precise contribution of each process and their aetiological substrates is not fully known, recent evidence has implicated oxidative damage as a major cause of tissue injury in MS. The degree of tissue injury caused by oxidative molecules, such as reactive oxygen species (ROS), is balanced by endogenous anti-oxidant enzymes which detoxify ROS. Understanding endogenous mechanisms which protect the brain against oxidative injury in MS is important, since enhancing anti-oxidant responses is a major therapeutic strategy for preventing irreversible tissue injury in the disease. Our aims were to determine expression and activity levels of the hydrogen peroxide-reducing enzyme catalase in MS grey matter (GM). In MS GM, a catalase enzyme activity was elevated compared to control GM. We measured catalase protein expression by immune dot-blotting and catalase mRNA by a real-time polymerase chain reaction (RT-PCR). Protein analysis studies showed a strong positive correlation between catalase and microglial marker IBA-1 in MS GM. In addition, calibration of catalase mRNA level with reference to the microglial-specific transcript AIF-1 revealed an increase in this transcript in MS. This was reflected by the extent of HLA-DR immunolabeling in MS GM which was significantly elevated compared to control GM. Collectively, these observations provide evidence that microglial catalase activity is elevated in MS grey matter and may be an important endogenous anti-oxidant defence mechanism in MS.

  15. Writer's cramp: increased dorsal premotor activity during intended writing.

    PubMed

    Delnooz, Cathérine C S; Helmich, Rick C; Medendorp, W P; Van de Warrenburg, Bart P C; Toni, Ivan

    2013-03-01

    Simple writer's cramp (WC) is a task-specific form of dystonia, characterized by abnormal movements and postures of the hand during writing. It is extremely task-specific, since dystonic symptoms can occur when a patient uses a pencil for writing, but not when it is used for sharpening. Maladaptive plasticity, loss of inhibition, and abnormal sensory processing are important pathophysiological elements of WC. However, it remains unclear how those elements can account for its task-specificity. We used fMRI to isolate cerebral alterations associated with the task-specificity of simple WC. Subjects (13 simple WC patients, 20 matched controls) imagined grasping a pencil to either write with it or sharpen it. On each trial, we manipulated the pencil's position and the number of imagined movements, while monitoring variations in motor output with electromyography. We show that simple WC is characterized by abnormally increased activity in the dorsal premotor cortex (PMd) when imagined actions are specifically related to writing. This cerebral effect was independent from the known deficits in dystonia in generating focal motor output and in processing somatosensory feedback. This abnormal activity of the PMd suggests that the task-specific element of simple WC is primarily due to alterations at the planning level, in the computations that transform a desired action outcome into the motor commands leading to that action. These findings open the way for testing the therapeutic value of interventions that take into account the computational substrate of task-specificity in simple WC, e.g. modulations of PMd activity during the planning phase of writing.

  16. Three-Dimensional Shallow Water Adaptive Hydraulics (ADH-SW3): Turbulence Closure

    DTIC Science & Technology

    2015-06-01

    ER D C/ CH L CR -1 5- 1 Three-Dimensional Shallow Water Adaptive Hydraulics (ADH-SW3): Turbulence Closure Co as ta l a nd H yd ra ul ic...military engineering, geospatial sciences, water resources, and environmental sciences for the Army, the Department of Defense, civilian agencies, and our...library at http://acwc.sdp.sirsi.net/client/default. ERDC/CHL CR-15-1 June 2015 Three-Dimensional Shallow Water Adaptive Hydraulics (ADH-SW3

  17. Increased oscillatory theta activation evoked by violent digital game events.

    PubMed

    Salminen, Mikko; Ravaja, Niklas

    2008-04-11

    The authors examined electroencephalographic (EEG) oscillatory responses to two violent events, the player character wounding and killing an opponent character with a gun, in the digital game James Bond 007: NightFire. EEG was recorded from 25 (16 male) right-handed healthy young adults. EEG data were segmented into one 1-s baseline epoch before each event and two 1-s epochs after event onset. Power estimates (microV(2)) were derived with the fast Fourier transform (FFT) for each artefact free event. Both of the studied events evoked increased occipital theta (4-6Hz) responses as compared to the pre-event baseline. The wounding event evoked also increased occipital high theta (6-8Hz) response and the killing event evoked low alpha (8-10Hz) asymmetry over the central electrodes, both relative to the pre-event baseline. The results are discussed in light of facial electromyographic and electrodermal activity responses evoked by these same events, and it is suggested that the reported EEG responses may be attributable to affective processes related to these violent game events.

  18. Acid-activated biochar increased sulfamethazine retention in soils.

    PubMed

    Vithanage, Meththika; Rajapaksha, Anushka Upamali; Zhang, Ming; Thiele-Bruhn, Sören; Lee, Sang Soo; Ok, Yong Sik

    2015-02-01

    Sulfamethazine (SMZ) is an ionizable and highly mobile antibiotic which is frequently found in soil and water environments. We investigated the sorption of SMZ onto soils amended with biochars (BCs) at varying pH and contact time. Invasive plants were pyrolyzed at 700 °C and were further activated with 30 % sulfuric (SBBC) and oxalic (OBBC) acids. The sorption rate of SMZ onto SBBC and OBBC was pronouncedly pH dependent and was decreased significantly when the values of soil pH increased from 3 to 5. Modeled effective sorption coefficients (K D,eff) values indicated excellent sorption on SBBC-treated loamy sand and sandy loam soils for 229 and 183 L/kg, respectively. On the other hand, the low sorption values were determined for OBBC- and BBC700-treated loamy sand and sandy loam soils. Kinetic modeling demonstrated that the pseudo second order model was the best followed by intra-particle diffusion and the Elovich model, indicating that multiple processes govern SMZ sorption. These findings were also supported by sorption edge experiments based on BC characteristics. Chemisorption onto protonated and ligand containing functional groups of the BC surface, and diffusion in macro-, meso-, and micro-pores of the acid-activated BCs are the proposed mechanisms of SMZ retention in soils. Calculated and experimental q e (amount adsorbed per kg of the adsorbent at equilibrium) values were well fitted to the pseudo second order model, and the predicted maximum equilibrium concentration of SBBC for loamy sand soils was 182 mg/kg. Overall, SBBC represents a suitable soil amendment because of its high sorption rate of SMZ in soils.

  19. Immobilization induces a very rapid increase in osteoclast activity

    NASA Astrophysics Data System (ADS)

    Heer, Martina; Baecker, Natalie; Mika, Claudia; Boese, Andrea; Gerzer, Rupert

    2005-07-01

    We studied in a randomized, strictly controlled cross-over design, the effects of 6 days 6° head-down tilt bed rest (HDT) in eight male healthy subjects in our metabolic ward. The study consisted of two periods (phases) of 11 days each in order to allow for the test subjects being their own controls. Both study phases were identical with respect to environmental conditions, study protocol and diet. Two days before arriving in the metabolic ward the subjects started with a diet. The diet was continued in the metabolic ward. The metabolic ward period (1l days) was divided into three parts: 4 ambulatory days, 6 days either HDT or control and 1 recovery day. Continuous urine collection started on the first day in the metabolic ward to analyze calcium excretion and bone resorption markers. On the 2nd ambulatory day in the metabolic ward and on the 5th day in HDT or control blood was drawn to analyze serum calcium, parathyroid hormone, and bone formation markers. Urinary calcium excretion was, as early as the first day in immobilization, increased (p<0.01). CTX- and NTX-excretion stayed unchanged in the first 24 h in HDT compared to the control. But already on the 2nd day of immobilization, both bone resorption markers significantly increased. We conclude from these results—pronounced rise of bone resorption markers—that already 24 h of immobilization induce a significant rise in osteoclast activity in healthy subjects. Thus, it appears possible to use short-term bed rest studies as a first step for the development of countermeasures to immobilization.

  20. Increased 5. cap alpha. -reductase activity in idiopathic hirsutism

    SciTech Connect

    Serafini, P.; Lobo, R.A.

    1985-01-01

    In vitro, genital skin 5..cap alpha..-reductase activity (5..cap alpha..-RA) was measured in ten hirsute women with normal androgen levels (idiopathic hirsutism (IH)) and in ten hirsute women with elevated androgen levels (polycystic ovary syndrome (PCO)) in order to determine the influence of secreted androgens on 5..cap alpha..-RA. In vitro 5..cap alpha..-RA was assessed by incubations of skin with /sup 14/C-testosterone (T) for 2 hours, after which steroids were separated and the radioactivity of dihydrotestosterone (DHT) and 5..cap alpha..-androstane 3..cap alpha..-17..beta..-estradiol (3..cap alpha..-diol) in specific eluates were determined. All androgens were normal in IH with the exception of higher levels of 3..cap alpha..-diol glucuronide which were similar to the levels of PCO. The conversion ratio (CR) of T to DHT in IH and PCO were similar, yet significantly greater than the CR of control subjects. The CR of T to 3..cap alpha..-diol in IH and PCO were similar, yet higher than in control subjects. Serum androgens showed no correlation with 5..cap alpha..-RA, while the CR of T to DHT showed a significant positive correlation with the Ferriman and Gallwey score. The increased 5..cap alpha..-RA in IH appears to be independent of serum androgen levels and is, therefore, an inherent abnormality. The term idiopathic is a misnomer, because hirsutism in these patients may be explained on the basis of increased skin 5..cap alpha..-RA.

  1. Altered behavior in spotted hyenas associated with increased human activity

    USGS Publications Warehouse

    Boydston, Erin E.; Kapheim, Karen M.; Watts, Heather E.; Szykman, Micaela; Holekamp, Kay E.

    2003-01-01

    To investigate how anthropogenic activity might affect large carnivores, we studied the behaviour of spotted hyenas (Crocuta crocuta) during two time periods. From 1996 to 1998, we documented the ecological correlates of space utilization patterns exhibited by adult female hyenas defending a territory at the edge of a wildlife reserve in Kenya. Hyenas preferred areas near dense vegetation but appeared to avoid areas containing the greatest abundance of prey, perhaps because these were also the areas of most intensive livestock grazing. We then compared hyena behaviour observed in 1996–98 with that observed several years earlier and found many differences. Female hyenas in 1996–98 were found farther from dens, but closer to dense vegetation and to the edges of their territory, than in 1988–90. Recent females also had larger home ranges, travelled farther between consecutive sightings, and were more nocturnal than in 1988–90. Finally, hyenas occurred in smaller groups in 1996–98 than in 1988–90. We also found several changes in hyena demography between periods. We next attempted to explain differences observed between time periods by testing predictions of hypotheses invoking prey abundance, climate, interactions with lions, tourism and livestock grazing. Our data were consistent with the hypothesis that increased reliance on the reserve for livestock grazing was responsible for observed changes. That behavioural changes were not associated with decreased hyena population density suggests the behavioural plasticity typical of this species may protect it from extinction.

  2. Platelet-activating factor-induced increases in glucose kinetics

    SciTech Connect

    Lang, C.H.; Dobrescu, C.; Hargrove, D.M.; Bagby, G.J.; Spitzer, J.J. )

    1988-02-01

    Platelet-activating factor (PAF) is a postulated mediator of many of the early hemodynamic effects of endotoxin. The aim of the present study was to determine whether in vivo administration of PAF could produce alterations in whole-body glucose metabolism that would mimic those seen during endotoxemia. Glucose kinetics were assessed in chronically catheterized conscious rats by the constant infusion of (6-{sup 3}H)- and (U-{sup 14}C)glucose before and for 4 h after either a bolus injection or a constant infusion of PAF. The bolus injection of PAF elevated the rate of glucose appearance (R{sub a}; 44%) for 1.5 h. The lower PAF infusion rate decreased blood pressure 11% to 104 mmHg, whereas the higher infusion rate decreased pressure 34% to 77 mmHg. Both PAF infusion rates produced elevations in plasma glucose and glucose R{sub a} throughout the 4-h infusion period in a dose-related manner. The PAF infusions also induced dose-related increases in plasma glucagon and catecholamine levels throughout the infusion period. Because the constant infusion of PAF did stimulate many of the hemodynamic and metabolic alterations produced by endotoxin, this study provides additional support for the potential importance of PAF as a mediator of the early hemodynamic and metabolic sequela of endotoxin shock. Furthermore, the PAF-induced changes in glucose metabolism appear to be mediated by the resultant elevation in plasma catecholamines.

  3. Increasing SK2 channel activity impairs associative learning

    PubMed Central

    McKay, Bridget M.; Oh, M. Matthew; Galvez, Roberto; Burgdorf, Jeffrey; Kroes, Roger A.; Weiss, Craig; Adelman, John P.; Moskal, Joseph R.

    2012-01-01

    Enhanced intrinsic neuronal excitability of hippocampal pyramidal neurons via reductions in the postburst afterhyperpolarization (AHP) has been hypothesized to be a biomarker of successful learning. This is supported by considerable evidence that pharmacologic enhancement of neuronal excitability facilitates learning. However, it has yet to be demonstrated that pharmacologic reduction of neuronal excitability restricted to the hippocampus can retard acquisition of a hippocampus-dependent task. Thus, the present study was designed to address this latter point using a small conductance potassium (SK) channel activator NS309 focally applied to the dorsal hippocampus. SK channels are important contributors to intrinsic excitability, as measured by the medium postburst AHP. NS309 increased the medium AHP and reduced excitatory postsynaptic potential width of CA1 neurons in vitro. In vivo, NS309 reduced the spontaneous firing rate of CA1 pyramidal neurons and impaired trace eyeblink conditioning in rats. Conversely, trace eyeblink conditioning reduced levels of SK2 channel mRNA and protein in the hippocampus. Therefore, the present findings indicate that modulation of SK channels is an important cellular mechanism for associative learning and further support postburst AHP reductions in hippocampal pyramidal neurons as a biomarker of successful learning. PMID:22552186

  4. Meta-Analyses of ALDH2 and ADH1B with Alcohol Dependence in Asians

    ERIC Educational Resources Information Center

    Luczak, Susan E.; Glatt, Stephen J.; Wall, Tamara J.

    2006-01-01

    Meta-analyses were conducted to determine the magnitude of relationships between polymorphisms in 2 genes, ALDH2 and ADH1B, with alcohol dependence in Asians. For each gene, possession of 1 variant [asterisk]2 allele was protective against alcohol dependence, and possession of a 2nd [asterisk]2 allele did not offer significant additional…

  5. Nest predation increases with parental activity: Separating nest site and parental activity effects

    USGS Publications Warehouse

    Martin, T.E.; Scott, J.; Menge, C.

    2000-01-01

    Alexander Skutch hypothesized that increased parental activity can increase the risk of nest predation. We tested this hypothesis using ten open-nesting bird species in Arizona, USA. Parental activity was greater during the nestling than incubation stage because parents visited the nest frequently to feed their young during the nestling stage. However, nest predation did not generally increase with parental activity between nesting stages across the ten study species. Previous investigators have found similar results. We tested whether nest site effects might yield higher predation during incubation because the most obvious sites are depredated most rapidly. We conducted experiments using nest sites from the previous year to remove parental activity. Our results showed that nest sites have highly repeatable effects on nest predation risk; poor nest sites incurred rapid predation and caused predation rates to be greater during the incubation than nestling stage. This pattern also was exhibited in a bird species with similar (i.e. controlled) parental activity between nesting stages. Once nest site effects are taken into account, nest predation shows a strong proximate increase with parental activity during the nestling stage within and across species. Parental activity and nest sites exert antagonistic influences on current estimates of nest predation between nesting stages and both must be considered in order to understand current patterns of nest predation, which is an important source of natural selection.

  6. Nest predation increases with parental activity: separating nest site and parental activity effects.

    PubMed Central

    Martin, T E; Scott, J; Menge, C

    2000-01-01

    Alexander Skutch hypothesized that increased parental activity can increase the risk of nest predation. We tested this hypothesis using ten open-nesting bird species in Arizona, USA. Parental activity was greater during the nestling than incubation stage because parents visited the nest frequently to feed their young during the nestling stage. However, nest predation did not generally increase with parental activity between nesting stages across the ten study species. Previous investigators have found similar results. We tested whether nest site effects might yield higher predation during incubation because the most obvious sites are depredated most rapidly. We conducted experiments using nest sites from the previous year to remove parental activity. Our results showed that nest sites have highly repeatable effects on nest predation risk; poor nest sites incurred rapid predation and caused predation rates to be greater during the incubation than nestling stage. This pattern also was exhibited in a bird species with similar (i.e. controlled) parental activity between nesting stages. Once nest site effects are taken into account, nest predation shows a strong proximate increase with parental activity during the nestling stage within and across species. Parental activity and nest sites exert antagonistic influences on current estimates of nest predation between nesting stages and both must be considered in order to understand current patterns of nest predation, which is an important source of natural selection. PMID:11413645

  7. Activation of protease activated receptor 1 increases the excitability of the dentate granule neurons of hippocampus

    PubMed Central

    2011-01-01

    Protease activated receptor-1 (PAR1) is expressed in multiple cell types in the CNS, with the most prominent expression in glial cells. PAR1 activation enhances excitatory synaptic transmission secondary to the release of glutamate from astrocytes following activation of astrocytically-expressed PAR1. In addition, PAR1 activation exacerbates neuronal damage in multiple in vivo models of brain injury in a manner that is dependent on NMDA receptors. In the hippocampal formation, PAR1 mRNA appears to be expressed by a subset of neurons, including granule cells in the dentate gyrus. In this study we investigate the role of PAR activation in controlling neuronal excitability of dentate granule cells. We confirm that PAR1 protein is expressed in neurons of the dentate cell body layer as well as in astrocytes throughout the dentate. Activation of PAR1 receptors by the selective peptide agonist TFLLR increased the intracellular Ca2+ concentration in a subset of acutely dissociated dentate neurons as well as non-neuronal cells. Bath application of TFLLR in acute hippocampal slices depolarized the dentate gyrus, including the hilar region in wild type but not in the PAR1-/- mice. PAR1 activation increased the frequency of action potential generation in a subset of dentate granule neurons; cells in which PAR1 activation triggered action potentials showed a significant depolarization. The activation of PAR1 by thrombin increased the amplitude of NMDA receptor-mediated component of EPSPs. These data suggest that activation of PAR1 during normal function or pathological conditions, such as during ischemia or hemorrhage, can increase the excitability of dentate granule cells. PMID:21827709

  8. Engaging parents to increase youth physical activity: A systematic review

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Parents are often involved in interventions to engage youth in physical activity, but it is not clear which methods for involving parents are effective. A systematic review was conducted of interventions with physical activity and parental components among healthy youth to identify how best to invol...

  9. Opportunities for Public Health to Increase Physical Activity Among Youths

    PubMed Central

    Dorn, Joan M.; Fulton, Janet E.; Janz, Kathleen F.; Lee, Sarah M.; McKinnon, Robin A.; Pate, Russell R.; Pfeiffer, Karin A.; Young, Deborah Rohm; Troiano, Richard P.; Lavizzo-Mourey, Risa

    2015-01-01

    Despite the well-known benefits of youths engaging in 60 or more minutes of daily physical activity, physical inactivity remains a significant public health concern. The 2008 Physical Activity Guidelines for Americans (PAG) provides recommendations on the amount of physical activity needed for overall health; the PAG Midcourse Report (2013) describes effective strategies to help youths meet these recommendations. Public health professionals can be dynamic change agents where youths live, learn, and play by changing environments and policies to empower youths to develop regular physical activity habits to maintain throughout life. We have summarized key findings from the PAG Midcourse Report and outlined actions that public health professionals can take to ensure that all youths regularly engage in health-enhancing physical activity. PMID:25602864

  10. Nurses’ perceptions of medication adherence in schizophrenia: results of the ADHES cross-sectional questionnaire survey

    PubMed Central

    Emsley, Robin; Alptekin, Koksal; Azorin, Jean-Michel; Cañas, Fernando; Dubois, Vincent; Gorwood, Philip; Haddad, Peter M.; Naber, Dieter; Olivares, José Manuel; Papageorgiou, Georgios; Roca, Miguel; Thomas, Pierre; Hargarter, Ludger; Schreiner, Andreas

    2015-01-01

    Objectives: Poor adherence to antipsychotic treatment is a widespread problem within schizophrenia therapy with serious consequences including increased risks of relapse and rehospitalization. Mounting evidence supports the key roles that nurses play in monitoring patient progress and facilitating long-term treatment adherence. The Adherencia Terapéutica en la Esquizofrenia (ADHES) nurses’ survey was designed to assess the opinions of nurses on the causes and management of partial/nonadherence to antipsychotic medication. Methods: A questionnaire-based cross-sectional survey of 4120 nurses from Europe, the Middle East and Africa. Interpretation of results was based on a descriptive comparison of responses. Results: Nurses perceived 54% of patients seen in the preceding month to be partially/nonadherent to treatment. Most nurses (90%) reported some level of experience with administration of long-acting injectable (LAI) antipsychotics, with 24% of nurses administering >10 injections per month. The majority (85%) of nurses surveyed believed that improving adherence would improve patient outcomes. Nearly half (49%) reported that most of their patients depend on a family member or other nonprofessional carer to remind them to take their medication as prescribed. A similar proportion of nurses (43%) reported that most of their patients relied on a professional to remind them to take medication. Most nurses (92%) felt that ensuring continuous medication with LAI antipsychotics would yield long-term benefits for patients, but their opinion was that over a third of patients were unaware of LAI antipsychotic treatments. In a series of forced options, the strategy used most often by respondents (89%) to promote medication adherence was to build trusting relationships with patients while listening to and interpreting their needs and concerns. Respondents also rated this as the most effective strategy that they used (48%). Conclusion: Nurses are highly aware of adherence

  11. Peroxisome proliferator-activated receptor delta activation leads to increased transintestinal cholesterol efflux

    PubMed Central

    Vrins, Carlos L. J.; van der Velde, Astrid E.; van den Oever, Karin; Levels, Johannes H. M.; Huet, Stephane; Oude Elferink, Ronald P. J.; Kuipers, Folkert; Groen, Albert K.

    2009-01-01

    Peroxisome proliferator-activated receptor delta (PPARδ) is involved in regulation of energy homeostasis. Activation of PPARδ markedly increases fecal neutral sterol secretion, the last step in reverse cholesterol transport. This phenomenon can neither be explained by increased hepatobiliary cholesterol secretion, nor by reduced cholesterol absorption. To test the hypothesis that PPARδ activation leads to stimulation of transintestinal cholesterol efflux (TICE), we quantified it by intestine perfusions in FVB mice treated with PPARδ agonist GW610742. To exclude the effects on cholesterol absorption, mice were also treated with cholesterol absorption inhibitor ezetimibe or ezetimibe/GW610742. GW601742 treatment had little effect on plasma lipid levels but stimulated both fecal neutral sterol excretion (∼200%) and TICE (∼100%). GW610742 decreased intestinal Npc1l1 expression but had no effect on Abcg5/Abcg8. Interestingly, expression of Rab9 and LIMPII, encoding proteins involved in intracellular cholesterol trafficking, was increased upon PPARδ activation. Although treatment with ezetimibe alone had no effect on TICE, it reduced the effect of GW610742 on TICE. These data show that activation of PPARδ stimulates fecal cholesterol excretion in mice, primarily by the two-fold increase in TICE, indicating that this pathway provides an interesting target for the development of drugs aiming at the prevention of atherosclerosis. PMID:19439761

  12. ROFA INCREASES CASPASE-3 ACTIVITY IN HUMAN ALVEOLAR MACRAPHAGE

    EPA Science Inventory

    Exposure to air pollution particles produces pulmonary inflammation and injury, but the mechanisms of this injury are unclear. Apoptosis, involving activation of caspases, may be one potential mechanism. In this study, we hypothesized that ROFA, a constituent of air pollution...

  13. State Legislation Related to Increasing Physical Activity: 2006-2012

    PubMed Central

    Eyler, Amy A.; Budd, Elizabeth; Camberos, Gabriela J.; Yan, Yan; Brownson, Ross C.

    2016-01-01

    Background Strategies to improve physical activity prevalence often include policy and environmental changes. State-level policies can be influential in supporting access and opportunities for physical activity in schools and communities. The purpose of this study was to explore the prevalence of state legislation related to physical activity and identify the correlates of enactment of this legislation. Methods An online legislative database was used to collect bills from 50 states in the U.S. from 2006-2012 for ten topics related to physical activity. Bills were coded for content and compiled into a database with state-level variables (e.g., obesity prevalence). With enactment status as the outcome, bivariate and multivariate analyses were conducted. Results Of the 1542 bills related to physical activity introduced, 30% (N=460) were enacted. Bills on public transportation and trails were more likely to be enacted than those without these topics. Primary sponsorship by the Republican Party, bipartisan sponsorship, and mention of specific funding amounts were also correlates of enactment. Conclusion Policy surveillance of bills and correlates of enactment are important for understanding patterns in legislative support for physical activity. This information can be used to prioritize advocacy efforts and identify ways for research to better inform policy. PMID:26104603

  14. Dependence of Ethanolic Fermentation, Cytoplasmic pH Regulation, and Viability on the Activity of Alcohol Dehydrogenase in Hypoxic Maize Root Tips 1

    PubMed Central

    Roberts, Justin K. M.; Chang, Keejong; Webster, Cecelia; Callis, Judy; Walbot, Virginia

    1989-01-01

    We examined the role of alcohol dehydrogenase (ADH) in the metabolism and survival of hypoxic maize (Zea mays L.) root tips. The dependence of the rate of ethanolic fermentation, cytoplasmic pH, and viability on the activity of ADH in maize root tips during extreme hypoxia was determined. Maize lines with ADH activities differing over about a 200-fold range were studied. Effects of genetic background were controlled by comparing pairs of F4 progeny of crosses between mutant (low ADH activity) and reference inbred lines. The capacity of hypoxic root tips to perform ethanolic fermentation exhibited a dependence on ADH activity only at activities found in Adh 1 nulls. The ability of maize root tips to withstand prolonged and extreme hypoxia was like-wise independent of ADH activity, except at the lowest activities. Root tips that exhibited lower tolerance of hypoxia had more acidic cytoplasm during extreme hypoxia. We conclude that the activity of ADH in normal maize root tips does not limit the capacity for energy production via fermentation, and does not determine viability under extreme hypoxia. The significance of the induction of ADH activity in plants by hypoxia is discussed. PMID:16666696

  15. Dependence of ethanolic fermentation, cytoplasmic pH regulation, and viability on the activity of alcohol dehydrogenase in hypoxic maize root tips

    SciTech Connect

    Roberts, J.; Chang, Keejong; Webster, C.; Callis, J.; Walbot, V. Stanford Univ., CA )

    1989-04-01

    We examined the role of alcohol dehydrogenase (ADH) in the metabolism and survival of hypoxic maize (Zea mays L.) root tips. The dependence of the rate of ethanolic fermentation, cytoplasmic pH, and viability on the activity of ADH in maize root tips during extreme hypoxia was determined. Maize lines with ADH activities differing over about a 200-fold range were studied. Effects of genetic background were controlled by comparing pairs of F4 progeny of crosses between mutant (low ADH activity) and reference inbred lines. The capacity of hypoxic root tips to perform ethanolic fermentation exhibited a dependence on ADH activity only at activities found in Adh 1 nulls. The ability of maize root tips to withstand prolonged and extreme hypoxia was likewise independent of ADH activity, except at the lowest activities. Root tips that exhibited lower tolerance of hypoxia had more acidic cytoplasm during extreme hypoxia. We conclude that the activity of ADH in normal maize root tips does not limit the capacity for energy production via fermentation, and does not determine viability under extreme hypoxia. The significance of the induction of ADH activity in plants by hypoxia is discussed.

  16. Dipeptides Increase Functional Activity of Human Skin Fibroblasts.

    PubMed

    Malinin, V V; Durnova, A O; Polyakova, V O; Kvetnoi, I M

    2015-05-01

    We analyzed the effect of dipeptide Glu-Trp and isovaleroyl-Glu-Trp in concentrations of 0.2, 2 and 20 μg/ml and Actovegin preparation on functional activity of human skin fibroblasts. Dipeptides, especially Glu-Trp, produce a stimulating effect on human skin fibroblasts and their effect is equivalent to that of Actovegin. Dipeptides stimulate cell renewal processes by activating synthesis of Ki-67 and reducing expression of caspase-9 and enhance antioxidant function of the cells by stimulating the expression of Hsp-90 and inducible NO-synthase. These findings suggest that dipeptides are promising candidates for preparations stimulating reparative processes.

  17. Soil disturbance increases soil microbial enzymatic activity in arid ecoregion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Functional diversity of the soil microbial community is commonly used in the assessment of soil health as it relates to the activity of soil microflora involved in carbon cycling. Soil microbes in different microenvironments will have varying responses to different substrates, thus catabolic fingerp...

  18. Increasing Pupil Physical Activity: A Comprehensive Professional Development Effort

    ERIC Educational Resources Information Center

    Kulinna, Pamela Hodges

    2012-01-01

    Study aim: To determine if pupil physical activity and Body Mass Index classifications maintained or improved after a one-year professional development program involving both classroom and physical education teachers. Guskey's model of teacher change guided this study. Material and methods: Indigenous children from ten schools (N = 320) in grades…

  19. Texting to increase physical activity in teens: Development & preliminary

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our purpose was to present formative research and preliminary results for a self-determination-theory (SDT)-based text messages to promote physical activity (PA) among teens. Thirty 14- to 17-year olds, stratified by gender and race/ethnicity (Black, Hispanic, White), were recruited to participate i...

  20. Increasing Physical Activity of Children during School Recess

    ERIC Educational Resources Information Center

    Hayes, Lynda B.; Van Camp, Carole M.

    2015-01-01

    Physical activity is crucial for children's health. Fitbit accelerometers were used to measure steps of 6 elementary students during recess. The intervention included reinforcement, self-monitoring, goal setting, and feedback. Steps taken during the intervention phase (M?=?1,956 steps) were 47% higher than in baseline (M?=?1,326 steps), and the…

  1. Somatosensory Anticipatory Alpha Activity Increases to Suppress Distracting Input

    ERIC Educational Resources Information Center

    Haegens, Saskia; Luther, Lisa; Jensen, Ole

    2012-01-01

    Effective processing of sensory input in daily life requires attentional selection and amplification of relevant input and, just as importantly, attenuation of irrelevant information. It has been proposed that top-down modulation of oscillatory alpha band activity (8-14 Hz) serves to allocate resources to various regions, depending on task…

  2. Activation of Transient Receptor Potential Vanilloid 4 Increases NMDA-Activated Current in Hippocampal Pyramidal Neurons

    PubMed Central

    Li, Lin; Qu, Weijun; Zhou, Libin; Lu, Zihong; Jie, Pinghui; Chen, Lei; Chen, Ling

    2013-01-01

    The glutamate excitotoxicity, mediated through N-methyl-d-aspartate receptors (NMDARs), plays an important role in cerebral ischemia injury. Transient receptor potential vanilloid 4 (TRPV4) can be activated by multiple stimuli that may happen during stroke. The present study evaluated the effect of TRPV4 activation on NMDA-activated current (INMDA) and that of blocking TRPV4 on brain injury after focal cerebral ischemia in mice. We herein report that activation of TRPV4 by 4α-PDD and hypotonic stimulation increased INMDA in hippocampal CA1 pyramidal neurons, which was sensitive to TRPV4 antagonist HC-067047 and NMDAR antagonist AP-5, indicating that TRPV4 activation potentiates NMDAR response. In addition, the increase in INMDA by hypotonicity was sensitive to the antagonist of NMDAR NR2B subunit, but not of NR2A subunit. Furthermore, antagonists of calcium/calmodulin-dependent protein kinase II (CaMKII) significantly attenuated hypotonicity-induced increase in INMDA, while antagonists of protein kinase C or casein kinase II had no such effect, indicating that phosphorylation of NR2B subunit by CaMKII is responsible for TRPV4-potentiated NMDAR response. Finally, we found that intracerebroventricular injection of HC-067047 after 60 min middle cerebral artery occlusion reduced the cerebral infarction with at least a 12 h efficacious time-window. These findings indicate that activation of TRPV4 increases NMDAR function, which may facilitate glutamate excitotoxicity. Closing TRPV4 may exert potent neuroprotection against cerebral ischemia injury through many mechanisms at least including the prevention of NMDAR-mediated glutamate excitotoxicity. PMID:23459987

  3. High diversity and no significant selection signal of human ADH1B gene in Tibet

    PubMed Central

    2012-01-01

    Background ADH1B is one of the most studied human genes with many polymorphic sites. One of the single nucleotide polymorphism (SNP), rs1229984, coding for the Arg48His substitution, have been associated with many serious diseases including alcoholism and cancers of the digestive system. The derived allele, ADH1B*48His, reaches high frequency only in East Asia and Southwest Asia, and is highly associated with agriculture. Micro-evolutionary study has defined seven haplogroups for ADH1B based on seven SNPs encompassing the gene. Three of those haplogroups, H5, H6, and H7, contain the ADH1B*48His allele. H5 occurs in Southwest Asia and the other two are found in East Asia. H7 is derived from H6 by the derived allele of rs3811801. The H7 haplotype has been shown to have undergone significant positive selection in Han Chinese, Hmong, Koreans, Japanese, Khazak, Mongols, and so on. Methods In the present study, we tested whether Tibetans also showed evidence for selection by typing 23 SNPs in the region covering the ADH1B gene in 1,175 individuals from 12 Tibetan populations representing all districts of the Tibet Autonomous Region. Multiple statistics were estimated to examine the gene diversities and positive selection signals among the Tibetans and other populations in East Asia. Results The larger Tibetan populations (Qamdo, Lhasa, Nagqu, Nyingchi, Shannan, and Shigatse) comprised mostly farmers, have around 12% of H7, and 2% of H6. The smaller populations, living on hunting or recently switched to farming, have lower H7 frequencies (Tingri 9%, Gongbo 8%, Monba and Sherpa 6%). Luoba (2%) and Deng (0%) have even lower frequencies. Long-range haplotype analyses revealed very weak signals of positive selection for H7 among Tibetans. Interestingly, the haplotype diversity of H7 is higher in Tibetans than in any other populations studied, indicating a longer diversification history for that haplogroup in Tibetans. Network analysis on the long-range haplotypes revealed

  4. T Lymphocyte Activation Threshold is Increased in Reduced Gravity

    NASA Technical Reports Server (NTRS)

    Adams, Charley L.; Gonzalez, M.; Sams, C. F.

    2000-01-01

    There have been substantial advances in molecular and cellular biology that have provided new insight into the biochemical and genetic basis of lymphocyte recognition, activation and expression of distinct functional phenotypes. It has now become evident that for both T and B cells, stimuli delivered through their receptors can result in either clonal expansion or apoptosis. In the case of T cells, clonal expansion of helper cells is accompanied by differentiation into two major functional subsets which regulate the immune response. The pathways between the membrane and the nucleus and their molecular components are an area of very active investigation. This meeting will draw together scientists working on diverse aspects of this problem, including receptor ligand interactions, intracellular pathways that transmit receptor mediated signals and the effect of such signal transduction pathways on gene regulation. The aim of this meeting is to integrate the information from these various experimental approaches into a new synthesis and molecular explanation of T cell activation, differentiation and death.

  5. Density increase due to active feedback in mirror machine

    NASA Astrophysics Data System (ADS)

    Seemann, Omri; Be'Ery, Ilan

    2014-10-01

    Mirror machines are one of the schemes for future fusion systems. Its main drawbacks are the flute instability and being open ended which results in plasma losses. A feedback system is used to stabilize the flute instability in a table top mirror machine with a continuous plasma source and RF heating. Under certain source density and temperature conditions, although the plasma was stabilized, plasma density increase was not measured. After decreasing the source density and increasing the temperature, Plasma density increase was achieved. It is theorized that these results are due to transition of the plasma main loss mechanism from collision dominated to instability dominated. In the former, the main density loss is through diffusion and In the latter, it is through flute instability which drives the plasma to the edge of the vacuum chamber. Future research directions are discussed for a planned machine which should achieve higher temperatures and better diagnostic capabilities. The research will focus on magnetic actuators and passive RF stabilization.

  6. The Analysis of Polymorphism of Alcohol Dehydrogenase 3 (ADH3) Gene and Influence of Liver Function Status in Indonesia.

    PubMed

    Suhartini; Mustofa; Nurhantari, Yudha; Rianto, Bambang Udji Djoko

    2017-01-31

    Indonesian culture actually has no historical record of behaviors in consuming alcohol, but there are many recent reports of alcohol abuse among Asian people involving their traditional drink. In genotype studies, the damage of the liver caused by consuming alcohol is influenced by the presence of the polymorphism enzyme gene. The lack of study regarding such topic is a signal to further investigate ADH3 gene distribution and its effect on liver function status. The total of 197 research subjects of Javanese descent received alcohol dehydrogenase 3 (ADH3) genetic polymorphism and liver status tests in the city of Yogyakarta, Indonesian. An analytical study with a cross-sectional design was then conducted on the subjects, with the resulting isolated DNAs amplified through polymerase chain reaction (PCR). The genotype of ADH3 was determined by means of restriction fragment length polymorphism (RFLP) using Ssp1 restricting enzyme. Liver function status was assessed by measuring serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT) and gamma glutamyl transferase (GGT) using a photometric system. Gene types of ADH3*1 (2.1%), ADH3*2 (82.7%) and ADH3*1/3*2 (15.2%) on the subjects were concluded, finding that there is no difference between the gender. In conclusion most of the ADH3 gene polymorphism of the subjects were ADH3*2 (82.7%). The influence of genetic polymorphisms on the status of liver function in the subjects showed significant difference according to GGT measurement, but the same cannot be said on the other two values measuring SGOT and SGPT.

  7. Analysis of the hypoxia-induced ADH2 promoter of the respiratory yeast Pichia stipitis reveals a new mechanism for sensing of oxygen limitation in yeast.

    PubMed

    Passoth, Volkmar; Cohn, Marita; Schäfer, Bernd; Hahn-Hägerdal, Bärbel; Klinner, Ulrich

    2003-01-15

    We introduced a reporter gene system into Pichia stipitis using the gene for the artificial green fluorescent protein (GFP), variant yEGFP. This system was used to analyse hypoxia-dependent PsADH2 regulation. Reporter gene activity was only found under oxygen limitation on a fermentable carbon source. The promoter was not induced by oxygen limitation in the Crabtree-positive yeast Saccharomyces cerevisiae. Promoter deletions revealed that a region of 15 bp contained the essential site for hypoxic induction. This motif was different from the known hypoxia response elements of S. cerevisiae but showed some similarity to the mammalian HIF-1 binding site. Electrophoretic mobility shift assays demonstrated specific protein binding to this region under oxygen limitation. Similar to the S. cerevisiae heme sensor system, the promoter was induced by Co(2+). Cyanide was not able to mimic the effect of oxygen limitation. The activation mechanism of PsADH2 also, in this respect, has similarities to the mammalian HIF-1 system, which is inducible by Co(2+) but not by cyanide. Thus, the very first promoter analysis in P. stipitis revealed a hitherto unknown mechanism of oxygen sensing in yeast.

  8. Active commuting to school in Finland, the potential for physical activity increase in different seasons

    PubMed Central

    Kallio, Jouni; Turpeinen, Salla; Hakonen, Harto; Tammelin, Tuija

    2016-01-01

    Background Active commuting to school (ACS) can be a significant source of physical activity and provide many health benefits. Objective This study identified the potential to increase physical activity levels by promoting ACS in Finnish schools and evaluated the effects of season, distance and age on ACS. Design Data were collected with a questionnaire from 5,107 students, aged 10–16, in 45 comprehensive schools in Finland. The distance and the mode of transport to school in different seasons were self-reported. Results The prevalence of ACS was over 80% during spring/fall for those living 0–5 km from school. ACS was inversely associated with the distance to school and was lower in winter compared to spring and fall. Cycling is less common in winter, especially among girls and younger students. The potential for increasing students’ physical activity levels via ACS seems to be largest in winter, especially among students living 1–5 km from school. The variation in the prevalence of ACS between schools was large, especially in winter. Conclusions When planning interventions to promote ACS, one is encouraged to acknowledge and evaluate the potential in the selected target schools in different seasons. The potential varies largely between schools and seasons and is highly dependent on students’ commuting distances. PMID:27924739

  9. DRYAD and ADH: Further comments on explaining age-related differences in memory.

    PubMed

    Naveh-Benjamin, Moshe; Smyth, Andrea C

    2016-02-01

    Recently, Smyth and Naveh-Benjamin (2016) questioned some of the main assumptions/hypotheses of DRYAD (or density of representations yields age-related deficits), a global-deficit model of aging and memory judgments (Benjamin, 2010; Benjamin et al., 2012). Smyth and Naveh-Benjamin (2016) provided empirical evidence that seems incompatible with DRYAD, but that fits the associative deficit hypothesis (ADH; Naveh-Benjamin, 2000), 1 specific-deficit theoretical view. In response, Aaron Benjamin (2016) offered a discussion of the complementary strengths and weaknesses of the DRYAD and the ADH, and the potential ways they might work together. We agree with many of his comments, but are not convinced that DRYAD is able to explain basic replicable empirical evidence of the type mentioned in Smyth and Naveh-Benjamin (2016). We discuss the reasons why we are not fully convinced by the demonstration of DRYAD's simulation of results presented in Benjamin (2016) and then present an implementation of ADH in a computationally based age-related impaired neuromodulation approach that was shown to simulate the basic empirical results of age-related associative memory deficits. We also discuss the issues of parsimony of theories and the appropriate type of representation, in the context of global versus specific deficits theoretical views. Finally, we show that the ADH's take on the distinction between items and associations has been adopted by some global computational models of memory. We believe that considerations of the above issues and others raised by Benjamin (2016) can lead to fruitful discussions that will benefit both theory development and existing knowledge of aging and memory.

  10. Is ADH1C genotype relevant for the cardioprotective effect of alcohol?

    PubMed

    Høiseth, Gudrun; Magnus, Per; Knudsen, Gun Peggy; Jansen, Mona Dverdal; Næss, Oyvind; Tambs, Kristian; Mørland, Jørg

    2013-03-01

    The cardioprotective effect of ethanol has been suggested to be linked to one of the ethanol metabolizing enzymes (ADH1C), which constitutes a high V(max) and a low V(max) variant. This has been demonstrated in some studies, while others have not been able to replicate the findings. The aim of the present study was to investigate the relation between the different ADH1C genotypes, death from coronary heart disease (CHD) and alcohol in a material larger than the previously published studies. Eight hundred CHD deaths as well as 1303 controls were genotyped for the high V(max) (γ1) and the low V(max) (γ2) ADH1C variant. Information of alcohol use was available for all subjects. Multiple logistic regression analyses was used to study if the decreased risk of death from CHD in alcohol consuming subjects was more pronounced in subjects homozygous for the γ2 allele (γ2γ2 subjects) compared to γ1γ1 and γ1γ2 subjects. The odds ratio (OR) for death from CHD in alcohol consumers compared to abstainers was similar in the genotype groups, i.e., 0.62 (95% CI: 0.43-0.88) in γ1γ1 subjects and 0.62 (95% CI: 0.42-0.91) in γ2γ2 subjects. Also when stratifying the results by gender and when dividing alcohol consumers into different alcohol consumption groups, there was no difference in the OR between the different genotype groups. This study, which included the largest study group published so far, failed to find any link between the ADH1C genotype and the cardioprotective effects of alcohol.

  11. Polymorphisms in Alcohol Metabolism Genes ADH1B and ALDH2, Alcohol Consumption and Colorectal Cancer

    PubMed Central

    Crous-Bou, Marta; Rennert, Gad; Cuadras, Daniel; Salazar, Ramon; Cordero, David; Saltz Rennert, Hedy; Lejbkowicz, Flavio; Kopelovich, Levy; Monroe Lipkin, Steven; Bernard Gruber, Stephen; Moreno, Victor

    2013-01-01

    Background Colorectal cancer (CRC) is a leading cause of cancer death worldwide. Epidemiological risk factors for CRC included alcohol intake, which is mainly metabolized to acetaldehyde by alcohol dehydrogenase and further oxidized to acetate by aldehyde dehydrogenase; consequently, the role of genes in the alcohol metabolism pathways is of particular interest. The aim of this study is to analyze the association between SNPs in ADH1B and ALDH2 genes and CRC risk, and also the main effect of alcohol consumption on CRC risk in the study population. Methodology/Principal Findings SNPs from ADH1B and ALDH2 genes, included in alcohol metabolism pathway, were genotyped in 1694 CRC cases and 1851 matched controls from the Molecular Epidemiology of Colorectal Cancer study. Information on clinicopathological characteristics, lifestyle and dietary habits were also obtained. Logistic regression and association analysis were conducted. A positive association between alcohol consumption and CRC risk was observed in male participants from the Molecular Epidemiology of Colorectal Cancer study (MECC) study (OR = 1.47; 95%CI = 1.18-1.81). Moreover, the SNPs rs1229984 in ADH1B gene was found to be associated with CRC risk: under the recessive model, the OR was 1.75 for A/A genotype (95%CI = 1.21-2.52; p-value = 0.0025). A path analysis based on structural equation modeling showed a direct effect of ADH1B gene polymorphisms on colorectal carcinogenesis and also an indirect effect mediated through alcohol consumption. Conclusions/Significance Genetic polymorphisms in the alcohol metabolism pathways have a potential role in colorectal carcinogenesis, probably due to the differences in the ethanol metabolism and acetaldehyde oxidation of these enzyme variants. PMID:24282520

  12. Increased intrathecal inflammatory activity in frontotemporal dementia: pathophysiological implications

    PubMed Central

    Sjogren, M; Folkesson, S; Blennow, K; Tarkowski, E

    2004-01-01

    Objective: Immunological mechanisms may be part of the pathophysiological mechanisms in frontotemporal dementia (FTD), but hitherto only vague evidence of such mechanisms has been presented. The aim of this study was to compare the cerebrospinal fluid (CSF) levels of the pro-inflammatory cytokines interleukin (IL)-1ß and tumour necrosis factor (TNF)-α, and the anti-inflammatory cytokine transforming growth factor (TGF)-ß in patients with FTD and normal controls. Furthermore, serum levels of TNF-α, TGF-ß, and IL-1ß were measured in FTD patients. Methods: The CSF levels of IL-1ß, TNFα, and TGF-ß were measured using ELISA in 19 patients with FTD and 24 sex and age matched healthy controls. Results: The CSF levels of TNF-α (FTD 0.6 pg/mL (median: lower, upper quartile 0.3, 0.7); controls: 0.0 pg/mL (0.0, 0.0); p = 0.008) and TGF-ß (FTD 266 pg/mL (157, 371), controls: 147 pg/mL (119, 156); p = 0.0001) were significantly increased in FTD patients compared with controls. No correlations were found between CSF and serum levels of the cytokines. In the controls, but not in the FTD patients, a positive correlation was found between the CSF levels of TGF-ß and age (r = 0.42, p<0.05). No correlation was found between any of the cytokines and degree of brain atrophy or white matter changes. No differences between the groups were found for age, gender, or CSF/serum albumin ratio. Conclusions: The results suggest an increased intrathecal production of both pro- and anti-inflammatory cytokines in FTD. As no correlations were found with the albumin ratio, and no correlations between CSF and serum levels of the cytokines were found, these changes in the CSF cannot be explained by a systemic overproduction of cytokines. PMID:15258209

  13. Complexing Methylene Blue with Phosphorus Dendrimers to Increase Photodynamic Activity.

    PubMed

    Dabrzalska, Monika; Janaszewska, Anna; Zablocka, Maria; Mignani, Serge; Majoral, Jean Pierre; Klajnert-Maculewicz, Barbara

    2017-02-23

    The efficiency of photodynamic therapy is limited mainly due to low selectivity, unfavorable biodistribution of photosensitizers, and long-lasting skin sensitivity to light. However, drug delivery systems based on nanoparticles may overcome the limitations mentioned above. Among others, dendrimers are particularly attractive as carriers, because of their globular architecture and high loading capacity. The goal of the study was to check whether an anionic phosphorus dendrimer is suitable as a carrier of a photosensitizer-methylene blue (MB). As a biological model, basal cell carcinoma cell lines were used. We checked the influence of the MB complexation on its singlet oxygen production ability using a commercial fluorescence probe. Next, cellular uptake, phototoxicity, reactive oxygen species (ROS) generation, and cell death were investigated. The MB-anionic dendrimer complex (MB-1an) was found to generate less singlet oxygen; however, the complex showed higher cellular uptake and phototoxicity against basal cell carcinoma cell lines, which was accompanied with enhanced ROS production. Owing to the obtained results, we conclude that the photodynamic activity of MB complexed with an anionic dendrimer is higher than free MB against basal cell carcinoma cell lines.

  14. Increased Visual Stimulation Systematically Decreases Activity in Lateral Intermediate Cortex

    PubMed Central

    Nasr, Shahin; Stemmann, Heiko; Vanduffel, Wim; Tootell, Roger B. H.

    2015-01-01

    Previous studies have attributed multiple diverse roles to the posterior superior temporal cortex (STC), both visually driven and cognitive, including part of the default mode network (DMN). Here, we demonstrate a unifying property across this multimodal region. Specifically, the lateral intermediate (LIM) portion of STC showed an unexpected feature: a progressively decreasing fMRI response to increases in visual stimulus size (or number). Such responses are reversed in sign, relative to well-known responses in classic occipital temporal visual cortex. In LIM, this “reversed” size function was present across multiple object categories and retinotopic eccentricities. Moreover, we found a significant interaction between the LIM size function and the distribution of subjects' attention. These findings suggest that LIM serves as a part of the DMN. Further analysis of functional connectivity, plus a meta-analysis of previous fMRI results, suggests that LIM is a heterogeneous area including different subdivisions. Surprisingly, analogous fMRI tests in macaque monkeys did not reveal a clear homolog of LIM. This interspecies discrepancy supports the idea that self-referential thinking and theory of mind are more prominent in humans, compared with monkeys. PMID:25480358

  15. Increased Visual Stimulation Systematically Decreases Activity in Lateral Intermediate Cortex.

    PubMed

    Nasr, Shahin; Stemmann, Heiko; Vanduffel, Wim; Tootell, Roger B H

    2015-10-01

    Previous studies have attributed multiple diverse roles to the posterior superior temporal cortex (STC), both visually driven and cognitive, including part of the default mode network (DMN). Here, we demonstrate a unifying property across this multimodal region. Specifically, the lateral intermediate (LIM) portion of STC showed an unexpected feature: a progressively decreasing fMRI response to increases in visual stimulus size (or number). Such responses are reversed in sign, relative to well-known responses in classic occipital temporal visual cortex. In LIM, this "reversed" size function was present across multiple object categories and retinotopic eccentricities. Moreover, we found a significant interaction between the LIM size function and the distribution of subjects' attention. These findings suggest that LIM serves as a part of the DMN. Further analysis of functional connectivity, plus a meta-analysis of previous fMRI results, suggests that LIM is a heterogeneous area including different subdivisions. Surprisingly, analogous fMRI tests in macaque monkeys did not reveal a clear homolog of LIM. This interspecies discrepancy supports the idea that self-referential thinking and theory of mind are more prominent in humans, compared with monkeys.

  16. Overexpression of the yeast transcriptional activator ADR1 induces mutation of the mitochondrial genome.

    PubMed

    Cherry, J R; Denis, C L

    1989-05-01

    It was previously observed that increased dosages of the ADR1 gene, which encodes a yeast transcriptional activator required for alcohol dehydrogenase II (ADH II) expression, cause a decreased rate of growth in medium containing ethanol as the carbon source. Here we show that observed reduction in growth rate is mediated by the ADR1 protein which, when overexpressed, increases the frequency of cytoplasmic petites. Unlike previously characterized mutations known to potentiate petite formation, the ADR1 effect is dominant, with the petite frequency rising concomitantly with increasing ADR1 dosage. The ability of ADR1 to increase the frequency of mitochondrial mutation is correlated with its ability to activate ADH II transcription but is independent of the level of ADH II being expressed. Based on restoration tests using characterized mit- strains, ADR1 appears to cause non-specific deletions within the mitochondrial genome to produce rho- petites. Pedigree analysis of ADR1-overproducing strains indicates that only daughter cells become petite. This pattern is analogous to that observed for petite induction by growth at elevated temperature and by treatment with the acridine dye euflavine. One strain resistant to ADR1-induced petite formation displayed cross-resistance to petite mutation by growth at elevated temperature and euflavine treatment, yet was susceptible to petite induction by ethidium bromide. These results suggest that ADR1 overexpression disrupts the fidelity of mitochondrial DNA replication or repair.

  17. Preventive effects of Flos Perariae (Gehua) water extract and its active ingredient puerarin in rodent alcoholism models

    PubMed Central

    2010-01-01

    Background Radix Puerariae is used in Chinese medicine to treat alcohol addiction and intoxication. The present study investigates the effects of Flos puerariae lobatae water extract (FPE) and its active ingredient puerarin on alcoholism using rodent models. Methods Alcoholic animals were given FPE or puerarin by oral intubation prior or after alcohol treatment. The loss of righting reflex (LORR) assay was used to evaluate sedative/hypnotic effects. Changes of gama-aminobutyric acid type A receptor (GABAAR) subunits induced by alcohol treatment in hippocampus were measured with western blot. In alcoholic mice, body weight gain was monitored throughout the experiments. Alcohol dehydrogenase (ADH) levels in liver were measured. Results FPE and puerarin pretreatment significantly prolonged the time of LORR induced by diazepam in acute alcoholic rat. Puerarin increased expression of gama-aminobutyric acid type A receptor alpha1 subunit and decreased expression of alpha4 subunit. In chronic alcoholic mice, puerarin pretreatment significantly increased body weight and liver ADH activity in a dose-dependent manner. Puerarin pretreatment, but not post-treatment, can reverse the changes of gama-aminobutyric acid type A receptor subunit expression and increase ADH activity in alcoholism models. Conclusion The present study demonstrates that FPE and its active ingredient puerarin have preventive effects on alcoholism related disorders. PMID:20974012

  18. The ADH1B and DRD2 gene polymorphism may modify the protective effect of the ALDH2 gene against heroin dependence.

    PubMed

    Wang, Tzu-Yun; Lee, Sheng-Yu; Chen, Shiou-Lan; Chang, Yun-Hsuan; Chen, Shih-Heng; Chu, Chun-Hsien; Huang, San-Yuan; Tzeng, Nian-Sheng; Wang, Chen-Lin; Yeh, Pin-Hsi; Lee, I Hui; Yeh, Tzung Lieh; Yang, Yen Kuang; Lu, Ru-Band

    2013-06-03

    Understanding the influences of genes involved in dopamine and serotonin metabolism, such as the aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 1B (ADH1B) genes, is critical for understanding addictive behavior. In addition, dopamine D2 receptor (DRD2) gene may also interact with the dopamine metabolizing genes and link to addiction. Therefore, we investigated the association between the ALDH2, ADH1B and DRD2 polymorphisms and heroin dependence. Heroin-dependent Han Chinese patients (n=304) and healthy controls (n=335) were recruited. Genotypes of ALDH2, ADH1B and DRD2 polymorphisms were analyzed using a polymerase chain reaction with restriction fragment length polymorphism. The frequency of the ALDH2*1/*1 genotype was significantly lower in heroin-dependent patients than in controls, but the frequency of ADH1B and DRD2 genotypes was not significantly different. Further stratification of the ALDH2 gene with the ADH1B gene showed that the protective effect of ALDH2*1/*1 existed only in patients who also carried the ADH1B*1/*1 and ADH1B*1/*2 genotype. Logistic regression analysis showed a significant interaction between ALDH2 and ADH1B (P=0.022) and DRD2, ALDH2 and ADH1B in patients (P=0.037). The ALDH2*1/*1, ADH1B*1/*1, and ADH1B*1/*2 genotypes may interact and protect their carriers against heroin dependence and the protective effect may be varied by the DRD2 gene polymorphism. We conclude that the protective effect of the ALDH2 polymorphism against heroin dependence may be modified by the ADH1B and DRD2 polymorphism.

  19. Maintenance of the Adh polymorphism in Ambystoma tigrinum nebulosum (tiger salamanders). I. Genotypic differences in time to metamorphosis in extreme oxygen environments.

    PubMed

    Carter, P A

    1997-01-01

    Populations of gilled tiger salamanders (Ambystoma tigrinum nebulosum) living in ephemeral ponds were studied in order to determine what evolutionary processes might be affecting genetic variation at the alcohol dehydrogenase (Adh) locus. Ponds frequently dried in late summer; salamanders that did not metamorphose and leave drying ponds died of desiccation. Low levels of water oxygen significantly slowed metamorphosis of tiger salamanders in both natural and laboratory populations. Adh- SS frequency was significantly positively correlated with daily oxygen maxima in ponds, Adh-FF frequency demonstrated a nonsignificant trend to be negatively correlated with this measure, and Adh-SF frequency was unrelated to pond oxygen. Genotype frequency changes across the season in hypoxic and supersaturated ponds suggested that differential mortality of genotypes might explain the relationships with pond oxygen, although other mechanisms cannot be ruled out. Individuals of the Adh-SS genotype metamorphosed more slowly in hypoxic water than in normoxic water in the laboratory, and Adh-FF individuals metamorphosed more slowly in supersaturated water in the field, and in hypoxic water in the laboratory, than they did in normoxic water. Adh-SF individuals metamorphosed at the same rate in all oxygen environments. These data suggest that the Adh polymorphism in tiger salamanders is being maintained by selection for Adh or for a linked locus through differential metamorphosis in extreme oxygen environments.

  20. Development of a universal approach to increase physical activity among adolescents: the GoActive intervention

    PubMed Central

    Corder, Kirsten; Schiff, Annie; Kesten, Joanna M; van Sluijs, Esther M F

    2015-01-01

    Objectives To develop a physical activity (PA) promotion intervention for adolescents using a process addressing gaps in the literature while considering participant engagement. We describe the initial development stages; (1) existing evidence, (2) large scale opinion gathering and (3) developmental qualitative work, aiming (A) to gain insight into how to increase PA among the whole of year 9 (13–14 years-old) by identifying elements for intervention inclusion (B) to improve participant engagement and (C) to develop and refine programme design. Methods Relevant systematic reviews and longitudinal analyses of change were examined. An intervention was developed iteratively with older adolescents (17.3±0.5 years) and teachers, using the following process: (1) focus groups with (A) adolescents (n=26) and (B) teachers (n=4); (2) individual interviews (n=5) with inactive and shy adolescents focusing on engagement and programme acceptability. Qualitative data were analysed thematically. Results Limitations of the existing literature include lack of evidence on whole population approaches, limited adolescent involvement in intervention development, and poor participant engagement. Qualitative work suggested six themes which may encourage adolescents to do more PA; choice, novelty, mentorship, competition, rewards and flexibility. Teachers discussed time pressures as a barrier to encouraging adolescent PA and suggested between-class competition as a strategy. GoActive aims to increase PA through increased peer support, self-efficacy, group cohesion, self-esteem and friendship quality, and is implemented in tutor groups using a student-led tiered-leadership system. Conclusions We have followed an evidence-based iterative approach to translate existing evidence into an adolescent PA promotion intervention. Qualitative work with adolescents and teachers supported intervention design and addressed lack of engagement with health promotion programmes within this age group

  1. Playground Designs to Increase Physical Activity Levels during School Recess: A Systematic Review

    ERIC Educational Resources Information Center

    Escalante, Yolanda; García-Hermoso, Antonio; Backx, Karianne; Saavedra, Jose M.

    2014-01-01

    School recess provides a major opportunity to increase children's physical activity levels. Various studies have described strategies to increase levels of physical activity. The purpose of this systematic review is therefore to examine the interventions proposed as forms of increasing children's physical activity levels during recess. A…

  2. Increased hepcidin in transferrin-treated thalassemic mice correlates with increased liver BMP2 expression and decreased hepatocyte ERK activation.

    PubMed

    Chen, Huiyong; Choesang, Tenzin; Li, Huihui; Sun, Shuming; Pham, Petra; Bao, Weili; Feola, Maria; Westerman, Mark; Li, Guiyuan; Follenzi, Antonia; Blanc, Lionel; Rivella, Stefano; Fleming, Robert E; Ginzburg, Yelena Z

    2016-03-01

    Iron overload results in significant morbidity and mortality in β-thalassemic patients. Insufficient hepcidin is implicated in parenchymal iron overload in β-thalassemia and approaches to increase hepcidin have therapeutic potential. We have previously shown that exogenous apo-transferrin markedly ameliorates ineffective erythropoiesis and increases hepcidin expression in Hbb(th1/th1) (thalassemic) mice. We utilize in vivo and in vitro systems to investigate effects of exogenous apo-transferrin on Smad and ERK1/2 signaling, pathways that participate in hepcidin regulation. Our results demonstrate that apo-transferrin increases hepcidin expression in vivo despite decreased circulating and parenchymal iron concentrations and unchanged liver Bmp6 mRNA expression in thalassemic mice. Hepatocytes from apo-transferrin-treated mice demonstrate decreased ERK1/2 pathway and increased serum BMP2 concentration and hepatocyte BMP2 expression. Furthermore, hepatocyte ERK1/2 phosphorylation is enhanced by neutralizing anti-BMP2/4 antibodies and suppressed in vitro in a dose-dependent manner by BMP2, resulting in converse effects on hepcidin expression, and hepatocytes treated with MEK/ERK1/2 inhibitor U0126 in combination with BMP2 exhibit an additive increase in hepcidin expression. Lastly, bone marrow erythroferrone expression is normalized in apo-transferrin treated thalassemic mice but increased in apo-transferrin injected wild-type mice. These findings suggest that increased hepcidin expression after exogenous apo-transferrin is in part independent of erythroferrone and support a model in which apo-transferrin treatment in thalassemic mice increases BMP2 expression in the liver and other organs, decreases hepatocellular ERK1/2 activation, and increases nuclear Smad to increase hepcidin expression in hepatocytes.

  3. Alpha-ketoglutarate reduces ethanol toxicity in Drosophila melanogaster by enhancing alcohol dehydrogenase activity and antioxidant capacity.

    PubMed

    Bayliak, Maria M; Shmihel, Halyna V; Lylyk, Maria P; Storey, Kenneth B; Lushchak, Volodymyr I

    2016-09-01

    Ethanol at low concentrations (<4%) can serve as a food source for fruit fly Drosophila melanogaster, whereas at higher concentrations it may be toxic. In this work, protective effects of dietary alpha-ketoglutarate (AKG) against ethanol toxicity were studied. Food supplementation with 10-mM AKG alleviated toxic effects of 8% ethanol added to food, and improved fly development. Two-day-old adult flies, reared on diet containing both AKG and ethanol, possessed higher alcohol dehydrogenase (ADH) activity as compared with those reared on control diet or diet with ethanol only. Native gel electrophoresis data suggested that this combination diet might promote post-translational modifications of ADH protein with the formation of a highly active ADH form. The ethanol-containing diet led to significantly higher levels of triacylglycerides stored in adult flies, and this parameter was not altered by AKG supplement. The influence of diet on antioxidant defenses was also assessed. In ethanol-fed flies, catalase activity was higher in males and the levels of low molecular mass thiols were unchanged in both sexes compared to control values. Feeding on a mixture of AKG and ethanol did not affect catalase activity but caused a higher level of low molecular mass thiols compared to ethanol-fed flies. It can be concluded that both a stimulation of some components of antioxidant defense and the increase in ADH activity may be responsible for the protective effects of AKG diet supplementation in combination with ethanol. The results suggest that AKG might be useful as a treatment option to neutralize toxic effects of excessive ethanol intake and to improve the physiological state of D. melanogaster and other animals, potentially including humans.

  4. Urea for management of the syndrome of inappropriate secretion of ADH: A systematic review.

    PubMed

    de Solà-Morales, Oriol; Riera, Maribel

    2014-11-01

    Urea has been recently proposed for the management of hyponatremia linked to the syndrome of inappropriate secretion of ADH (SIADH). The objective of the study was to review the levels of evidence for treatment of hyponatremia associated with SIADH with urea. We performed a: systematic review of experimental trials and grading according to SIGN. No clinical trials were found. The 6 studies analysed had methodological limitations and were prone to biases. In conclusion, there is no evidence to support the efficacy of urea for the treatment of hyponatremia following SIADH.

  5. The effect of increasing autonomy through choice on young children’s physical activity behavior

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Increasing autonomy by manipulating the choice of available physical activity options in a laboratory setting can increase physical activity in older children and adults. However, the effect of manipulating the number of physically active choices has yet to be examined in young children in a gymnas...

  6. Promising School-Based Strategies and Intervention Guidelines to Increase Physical Activity of Adolescents

    ERIC Educational Resources Information Center

    Pardo, Berta Murillo; Bengoechea, Enrique Garcia; Lanaspa, Eduardo Generelo; Bush, Paula L.; Casterad, Javier Zaragoza; Clemente, Jose A. Julian; Gonzalez, Luis Garcia

    2013-01-01

    This narrative review describes the available scientific evidence regarding promising school-based strategies to increase physical activity of adolescents. We conducted a literature search for studies published up to 2011, regarding adolescent physical activity intervention studies that resulted in increased physical activity (regardless of…

  7. An Evaluation of Photographic Activity Schedules to Increase Independent Playground Skills in Young Children with Autism

    ERIC Educational Resources Information Center

    Akers, Jessica S.; Higbee, Thomas S.; Pollard, Joy S.; Pellegrino, Azure J.; Gerencser, Kristina R.

    2016-01-01

    We used photographic activity schedules to increase the number of play activities completed by children with autism during unstructured time on the playground. All 3 participants engaged in more playground activities during and after training, and they continued to complete activities when novel photographs were introduced.

  8. [Two cases of Lambert-Eaton syndrome with an increase of serum cholinesterase activity].

    PubMed

    Ciechanowski, K; Cebula, D

    1997-02-01

    Paraneoplastic Lambert-Eaton myasthenia syndrome is presented in two cases with small cell lung cancer. An increase of serum cholinesterase activity was explained by induced release of biologically active proteins by neoplastic tissue.

  9. Dynamically Coupled Food-web and Hydrodynamic Modeling with ADH-CASM

    NASA Astrophysics Data System (ADS)

    Piercy, C.; Swannack, T. M.

    2012-12-01

    Oysters and freshwater mussels are "ecological engineers," modifying the local water quality by filtering zooplankton and other suspended particulate matter from the water column and flow hydraulics by impinging on the near-bed flow environment. The success of sessile, benthic invertebrates such as oysters depends on environmental factors including but not limited to temperature, salinity, and flow regime. Typically food-web and other types of ecological models use flow and water quality data as direct input without regard to the feedback between the ecosystem and the physical environment. The USACE-ERDC has developed a coupled hydrodynamic-ecological modeling approach that dynamically couples a 2-D hydrodynamic and constituent transport model, Adaptive Hydraulics (ADH), with a bioenergetics food-web model, the Comprehensive Aquatics Systems Model (CASM), which captures the dynamic feedback between aquatic ecological systems and the environment. We present modeling results from restored oyster reefs in the Great Wicomico River on the western shore of the Chesapeake Bay, which quantify ecosystem services such as the influence of the benthic ecosystem on water quality. Preliminary results indicate that while the influence of oyster reefs on bulk flow dynamics is limited due to the localized influence of oyster reefs, large reefs and the associated benthic ecosystem can create measurable changes in the concentrations of nitrogen, phosphorus, and carbon in the areas around reefs. We also present a sensitivity analysis to quantify the relative sensitivity of the coupled ADH-CASM model to both hydrodynamic and ecological parameter choice.

  10. The Arabidopsis Adh gene exhibits diverse nucleosome arrangements within a small DNase I-sensitive domain.

    PubMed Central

    Vega-Palas, M A; Ferl, R J

    1995-01-01

    The alcohol dehydrogenase (Adh) gene from Arabidopsis shows enhanced sensitivity to DNase I in cells that express the gene. This generalized sensitivity to DNase I is demarcated by position -500 on the 5' side and the end of the mRNA on the 3' side. Thus, the gene defined as the promoter and mRNA coding region corresponds very closely in size with the gene defined as a nuclease-sensitive domain. This is a remarkably close correspondence between a sensitive domain and a eukaryotic transcriptional unit, because previously reported DNase I-sensitive domains include large regions of DNA that are not transcribed. Nucleosomes are present in the coding region of the Adh gene when it is expressed, indicating that the transcriptional elongation process causes nucleosome disruption rather than release of nucleosomes from the coding region. In addition, the regulatory region contains a loosely positioned nucleosome that is separated from adjacent nucleosomes by internucleosomic DNA segments longer than the average linker DNA in bulk chromatin. This specific array of nucleosomes coexists with bound transcription factors that could contribute to the organization of the nucleosome arrangement. These results enhance our understanding of the complex interactions among DNA, nucleosomes, and transcription factors during gene expression in plants. PMID:8535143

  11. Vitamin E supplementation increases the resistance of both LDL and HDL to oxidation and increases cholesteryl ester transfer activity.

    PubMed

    Arrol, S; Mackness, M I; Durrington, P N

    2000-05-01

    There is increasing evidence that lipid peroxidation and oxidative modification of low density lipoprotein (LDL) is important in atherogenesis. Evidence that antioxidant therapy decreases mortality is, however, inconclusive. We have examined the effects of vitamin E on the susceptibility of LDL and high density lipoprotein (HDL) to oxidation, and on cholesteryl ester heteroexchange in an in vitro system using autologous serum lipoproteins. Vitamin E in doses of 200 and 400 mg/day were administered orally to 21 healthy volunteers (12 females and nine males) aged between 23 and 50 years, and to 16 healthy volunteers (eight females and eight males) aged between 22 and 51 years for 50 days, respectively. Fasting serum lipoproteins, susceptibility of lipoproteins to oxidation and cholesteryl ester transfer activity (CETA) were measured before and after vitamin E supplementation. Serum lipoprotein and lipid concentrations did not change significantly in either group. The LDL-conjugated diene (CD) lag phase during incubation with Cu(2+) was increased by 157% (110-232%) (median (interquartile range)) (P<0.05) on vitamin E (200 mg/day) and by 235% (185-259%) (P<0.0001) on 400 mg/day. The lag phases for LDL-lipid peroxide (LPO) generation were also significantly increased by 146% (122-192%) (P<0.005) and 177% (101-267%) (P<0.005), respectively. The HDL-CD lag phase also increased on both doses 140% (115-169%) (P<0.005) and 171% (122-192%) (P<0.005), as did the HDL-LPO lag phase by 123% (104-153%) (P<0.05) on 200 mg/day and 240% (97-360%) (P<0.005) on 400 mg daily. Cholesteryl ester transfer activity from HDL to very low and low density lipoproteins significantly increased from 12. 7+/-2.6 (mean+/-SEM) to 16+/-3.4 nmol/ml/h (P<0.05) on 200 mg/daily and 10.4+/-2.0 to 19.2+/-3.3 nmol/ml/h (P<0.005) on vitamin E, 400mg day. Thus, vitamin E (200 and 400mg daily) significantly decreased the susceptibility of LDL and HDL to oxidation in vitro. However, the increase in CETA

  12. Increased von Willebrand factor levels in patients with systemic lupus erythematosus reflect inflammation rather than increased propensity for platelet activation

    PubMed Central

    Raymond, Warren D; Eilertsen, Gro Østli

    2016-01-01

    Background von Willebrand factor (VWF) is involved in platelet plug formation and protein transport. Increased VWF levels in systemic lupus erythematous (SLE) are considered risk factors for vascular events. VWF protein levels, however, do not accurately reflect its platelet-aggregating function, which has not been examined in SLE. Methods Cross-sectional study with clinical and laboratory data obtained in patients with SLE (n=92) from a regional lupus registry. VWF function was determined by ristocetin-induced platelet aggregation (VWF ristocetin cofactor, VWF:RCo) and VWF levels by turbidimetric assay (VWF antigen, VWF:Ag). The platelet-aggregating activity per VWF unit was estimated by the VWF RCo/Ag ratio. Healthy controls served as comparators and associations were evaluated by non-parametric methods. Results VWF:Ag (142% vs 107%, p=0.001) and VWF:RCo levels (123% vs 78%, p<0.041) were increased in patients with SLE, but VWF RCo/Ag ratio was similar as in controls (0.83 vs 0.82, p=0.8). VWF:Ag levels were higher in patients experiencing serositis but unrelated to other manifestations, thrombotic disease, Systemic Lupus Erythematous Disease Activity Index 2000 or Systemic Lupus International Collaborative Clinics-Damage Index. VWF:Ag levels correlated significantly with VWF:RCo levels (Rs 0.8, p<0.001), erythrocyte sedimentation rate (ESR) (Rs 0.32, p<0.01), anti-dsDNA Ab (Rs 0.27, p<0.01), total IgG (Rs 0.33 p<0.01), fibrinogen (Rs 0.28, p<0.01) and ceruloplasmin (Rs 0.367, p<0.01) levels. VWF:RCo levels were not related to clinical findings but were correlated with ESR, anti-dsDNA and transferrin levels. No serological associations existed for VWF RCo/Ag ratio (all p>0.2). Conclusions In this SLE cohort, VWF:Ag behaved similarly to acute-phase reactants, but VWF:Ag increases were not matched by increases in functional activity per unit of VWF. Thus, more VWF did not increase the propensity for platelet aggregation in SLE. PMID:27651919

  13. Clinical implication of the antidiuretic hormone (ADH) receptor antagonist mozavaptan hydrochloride in patients with ectopic ADH syndrome.

    PubMed

    Yamaguchi, Ken; Shijubo, Noriharu; Kodama, Tetsuro; Mori, Kiyoshi; Sugiura, Takahiko; Kuriyama, Takayuki; Kawahara, Masaaki; Shinkai, Tetsu; Iguchi, Haruo; Sakurai, Masanori

    2011-01-01

    Ectopic antidiuretic hormone syndrome is a medical emergency characterized by dilutional hyponatremia. Clinical effectiveness of the vasopressin V2 receptor antagonist mozavaptan was evaluated in 16 patients. In short-term (7-day) treatment with the drug, serum sodium concentration (mean ± standard deviation) significantly (P = 0.002) increased from 122.8 ± 6.7 to 133.3 ± 8.3 mEq/l, and symptoms due to hyponatremia were improved. On the basis of these results, mozavaptan (Physuline(®)) was approved as an orphan drug for the treatment of the syndrome in 2006 in Japan. During the 43 months following its launch, 100 patients have been treated with the drug; overall clinical effects of the drug were found similar to those of this clinical trial. Clinically, mozavaptan may allow hyponatremic patients to be treated by aggressive cancer chemotherapy with platinum-containing drugs. Moreover, the drug may free patients from strict fluid-intake restrictions and thereby improve their quality of life.

  14. Increasing Physical Activity during the School Day through Physical Activity Classes: Implications for Physical Educators

    ERIC Educational Resources Information Center

    Adkins, Megan; Bice, Matt; Bartee, Todd; Heelan, Kate

    2015-01-01

    Across the nation schools are adopting health and wellness policies, specifically physical activity (PA) initiatives that aid healthy long-term lifestyles. Interest has been generated about the inclusion of physical activity classes to complement existing physical education classes. Furthermore, discussion has evolved as to if additional…

  15. DkPK Genes Promote Natural Deastringency in C-PCNA Persimmon by Up-regulating DkPDC and DkADH Expression

    PubMed Central

    Guan, Changfei; Du, Xiaoyun; Zhang, Qinglin; Ma, Fengwang; Luo, Zhengrong; Yang, Yong

    2017-01-01

    The astringency of Chinese pollination-constant non-astringent (C-PCNA) persimmon (Diospyros kaki Thunb.) can be naturally removed on the tree. This process is controlled by a single locus and is dominant against other types of persimmons; therefore, this variant is an important candidate for commercial cultivation and the breeding of PCNA cultivars. In our previous study, six full-length coding sequences (CDS) for pyruvate kinase genes (DkPK1-6) were isolated, and DkPK1 is thought to be involved in the natural deastringency of C-PCNA persimmon fruit. Here, we characterize the eight other DkPK genes (DkPK7-14) from C-PCNA persimmon fruit based on transcriptome data. The transcript changes in DkPK7-14 genes and correlations with the proanthocyanidin (PA) content were investigated during different fruit development stages in C-PCNA, J-PCNA, and non-PCNA persimmon; DkPK7 and DkPK8 exhibited up-regulation patterns during the last developmental stage in C-PCNA persimmon that was negatively correlated with the decrease in soluble PAs. Phylogenetic analysis and subcellular localization analysis revealed that DkPK7 and DkPK8 are cytosolic proteins. Notably, DkPK7 and DkPK8 were ubiquitously expressed in various persimmon organs and abundantly up-regulated in seeds. Furthermore, transient over-expression of DkPK7 and DkPK8 in persimmon leaves led to a significant decrease in the content of soluble PAs but a significant increase in the expression levels of the pyruvate decarboxylase (DkPDC) and alcohol dehydrogenase genes (DkADH), which are closely related to acetaldehyde metabolism. The accumulated acetaldehyde that results from the up-regulation of the DkPDC and DkADH genes can combine with soluble PAs to form insoluble PAs, resulting in the removal of astringency from persimmon fruit. Thus, we suggest that both DkPK7 and DkPK8 are likely to be involved in natural deastringency via the up-regulation of DkPDC and DkADH expression during the last developmental stage in C

  16. Decreasing Stereotypy in Preschoolers with Autism Spectrum Disorder: The Role of Increased Physical Activity and Function

    ERIC Educational Resources Information Center

    McLaughlin, Constance Ann Hylton

    2010-01-01

    This study used increased physical activity during recess to reduce stereotypy in preschoolers with Autism Spectrum Disorder. Results indicate increasing physical activity can be used as an intervention to reduce automatically maintained stereotypy in preschoolers with ASD. The intervention had a lesser effect on a preschooler whose stereotypy was…

  17. Men on the Move: A Pilot Program to Increase Physical Activity among African American Men

    ERIC Educational Resources Information Center

    Griffith, Derek M.; Allen, Julie Ober; Johnson-Lawrence, Vicki; Langford, Aisha

    2014-01-01

    Despite the important contribution increasing physical activity levels may play in reducing chronic disease morbidity and mortality, there is a paucity of interventions and research indicating how to improve physical activity levels in African American men. "Men on the Move" was a pilot study to increase African American men's levels of…

  18. Evidence-Based Practice Guideline: Increasing Physical Activity in Schools--Kindergarten through 8th Grade

    ERIC Educational Resources Information Center

    Bagby, Karen; Adams, Susan

    2007-01-01

    Because of the growing obesity epidemic across all age groups in the United States, interventions to increase physical activity and reduce sedentary behaviors have become a priority. Evidence is growing that interventions to increase physical activity and reduce sedentary behaviors have positive results and are generally inexpensive to implement.…

  19. Increasing Activity Attendance and Engagement in Individuals with Dementia Using Descriptive Prompts

    ERIC Educational Resources Information Center

    Brenske, Shasta; Rudrud, Eric H.; Schulze, Kimberly A.; Rapp, John T.

    2008-01-01

    The effects of providing descriptive prompts to increase activity attendance and engagement in 6 individuals with dementia were evaluated using a reversal design. The results showed that providing descriptive prompts increased activity attendance and engagement for all participants. The results support the use of antecedent interventions for…

  20. Evidence-based practice guideline: increasing physical activity in schools--kindergarten through 8th grade.

    PubMed

    Bagby, Karen; Adams, Susan

    2007-06-01

    Because of the growing obesity epidemic across all age groups in the United States, interventions to increase physical activity and reduce sedentary behaviors have become a priority. Evidence is growing that interventions to increase physical activity and reduce sedentary behaviors have positive results and are generally inexpensive to implement. National and international health organizations are calling for a comprehensive approach for reducing obesity in children that includes increasing physical activity in the school setting. Although the call to increase activity levels in schools is clear, little guidance has been given to schools on specific methods to accomplish this task. This article provides an overview of an evidence-based guideline developed by a physical education teacher and a school nurse to provide inexpensive, easy-to-implement, effective strategies to increase physical activity in students. Tools are also included in the guideline to measure the effectiveness of the intervention.

  1. Use of a lag differential reinforcement contingency to increase varied selections of classroom activities.

    PubMed

    Cammilleri, Anthony P; Hanley, Gregory P

    2005-01-01

    The present study evaluated the effects of a lag differential reinforcement contingency on 2 students' activity selections using reversal designs. Results showed that the lag contingency was responsible for promoting increased novel selections, engagement in diverse activities, and greater progress with respect to programmed academic activities.

  2. Use of an open-loop system to increase physical activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study evaluated the effectiveness of an open-loop system that reinforces physical activity with TV watching to increase children’s physical activity. Non-overweight, sedentary boys and girls (8-12 y) were randomized to a group that received feedback of activity counts + reinforcement for physic...

  3. Use of a Lag Differential Reinforcement Contingency to Increase Varied Selections of Classroom Activities

    ERIC Educational Resources Information Center

    Cammilleri, Anthony P.; Hanley, Gregory P.

    2005-01-01

    The present study evaluated the effects of a lag differential reinforcement contingency on 2 students' activity selections using reversal designs. Results showed that the lag contingency was responsible for promoting increased novel selections, engagement in diverse activities, and greater progress with respect to programmed academic activities.

  4. Texting to increase physical activity among teenagers (TXT Me!): Rationale, design, and methods proposal

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Physical activity decreases from childhood through adulthood. Among youth, teenagers (teens) achieve the lowest levels of physical activity, and high school age youth are particularly at risk of inactivity. Effective methods are needed to increase youth physical activity in a way that can be maintai...

  5. Structural insights into substrate specificity and solvent tolerance in alcohol dehydrogenase ADH-'A' from Rhodococcus ruber DSM 44541.

    PubMed

    Karabec, Martin; Łyskowski, Andrzej; Tauber, Katharina C; Steinkellner, Georg; Kroutil, Wolfgang; Grogan, Gideon; Gruber, Karl

    2010-09-14

    The structure of the alcohol dehydrogenase ADH-'A' from Rhodococcus ruber reveals possible reasons for its remarkable tolerance to organic co-solvents and suggests new directions for structure-informed mutagenesis to produce enzymes of altered substrate specificity or improved selectivity.

  6. Increases in nuclear p65 activation in dystrophic skeletal muscle are secondary to increases in the cellular expression of p65 and are not solely produced by increases in IkappaB-alpha kinase activity.

    PubMed

    Singh, Rajvir; Millman, Gregory; Turin, Eric; Polisiakeiwicz, Lucasz; Lee, Brian; Gatti, Francesca; Berge, Jonas; Smith, Emily; Rutter, John; Sumski, Chris; Winders, W Tyler; Samadi, Abbas; Carlson, C George

    2009-10-15

    Dystrophin-deficient muscle exhibits substantial increases in nuclear NF-kappaB activation. To examine potential mechanisms for this enhanced activation, the present study employs conventional Western blot techniques to provide the first determination of the relative expression of NF-kappaB signaling molecules in adult nondystrophic and dystrophic (mdx) skeletal muscle. The results indicate that dystrophic muscle is characterized by increases in the whole cell expression of IkappaB-alpha, p65, p50, RelB, p100, p52, IKK, and TRAF-3. The proportion of phosphorylated IkappaB-alpha, p65, NIK, and IKKbeta, and the level of cytosolic IkappaB-alpha, were also increased in the mdx diaphragm. Proteasomal inhibition using MG-132 increased the proportion of phosphorylated IkappaB-alpha in nondystrophic diaphragm, but did not significantly increase this proportion in the mdx diaphragm. This result suggests that phosphorylated IkappaB-alpha accumulates in dystrophic cytosol because the rate of IkappaB-alpha degradation is lower than the effective rate of IkappaB-alpha synthesis and phosphorylation. Dystrophic increases in SUMO-1 (small ubiquitin modifier-1) protein and in Akt activation were also observed. The results indicate that increases in nuclear p65 activation in dystrophic muscle are not produced solely by increases in the activity of IkappaB-alpha kinase (IKK), but are due primarily to increases in the expression of p65 and other NF-kappaB signaling components.

  7. Botulinum Toxin Complex Increases Paracellular Permeability in Intestinal Epithelial Cells via Activation of p38 Mitogen-Activated Protein Kinase

    PubMed Central

    MIYASHITA, Shin-ichiro; SAGANE, Yoshimasa; INUI, Ken; HAYASHI, Shintaro; MIYATA, Keita; SUZUKI, Tomonori; OHYAMA, Tohru; WATANABE, Toshihiro; NIWA, Koichi

    2013-01-01

    ABSTRACT Clostridium botulinum produces a large toxin complex (L-TC) that increases paracellular permeability in intestinal epithelial cells by a mechanism that remains unclear. Here, we show that mitogen-activated protein kinases (MAPKs) are involved in this permeability increase. Paracellular permeability was measured by FITC-dextran flux through a monolayer of rat intestinal epithelial IEC-6 cells, and MAPK activation was estimated from western blots. L-TC of C. botulinum serotype D strain 4947 increased paracellular dextran flux and activated extracellular signal-regulated kinase (ERK), p38, but not c-Jun N-terminal kinase (JNK) in IEC-6 cells. The permeability increase induced by L-TC was abrogated by the p38 inhibitor SB203580. These results indicate that L-TC increases paracellular permeability by activating p38, but not JNK and ERK. PMID:23884081

  8. Increased peroxisome proliferator-activated receptor-gamma activity reduces imatinib uptake and efficacy in chronic myeloid leukemia mononuclear cells.

    PubMed

    Wang, Jueqiong; Lu, Liu; Kok, Chung H; Saunders, Verity A; Goyne, Jarrad M; Dang, Phuong; Leclercq, Tamara M; Hughes, Timothy P; White, Deborah L

    2017-02-02

    Imatinib is actively transported by OCT-1 influx transporter, and low OCT-1 activity in diagnostic chronic myeloid leukemia blood mononuclear cells is significantly associated with poor molecular response to imatinib. Here we report that, in diagnostic chronic myeloid leukemia mononuclear cells and BCR-ABL1+ cell lines, peroxisome proliferator-activated receptor gamma agonists (GW1929, rosiglitazone, pioglitazone) significantly decrease OCT-1 activity; conversely, peroxisome proliferator-activated receptor gamma antagonists (GW9662, T0070907) increase OCT-1 activity. Importantly, these effects can lead to corresponding changes in sensitivity to Bcr-Abl kinase inhibition. Results were confirmed in peroxisome proliferator-activated receptor gamma-transduced K562 cells. Furthermore, we identified a strong negative correlation between OCT-1 activity and peroxisome proliferator-activated receptor gamma transcriptional activity in diagnostic chronic myeloid leukemia patients (n=84; p<0.0001), suggesting that peroxisome proliferator-activated receptor gamma activation has a negative impact on the intracellular uptake of imatinib and consequent Bcr-Abl kinase inhibition. The inter-patient variability of peroxisome proliferator-activated receptor gamma activation likely accounts for the heterogeneity observed in patient OCT-1 activity at diagnosis. Recently, the peroxisome proliferator-activated receptor gamma agonist pioglitazone was reported to act synergistically with imatinib targeting the residual chronic myeloid leukemia stem cell pool. Our findings suggest that peroxisome proliferator-activated receptor gamma ligands have differential effects on circulating mononuclear cells compared to stem cells. Since the effect of peroxisome proliferator-activated receptor gamma activation on imatinib uptake in mononuclear cells may counteract the clinical benefit of this activation in stem cells, caution should be applied when combining these therapies, especially in patients

  9. Longterm persistence of proteolytic activities in frass of Blattella germanica increases its allergenic potential.

    PubMed

    Erban, T; Hubert, J

    2011-06-01

    Chromogenic microplate assays in 96 wells were used to determine the stability of enzyme activity in frass of Blattella germanica (Blattodea: Blattellidae). Frass samples were exposed to controlled conditions [temperature 15-35 °C and/or 53-100% relative humidity (RH)] and to household conditions (apartment). Exposure times were 0 (control), 90, 183 and 276 days. Starch digestion and cellulolytic activities decreased during exposure. Non-specific proteolytic activities were affected by changes in selective proteolytic activities. Activities towards AAPpNA and SA(3) pNA strongly increased at 100% RH, indicating the possible influence of microorganisms growing on frass. Activities towards BApNA and ArgpNA decreased with increasing decomposition time, whereas activity towards ZRRpNA was not influenced by exposure time. The largest decrease in activities towards ArgpNA and BApNA occurred at temperatures of 15 °C, 30 °C and 35 °C and at 100% RH. Activities towards BApNA and ZRRpNA were very stable under different temperature and RH conditions; this was confirmed by findings showing that these activities were stable in the experimental apartment. In comparison with the control, activities towards ZRRpNA and BApNA after 276 days decreased by 1% and 19%, respectively. The longterm persistence of proteolytic activities in cockroach frass increases their allergenic hazard potential.

  10. Vertebrate blood cell volume increases with temperature: implications for aerobic activity

    PubMed Central

    Zenil-Ferguson, Rosana

    2014-01-01

    Aerobic activity levels increase with body temperature across vertebrates. Differences in these levels, from highly active to sedentary, are reflected in their ecology and behavior. Yet, the changes in the cardiovascular system that allow for greater oxygen supply at higher temperatures, and thus greater aerobic activity, remain unclear. Here we show that the total volume of red blood cells in the body increases exponentially with temperature across vertebrates, after controlling for effects of body size and taxonomy. These changes are accompanied by increases in relative heart mass, an indicator of aerobic activity. The results point to one way vertebrates may increase oxygen supply to meet the demands of greater activity at higher temperatures. PMID:24765580

  11. Diabetes or peroxisome proliferator-activated receptor alpha agonist increases mitochondrial thioesterase I activity in heart

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Peroxisome proliferator-activated receptor alpha (PPAR alpha) is a transcriptional regulator of the expression of mitochondrial thioesterase I (MTE-I) and uncoupling protein 3 (UCP3), which are induced in the heart at the mRNA level in response to diabetes. Little is known about the regulation of pr...

  12. Feasibility and Effects of Short Activity Breaks for Increasing Preschool-Age Children's Physical Activity Levels

    ERIC Educational Resources Information Center

    Alhassan, Sofiya; Nwaokelemeh, Ogechi; Mendoza, Albert; Shitole, Sanyog; Puleo, Elaine; Pfeiffer, Karin A.; Whitt-Glover, Melicia C.

    2016-01-01

    Background: We examined the effects of short bouts of structured physical activity (SBS-PA) implemented within the classroom setting as part of designated gross-motor playtime on preschoolers PA. Methods: Preschools were randomized to SBS-PA (centers, N = 5; participants, N = 141) or unstructured free playtime (UPA) (centers, N = 5; participants,…

  13. INCREASED ENDOCRINE ACTIVITY OF XENOBIOTIC CHEMICALS AS MEDIATED BY METABOLIC ACTIVATION

    EPA Science Inventory

    This research is part of an effort to develop in vitro assays and QSARs applicable to untested chemicals on EPA inventories through study of estrogen receptor (ER) binding and estrogen mediated gene expression in fish. The current effort investigates metabolic activation of chemi...

  14. Geomagnetic activity during the previous day is correlated with increased consumption of sucrose during subsequent days: is increased geomagnetic activity aversive?

    PubMed

    Galic, M A; Persinger, M A

    2004-06-01

    In five separate blocks over a period of several months for 33 female rats the amount of geomagnetic activity during the day before ad libitum access to 10% sucrose or water was positively correlated with the volume of sucrose consumed per 24-hr. period. The strength of the correlation (.62 to .77) declined over the subsequent 10 days from between .12 to -.18 and resembled an extinction curve. In a subsequent experiment four rats exposed to 5 nT to 8 nT, 0.5-Hz magnetic fields that ceased for 30 min. once every 4 hr. for 4 days consumed 11% more sucrose than the four rats exposed to no field. We suggest that the initial consumption of 10% sucrose may have been reinforced because it diminished the aversive physiological effects associated with the increased geomagnetic activity. However, over the subsequent days, as geomagnetic activity decreased or habituation occurred, negative reinforcement did not maintain this behavior.

  15. An active site mutation increases the polymerase activity of the guinea pig-lethal Marburg virus.

    PubMed

    Koehler, Alexander; Kolesnikova, Larissa; Becker, Stephan

    2016-10-01

    Marburg virus (MARV) causes severe, often fatal, disease in humans and transient illness in rodents. Sequential passaging of MARV in guinea pigs resulted in selection of a lethal virus containing 4 aa changes. A D184N mutation in VP40 (VP40D184N), which leads to a species-specific gain of viral fitness, and three mutations in the active site of viral RNA-dependent RNA polymerase L, which were investigated in the present study for functional significance in human and guinea pig cells. The transcription/replication activity of L mutants was strongly enhanced by a substitution at position 741 (S741C), and inhibited by other substitutions (D758A and A759D) in both species. The polymerase activity of L carrying the S741C substitution was eightfold higher in guinea pig cells than in human cells upon co-expression with VP40D184N, suggesting that the additive effect of the two mutations provides MARV a replicative advantage in the new host.

  16. The rate of synthesis and decomposition of tissue proteins in hypokinesia and increased muscular activity

    NASA Technical Reports Server (NTRS)

    Fedorov, I. V.; Chernyy, A. V.; Fedorov, A. I.

    1978-01-01

    During hypokinesia and physical loading (swimming) of rats, the radioactivity of skeletal muscle, liver, kidney, heart, and blood proteins was determined after administration of radioactive amino acids. Tissue protein synthesis decreased during hypokinesia, and decomposition increased. Both synthesis and decomposition increased during physical loading, but anabolic processes predominated in the total tissue balance. The weights of the animals decreased in hypokinesia and increased during increased muscle activity.

  17. Exercise increases hexokinase II mRNA, but not activity in obesity and type 2 diabetes.

    PubMed

    Cusi, K J; Pratipanawatr, T; Koval, J; Printz, R; Ardehali, H; Granner, D K; Defronzo, R A; Mandarino, L J

    2001-05-01

    Glucose phosphorylation, catalyzed by hexokinase, is the first committed step in glucose uptake in skeletal muscle. Hexokinase II (HKII) is the isoform that is present in muscle and is regulated by insulin and muscle contraction. Glucose phosphorylation and HKII expression are both reduced in obese and type 2 diabetic subjects. A single bout of exercise increases HKII mRNA and activity in muscle from healthy subjects. The present study was performed to determine if a moderate exercise increases HKII mRNA expression and activity in patients with type 2 diabetes. Muscle biopsies were performed before and 3 hours after a single bout of cycle ergometer exercise in obese and type 2 diabetic patients. HKII mRNA and activity and glycogen synthase activity were determined in the muscle biopsies. Exercise increased HKII mRNA in obese and diabetic subjects by 1.67 +/- 0.34 and 1.87 +/- 0.26-fold, respectively (P <.05 for both). Exercise did not significantly increase HKI mRNA. When HKII mRNA increases were compared with the 2.26 +/- 0.36-fold increase in HKII mRNA previously reported for healthy lean subjects, no statistically significant differences were found. In contrast to the increase in HKII activity observed after exercise by lean healthy controls, exercise did not increase HKII activity in obese nondiabetic or diabetic subjects. Exercise increased glycogen synthase activity (GS(0.1) and GS(FV)) significantly in both obese nondiabetic and type 2 diabetic patients. The present results indicate that there is a posttranscriptional defect in the response of HKII expression to exercise in obese and type 2 diabetic subjects. This defect may contribute to reduced HKII activity and glucose uptake in these patients.

  18. Morphine treatment during juvenile isolation increases social activity and opioid peptides release in the adult rat.

    PubMed

    Van den Berg, C L; Kitchen, I; Gerrits, M A; Spruijt, B M; Van Ree, J M

    1999-05-29

    The consequences of juvenile isolation and morphine treatment on general activity, social activity and endogenous opioid release during a social interaction test were investigated in the adult rat. Rats were either isolated or socially housed during weeks 4 and 5 of age and treated daily during this isolation period subcutaneously with either saline or morphine. Directly after a social interaction test at 10 weeks of age, rats were injected with [3H]-diprenorphine and subsequently prepared for in vivo autoradiography. The autoradiographic technique was used to visualise neuroanatomical changes in opioid receptor occupancy, probably reflecting changes in opioid peptide release, as a result of social activity. Juvenile isolation increased general activity during the social interaction test, an effect which was accompanied by a reduction of opioid receptor occupancy in many brain areas, suggesting an increased opioid peptide release as a consequence of socially-induced general activity. Morphine treatment in isolated rats caused an increase in adult social activity and enhanced opioid peptide release in some cortical regions and the ventral tegmental area as compared to saline treated rats. Both social activity and opioid receptor occupancy were unaffected by morphine treatment in non-isolated rats. The present study underscores the role of opioid systems in adult social behaviors as a consequence of juvenile isolation. The results suggest a relationship between social activity and opioid peptide release during social contact. Increased social activity seems to be accompanied by elevated opioid peptide release in distinct brain areas after morphine treatment during juvenile isolation.

  19. Resistance training increases total energy expenditure and free-living physical activity in older adults.

    PubMed

    Hunter, G R; Wetzstein, C J; Fields, D A; Brown, A; Bamman, M M

    2000-09-01

    The purpose of this study was to determine what effects 26 wk of resistance training have on resting energy expenditure (REE), total free-living energy expenditure (TEE), activity-related energy expenditure (AEE), engagement in free-living physical activity as measured by the activity-related time equivalent (ARTE) index, and respiratory exchange ratio (RER) in 61- to 77-yr-old men (n = 8) and women (n = 7). Before and after training, body composition (four-compartment model), strength, REE, TEE (doubly labeled water), AEE (TEE - REE + thermic response to meals), and ARTE (AEE adjusted for energy cost of standard activities) were evaluated. Strength (36%) and fat-free mass (2 kg) significantly increased, but body weight did not change. REE increased 6.8%, whereas resting RER decreased from 0.86 to 0.83. TEE (12%) and ARTE (38%) increased significantly, and AEE (30%) approached significance (P = 0.06). The TEE increase remained significant even after adjustment for the energy expenditure of the resistance training. In response to resistance training, TEE increased and RER decreased. The increase in TEE occurred as a result of increases in both REE and physical activity. These results suggest that resistance training may have value in increasing energy expenditure and lipid oxidation rates in older adults, thereby improving their metabolic profiles.

  20. Short-term disruption in regional left ventricular electrical conduction patterns increases interstitial matrix metalloproteinase activity

    PubMed Central

    Zavadzkas, Juozas A.; Rivers, William T.; McLean, Julie E.; Chang, Eileen I.; Bouges, Shenikqua; Matthews, Robert G.; Koval, Christine N.; Stroud, Robert E.; Spinale, Francis G.

    2010-01-01

    Increased matrix metalloproteinase (MMP) abundance occurs with adverse left ventricular (LV) remodeling in a number of cardiac disease states, including those induced by long-standing arrhythmias. However, whether regionally contained aberrant electrical activation of the LV, with consequent dyskinesia, alters interstitial MMP activation remained unknown. Electrical activation of the LV of pigs (n = 10, 30–35 kg) was achieved by pacing (150 beats/min) at left atrial and LV sites such that normal atrioventricular activation (60 min) was followed by regional early LV activation for 60 min within 1.5 cm of the paced site and restoration of normal atrioventricular pacing for 120 min. Regional shortening (piezoelectric crystals) and interstitial MMP activity (microdialysis with MMP fluorogenic substrate) at the LV pacing site and a remote LV site were monitored at 30-min intervals. During aberrant electrical stimulation, interstitial MMP activity at the paced site was increased (122 ± 4%) compared with the remote region (100%, P < 0.05). Restoration of atrioventricular pacing after the 60-min period of aberrant electrical activation normalized segmental shortening (8.5 ± 0.4%), but MMP activity remained elevated (121 ± 6%, P < 0.05). This study demonstrates that despite the restoration of mechanical function, disturbances in electrical conduction, in and of itself, can cause acute increases in regional in vivo MMP activation and, therefore, contribute to myocardial remodeling. PMID:20472759

  1. Short-term disruption in regional left ventricular electrical conduction patterns increases interstitial matrix metalloproteinase activity.

    PubMed

    Mukherjee, Rupak; Zavadzkas, Juozas A; Rivers, William T; McLean, Julie E; Chang, Eileen I; Bouges, Shenikqua; Matthews, Robert G; Koval, Christine N; Stroud, Robert E; Spinale, Francis G

    2010-07-01

    Increased matrix metalloproteinase (MMP) abundance occurs with adverse left ventricular (LV) remodeling in a number of cardiac disease states, including those induced by long-standing arrhythmias. However, whether regionally contained aberrant electrical activation of the LV, with consequent dyskinesia, alters interstitial MMP activation remained unknown. Electrical activation of the LV of pigs (n = 10, 30-35 kg) was achieved by pacing (150 beats/min) at left atrial and LV sites such that normal atrioventricular activation (60 min) was followed by regional early LV activation for 60 min within 1.5 cm of the paced site and restoration of normal atrioventricular pacing for 120 min. Regional shortening (piezoelectric crystals) and interstitial MMP activity (microdialysis with MMP fluorogenic substrate) at the LV pacing site and a remote LV site were monitored at 30-min intervals. During aberrant electrical stimulation, interstitial MMP activity at the paced site was increased (122 +/- 4%) compared with the remote region (100%, P < 0.05). Restoration of atrioventricular pacing after the 60-min period of aberrant electrical activation normalized segmental shortening (8.5 +/- 0.4%), but MMP activity remained elevated (121 +/- 6%, P < 0.05). This study demonstrates that despite the restoration of mechanical function, disturbances in electrical conduction, in and of itself, can cause acute increases in regional in vivo MMP activation and, therefore, contribute to myocardial remodeling.

  2. Bacterial Manipulation of NK Cell Regulatory Activity Increases Susceptibility to Listeria monocytogenes Infection

    PubMed Central

    Guthrie, Brandon S.; Schmidt, Rebecca L.; Jamieson, Amanda; Merkel, Patricia; Knight, Vijaya; Cole, Caroline M.; Raulet, David H.; Lenz, Laurel L.

    2016-01-01

    Natural killer (NK) cells produce interferon (IFN)-γ and thus have been suggested to promote type I immunity during bacterial infections. Yet, Listeria monocytogenes (Lm) and some other pathogens encode proteins that cause increased NK cell activation. Here, we show that stimulation of NK cell activation increases susceptibility during Lm infection despite and independent from robust NK cell production of IFNγ. The increased susceptibility correlated with IL-10 production by responding NK cells. NK cells produced IL-10 as their IFNγ production waned and the Lm virulence protein p60 promoted induction of IL-10 production by mouse and human NK cells. NK cells consequently exerted regulatory effects to suppress accumulation and activation of inflammatory myeloid cells. Our results reveal new dimensions of the role played by NK cells during Lm infection and demonstrate the ability of this bacterial pathogen to exploit the induction of regulatory NK cell activity to increase host susceptibility. PMID:27295349

  3. Understanding dog owners' increased levels of physical activity: results from RESIDE.

    PubMed

    Cutt, Hayley; Giles-Corti, Billie; Knuiman, Matthew; Timperio, Anna; Bull, Fiona

    2008-01-01

    We examined the influence of dog ownership on physical activity, independent of demographic, intrapersonal, and perceived environmental factors, in a cross-sectional survey of 1813 adults. Although only 23% of the dog owners walked their dogs 5 or more times per week, the adjusted odds of achieving sufficient physical activity and walking were 57% to 77% higher among dog owners compared with those not owning dogs (P< .05). Dog ownership was independently associated with physical activity and walking. Actively encouraging more dog walking may increase community physical activity levels.

  4. Using targeted messaging to increase physical activity in older adults: a review.

    PubMed

    Ostrander, Rachel E; Thompson, Hilaire J; Demiris, George

    2014-09-01

    Physical activity has many benefits for older adults; however, motivating older adults to engage in and maintain optimal levels of physical activity can be challenging for health care providers. A comprehensive literature review was performed to determine whether any evidence-based methods of delivery or particular content for targeted messaging exist that result in actual improvements in physical activity of older adults. Findings of the review demonstrate that messaging directed toward older adults to be physically active resulted in improvements in physical activity up to 1 year. Across studies many different modes of message delivery were shown to be effective. Message content, whether tailored or not, resulted in significant increases in physical activity. There is evidence to support the use of environmentally mediated messaging (i.e., local walking paths) for stronger results. Targeting the client's stage of change, having an activity partner if preferred, and scheduling physical activity also contribute to improved effects.

  5. Newspaper Content Analysis in Evaluation of a Community-Based Participatory Project to Increase Physical Activity

    ERIC Educational Resources Information Center

    Granner, Michelle L.; Sharpe, Patricia A.; Burroughs, Ericka L.; Fields, Regina; Hallenbeck, Joyce

    2010-01-01

    This study conducted a newspaper content analysis as part of an evaluation of a community-based participatory research project focused on increasing physical activity through policy and environmental changes, which included activities related to media advocacy and media-based community education. Daily papers (May 2003 to December 2005) from both…

  6. Increasing Student Physical Activity during the School Day: Opportunities for the Physical Educator

    ERIC Educational Resources Information Center

    Brewer, Joan D.; Luebbers, Paul E.; Shane, Shawna D.

    2009-01-01

    America is facing an obesity epidemic--one that is difficult to ignore. In order to combat the nation's obesity crisis, it is imperative that schools find ways to increase the physical activity levels of students during the school day, as well as encourage additional activity outside of school. By teaching youth to incorporate physical activity…

  7. Physical Activity and Executive Control: Implications for Increased Cognitive Health during Older Adulthood

    ERIC Educational Resources Information Center

    Hillman, Charles H.; Belopolsky, Artem V.; Snook, Erin M.; Kramer, Arthur F.; McAuley, Edward

    2004-01-01

    Electrocortical and behavioral responses of low, moderate, and high physically active older adults where compared with a younger control group on neutral and incompatible conditions of a flankers task. Compared to younger adults, high and moderate active older adults exhibited increased event-related potentials component P3 amplitude for the…

  8. Focused Campaign Increases Activity among Participants in "Nature's Notebook," a Citizen Science Project

    ERIC Educational Resources Information Center

    Crimmins, Theresa M.; Weltzin, Jake F.; Rosemartin, Alyssa H.; Surina, Echo M.; Marsh, Lee; Denny, Ellen G.

    2014-01-01

    Science projects, which engage non-professional scientists in one or more stages of scientific research, have been gaining popularity; yet maintaining participants' activity level over time remains a challenge. The objective of this study was to evaluate the potential for a short-term, focused campaign to increase participant activity in a…

  9. [Methods of increasing the activity of extracellular esterase, beta-fructofuranosidase and proteases of wine yeast].

    PubMed

    Abdurazakova, S Kh; Salomov, Kh T

    1975-01-01

    Upon regular fermentation changes in the activity of the enzymes esterase, beta-fructofuranosidase and protease of the yeast Saccharomyces mini of the Parkent I race were examined. The maximum activity of the enzymes occurred in the stationary phase of the yeast growth. An increase in the activity of the above enzymes was shown possible during a prolonged stabilization of the stationary conditions in the process of a continuous chemostat cultivation of wine yeast.

  10. Activation of protein kinase C by phorbol ester increases red blood cell scramblase activity and external phosphatidylserine.

    PubMed

    Barber, Latorya A; Palascak, Mary B; Qi, Xiaoyang; Joiner, Clinton H; Franco, Robert S

    2015-11-01

    Externalization of phosphatidylserine (PS) is thought to contribute to sickle cell disease (SCD) pathophysiology. The red blood cell (RBC) aminophospholipid translocase (APLT) mediates the transport of PS from the outer to the inner RBC membrane leaflet to maintain an asymmetric distribution of PL, while phospholipid scramblase (PLSCR) equilibrates PL across the RBC membrane, promoting PS externalization. We previously identified an association between PS externalization level and PLSCR activity in sickle RBC under basal conditions. Other studies showed that activation of protein kinase C (PKC) by PMA (phorbol-12-myristate-13-acetate) causes increased external PS on RBC. Therefore, we hypothesized that PMA-activated PKC stimulates PLSCR activity in RBC and thereby contributes to increased PS externalization. In the current studies, we show that PMA treatment causes immediate and variable PLSCR activation and subsequent PS externalization in control and sickle RBC. While TfR+ sickle reticulocytes display some endogenous PLSCR activity, we observed a robust activation of PLSCR in sickle reticulocytes treated with PMA. The PKC inhibitor, chelerythrine (Chel), significantly inhibited PMA-dependent PLSCR activation and PS externalization. Chel also inhibited endogenous PLSCR activity in sickle reticulocytes. These data provide evidence that PKC mediates PS externalization in RBC through activation of PLSCR.

  11. Effects of increasing physical activity on foot structure and ankle muscle strength in adults with obesity

    PubMed Central

    Zhao, Xiaoguang; Tsujimoto, Takehiko; Kim, Bokun; Katayama, Yasutomi; Wakaba, Kyousuke; Wang, Zhennan; Tanaka, Kiyoji

    2016-01-01

    [Purpose] The purpose of this study was to examine the effects of increasing physical activity on foot structure and ankle muscle strength in adults with obesity and to verify whether the rate of change in foot structure is related to that in ankle muscle strength. [Subjects and Methods] Twenty-seven adults with obesity completed a 12-week program in which the intensity of physical activity performed was gradually increased. Physical activity was monitored using a three-axis accelerometer. Foot structure was assessed using a three-dimensional foot scanner, while ankle muscle strength was measured using a dynamometry. [Results] With the increasing physical activity, the participants’ feet became thinner (the rearfoot width, instep height, and girth decreased) and the arch became higher (the arch height index increased) and stiffer (the arch stiffness index increased); the ankle muscle strength also increased after the intervention. Additionally, the changes in the arch height index and arch stiffness index were not associated with changes in ankle muscle strength. [Conclusion] Increasing physical activity may be one possible approach to improve foot structure and function in individuals with obesity. PMID:27630426

  12. Effects of DNA on immunoglobulin production stimulating activity of alcohol dehydrogenase.

    PubMed

    Okamoto, T; Furutani, H; Sasaki, T; Sugahara, T

    1999-09-01

    Alcohol dehydrogenase-I (ADH-I) derived from horse liver stimulated IgM production by human-human hybridoma, HB4C5 cells and lymphocytes. The IPSF activity of ADH-I was suppressed by coexistence of short DNA whose chain length is less than 200 base pairs (bp) and fibrous DNA in a dose-dependent manner. These DNA preparations completely inhibited the IPSF activity at the concentration of 250 mug/ml and 1.0 mg/ml, respectively. DNA sample termed long DNA whose average chain length is 400-7000 bp slightly stimulated IPSF activity at 0.06 mug/ml. However, long DNA suppressed IPSF activity by half at 1.0 mg/ml. The laser confocal microscopic analysis had revealed that ADH-I was incorporated by HB4C5 cells. The uptake of ADH-I was strongly inhibited by short DNA and fibrous DNA. However, long DNA did not suppress the internalization of ADH-I into HB4C5 cells. These findings indicate that short DNA and fibrous DNA depress IPSF activity of ADH-I by inhibiting the internalization of this enzyme. According to the gel-filtration analysis using HPLC, ADH-I did not directly interact with short DNA. It is expected from these findings that short DNA influences HB4C5 cells to suppress the internalization of ADH-I. Moreover, these facts also strongly suggest that ADH-I acts as IPSF after internalization into the cell.

  13. Proximal aortic stiffness is increased in systemic lupus erythematosus activity in children and adolescents.

    PubMed

    El Gamal, Yehia Mohamad; Elmasry, Ola Abd Elaziz; El Hadidi, Iman Saleh; Soliman, Ola Kamel

    2013-01-01

    Patients with systemic lupus erythematosus (SLE) are prone to premature atherosclerosis and are at risk for the development of cardiovascular disease. Increased arterial stiffness is emerging as a marker of subclinical atherosclerosis. Purpose. To measure proximal aortic stiffness in children and adolescents with SLE. Methods. We studied 16 patients with SLE in activity (mean age 15 ± 2.42 years; 16 females), 14 patients with SLE not in activity (mean age 15.7 ± 1.89 years; 4 males, 10 females), and 16 age- and sex-comparable healthy children and adolescents (15.5 ± 1.71 years; 4 males, 12 females). Disease activity was determined by the SLE disease activity index (SLEDAI). All subjects underwent echocardiography for assessment of proximal aortic pulse wave velocity (PWV) [Ao distance/Ao wave transit time in the aortic arch]. Venous blood samples were collected for ESR. Results. Patients in activity had significantly higher PWV values than controls (P < 0.05), while no significant difference was found between patients not in activity and controls. Conclusions. SLE patients with disease activity demonstrate increased PWV and arterial stiffness of the proximal aorta, while patients without disease activity do not. This suggests that inflammation secondary to SLE activity, and not subclinical atherosclerosis, is the major underlying cause for increased arterial stiffness in this age group.

  14. Influence of season on plasma antidiuretic hormone, angiotensin II, aldosterone and plasma renin activity in young volunteers.

    PubMed

    Kanikowska, Dominika; Sugenoya, Junichi; Sato, Maki; Shimizu, Yuuki; Inukai, Yoko; Nishimura, Naoki; Iwase, Satoshi

    2010-05-01

    We investigated seasonal changes in hormonal and thermoregulatory responses. Eight volunteers were subjected to the experiment at four times of the year: around the vernal and autumnal equinoxes, and at the summer and winter solstices at latitude 35 degrees N. Plasma antidiuretic hormone (ADH), angiotensin II (ANG II), aldosterone (ALD) and plasma renin activity (PRA) were analyzed before and after water immersion. Seasonal changes in thermoregulatory responses were assessed by measuring core temperature and sweat rate during immersion of the leg in hot water (at 42 degrees C) for 30 min in a room maintained at 26 degrees C. The concentration of plasma ADH and ALD before water immersion was significantly higher in summer than in other seasons. The concentrations of ANG II and PRA did not show seasonal variations. Changes in tympanic temperature during water immersion showed significant differences between seasons, and were higher in winter than in other seasons. The sweat rate was significantly higher in summer than in other seasons. In summary, ADH and ALD concentrations displayed a seasonal rhythm with marked elevation in summer; this may be a compensative mechanism to prevent dehydration from increased sweat loss during summer due to heat acclimatization.

  15. Targeting Reductions in Sitting Time to Increase Physical Activity and Improve Health.

    PubMed

    Keadle, Sarah K; Conroy, David E; Buman, Matthew P; Dunstan, David W; Matthews, Charles E

    2017-03-08

    New evidence suggests that reductions in sedentary behavior may increase physical activity and improve health. These findings point to new behavioral targets for intervention and new ways to think about intervening to increase overall physical activity in the population. This report provides a knowledge update reflecting the rapid accumulation of new evidence related to sedentary behavior and health among adults. Recent observational studies suggest that leveraging the time-inverse relationship between sedentary and active behaviors by replacing sitting with standing, light or moderate-intensity activity can have important health benefits, particularly among less active adults. Clinical studies are providing evidence of the probable physiologic mechanisms underlying these associations, as well as insights into the cardiometabolic impact of breaking up and reducing sedentary behavior. In contrast to the well-established behavioral theories that guide the development and dissemination of evidence-based interventions to increase moderate-vigorous intensity physical activity (MVPA), much less is known about how to reduce sedentary time in order to increase daily activities. It has become clear that the environmental, social and individual level-determinants for sedentary time are distinct from those linked to the adoption and maintenance of MVPA. As a result, novel intervention strategies that focus on sitting and lower intensity activities by leveraging the surrounding environment (e.g., workplace, school, home) as well as individual-level cues and habits of sedentary behavior are being tested to increase the potency of interventions designed to increase overall physical activity. Herein we summarize the solutions-oriented research across the behavioral research framework, with a focus on highlighting areas of synergy across disciplines and identifying gaps for future research.

  16. Lung arginase expression and activity is increased in cystic fibrosis mouse models.

    PubMed

    Jaecklin, Thomas; Duerr, Julia; Huang, Hailu; Rafii, Mahroukh; Bear, Christine E; Ratjen, Felix; Pencharz, Paul; Kavanagh, Brian P; Mall, Marcus A; Grasemann, Hartmut

    2014-08-01

    The activity of arginase is increased in airway secretions of patients with cystic fibrosis (CF). Downstream products of arginase activity may contribute to CF lung disease. We hypothesized that pulmonary arginase expression and activity would be increased in mouse models of CF and disproportionally increased in CF mice with Pseudomonas aeruginosa pneumonia. Expression of arginase isoforms in lung tissue was quantified with reverse transcriptase-PCR in naive cystic fibrosis transmembrane conductance regulator (Cftr)-deficient mice and β-epithelial sodium channel-overexpressing [β-ENaC-transgenic (Tg)] mice. An isolated lung stable isotope perfusion model was used to measure arginase activity in Cftr-deficient mice before and after intratracheal instillation of Pseudomonas aeruginosa. The expression of arginase-2 in lung was increased in adult Cftr-deficient animals and in newborn β-ENaC-Tg. Arginase-1 lung expression was normal in Cftr-deficient and in newborn β-ENaC-Tg mice, but was increased in β-ENaC-Tg mice at age 1, 3, and 6 wk. Arginase activity was significantly higher in lung (5.0 ± 0.7 vs. 3.2 ± 0.3 nmol·(-1)·h(-1), P = 0.016) and airways (204.6 ± 49.8 vs. 79.3 ± 17.2 nmol·(-1)·h(-1), P = 0.045) of naive Cftr-deficient mice compared with sex-matched wild-type littermate controls. Infection with Pseudomonas aeruginosa resulted in a far greater increase in lung arginase activity in Cftr-deficient mice (10-fold) than in wild-type controls (6-fold) (P = 0.01). This is the first ex vivo characterization of arginase expression and activity in CF mouse lung and airways. Our data show that pulmonary arginase expression and activity is increased in CF mice, especially with Pseudomonas aeruginosa infections.

  17. Increased Mucosal CD4+ T Cell Activation in Rhesus Macaques following Vaccination with an Adenoviral Vector

    PubMed Central

    Bukh, Irene; Calcedo, Roberto; Roy, Soumitra; Carnathan, Diane G.; Grant, Rebecca; Qin, Qiuyue; Boyd, Surina; Ratcliffe, Sarah J.; Veeder, Christin L.; Bellamy, Scarlett L.; Betts, Michael R.

    2014-01-01

    ABSTRACT The possibility that vaccination with adenovirus (AdV) vectors increased mucosal T cell activation remains a central hypothesis to explain the potential enhancement of HIV acquisition within the Step trial. Modeling this within rhesus macaques is complicated because human adenoviruses, including human adenovirus type 5 (HAdV-5), are not endogenous to macaques. Here, we tested whether vaccination with a rhesus macaque-derived adenoviral vector (simian adenovirus 7 [SAdV-7]) enhances mucosal T cell activation within rhesus macaques. Following intramuscular SAdV-7 vaccination, we observed a pronounced increase in SAdV-7-specific CD4+ T cell responses in peripheral blood and, more dramatically, in rectal mucosa tissue. Vaccination also induced a significant increase in the frequency of activated memory CD4+ T cells in SAdV-7- and HAdV-5-vaccinated animals in the rectal mucosa but not in peripheral blood. These fluctuations within the rectal mucosa were also associated with a pronounced decrease in the relative frequency of naive resting CD4+ T cells. Together, these results indicate that peripheral vaccination with an AdV vector can increase the activation of mucosal CD4+ T cells, potentially providing an experimental model to further evaluate the role of host-vector interactions in increased HIV acquisition after AdV vector vaccination. IMPORTANCE The possibility that vaccination with a human adenovirus 5 vector increased mucosal T cell activation remains a central hypothesis to explain the potential enhancement of human immunodeficiency virus (HIV) acquisition within the Step trial. In this study, we tested whether vaccination with a rhesus macaque-derived adenoviral vector in rhesus macaques enhances mucosal CD4+ T cell activation, the main cell target of simian immunodeficiency virus (SIV)/HIV. The results showed that vaccination with an adenoviral vector indeed increases activation of mucosal CD4+ T cells and potentially increases susceptibility to SIV

  18. Increasing Physical Activity in Preschool: A Pilot Study to Evaluate Animal Trackers

    ERIC Educational Resources Information Center

    Williams, Christine L.; Carter, Betty Jean; Kibbe, Debra L.; Dennison, David

    2009-01-01

    Objective: This report describes a pilot study to evaluate Animal Trackers (AT), a preschool program designed to (1) increase structured physical activity (PA) during the preschool day; (2) increase practice of gross motor skills; (3) provide teachers with an easy-to-use PA program regardless of teacher experience; and (4) implement a teacher…

  19. Hematopoietic cell transplantation activity of Turkey in 2014: Ongoing increase in HCT rates.

    PubMed

    Tekgündüz, Emre; Şencan, İrfan; Kapuağası, Arif; Ünal, Doğan; Öztürk, Murat; Gümüş, Eyüp; Göker, Hakan; Tavil, Emine Betül; Ertem, Mehmet; Çetin, Mustafa; Arat, Mutlu; Soysal, Teoman; Karakaşlı, Osman; Sur, Halil Yılmaz; Yeşilipek, Akif; Ferhanoğlu, Burhan; Uçkan, Duygu; İlhan, Osman; Altuntaş, Fevzi

    2016-02-01

    Hematopoietic cell transplantation is an established treatment option with curative potential for a variety of clinical conditions. The last decade especially witnessed a remarkable increase in HCT activity in Turkey. In 2014, 696 pediatric and 2631 adult (total 3327) HCT were performed in Turkey. Corresponding transplant rates per 10 million inhabitants for autologous-HCT and allogeneic-HCT were 226 and 202, respectively. Total HCT procedures in Turkey increased 177% in the last 5 years and 791% in the last 14 years. This report focuses mainly on HCT activity of Turkey in 2014 based on the national HCT registry and presents a general picture of national HCT activity.

  20. Enzyme-assisted processing increases antimicrobial and antioxidant activity of bilberry.

    PubMed

    Puupponen-Pimiä, Riitta; Nohynek, Liisa; Ammann, Sabine; Oksman-Caldentey, Kirsi-Marja; Buchert, Johanna

    2008-02-13

    The effects of nine cell wall-degrading enzymes on the antimicrobial and antioxidant activities of bilberry were studied. Antimicrobial activity was measured using the human pathogens Salmonella enterica sv. Typhimurium and Staphylococcus aureus as test strains. Enzyme treatments liberated phenolics from the cell wall matrix, which clearly increased the antimicrobial activity of berry juices, press cakes, and berry mashes on the basis of plate counts. Antibacterial effects were stronger against Salmonella than against Staphylococcus bacteria. In general, the increase in activity measured as colony-forming units per milliliter was 3-5 logarithmic units against Salmonella and 1-2 units against Staphylococcus bacteria. Increase in antimicrobial activity was observed only in acidic conditions, which is also the natural environment in various berry products, such as juices. The activity profile of the pectinase preparation affected the chemistry of the phenolics due to the presence of deglycosylating activities in some preparations. The difference in phenolic profiles was reflected in the antimicrobial effects. Bilberry mashes treated with Pectinex Ultra SP-L, Pectinex 3 XL, and Pectinex BE XXL were most efficient against Salmonella bacteria, whereas mashes treated with Pectinex Smash, Pectinex BE 3-L, and Biopectinase CCM showed the strongest antimicrobial activity against Staphylococcus bacteria. Due to the liberation of phenolics from the cell wall matrix the antioxidant activity measured as radical scavenging activity was also increased on average about 30% by the enzymatic treatments. The highest increase in phenolic compounds was about 40%. Highest increases in anthocyanins and in antioxidant activity were observed in berry mash treated with Pectinex Smash XXL enzyme, and the lowest increase was observed after treatment with Pectinex BE 3-L. Enzyme-assisted processing is traditionally used to improve berry and fruit juice yields. However, enzymatic treatments also

  1. DMH1 increases glucose metabolism through activating Akt in L6 rat skeletal muscle cells.

    PubMed

    Xie, Xin; Xu, Xiao-Ming; Li, Na; Zhang, Yong-Hui; Zhao, Yu; Ma, Chun-Yan; Dong, De-Li

    2014-01-01

    DMH1(4-[6-(4-Isopropoxyphenyl)pyrazolo [1,5-a]pyrimidin-3-yl] quinoline) is a compound C analogue with the structural modifications at the 3- and 6-positions in pyrazolo[1,5-a]pyrimidine backbone. Compound C was reported to inhibit both AMPK and Akt. Our preliminary work found that DMH1 activated Akt. Since Akt was involved in glucose metabolism, we aimed to identify the effects of DMH1 on glucose metabolism in L6 rat muscle cells and the potential mechanism. Results showed that DMH1 increased lactic acid release and glucose consumption in L6 rat muscle cells in a dose-dependent manner. DMH1 activated Akt in L6 cells. Akt inhibitor inhibited DMH1-induced Akt activation and DMH1-induced increases of glucose uptake and consumption. DMH1 had no cytotoxicity in L6 cells, but inhibited mitochondrial function and reduced ATP production. DMH1 showed no effect on AMPK, but in the presence of Akt inhibitor, DMH1 significantly activated AMPK. Compound C inhibited DMH1-induced Akt activation in L6 cells. Compound C inhibited DMH1-induced increase of glucose uptake, consumption and lactic acid release in L6 cells. DMH1 inhibited PP2A activity, and PP2A activator forskolin reversed DMH1-induced Akt activation. We concluded that DMH1 increased glucose metabolism through activating Akt and DMH1 activated Akt through inhibiting PP2A activity in L6 rat muscle cells. In view of the analogue structure of DMH1 and compound C and the contrasting effects of DMH1 and compound C on Akt, the present study provides a novel leading chemical structure targeting Akt with potential use for regulating glucose metabolism.

  2. Increased physical activity decreases hepatic free fatty acid uptake: a study in human monozygotic twins

    PubMed Central

    Hannukainen, Jarna C; Nuutila, Pirjo; Ronald, Borra; Kaprio, Jaakko; Kujala, Urho M; Janatuinen, Tuula; Heinonen, Olli J; Kapanen, Jukka; Viljanen, Tapio; Haaparanta, Merja; Rönnemaa, Tapani; Parkkola, Riitta; Knuuti, Juhani; Kalliokoski, Kari K

    2007-01-01

    Exercise is considered to be beneficial for free fatty acid (FFA) metabolism, although reports of the effects of increased physical activity on FFA uptake and oxidation in different tissues in vivo in humans have been inconsistent. To investigate the heredity-independent effects of physical activity and fitness on FFA uptake in skeletal muscle, the myocardium, and liver we used positron emission tomography (PET) in nine healthy young male monozygotic twin pairs discordant for physical activity and fitness. The cotwins with higher physical activity constituting the more active group had a similar body mass index but less body fat and 18 ± 10% higher V˙O2,max (P < 0.001) compared to the less active brothers with lower physical activity. Low-intensity knee-extension exercise increased skeletal muscle FFA and oxygen uptake six to 10 times compared to resting values but no differences were observed between the groups at rest or during exercise. At rest the more active group had lower hepatic FFA uptake compared to the less active group (5.5 ± 4.3 versus 9.0 ± 6.1 μmol (100 ml)−1 min−1, P = 0.04). Hepatic FFA uptake associated significantly with body fat percentage (P = 0.05). Myocardial FFA uptake was similar between the groups. In conclusion, in the absence of the confounding effects of genetic factors, moderately increased physical activity and aerobic fitness decrease body adiposity even in normal-weighted healthy young adult men. Further, increased physical activity together with decreased intra-abdominal adiposity seems to decrease hepatic FFA uptake but has no effects on skeletal muscle or myocardial FFA uptake. PMID:17053033

  3. Increased anterior insula activity in anxious individuals is linked to diminished perceived control

    PubMed Central

    Alvarez, R P; Kirlic, N; Misaki, M; Bodurka, J; Rhudy, J L; Paulus, M P; Drevets, W C

    2015-01-01

    Individuals with high-trait anxiety frequently report decreased perceived control. However, it is unclear how these processes are instantiated at a neural level. Prior research suggests that individuals prone to anxiety may have exaggerated activity in the anterior insula and altered activity in the cingulate cortex during anticipation of aversive events. Thus, we hypothesized that anxiety proneness influences anterior insula activation during anticipation of unpredictable threat through decreased perceived control. Forty physically healthy adults underwent neuroimaging while they explored computer-simulated contexts associated either with or without the threat of an unpredictable shock. Skin conductance, anxiety ratings and blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging were used to assess responses to threat versus no threat. Perceived control was measured using the Anxiety Control Questionnaire-Revised. Mediation analysis examined how anxiety proneness influenced BOLD activity. Anticipation of unpredictable threat resulted in increased skin conductance responses, anxiety ratings and enhanced activation in bilateral insula, anterior midcingulate cortex (aMCC) and bed nucleus of the stria terminalis. Individuals with greater anxiety proneness and less perceived control showed greater activity in dorsal anterior insula (dAI). Perceived control mediated the relationship between anxiety proneness and dAI activity. Increased dAI activity was associated with increased activity in aMCC, which correlated with increased exploratory behavior. Results provide evidence that exaggerated insula activation during the threat of unpredictable shock is directly related to low perceived control in anxiety-prone individuals. Perceived control thus may constitute an important treatment target to modulate insula activity during anxious anticipation in anxiety-disordered individuals. PMID:26125154

  4. Salivary Acetylcholinesterase Activity Is Increased in Parkinson's Disease: A Potential Marker of Parasympathetic Dysfunction

    PubMed Central

    Fedorova, Tatyana; Knudsen, Cindy Soendersoe; Mouridsen, Kim; Nexo, Ebba; Borghammer, Per

    2015-01-01

    Introduction. Decreased salivary flow and xerostomia are frequent findings in Parkinson's disease (PD), possibly caused by alterations in the parasympathetic tonus. Here we explore salivary acetylcholinesterase (AChE) activity as a potential biomarker in PD. Methods. We measured salivary flow, AChE activity, and total protein concentration in 30 PD patients and 49 healthy controls. We also performed exploratory correlation analyses with disease duration, motor symptom severity, autonomic complaints, and other nonmotor symptoms. Results. PD patients displayed significantly decreased salivary flow rate, significantly increased salivary AChE activity, and total protein concentration. Importantly, the AChE activity/total protein ratio was significantly increased in PD patients, suggesting that increased AChE activity cannot be explained solely by upconcentration of saliva. The Unified PD Rating Scale (UPDRS) score displayed significant correlation with total salivary protein (P = 0.002) and near-significant correlation with salivary flow (P = 0.07). Color vision test scores were also significantly correlated with AChE activity (P = 0.04) and total protein levels (P = 0.002). Conclusion. Salivary AChE activity is increased in PD patients compared to healthy controls. Future studies are needed to elucidate whether this parameter reflects the extent of neuronal damage and parasympathetic denervation in the salivary glands of PD patients. PMID:25767737

  5. Increased chitotriosidase activity in plasma of patients with type 2 diabetes

    PubMed Central

    Knapik-Kordecka, Maria; Rorbach-Dolata, Anna; Piwowar, Agnieszka

    2016-01-01

    Introduction Chitotriosidase (CHIT1) is a chitinolytic enzyme involved mainly in the immune and inflammatory response. It shows increased activity in many pathologies, including in newly diagnosed type 2 diabetes (T2D). This study aimed to investigate this enzyme's activity in plasma of patients with ongoing T2D and indicate factors related to the increased activity of this enzyme. Material and methods Ninety-one patients and 46 control subjects without abnormalities in carbohydrate metabolism and inflammatory states were enrolled in the study. Plasma CHIT1 activity was measured by a spectrofluorometric method. Routine laboratory parameters such as blood glucose, total cholesterol and HDL fraction, triglyceride, glycated hemoglobin, white blood cell count and C-reactive protein were measured by standard methods. Results We found that the chitotriosidase activity was significantly higher (p < 0.001) in type 2 diabetic patients and positively associated with parameters of glycemic control (levels of glucose and glycated hemoglobin) and blood pressure. Plasma glucose level and systolic blood pressure were independent determinants of increased CHIT1 activity in T2D patients, even after adjustment for disease duration, body mass index, parameters of inflammation and lipid metabolism. We also found that increased CHIT1 activity was associated with occurrence of diabetic angiopathies. Conclusions This investigation indicates a possible role of chitotriosidase in the course of T2D, especially in relation to development of diabetic angiopathies. PMID:27695487

  6. Increased endocytotic and lysosomal activities in denervated type I and type II muscle fibres.

    PubMed

    Lawoko, G; Tågerud, S; Libelius, R

    1992-01-01

    Previous work has shown that increased endocytotic and lysosomal activities occur in the endplate region of denervated skeletal muscle fibres. This, however, does not engage all fibres of a muscle at a given time after denervation. The present study was carried out in order to determine if both type I (slow) and type II (fast) muscle fibres can react to denervation by increased endocytotic and lysosomal activities. Uptake of horseradish peroxidase as a marker for endocytosis was studied in conjunction with acid phosphatase staining for lysosomal activity in type I and type II fibres of the denervated mouse hemidiaphragm. Fibre typing was performed using a monoclonal antibody against fast skeletal myosin and by adenosine triphosphatase staining. The results show that increased endocytosis and lysosomal activation occur in both type I and type II fibres after denervation.

  7. Increase of histidine decarboxylase activity in mice hypothalamus after intracerebroventricular administration of lipopolysaccharide.

    PubMed

    Niimi, M; Mochizuki, T; Cacabelos, R; Yamatodani, A

    1993-10-01

    The effect of intracerebroventricular (icv) administration of lipopolysaccharide on histidine decarboxylase activity and histamine content in the hypothalamus were investigated in male mice of ddY strain in vivo. Two-fold increase in histidine decarboxylase activity (HDC) was observed 4 h after administration of 50 mcg lipopolysaccharide, and HDC activity returned to the basal level within 12 h after injection. Furthermore, histamine contents showed a slight decrease at 1 and 2 h and a mild increase at 12 h after administration. However, changes in histamine content were not statistically significant. These results suggest that the increase of HDC activity in the hypothalamus by lipopolysaccharide may be involved in the central neuroimmune responses.

  8. Prenatal Iron Deficiency in Guinea Pigs Increases Locomotor Activity but Does Not Influence Learning and Memory.

    PubMed

    Fiset, Catherine; Rioux, France M; Surette, Marc E; Fiset, Sylvain

    2015-01-01

    The objective of the current study was to determine whether prenatal iron deficiency induced during gestation in guinea pigs affected locomotor activity and learning and memory processes in the progeny. Dams were fed either iron-deficient anemic or iron-sufficient diets throughout gestation and lactation. After weaning, all pups were fed an iron-sufficient diet. On postnatal day 24 and 40, the pups' locomotor activity was observed within an open-field test, and from postnatal day 25 to 40, their learning and memory processes were assessed within a Morris Water Maze. The behavioural and cognitive tests revealed that the iron deficient pup group had increased locomotor activity, but solely on postnatal day 40, and that there were no group differences in the Morris Water Maze. In the general discussion, we propose that prenatal iron deficiency induces an increase in nervousness due to anxiety in the progeny, which, in the current study, resulted in an increase of locomotor activity.

  9. Calpain activity and expression are increased in splenic inflammatory cells associated with experimental allergic encephalomyelitis.

    PubMed

    Shields, D C; Schaecher, K E; Goust, J M; Banik, N L

    1999-09-01

    Since calcium-activated neutral proteinase (calpain) activity and expression are significantly increased in activated glial/inflammatory cells in the central nervous system of animals with autoimmune demyelinating diseases, this enzyme may also play a role in peripheral organ systems in these diseases. In this study, the activity and expression of calpain and the endogenous inhibitor, calpastatin, were evaluated at transcriptional and translational levels in spleens of Lewis rats with acute experimental allergic encephalomyelitis (EAE) prior to the onset of clinical symptoms. Calpain activity and translational expression were increased by 475.5% and 44.3% respectively, on day 4 post-induction in adjuvant controls and animals with EAE. These levels remained elevated compared to normal controls on days 8 and 12. Calpastatin translational expression was similarly increased at these time points although transcriptional expression was not significantly altered at any time following induction of EAE. Likewise, transcriptional expression of mu-calpain was unchanged following induction, while small increases in m-calpain transcriptional expression were observed on days 2 and 8. Most calpain expression was observed in activated splenic macrophages at day 8 post-induction even though activated T cells were also calpain positive. In spinal cords of animals with EAE, calpain expression was significantly increased in rats with severe disease compared to those exhibiting only mild symptoms at day 12 post-induction. Thus, prior to symptomatic EAE, increased calpain activity and expression in peripheral lymphoid organs may play an important role in T cell migration and subsequent disease progression.

  10. Increase in larval gut proteolytic activities and Bti resistance in the Dengue fever mosquito.

    PubMed

    Tetreau, Guillaume; Stalinski, Renaud; David, Jean-Philippe; Després, Laurence

    2013-02-01

    The bioinsecticide Bacillus thuringiensis var. israelensis (Bti) is increasingly used worldwide for mosquito control. Although no established resistance to Bti has been described in the field so far, a resistant Aedes aegypti strain (LiTOX strain) was selected in the laboratory using field-collected leaf litter containing Bti toxins. This selected strain exhibits a moderate resistance level to Bti, but a high resistance level to individual Cry toxins. As Bti contains four different toxins, generalist resistance mechanisms affecting mosquito tolerance to different toxins were expected in the resistant strain. In the present work, we show that the resistant strain exhibits an increase of various gut proteolytic activities including trypsins, leucine-aminopeptidases, and carboxypeptidase A activities. These elevated proteolytic activities resulted in a faster activation of Cry4Aa protoxins while Cry4Ba or Cry11Aa were not affected. These results suggest that changes in proteolytic activities may contribute to Bti resistance in mosquitoes together with other mechanisms.

  11. Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression.

    PubMed

    Liu, Xin-Hua; Yao, Shen; Qiao, Rui-Fang; Levine, Alice C; Kirschenbaum, Alexander; Pan, Jiangping; Wu, Yong; Qin, Weiping; Bauman, William A; Cardozo, Christopher P

    2011-10-14

    Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.

  12. Preliminary efficacy of prize-based contingency management to increase activity levels in healthy adults.

    PubMed

    Washington, Wendy Donlin; Banna, Kelly M; Gibson, Amanda L

    2014-01-01

    An estimated 30% of Americans meet the criteria for obesity. Effective, low-cost interventions to increase physical activity are needed to prevent and treat obesity. In this study, 11 healthy adults wore Fitbit accelerometers for 3 weeks. During the initial baseline, subjects earned prize draws for wearing the Fitbit. During intervention, percentile schedules were used to calculate individual prize-draw criteria. The final week was a return to baseline. Four subjects increased step counts as a result of the intervention. A bout analysis of interresponse times revealed that subjects increased overall step counts by increasing daily minutes active and within-bout response rates and decreasing pauses between bouts of activity. Strategies to improve effectiveness are suggested, such as modification of reinforcement probability and amount and identification of the function of periods of inactivity.

  13. ABDOMINAL MUSCLE ACTIVATION INCREASES LUMBAR SPINAL STABILITY: ANALYSIS OF CONTRIBUTIONS OF DIFFERENT MUSCLE GROUPS

    PubMed Central

    Stokes, Ian A.F.; Gardner-Morse, Mack G.; Henry, Sharon M.

    2011-01-01

    Background Antagonistic activation of abdominal muscles and raised intra-abdominal pressure are associated with both spinal unloading and spinal stabilization. Rehabilitation regimens have been proposed to improve spinal stability via selective recruitment of certain trunk muscle groups. This biomechanical study used an analytical model to address whether lumbar spinal stability is increased by selective activation of abdominal muscles. Methods The biomechanical model included anatomically realistic three-layers of curved abdominal musculature connected by fascia, rectus abdominis and 77 symmetrical pairs of dorsal muscles. The muscle activations were calculated with the model loaded with either flexion, extension, lateral bending or axial rotation moments up to 60 Nm, along with intra-abdominal pressure up to 5 or 10 kPa (37.5 or 75 mm Hg) and partial bodyweight. After solving for muscle forces, a buckling analysis quantified spinal stability. Subsequently, different patterns of muscle activation were studied by forcing activation of selected abdominal muscles to at least 10% or 20% of maximum. Findings The spinal stability increased by an average factor of 1.8 with doubling of intra-abdominal pressure. Forced activation of obliques or transversus abdominis muscles to at least 10% of maximum increased stability slightly for efforts other than flexion, but forcing at least 20% activation generally did not produce further increase in stability. Forced activation of rectus abdominis did not increase stability. Interpretation Based on predictions from an analytical spinal buckling model, the degree of stability was not substantially influenced by selective forcing of muscle activation. This casts doubt on the supposed mechanism of action of specific abdominal muscle exercise regimens that have been proposed for low back pain rehabilitation. PMID:21571410

  14. Peripheral Sensitization Increases Opioid Receptor Expression and Activation by Crotalphine in Rats

    PubMed Central

    Zambelli, Vanessa Olzon; Fernandes, Ana Carolina de Oliveira; Gutierrez, Vanessa Pacciari; Ferreira, Julio Cesar Batista; Parada, Carlos Amilcar; Mochly-Rosen, Daria; Cury, Yara

    2014-01-01

    Inflammation enhances the peripheral analgesic efficacy of opioid drugs, but the mechanisms involved in this phenomenon have not been fully elucidated. Crotalphine (CRP), a peptide that was first isolated from South American rattlesnake C.d. terrificus venom, induces a potent and long-lasting anti-nociceptive effect that is mediated by the activation of peripheral opioid receptors. Because the high efficacy of CRP is only observed in the presence of inflammation, we aimed to elucidate the mechanisms involved in the CRP anti-nociceptive effect induced by inflammation. Using real-time RT-PCR, western blot analysis and ELISA assays, we demonstrate that the intraplantar injection of prostaglandin E2 (PGE2) increases the mRNA and protein levels of the µ- and κ-opioid receptors in the dorsal root ganglia (DRG) and paw tissue of rats within 3 h of the injection. Using conformation state-sensitive antibodies that recognize activated opioid receptors, we show that PGE2, alone does not increase the activation of these opioid receptors but that in the presence of PGE2, the activation of specific opioid receptors by CRP and selective µ- and κ-opioid receptor agonists (positive controls) increases. Furthermore, PGE2 down-regulated the expression and activation of the δ-opioid receptor. CRP increased the level of activated mitogen-activated protein kinases in cultured DRG neurons, and this increase was dependent on the activation of protein kinase Cζ. This CRP effect was much more prominent when the cells were pretreated with PGE2. These results indicate that the expression and activation of peripheral opioid receptors by opioid-like drugs can be up- or down-regulated in the presence of an acute injury and that acute tissue injury enhances the efficacy of peripheral opioids. PMID:24594607

  15. Activation of muscarinic receptors in porcine airway smooth muscle elicits a transient increase in phospholipase D activity.

    PubMed

    Mamoon, A M; Smith, J; Baker, R C; Farley, J M

    1999-01-01

    Phospholipase D (PLD) is a phosphodiesterase that catalyses hydrolysis of phosphatidylcholine to produce phosphatidic acid and choline. In the presence of ethanol, PLD also catalyses the formation of phosphatidylethanol, which is a unique characteristic of this enzyme. Muscarinic receptor-induced changes in the activity of PLD were investigated in porcine tracheal smooth muscle by measuring the formation of [3H]phosphatidic acid ([3H]PA) and [3H]phosphatidylethanol ([3H]PEth) after labeling the muscle strips with [3H]palmitic acid. The cholinergic receptor agonist acetylcholine (Ach) significantly but transiently increased formation of both [3H]PA and [3H]PEth in a concentration-dependent manner (>105-400% vs. controls in the presence of 10(-6) to 10(-4) M Ach) when pretreated with 100 mM ethanol. The Ach receptor-mediated increase in PLD activity was inhibited by atropine (10(-6) M), indicating that activation of PLD occurred via muscarinic receptors. Activation of protein kinase C (PKC) by phorbol-12-myristate-13-acetate (PMA) increased PLD activity that was effectively blocked by the PKC inhibitors calphostin C (10(-8) to 10(-6) M) and GFX (10(-8) to 10(-6) M). Ach-induced increases in PLD activity were also significantly, but incompletely, inhibited by both GFX and calphostin C. From the present data, we conclude that in tracheal smooth muscle, muscarinic acetylcholine receptor-induced PLD activation is transient in nature and coupled to these receptors via PKC. However, PKC activation is not solely responsible for Ach-induced activation of PLD in porcine tracheal smooth muscle.

  16. The Genetics of a Small Autosomal Region of DROSOPHILA MELANOGASTER Containing the Structural Gene for Alcohol Dehydrogenase. I. Characterization of Deficiencies and Mapping of ADH and Visible Mutations

    PubMed Central

    Woodruff, R. C.; Ashburner, M.

    1979-01-01

    The position of the structural gene coding for alcohol dehydrogenase (ADH) in Drosophila melanogaster has been shown to be within polytene chromosome bands 35B1 and 35B3, most probably within 35B2. The genetic and cytological properties of twelve deficiencies in polytene chromosome region 34–35 have been characterized, eleven of which include Adh. Also mapped cytogenetically are seven other recessive visible mutant loci. Flies heterozygous for overlapping deficiencies that include both the Adh locus and that for the outspread mutant (osp: a recessive wing phenotype) are homozygous viable and show a complete ADH negative phenotype and strong osp phenotype. These deficiencies probably include two polytene chromosome bands, 35B2 and 35B3. PMID:115743

  17. Adolescent Activity-Based Anorexia Increases Anxiety-Like Behavior in Adulthood

    PubMed Central

    Kinzig, Kimberly P.; Hargrave, Sara L.

    2010-01-01

    Activity-based anorexia is a paradigm that induces increased physical activity, reduced food intake, and heightened activity of the hypothalamic-pituitary-adrenal axis in adult rats. To investigate whether experience with activity-based anorexia produced enduring effects on brain and behavior, female adolescent rats experienced activity-based anorexia during adolescence and were tested in adulthood for anxiety-like behavior on an elevated plus maze and in an open field. Analysis of elevated plus maze and open field behavior in adulthood revealed that rats that experienced activity-based anorexia during adolescence, but not rats that were simply food restricted, displayed increased anxiety-like behavior in adulthood. Plasma corticosterone and expression levels of corticotropin- releasing hormone mRNA in the hypothalamic paraventricular nucleus and in the central nucleus of the amygdala were significantly elevated in adult rats that had undergone activity-based anorexia in adolescence in response to the open field exposure, as compared to control rats. These data demonstrate enduring effects of adolescent activity-based anorexia on anxiety-like behavior and neuroendocrine factors critical in stress responsivity in adulthood. Furthermore, we demonstrate that activity-based anorexia during adolescence serves as a model whereby prolonged anxiety is induced, allowing for evaluation of the behavioral and neural correlates of mediating anxiety-like behaviors in adulthood. PMID:20566408

  18. Novel pathway engineering design of the anaerobic central metabolic pathway in Escherichia coli to increase succinate yield and productivity.

    PubMed

    Sánchez, Ailen M; Bennett, George N; San, Ka-Yiu

    2005-05-01

    A novel in vivo method of producing succinate has been developed. A genetically engineered Escherichia coli strain has been constructed to meet the NADH requirement and carbon demand to produce high quantities and yield of succinate by strategically implementing metabolic pathway alterations. Currently, the maximum theoretical succinate yield under strictly anaerobic conditions through the fermentative succinate biosynthesis pathway is limited to one mole per mole of glucose due to NADH limitation. The implemented strategic design involves the construction of a dual succinate synthesis route, which diverts required quantities of NADH through the traditional fermentative pathway and maximizes the carbon converted to succinate by balancing the carbon flux through the fermentative pathway and the glyoxylate pathway (which has less NADH requirement). The synthesis of succinate uses a combination of the two pathways to balance the NADH. Consequently, experimental results indicated that these combined pathways gave the most efficient conversion of glucose to succinate with the highest yield using only 1.25 moles of NADH per mole of succinate in contrast to the sole fermentative pathway, which uses 2 moles of NADH per mole of succinate. A recombinant E. coli strain, SBS550MG, was created by deactivating adhE, ldhA and ack-pta from the central metabolic pathway and by activating the glyoxylate pathway through the inactivation of iclR, which encodes a transcriptional repressor protein of the glyoxylate bypass. The inactivation of these genes in SBS550MG increased the succinate yield from glucose to about 1.6 mol/mol with an average anaerobic productivity rate of 10 mM/h (approximately 0.64 mM/h-OD600). This strain is capable of fermenting high concentrations of glucose in less than 24 h. Additional derepression of the glyxoylate pathway by inactivation of arcA, leading to a strain designated as SBS660MG, did not significantly increase the succinate yield and it decreased

  19. Vagus Nerve Stimulation Increases Energy Expenditure: Relation to Brown Adipose Tissue Activity

    PubMed Central

    Vijgen, Guy H. E. J.; Bouvy, Nicole D.; Leenen, Loes; Rijkers, Kim; Cornips, Erwin; Majoie, Marian; Brans, Boudewijn; van Marken Lichtenbelt, Wouter D.

    2013-01-01

    Background Human brown adipose tissue (BAT) activity is inversely related to obesity and positively related to energy expenditure. BAT is highly innervated and it is suggested the vagus nerve mediates peripheral signals to the central nervous system, there connecting to sympathetic nerves that innervate BAT. Vagus nerve stimulation (VNS) is used for refractory epilepsy, but is also reported to generate weight loss. We hypothesize VNS increases energy expenditure by activating BAT. Methods and Findings Fifteen patients with stable VNS therapy (age: 45±10yrs; body mass index; 25.2±3.5 kg/m2) were included between January 2011 and June 2012. Ten subjects were measured twice, once with active and once with inactivated VNS. Five other subjects were measured twice, once with active VNS at room temperature and once with active VNS under cold exposure in order to determine maximal cold-induced BAT activity. BAT activity was assessed by 18-Fluoro-Deoxy-Glucose-Positron-Emission-Tomography-and-Computed-Tomography. Basal metabolic rate (BMR) was significantly higher when VNS was turned on (mean change; +2.2%). Mean BAT activity was not significantly different between active VNS and inactive VNS (BAT SUVMean; 0.55±0.25 versus 0.67±0.46, P = 0.619). However, the change in energy expenditure upon VNS intervention (On-Off) was significantly correlated to the change in BAT activity (r = 0.935, P<0.001). Conclusions VNS significantly increases energy expenditure. The observed change in energy expenditure was significantly related to the change in BAT activity. This suggests a role for BAT in the VNS increase in energy expenditure. Chronic VNS may have a beneficial effect on the human energy balance that has potential application for weight management therapy. Trial Registration The study was registered in the Clinical Trial Register under the ClinicalTrials.gov Identifier NCT01491282. PMID:24194874

  20. Hyperthyroidism increases the uncoupled ATPase activity and heat production by the sarcoplasmic reticulum Ca2+-ATPase.

    PubMed Central

    Arruda, Ana Paula; Da-Silva, Wagner S; Carvalho, Denise P; De Meis, Leopoldo

    2003-01-01

    The sarcoplasmic reticulum Ca2+-ATPase is able to modulate the distribution of energy released during ATP hydrolysis, so that a portion of energy is used for Ca2+ transport (coupled ATPase activity) and a portion is converted into heat (uncoupled ATPase activity). In this report it is shown that T4 administration to rabbits promotes an increase in the rates of both the uncoupled ATPase activity and heat production in sarcoplasmic reticulum vesicles, and that the degree of activation varies depending on the muscle type used. In white muscles hyperthyroidism promotes a 0.8-fold increase of the uncoupled ATPase activity and in red muscle a 4-fold increase. The yield of vesicles from hyperthyroid muscles is 3-4-fold larger than that obtained from normal muscles; thus the rate of heat production by the Ca2+-ATPase expressed in terms of g of muscle in hyperthyroidism is increased by a factor of 3.6 in white muscles and 12.0 in red muscles. The data presented suggest that the Ca2+-ATPase uncoupled activity may represent one of the heat sources that contributes to the enhanced thermogenesis noted in hyperthyroidism. PMID:12887329

  1. Increased KGF expression promotes fibroblast activation in a double paracrine manner resulting in cutaneous fibrosis.

    PubMed

    Canady, Johanna; Arndt, Stephanie; Karrer, Sigrid; Bosserhoff, Anja K

    2013-03-01

    Fibrotic disorders of the skin share the characteristic features of increased production and deposition of extracellular matrix components by activated fibroblasts. Their clinical course ranges from benign with localized cutaneous involvement to a systemic, life-threatening disease. The molecular cause for fibroblast activation remains unknown, yet epithelial-mesenchymal interactions draw mounting attention in the research field of fibrogenesis. We examined keratinocyte growth factor (KGF), a crucial molecule in fibroblast-keratinocyte cross talk, exemplarily in keloid and scleroderma, and found its expression to be increased in disease-derived fibroblasts and tissues compared with healthy controls. This overexpression induces fibroblast activation through a double paracrine mode of action. Upon KGF stimulation, the keratinocytes produced and secreted OSM (oncostatin M). Fibroblasts were in turn activated by OSM reacting with the increased expression of collagen type I-α1, fibroblast activation protein, and enhanced migration. The observed increase in collagen expression and fibroblast migration can be traced back to OSM-regulated STAT3 phosphorylation, leading to enhanced urokinase plasminogen activator expression. Hence, we propose a causative loop in the pathogenesis of fibrosing disorders of the skin mediated by the overexpression of KGF in mesenchymal cells.

  2. Exogenous methyl jasmonate treatment increases glucosinolate biosynthesis and quinone reductase activity in kale leaf tissue.

    PubMed

    Ku, Kang-Mo; Jeffery, Elizabeth H; Juvik, John A

    2014-01-01

    Methyl jasmonate (MeJA) spray treatments were applied to the kale varieties 'Dwarf Blue Curled Vates' and 'Red Winter' in replicated field plantings in 2010 and 2011 to investigate alteration of glucosinolate (GS) composition in harvested leaf tissue. Aqueous solutions of 250 µM MeJA were sprayed to saturation on aerial plant tissues four days prior to harvest at commercial maturity. The MeJA treatment significantly increased gluconasturtiin (56%), glucobrassicin (98%), and neoglucobrassicin (150%) concentrations in the apical leaf tissue of these genotypes over two seasons. Induction of quinone reductase (QR) activity, a biomarker for anti-carcinogenesis, was significantly increased by the extracts from the leaf tissue of these two cultivars. Extracts of apical leaf tissues had greater MeJA mediated increases in phenolics, glucosinolate concentrations, GS hydrolysis products, and QR activity than extracts from basal leaf tissue samples. The concentration of the hydrolysis product of glucoraphanin, sulforphane was significantly increased in apical leaf tissue of the cultivar 'Red Winter' in both 2010 and 2011. There was interaction between exogenous MeJA treatment and environmental conditions to induce endogenous JA. Correlation analysis revealed that indole-3-carbanol (I3C) generated from the hydrolysis of glucobrassicin significantly correlated with QR activity (r = 0.800, P<0.001). Concentrations required to double the specific QR activity (CD values) of I3C was calculated at 230 µM, which is considerably weaker at induction than other isothiocyanates like sulforphane. To confirm relationships between GS hydrolysis products and QR activity, a range of concentrations of MeJA sprays were applied to kale leaf tissues of both cultivars in 2011. Correlation analysis of these results indicated that sulforaphane, NI3C, neoascorbigen, I3C, and diindolylmethane were all significantly correlated with QR activity. Thus, increased QR activity may be due to combined

  3. Increasing activity and thermal resistance of Bacillus gibsonii alkaline protease (BgAP) by directed evolution.

    PubMed

    Martinez, Ronny; Jakob, Felix; Tu, Ran; Siegert, Petra; Maurer, Karl-Heinz; Schwaneberg, Ulrich

    2013-03-01

    Bacillus gibsonii Alkaline Protease (BgAP) is a recently reported subtilisin protease exhibiting activity and stability properties suitable for applications in laundry and dish washing detergents. However, BgAP suffers from a significant decrease of activity at low temperatures. In order to increase BgAP activity at 15°C, a directed evolution campaign based on the SeSaM random mutagenesis method was performed. An optimized microtiter plate expression system in B. subtilis was established and classical proteolytic detection methods were adapted for high throughput screening. In parallel, the libraries were screened for increased residual proteolytic activity after incubation at 58°C. Three iterative rounds of directed BgAP evolution yielded a set of BgAP variants with increased specific activity (K(cat)) at 15°C and increased thermal resistance. Recombination of both sets of amino acid substitutions resulted finally in variant MF1 with a 1.5-fold increased specific activity (15°C) and over 100 times prolonged half-life at 60°C (224 min compared to 2 min of the WT BgAP). None of the introduced amino acid substitutions were close to the active site of BgAP. Activity-altering amino acid substitutions were from non-charged to non-charged or from sterically demanding to less demanding. Thermal stability improvements were achieved by substitutions to negatively charged amino acids in loop areas of the BgAP surface which probably fostered ionic and hydrogen bonds interactions.

  4. 92-kd type IV collagenase (matrix metalloproteinase-9) activity in human amniochorion increases with labor.

    PubMed Central

    Vadillo-Ortega, F.; González-Avila, G.; Furth, E. E.; Lei, H.; Muschel, R. J.; Stetler-Stevenson, W. G.; Strauss, J. F.

    1995-01-01

    To determine whether specific collagenolytic enzymes are expressed in human fetal membranes with labor, we examined gelatinase activity in extracts of amniochorion by zymography. The 92-kd gelatinase (MMP-9) was barely detectable in extracts of fetal membranes before the onset of labor but was readily demonstrable in extracts prepared from membranes isolated from laboring women or membranes collected immediately after delivery. In contrast, the 72-kd gelatinase (MMP-2) was detectable in extracts from pre- and post-labor membranes. Ethylenediaminetetracetic acid and the tissue inhibitor of metalloproteinases, TIMP-1, inhibited the gelatinase activities detected by zymography, confirming that the enzymes are metalloproteinase. Assay of amniochorion gelatinase activity using a radiolabeled denatured collagen substrate revealed a more than twofold increase in activity comparing pre-labor with post-labor fetal membrane extracts. A function-blocking anti-MMP-9 monoclonal antibody inhibited pre-labor membrane gelatinase activity by approximately 11.5%, which was only slightly greater inhibition than observed with irrelevant monoclonal antibodies. However, post-labor membrane gelatinase activity was reduced by 53% by the function-blocking antibody, indicating that MMP-9 is a major contributor to the increased gelatinase activity extractable from post-labor membranes. Western blot analyses demonstrated increased MMP-9 protein in amniochorion extracts after onset of labor. MMP-9 protein and mRNA were co-localized in amnion epithelium, underlying macrophages and chorion laeve trophoblast and decidual cells after labor. We conclude that 1) MMP-9 activity and protein in human amniochorion increases with labor and 2) MMP-9 is expressed by amnion epithelium, macrophages and chorion laeve trophoblast and decidual cells. The increased expression of MMP-9 may result in degradation of the extracellular matrix of the fetal membranes and facilitate their rupture under both

  5. Oxytocin increases VTA activation to infant and sexual stimuli in nulliparous and postpartum women.

    PubMed

    Gregory, Rebecca; Cheng, Hu; Rupp, Heather A; Sengelaub, Dale R; Heiman, Julia R

    2015-03-01

    After giving birth, women typically experience decreased sexual desire and increased responsiveness to infant stimuli. These postpartum changes may be viewed as a trade-off in reproductive interests, which could be due to alterations in brain activity including areas associated with reward. The goal of this study was to describe the roles of oxytocin and parity on reward area activation in response to reproductive stimuli, specifically infant and sexual images. Because they have been shown to be associated with reward, the ventral tegmental area (VTA) and nucleus accumbens (NAc) were targeted as areas of expected alterations in activity. Oxytocin was chosen as a potential mediator of reproductive trade-offs because of its relationship to both mother-infant interactions, including breastfeeding and bonding, and sexual responses. We predicted that postpartum women would show higher reward area activation to infant stimuli and nulliparous women would show higher activation to sexual stimuli and that oxytocin would increase activation to infant stimuli in nulliparous women. To test this, we measured VTA and NAc activation using fMRI in response to infant photos, sexual photos, and neutral photos in 29 postpartum and 30 nulliparous women. Participants completed the Sexual Inhibition (SIS) and Sexual Excitation (SES) Scales and the Brief Index of Sexual Function for Women (BISF-W), which includes a sexual desire dimension, and received either oxytocin or placebo nasal spray before viewing crying and smiling infant and sexual images in an fMRI scanner. For both groups of women, intranasal oxytocin administration increased VTA activation to both crying infant and sexual images but not to smiling infant images. We found that postpartum women showed lower SES, higher SIS, and lower sexual desire compared to nulliparous women. Across parity groups, SES scores were correlated with VTA activation and subjective arousal ratings to sexual images. In postpartum women, sexual

  6. Fenofibrate activates AMPK and increases eNOS phosphorylation in HUVEC

    SciTech Connect

    Murakami, Hisashi; Murakami, Ryuichiro . E-mail: ryuichi@med.nagoya-u.ac.jp; Kambe, Fukushi; Cao, Xia; Takahashi, Ryotaro; Asai, Toru; Hirai, Toshihisa; Numaguchi, Yasushi; Okumura, Kenji; Seo, Hisao; Murohara, Toyoaki

    2006-03-24

    Fenofibrate improves endothelial function by lipid-lowering and anti-inflammatory effects. Additionally, fenofibrate has been demonstrated to upregulate endothelial nitric oxide synthase (eNOS). AMP-activated protein kinase (AMPK) has been reported to phosphorylate eNOS at Ser-1177 and stimulate vascular endothelium-derived nitric oxide (NO) production. We report here that fenofibrate activates AMPK and increases eNOS phosphorylation and NO production in human umbilical vein endothelial cells (HUVEC). Incubation of HUVEC with fenofibrate increased the phosphorylation of AMPK and acetyl-CoA carboxylase. Fenofibrate simultaneously increased eNOS phosphorylation and NO production. Inhibitors of protein kinase A and phosphatidylinositol 3-kinase failed to suppress the fenofibrate-induced eNOS phosphorylation. Neither bezafibrate nor WY-14643 activated AMPK in HUVEC. Furthermore, fenofibrate activated AMPK without requiring any transcriptional activities. These results indicate that fenofibrate stimulates eNOS phosphorylation and NO production through AMPK activation, which is suggested to be a novel characteristic of this agonist and unrelated to its effects on peroxisome proliferator-activated receptor {alpha}.

  7. Increased alpha 2-macroglobulin in diabetes: a hyperglycemia related phenomenon associated with reduced antithrombin III activity.

    PubMed

    Ceriello, A; Giugliano, D; Quatraro, A; Stante, A; Dello Russo, P; Torella, R

    1989-01-01

    Increased alpha 2-macroglobulin (alpha 2M) activity and concentration, and decreased antithrombin III (ATIII) plasma concentration are reported in diabetic subjects. In diabetes an inverse correlation between ATIII activity and blood glucose, HbA1, alpha 2M activity and alpha 2M concentration, and a direct correlation between both alpha 2M activity and alpha 2M concentration with blood glucose and HbA1 are found. Moreover, a direct correlation between alpha 2M activity and alpha 2M concentration fails. In both diabetic and normal subjects induced hyperglycemia increases alpha 2M activity and alpha 2M concentration reduces ATIII activity, while ATIII concentration is not affected. These data which show that hyperglycemia may increase alpha 2M molecule levels while altering only the biological function of ATIII, provide evidence that hyperglycemia may decrease, directly, the biological function of some proteins and may condition the levels of some risk factors for the development of diabetic complications such as alpha 2M.

  8. TNFα Increases RANKL Expression via PGE2-Induced Activation of NFATc1

    PubMed Central

    Park, Hyun-Jung; Baek, Kyunghwa; Baek, Jeong-Hwa; Kim, Hyung-Ryong

    2017-01-01

    Tumor necrosis factor α (TNFα) is known to upregulate the expression of receptor activator of NF-κB ligand (RANKL). We investigated the role of the calcineurin/nuclear factor of activated T-cells (NFAT) signaling pathway in TNFα-induced RANKL expression in C2C12 and primary cultured mouse calvarial cells. TNFα-induced RANKL expression was blocked by the calcineurin/NFAT pathway inhibitors. TNFα increased NFAT transcriptional activity and subsequent RANKL promoter binding. Mutations in the NFAT-binding element (MT(N)) suppressed TNFα-induced RANKL promoter activity. TNFα increased prostaglandin E2 (PGE2) production, which in turn enhanced NFAT transcriptional activity and binding to the RANKL promoter. MT(N) suppressed PGE2-induced RANKL promoter activity. TNFα and PGE2 increased the expression of RANKL, NFAT cytoplasmic-1 (NFATc1), cAMP response element-binding protein (CREB), and cyclooxygenase 2 (COX2); which increment was suppressed by indomethacin, a COX inhibitor. Mutations in the CRE-like element blocked PGE2-induced RANKL promoter activity. PGE2 induced the binding of CREB to the RANKL promoter, whereas TNFα increased the binding of both CREB and NFATc1 to this promoter through a process blocked by indomethacin. The PGE2 receptor antagonists AH6809 and AH23848 blocked TNFα-induced expression of RANKL, NFATc1, and CREB; transcriptional activity of NFAT; and binding of NFATc1 or CREB to the RANKL promoter. These results suggest that TNFα-induced RANKL expression depends on PGE2 production and subsequent transcriptional activation/enhanced binding of NFATc1 and CREB to the RANKL promoter. PMID:28245593

  9. Dietary resveratrol administration increases MnSOD expression and activity in mouse brain

    SciTech Connect

    Robb, Ellen L.; Winkelmolen, Lieke; Visanji, Naomi; Brotchie, Jonathan; Stuart, Jeffrey A.

    2008-07-18

    trans-Resveratrol (3,4',5-trihydroxystilbene; RES) is of interest for its reported protective effects in a variety of pathologies, including neurodegeneration. Many of these protective properties have been attributed to the ability of RES to reduce oxidative stress. In vitro studies have shown an increase in antioxidant enzyme activities following exposure to RES, including upregulation of mitochondrial superoxide dismutase, an enzyme that is capable of reducing both oxidative stress and cell death. We sought to determine if a similar increase in endogenous antioxidant enzymes is observed with RES treatment in vivo. Three separate modes of RES delivery were utilized; in a standard diet, a high fat diet and through a subcutaneous osmotic minipump. RES given in a high fat diet proved to be effective in elevating antioxidant capacity in brain resulting in an increase in both MnSOD protein level (140%) and activity (75%). The increase in MnSOD was not due to a substantial proliferation of mitochondria, as RES treatment induced a 10% increase in mitochondrial abundance (Citrate Synthase activity). The potential neuroprotective properties of MnSOD have been well established, and we demonstrate that a dietary delivery of RES is able to increase the expression and activity of this enzyme in vivo.

  10. Increased β-cyanoalanine nitrilase activity improves cyanide tolerance and assimilation in Arabidopsis.

    PubMed

    O'Leary, Brendan; Preston, Gail M; Sweetlove, Lee J

    2014-01-01

    Plants naturally produce cyanide (CN) which is maintained at low levels in their cells by a process of rapid assimilation. However, high concentrations of environmental CN associated with activities such as industrial pollution are toxic to plants. There is thus an interest in increasing the CN detoxification capacity of plants as a potential route to phytoremediation. Here, Arabidopsis seedlings overexpressing the Pseudomonas fluorescens β-cyanoalanine nitrilase pinA were compared with wild-type and a β-cyanoalanine nitrilase knockout line (ΔAtnit4) for growth in the presence of exogenous CN. After incubation with CN, +PfpinA seedlings had increased root length, increased fresh weight, and decreased leaf bleaching compared with wild-type, indicating increased CN tolerance. The increased tolerance was achieved without an increase in β-cyanoalanine synthase activity, the other enzyme in the cyanide assimilation pathway, suggesting that nitrilase activity is the limiting factor for cyanide detoxification. Labeling experiments with [¹³C]KCN demonstrated that the altered CN tolerance could be explained by differences in flux from CN to Asn caused by altered β-cyanoalanine nitrilase activity. Metabolite profiling after CN treatment provided new insight into downstream metabolism, revealing onward metabolism of Asn by the photorespiratory nitrogen cycle and accumulation of aromatic amino acids.

  11. Long-term aerobic exercise increases redox-active iron through nitric oxide in rat hippocampus.

    PubMed

    Chen, Qian; Xiao, De-Sheng

    2014-01-30

    Adult hippocampus is highly vulnerable to iron-induced oxidative stress. Aerobic exercise has been proposed to reduce oxidative stress but the findings in the hippocampus are conflicting. This study aimed to observe the changes of redox-active iron and concomitant regulation of cellular iron homeostasis in the hippocampus by aerobic exercise, and possible regulatory effect of nitric oxide (NO). A randomized controlled study was designed in the rats with swimming exercise treatment (for 3 months) and/or an unselective inhibitor of NO synthase (NOS) (L-NAME) treatment. The results from the bleomycin-detectable iron assay showed additional redox-active iron in the hippocampus by exercise treatment. The results from nonheme iron content assay, combined with the redox-active iron content, showed increased storage iron content by exercise treatment. NOx (nitrate plus nitrite) assay showed increased NOx content by exercise treatment. The results from the Western blot assay showed decreased ferroportin expression, no changes of TfR1 and DMT1 expressions, increased IRP1 and IRP2 expression, increased expressions of eNOS and nNOS rather than iNOS. In these effects of exercise treatment, the increased redox-active iron content, storage iron content, IRP1 and IRP2 expressions were completely reversed by L-NAME treatment, and decreased ferroportin expression was in part reversed by L-NAME. L-NAME treatment completely inhibited increased NOx and both eNOS and nNOS expression in the hippocampus. Our findings suggest that aerobic exercise could increase the redox-active iron in the hippocampus, indicating an increase in the capacity to generate hydroxyl radicals through the Fenton reactions, and aerobic exercise-induced iron accumulation in the hippocampus might mainly result from the role of the endogenous NO.

  12. Increasing brain angiotensin converting enzyme 2 activity decreases anxiety-like behavior in male mice by activating central Mas receptors.

    PubMed

    Wang, Lei; de Kloet, Annette D; Pati, Dipanwita; Hiller, Helmut; Smith, Justin A; Pioquinto, David J; Ludin, Jacob A; Oh, S Paul; Katovich, Michael J; Frazier, Charles J; Raizada, Mohan K; Krause, Eric G

    2016-06-01

    Over-activation of the brain renin-angiotensin system (RAS) has been implicated in the etiology of anxiety disorders. Angiotensin converting enzyme 2 (ACE2) inhibits RAS activity by converting angiotensin-II, the effector peptide of RAS, to angiotensin-(1-7), which activates the Mas receptor (MasR). Whether increasing brain ACE2 activity reduces anxiety by stimulating central MasR is unknown. To test the hypothesis that increasing brain ACE2 activity reduces anxiety-like behavior via central MasR stimulation, we generated male mice overexpressing ACE2 (ACE2 KI mice) and wild type littermate controls (WT). ACE2 KI mice explored the open arms of the elevated plus maze (EPM) significantly more than WT, suggesting increasing ACE2 activity is anxiolytic. Central delivery of diminazene aceturate, an ACE2 activator, to C57BL/6 mice also reduced anxiety-like behavior in the EPM, but centrally administering ACE2 KI mice A-779, a MasR antagonist, abolished their anxiolytic phenotype, suggesting that ACE2 reduces anxiety-like behavior by activating central MasR. To identify the brain circuits mediating these effects, we measured Fos, a marker of neuronal activation, subsequent to EPM exposure and found that ACE2 KI mice had decreased Fos in the bed nucleus of stria terminalis but had increased Fos in the basolateral amygdala (BLA). Within the BLA, we determined that ∼62% of GABAergic neurons contained MasR mRNA and expression of MasR mRNA was upregulated by ACE2 overexpression, suggesting that ACE2 may influence GABA neurotransmission within the BLA via MasR activation. Indeed, ACE2 overexpression was associated with increased frequency of spontaneous inhibitory postsynaptic currents (indicative of presynaptic release of GABA) onto BLA pyramidal neurons and central infusion of A-779 eliminated this effect. Collectively, these results suggest that ACE2 may reduce anxiety-like behavior by activating central MasR that facilitate GABA release onto pyramidal neurons within the

  13. The Influence of Neighborhood Crime on Increases in Physical Activity during a Pilot Physical Activity Intervention in Children.

    PubMed

    Broyles, Stephanie T; Myers, Candice A; Drazba, Kathryn T; Marker, Arwen M; Church, Timothy S; Newton, Robert L

    2016-04-01

    The purpose of this study was to examine whether neighborhood crime moderated the response (increases in steps) to a pilot intervention to increase physical activity in children. Twenty-seven insufficiently active children aged 6-10 years (mean age = 8.7 years; 56 % female; 59 % African American) were randomly assigned to an intensive intervention group (IIG) or minimal intervention group (MIG). Change in average daily number of steps from baseline was regressed against an index of neighborhood crime in a multilevel repeated-measures model that included a propensity score to reduce confounding. Safer neighborhoods were associated with higher increases in steps during the pilot intervention (interaction p = 0.008). Children in the IIG living in low-crime neighborhoods significantly increased their physical activity (5275 ± 1040 steps/day) while those living in high-crime neighborhoods did not (1118 ± 1007) (p for difference = 0.046). In the IIG, the increase in daily steps was highly correlated with neighborhood crime (r = 0.58, p = 0.04). These findings suggest the need for physical activity interventions to account for participants' environments in their design and/or delivery. To promote healthy behaviors in less-supportive environments, future studies should seek to understand how environments modify intervention response and to identify mediators of the relationship between environment and intervention.

  14. Interventions to Increase Physical Activity in Children Aged 2-5 Years: A Systematic Review.

    PubMed

    Ling, Jiying; Robbins, Lorraine B; Wen, Fujun; Peng, Wei

    2015-08-01

    Comprehensive evaluation of prior interventions designed to increase preschoolers' physical activity is lacking. This systematic review aimed to examine the effect of interventions on objectively measured physical activity in children aged 2-5 years. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. In May 2014, we searched PubMed, CINAHL, PsycINFO, ERIC, SPORTDiscus, Cochrane, and Embase. Two reviewers independently identified and appraised the studies. Twenty-four articles describing 23 independent studies and 20 unique interventions met inclusion criteria. Of the 8 interventions resulting in a significant effect in objectively measured physical activity, all were center-based and included a structured physical activity component, 6 included multiple components, 5 integrated theories or models, and 4 actively involved parents. Seven of the 8 were randomized controlled trials. Due to the heterogeneity of the study designs, physical activity measures, and interventions, drawing definitive conclusions was difficult. Although the overall intervention effect was less than optimal, the review indicated that theory-driven, multicomponent interventions including a structured physical activity component and targeting both parents and their children may be a promising approach for increasing preschoolers' physical activity and warrant continued investigation using rigorous designs to identify those that are most effective.

  15. ADH1B and CDH1 polymorphisms predict prognosis in male patients with non-metastatic laryngeal cancer

    PubMed Central

    Jin, Tianbo; He, Na; Ren, Le; Zhang, Zhe; Zhang, Qingna; Xu, Ran; Tao, Hong; Zeng, Guang; Gao, Jing

    2016-01-01

    In this study, we assessed the association between single nucleotide polymorphisms (SNPs) in candidate genes and the prognosis of laryngeal cancer (LC) patients. Thirty-seven SNPs in 26 genes were genotyped in 170 male Han Chinese patients with LC. The effects of the candidate genes on the prognosis of LC patients were evaluated using Kaplan-Meier curves and Cox proportional hazards regression models. The GA genotype of rs1229984 (hazard ratio [HR], 0.537; 95% confidence interval [CI], 0.340–0.848; p = 0.008) in alcohol dehydrogenase 1B (ADH1B), and the AA genotype of rs9929218 (HR, 6.074; 95% CI, 1.426–25.870; p = 0.015) in CDH1 were associated with overall survival. Our data suggest that polymorphisms in ADH1B and CDH1 may be prognostic indicators in LC. PMID:27689323

  16. Estrogen increases Nrf2 activity through activation of the PI3K pathway in MCF-7 breast cancer cells

    SciTech Connect

    Wu, Juanjuan; Williams, Devin; Walter, Grant A.; Thompson, Winston E.; Sidell, Neil

    2014-11-01

    The actions of the transcription factor Nuclear factor erythroid 2-related factor (Nrf2) in breast cancer have been shown to include both pro-oncogenic and anti-oncogenic activities which is influenced, at least in part, by the hormonal environment. However, direct regulation of Nrf2 by steroid hormones (estrogen and progesterone) has received only scant attention. Nrf2 is known to be regulated by its cytosolic binding protein, Kelch-like ECH-associated protein 1 (Keap1), and by a Keap1-independent mechanism involving a series of phosphorylation steps mediated by phosphatidylinositol 3-kinase (PI3K) and glycogen synthase kinase 3 beta (GSK3β). Here, we report that estrogen (E2) increases Nrf2 activity in MCF7 breast cancer cells through activation of the PI3K/GSK3β pathway. Utilizing antioxidant response element (ARE)-containing luciferase reporter constructs as read-outs for Nrf2 activity, our data indicated that E2 increased ARE activity >14-fold and enhanced the action of the Nrf2 activators, tertiary butylhydroquinone (tBHQ) and sulforaphane (Sul) 4 to 9 fold compared with cells treated with tBHQ or Sul as single agents. This activity was shown to be an estrogen receptor-mediated phenomenon and was antagonized by progesterone. In addition to its action on the reporter constructs, mRNA and protein levels of heme oxygenase 1, an endogenous target gene of Nrf2, was markedly upregulated by E2 both alone and in combination with tBHQ. Importantly, E2-induced Nrf2 activation was completely suppressed by the PI3K inhibitors LY294002 and Wortmannin while the GSK3β inhibitor CT99021 upregulated Nrf2 activity. Confirmation that E2 was, at least partly, acting through the PI3K/GSK3β pathway was indicated by our finding that E2 increased the phosphorylation status of both GSK3β and Akt, a well-characterized downstream target of PI3K. Together, these results demonstrate a novel mechanism by which E2 can regulate Nrf2 activity in estrogen receptor-positive breast cancer

  17. Increased activity in frontal motor cortex compensates impaired speech perception in older adults

    PubMed Central

    Du, Yi; Buchsbaum, Bradley R.; Grady, Cheryl L.; Alain, Claude

    2016-01-01

    Understanding speech in noisy environments is challenging, especially for seniors. Although evidence suggests that older adults increasingly recruit prefrontal cortices to offset reduced periphery and central auditory processing, the brain mechanisms underlying such compensation remain elusive. Here we show that relative to young adults, older adults show higher activation of frontal speech motor areas as measured by functional MRI during a syllable identification task at varying signal-to-noise ratios. This increased activity correlates with improved speech discrimination performance in older adults. Multivoxel pattern classification reveals that despite an overall phoneme dedifferentiation, older adults show greater specificity of phoneme representations in frontal articulatory regions than auditory regions. Moreover, older adults with stronger frontal activity have higher phoneme specificity in frontal and auditory regions. Thus, preserved phoneme specificity and upregulation of activity in speech motor regions provide a means of compensation in older adults for decoding impoverished speech representations in adverse listening conditions. PMID:27483187

  18. Alternative complement pathway activation increases mortality in a model of burn injury in mice.

    PubMed Central

    Gelfand, J A; Donelan, M; Hawiger, A; Burke, J F

    1982-01-01

    We have studied the role of the complement system in burn injury in an experimental model in mice. A 25% body surface area, full-thickness scald wound was produced in anesthetized animals. Massive activation of the alternative complement pathway, but not the classical pathway, was seen. This activation was associated with the generation of neutrophil aggregating activity in the plasma, neutrophil aggregates in the lungs, increased pulmonary vascular permeability, and increased lung edema formation. Decomplementation with cobra venom factor (CVF) or genetic C5 deficiency diminished these pathologic changes, and CVF pretreatment substantially reduced burn mortality in the first 24 h. Preliminary data show that human burn patients have a similar pattern of complement activation involving predominantly the alternative pathway, indicating the possible relevance of the murine model to human disease. Images PMID:7174787

  19. Global increase in task-related fronto-parietal activity after focal frontal lobe lesion.

    PubMed

    Woolgar, Alexandra; Bor, Daniel; Duncan, John

    2013-09-01

    A critical question for neuropsychology is how complex brain networks react to damage. Here, we address this question for the well-known executive control or multiple-demand (MD) system, a fronto-parietal network showing increased activity with many different kinds of cognitive demand, including standard tests of fluid intelligence. Using fMRI, we ask how focal frontal lobe damage affects MD activity during a standard fluid intelligence task. Despite poor behavioral performance, frontal patients showed increased fronto-parietal activity relative to controls. The activation difference was not accounted for by difference in IQ. Moreover, rather than specific focus on perilesional or contralesional cortex, additional recruitment was distributed throughout the MD regions and surrounding cortex and included parietal MD regions distant from the injury. The data suggest that, following local frontal lobe damage, there is a global compensatory recruitment of an adaptive and integrated fronto-parietal network.

  20. Engineering of TM1459 from Thermotoga maritima for Increased Oxidative Alkene Cleavage Activity

    PubMed Central

    Fink, Matthias; Trunk, Sarah; Hall, Mélanie; Schwab, Helmut; Steiner, Kerstin

    2016-01-01

    Oxidative cleavage of alkenes is a widely employed process allowing oxyfunctionalization to corresponding carbonyl compounds. Recently, a novel biocatalytic oxidative alkene cleavage activity on styrene derivatives was identified in TM1459 from Thermotoga maritima. In this work we engineered the enzyme by site-saturation mutagenesis of active site amino acids to increase its activity and to broaden its substrate scope. A high-throughput assay for the detection of the ketone products was successfully developed. Several variants with up to twofold improved conversion level of styrene derivatives were successfully identified. Especially, changes in or removal of the C-terminus of TM1459 increased the activity most significantly. These best variants also displayed a slightly enlarged substrate scope. PMID:27713741

  1. A single nucleotide polymorphism (SNP839) in the adh1 reference gene affects the quantitation of genetically modified maize (Zea mays L.).

    PubMed

    Broothaerts, Wim; Corbisier, Philippe; Schimmel, Heinz; Trapmann, Stefanie; Vincent, Sandra; Emons, Hendrik

    2008-10-08

    The real-time PCR methods recommended in the European Union for the quantitation of genetically modified (GM) maize events NK603, GA21, and MON 863 measure the number of copies of the GM event in relation to those of the maize-specific adh1 reference gene. The study reported here revealed that the targeted 70 base pair adh1 region exhibits a single nucleotide polymorphism (SNP839) that hampers the binding of the reverse primer used in the adh1 detection method. Partial fragments of the adh1-A and adh1-F allele were cloned. By allele-specific real-time PCR, it was shown that SNP839 corresponds to a common allelic polymorphism in maize. As a result, the quantitation of the GM maize events mentioned is positively or negatively biased, depending on the adh1 genotype of sample and calibrant. Therefore, it is proposed to revise the quantitative detection methods for NK603, GA21, and MON 863 maize.

  2. Increased Myeloperoxidase Activity and Protein Nitration Are Indicators of Inflammation in Patients with Chagas' Disease▿

    PubMed Central

    Dhiman, Monisha; Estrada-Franco, Jose Guillermo; Pando, Jasmine M.; Ramirez-Aguilar, Francisco J.; Spratt, Heidi; Vazquez-Corzo, Sara; Perez-Molina, Gladys; Gallegos-Sandoval, Rosa; Moreno, Roberto; Garg, Nisha Jain

    2009-01-01

    In this study, we investigated whether inflammatory responses contribute to oxidative/nitrosative stress in patients with Chagas' disease. We used three tests (enzyme-linked immunosorbent assay, immuno-flow cytometry, and STAT-PAK immunochromatography) to screen human serum samples (n = 1,481) originating from Chiapas, Mexico, for Trypanosoma cruzi-specific antibodies. We identified 121 subjects who were seropositive for T. cruzi-specific antibodies, a finding indicative of an 8.5% seroprevalence in the rural population from Chiapas. Seropositive and seronegative subjects were examined for plasma levels of biomarkers of inflammation, i.e., myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), and xanthine oxidase (XOD), as well as for oxidative (advanced oxidation protein products [AOPPs]) and nitrosative (3-nitrotyrosine [3NT]) biomarkers. The seropositive subjects exhibited a significant increase in MPO activity and protein level, the indicator of neutrophil activation. Subsequently, a corresponding increase in AOPP contents, formed by MPO-dependent hypochlorous acid and chloramine formation, was noted in seropositive subjects. The plasma level of 3NT was significantly increased in seropositive subjects, yet we observed no change in XOD activity (O2− source) and nitrate/nitrite contents (denotes iNOS activation and NO production), which implied that direct peroxynitrite formation does not contribute to increased nitrosative damage in chagasic subjects. Instead, a positive correlation between increased MPO activity and protein 3NT formation was observed, which suggested to us that MPO-dependent formation of nitrylchloride that occurs in the presence of physiological NO and O2− concentrations contributes to protein nitration. Overall, our data demonstrate that T. cruzi-induced neutrophil activation is pathological and contributes to MPO-mediated collateral protein oxidative and nitrosative damage in human patients with Chagas' disease. Therapies

  3. Carbon-Degrading Enzyme Activities Stimulated by Increased Nutrient Availability in Arctic Tundra Soils

    PubMed Central

    Koyama, Akihiro; Wallenstein, Matthew D.; Simpson, Rodney T.; Moore, John C.

    2013-01-01

    Climate-induced warming of the Arctic tundra is expected to increase nutrient availability to soil microbes, which in turn may accelerate soil organic matter (SOM) decomposition. We increased nutrient availability via fertilization to investigate the microbial response via soil enzyme activities. Specifically, we measured potential activities of seven enzymes at four temperatures in three soil profiles (organic, organic/mineral interface, and mineral) from untreated native soils and from soils which had been fertilized with nitrogen (N) and phosphorus (P) since 1989 (23 years) and 2006 (six years). Fertilized plots within the 1989 site received annual additions of 10 g N⋅m-2⋅year-1 and 5 g P⋅m-2⋅year-1. Within the 2006 site, two fertilizer regimes were established – one in which plots received 5 g N⋅m-2⋅year-1 and 2.5 g P⋅m-2⋅year-1 and one in which plots received 10 g N⋅m-2⋅year-1 and 5 g P⋅m-2⋅year-1. The fertilization treatments increased activities of enzymes hydrolyzing carbon (C)-rich compounds but decreased phosphatase activities, especially in the organic soils. Activities of two enzymes that degrade N-rich compounds were not affected by the fertilization treatments. The fertilization treatments increased ratios of enzyme activities degrading C-rich compounds to those for N-rich compounds or phosphate, which could lead to changes in SOM chemistry over the long term and to losses of soil C. Accelerated SOM decomposition caused by increased nutrient availability could significantly offset predicted increased C fixation via stimulated net primary productivity in Arctic tundra ecosystems. PMID:24204773

  4. Increasing physical activity through health-enabling technologies: the project "being strong without violence".

    PubMed

    Scharnweber, Corinna; Ludwig, Wolfram; Marschollek, Michael; Pein, Wolfgang; Schack, Peter; Schubert, Reiner; Haux, Reinhold

    2011-01-01

    Due to the increasing prevalence of adiposity in children numerous schools are introducing prevention programmes. Among these is "Gewaltlos Starksein" ("Being strong without violence"), a project of Hauptschule Sophienstraße Braunschweig, Germany (a general education secondary school for grades 5-10). This study aims to discover possible increases in activity through "Gewaltlos Starksein" where health-enabling technologies play a major role. A prospective intervention study with a span of 1.5 years was designed to measure this increase in activity. Partners in this study were Hauptschule Sophienstraße as the intervention group and Grund- und Hauptschule Pestalozzistraße as control group. Data collection was performed using a multi-sensor device, and questionnaires. Confirmatory data analysis of average metabolic equivalent (METs) yielded no significant results. Exploratory analysis showed interesting results, especially concerning the number of steps during leisure time. Descriptive analysis of questionnaires showed that all children enjoy physical activity. There were differences in sports team participation, open-air games and club affiliation. The study could not prove that the intervention "Gewaltlos Starksein" improves physical activity in children. However, the increased leisure activity step count indicates that "Gewaltlos Starksein" has positive effects on children's behaviour. This should be investigated in a further study in cooperation with psychologists.

  5. Increase of renal sympathetic nerve activity by metoprolol or propranolol in conscious spontaneously hypertensive rats.

    PubMed

    Majcherczyk, S; Mikulski, A; Sjölander, M; Thorén, P

    1987-08-01

    1 Mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were recorded in conscious spontaneously hypertensive rats (SHR). 2 Infusion of metoprolol (4 mumol kg-1 h-1) or propranolol (1.5 mumol kg-1 h-1) reduced HR and significantly increased RSNA. 3 Administration of metoprolol caused a sustained decrease of MAP starting in the third hour of infusion. In contrast, administration of propranolol induced a biphasic response in MAP. It is suggested that the increase of RSNA after both beta-adrenoceptor blocking drugs is due to a decrease in arterial baroreceptor activity.

  6. O-GlcNAcylation of ATG4B positively regulates autophagy by increasing its hydroxylase activity.

    PubMed

    Jo, Yoon Kyung; Park, Na Yeon; Park, So Jung; Kim, Byung-Gyu; Shin, Ji Hyun; Jo, Doo Sin; Bae, Dong-Jun; Suh, Young-Ah; Chang, Jeong Ho; Lee, Eun Kyung; Kim, Sang-Yeob; Kim, Jin Cheon; Cho, Dong-Hyung

    2016-08-30

    Autophagy is a catabolic degradation process and maintains cellular homeostasis. And autophagy is activated in response to various stress conditions. Although O-GlcNAcylation functions a sensor for nutrient and stress, the relationship between O-GlcNAcylation and autophagy is largely unknown. Here, we identified that ATG4B is novel target for O-GlcNAcylation under metabolic stress condition. Treatment with PugNAc, an O-GlcNAcase inhibitor increased activation of autophagy in SH-SY5Y cells. Both bimolecular fluorescence complementation and immunoprecipitation assay indicated that OGT directly interacts with ATG4B in SH-SY5Y cells. We also found that the O-GlcNAcylated ATG4B was increased in autophagy activation conditions, and down-regulation of OGT reduces O-GlcNAcylation of ATG4B under low glucose condition. Furthermore, the proteolytic activity of ATG4B for LC3 cleavage was enhanced in PugNAc-treated cells. Taken together, these results imply that O-GlcNAcylation of ATG4B regulates autophagy activation by increasing its proteolytic activity under metabolic stress condition.

  7. Functional differences in the activity of the hamstring muscles with increasing running speed.

    PubMed

    Higashihara, Ayako; Ono, Takashi; Kubota, Jun; Okuwaki, Toru; Fukubayashi, Toru

    2010-08-01

    In this study, we examined hamstring muscle activation at different running speeds to help better understand the functional characteristics of each hamstring muscle. Eight healthy male track and field athletes (20.1 +/- 1.1 years) performed treadmill running at 50%, 75%, 85%, and 95% of their maximum velocity. Lower extremity kinematics of the hip and knee joint were calculated. The surface electromyographic activities of the biceps femoris and semitendinosus muscles were also recorded. Increasing the running speed from 85% to 95% significantly increased the activation of the hamstring muscles during the late swing phase, while lower extremity kinematics did not change significantly. During the middle swing phase, the activity of the semitendinosus muscle was significantly greater than that of the biceps femoris muscle at 75%, 85%, and 95% of running speed. Statistically significant differences in peak activation time were observed between the biceps femoris and semitendinosus during 95%max running (P < 0.05 for stance phase, P < 0.01 for late swing phase). Significant differences in the activation patterns between the biceps femoris and semitendinosus muscles were observed as running speed was increased, indicating that complex neuromuscular coordination patterns occurred during the running cycle at near maximum sprinting speeds.

  8. Use of an open-loop system to increase physical activity.

    PubMed

    Roemmich, James N; Lobarinas, Christina L; Barkley, Jacob E; White, Tressa M; Paluch, Rocco; Epstein, Leonard H

    2012-08-01

    This study evaluated the effectiveness of an open-loop system that reinforces physical activity with TV watching to increase children's physical activity. Nonoverweight, sedentary boys and girls (8-12 y) were randomized to a group that received feedback of activity counts + reinforcement for physical activity by providing access to television (F+R, n = 20); or to feedback, no reinforcement (Feedback, n = 20) or no feedback, no reinforcement control (Control, n = 21) groups. Children wore an accelerometer with a count display for 4-months with a 1-year follow-up. F+R reduced TV by 68 min/day and TV time was lower than the Feedback (p < .005) and Control (p < .002) groups. TV time of F+R remained 31 min lower (p < .02) than baseline at 1-year. F+R had a 44% increase in physical activity, which was greater than the feedback (p < .04) and control (p < .01) groups. An open-loop system decreases TV viewing and increases physical activity of children for 4-months. TV of the F+R group remained lower at 12 months, suggesting a reduction in screen-time habits.

  9. O-GlcNAcylation of ATG4B positively regulates autophagy by increasing its hydroxylase activity

    PubMed Central

    Jo, Yoon Kyung; Park, Na Yeon; Park, So Jung; Kim, Byung-Gyu; Shin, Ji Hyun; Jo, Doo Sin; Bae, Dong-Jun; Suh, Young-Ah; Chang, Jeong Ho; Lee, Eun Kyung; Kim, Sang-Yeob; Kim, Jin Cheon; Cho, Dong-Hyung

    2016-01-01

    Autophagy is a catabolic degradation process and maintains cellular homeostasis. And autophagy is activated in response to various stress conditions. Although O-GlcNAcylation functions a sensor for nutrient and stress, the relationship between O-GlcNAcylation and autophagy is largely unknown. Here, we identified that ATG4B is novel target for O-GlcNAcylation under metabolic stress condition. Treatment with PugNAc, an O-GlcNAcase inhibitor increased activation of autophagy in SH-SY5Y cells. Both bimolecular fluorescence complementation and immunoprecipitation assay indicated that OGT directly interacts with ATG4B in SH-SY5Y cells. We also found that the O-GlcNAcylated ATG4B was increased in autophagy activation conditions, and down-regulation of OGT reduces O-GlcNAcylation of ATG4B under low glucose condition. Furthermore, the proteolytic activity of ATG4B for LC3 cleavage was enhanced in PugNAc-treated cells. Taken together, these results imply that O-GlcNAcylation of ATG4B regulates autophagy activation by increasing its proteolytic activity under metabolic stress condition. PMID:27527864

  10. Acute and Chronic Treatments with Quetiapine Increase Mitochondrial Respiratory Chain Complex Activity in the Rat Brain.

    PubMed

    Ignácio, Zuleide M; Réus, Gislaine Z; Abelaira, Helena M; Titus, Stephanie E; Carlessi, Anelise S; da Luz, Jaine R; Matias, Beatriz I; Bruchchen, Livia; Carvalho-Silva, Milena; Gomes, Lara M; Rebelo, Joyce; Streck, Emilio L; Quevedo, João

    2015-01-01

    Several studies have found that the molecular mechanisms of mitochondrial energy metabolism are impaired in major depressive disorder (MDD). Classic antidepressants and atypical antipsychotics can alter the function of enzymes involved in adenosine triphosphate (ATP) metabolism. Quetiapine is an atypical antipsychotic that, in addition to having a therapeutic benefit in treating MDD, appears to exert antioxidant and neuroprotective effects. Therefore, we aimed to evaluate the acute and chronic effects of quetiapine on the activity of enzyme complexes I to IV of the mitochondrial respiratory chain and creatine kinase (CK) in brain regions involved with MDD. After a single dose or serial injections over 14 days of quetiapine (20, 40, and 80 mg) were administered, isolates from the pre- frontal cortex, hippocampus, amygdala and nucleus accumbens were analyzed for enzyme activity levels. The enzyme activity varied according to the dose, brain region, and acute or chronic dosing protocols. In general, complexes I-III activity was increased, especially after acute administration. Acute administration also increased the activity of complex IV and CK in the amygdala while complex I was inhibited in the prefrontal cortex and nucleus accumbens. These results suggest that quetiapine produces an increase in respiratory chain complex activity, which may be underlying its efficacy against psychiatric disorders and neuronal damage.

  11. Diagnosis and characterization of mania: Quantifying increased energy and activity in the human behavioral pattern monitor.

    PubMed

    Perry, William; McIlwain, Meghan; Kloezeman, Karen; Henry, Brook L; Minassian, Arpi

    2016-06-30

    Increased energy or activity is now an essential feature of the mania of Bipolar Disorder (BD) according to DSM-5. This study examined whether objective measures of increased energy can differentiate manic BD individuals and provide greater diagnostic accuracy compared to rating scales, extending the work of previous studies with smaller samples. We also tested the relationship between objective measures of energy and rating scales. 50 hospitalized manic BD patients were compared to healthy subjects (HCS, n=39) in the human Behavioral Pattern Monitor (hBPM) which quantifies motor activity and goal-directed behavior in an environment containing novel stimuli. Archival hBPM data from 17 schizophrenia patients were used in sensitivity and specificity analyses. Manic BD patients exhibited higher motor activity than HCS and higher novel object interactions. hBPM activity measures were not correlated with observer-rated symptoms, and hBPM activity was more sensitive in accurately classifying hospitalized BD subjects than observer ratings. Although the findings can only be generalized to inpatient populations, they suggest that increased energy, particularly specific and goal-directed exploration, is a distinguishing feature of BD mania and is best quantified by objective measures of motor activity. A better understanding is needed of the biological underpinnings of this cardinal feature.

  12. Increasing physical activity. A report on recommendations of the Task Force on Community Preventive Services.

    PubMed

    2001-10-26

    The Task Force on Community Preventive Services (the Task Force) has conducted systematic reviews of community interventions to increase physical activity. The Task Force either strongly recommends or recommends six interventions: two informational approaches (i.e., communitywide campaigns and point-of-decision prompts to encourage use of stairs); three behavioral and social approaches (i.e., school-based physical education, social support interventions in community settings [e.g., setting up a buddy system or contracting with another person to complete specified levels of physical activity], and individually adapted health behavior change programs); and one intervention to increase physical activity by using environmental and policy approaches (i.e., creation of or enhanced access to places for physical activity, combined with informational outreach activities). The Task Force found insufficient evidence on which to base recommendations for classroom-based health education focused on information provision, behavioral skills, and social support interventions in family settings because of inconsistent findings; mass media campaigns, college-age physical education, and health education because of an insufficient number of studies; and classroom-based health education focusing on reducing television viewing and video game playing because of the lack of a demonstrated link between reduced time spent watching television or playing video games and increased physical activity. This report provides additional information regarding the recommendations, briefly describes how the reviews were conducted, and provides information that can help in applying the interventions locally.

  13. Texting to Increase Physical Activity Among Teenagers (TXT Me!): Rationale, Design, and Methods Proposal

    PubMed Central

    Cantu, Dora; Bhatt, Riddhi; Baranowski, Tom; Rodgers, Wendy; Jago, Russell; Anderson, Barbara; Liu, Yan; Mendoza, Jason A; Tapia, Ramsey; Buday, Richard

    2014-01-01

    Background Physical activity decreases from childhood through adulthood. Among youth, teenagers (teens) achieve the lowest levels of physical activity, and high school age youth are particularly at risk of inactivity. Effective methods are needed to increase youth physical activity in a way that can be maintained through adulthood. Because teens text a great deal, text messages promoting walking, a low cost physical activity, may be an effective method for promoting sustainable physical activity. Objective The objective of our study was to determine the effect of pedometers, self selected step goals, and texts grounded in the self-determination theory (SDT) on physical activity among the teens. Methods “TXT Me!” was a 12 week intervention that texted 14-17 year olds to increase their daily physical activity by increasing the number of steps they take each day. The intervention was grounded in the SDT. Formative research with the teens helped construct the intervention and develop the texts. A total of 84 texts were developed (12 to set a step goal, and 72 promoting autonomy, competence, and relatedness). The pilot evaluation used a four group, randomized design (n=160). After baseline data collection, the participants were randomized to one of four conditions (no treatment control, pedometer only, pedometer + weekly prompts, pedometer + weekly prompts + SDT grounded texts). Data were collected at baseline and immediately upon completion of the study. The primary outcome was physical activity, measured by 7 days of accelerometry. Basic psychological needs, physical activity motivation, process evaluation, and program satisfaction data were also collected. Results To our knowledge, this is one of the first studies to explore the use of stand alone, SDT grounded texts, supported by pedometers and prompts to set a self selected step goal, as a method for increasing physical activity among teens. Conclusions This pilot study will contribute valuable information

  14. Let's Move for Pacific Islander Communities: an Evidence-Based Intervention to Increase Physical Activity.

    PubMed

    LaBreche, Mandy; Cheri, Ashley; Custodio, Harold; Fex, Cleo Carlos; Foo, Mary Anne; Lepule, Jonathan Tana; May, Vanessa Tui'one; Orne, Annette; Pang, Jane Ka'ala; Pang, Victor Kaiwi; Sablan-Santos, Lola; Schmidt-Vaivao, Dorothy; Surani, Zul; Talavou, Melevesi Fifita; Toilolo, Tupou; Palmer, Paula Healani; Tanjasiri, Sora Park

    2016-06-01

    Pacific Islander (PI) populations of Southern California experience high obesity and low physical activity levels. Given PI's rich cultural ties, efforts to increase physical activity using a community-tailored strategy may motivate members in a more sustainable manner. In this paper, we (1) detail the program adaptation methodology that was utilized to develop the Weaving an Islander Network for Cancer Awareness, Research and Training (WINCART) Center's PI Let's Move Program, a culturally tailored program aimed to increase physical activity levels among members of PI organizations in Southern California, and (2) share the program's pilot evaluation results on individual and organizational changes. The WINCART Center applied the National Cancer Institute's program adaptation guidelines to tailor the evidence-based Instant Recess program to fit the needs of PIs. The end product, the PI Let's Move Program, was piloted in 2012 with eight PI organizations, reaching 106 PI adults. At baseline, 52 % of participants reported that they were not physically active, with the average number of days engaged in medium-intensity physical activity at 2.09 days/week. After the 2-month program, participants increased the number of days that they engaged in medium-intensity physical activity from 2.09 to 2.90 days/week. Post-pilot results found that 82 % of participants reported intentions to engage in physical activity for at least the next 6 months. At baseline, only one organization was currently implementing a physical activity program, and none had implemented an evidence-based physical activity program tailored for PIs. After the 2-month timeframe, despite varying levels of capacity, all eight organizations were able to successfully implement the program. In conclusion, results from our program provide evidence that disparity populations, such as PIs, can be successfully reached through programs that are culturally tailored to both individuals and their community

  15. Spirulina elicits the activation of innate immunity and increases resistance against Vibrio alginolyticus in shrimp.

    PubMed

    Chen, Yu-Yuan; Chen, Jiann-Chu; Tayag, Carina Miranda; Li, Hui-Fang; Putra, Dedi Fazriansyah; Kuo, Yi-Hsuan; Bai, Jia-Chin; Chang, Yu-Hsuan

    2016-08-01

    The effect of Spirulina dried powder (SDP) on the immune response of white shrimp Litopenaeus vannamei was studied in vitro and in vivo. Incubating shrimp haemocytes in 0.5 mg ml(-1) SDP caused the degranulation of haemocytes and a reduction in the percentage of large cells within 30 min. Shrimp haemocytes incubated in 1 mg ml(-1) SDP significantly increased their phenoloxidase (PO) activity, serine proteinase activity, and respiratory burst activity (RB, release of superoxide anion). A recombinant protein of lipopolysaccharide and β-1,3-glucan binding protein (LGBP) of the white shrimp was produced, named rLvLGBP, and examined for its binding with SDP. An ELISA binding assay showed that rLvLGBP binds to SDP with a dissociation constant of 0.0507 μM. In another experiment, shrimp fed diets containing SDP at 0 (control), 30, and 60 g kg(-1) after four weeks were examined for LGBP transcript level and lysozyme activity, as well as phagocytic activity, clearance efficiency, and resistance to Vibrio alginolyticus. These parameters were significantly higher in shrimp receiving diets containing SDP at 60 g kg(-1) or 30 g kg(-1) than in controls. In conclusion, shrimp haemocytes receiving SDP provoked the activation of innate immunity as evidenced by the recognition and binding of LGBP, degranulation of haemocytes, reduction in the percentage of large cells, increases in PO activity, serine proteinase activity, superoxide anion levels, and up-regulated LGBP transcript levels. Shrimp receiving diets containing SDP had increased lysozyme activity and resistance against V. alginolyticus infection. This study showed the mechanism underlying the immunostimulatory action of Spirulina and its immune response in shrimp.

  16. Warming and earlier spring increase Western U.S. forest wildfire activity

    USGS Publications Warehouse

    Westerling, A.L.; Hidalgo, H.G.; Cayan, D.R.; Swetnam, T.W.

    2006-01-01

    Western United States forest wildfire activity is widely thought to have increased in recent decades, yet neither the extent of recent changes nor the degree to which climate may be driving regional changes in wildfire has been systematically documented. Much of the public and scientific discussion of changes in western United States wildfire has focused instead on the effects of 19th- and 20th-century land-use history. We compiled a comprehensive database of large wildfires in western United States forests since 1970 and compared it with hydroclimatic and land-surface data. Here, we show that large wildfire activity increased suddenly and markedly in the mid-1980s, with higher large-wildfire frequency, longer wildfire durations, and longer wildfire seasons. The greatest increases occurred in mid-elevation, Northern Rockies forests, where land-use histories have relatively little effect on fire risks and are strongly associated with increased spring and summer temperatures and an earlier spring snowmelt.

  17. [Secretory activity of the stomach during modeling of increased filling of abdominal veins].

    PubMed

    Afonin, B V; Goncharova, N P

    2009-01-01

    Determination of the stomach secretory activity and ultrasonic investigation of the gastroduodenal organs and vessels were performed in test-subjects tilted at -12 degrees and -15 degrees. Short HDT(12-24 hrs.) as a hypokinesia factor was minimized which caused enlargement of the parenchymatous and thickening of walls of the hollow organs. Increased filling of the abdominal veins was paralleled by rise in pepsinogen levels in blood and urine, and increase in the intravitelline content in fasting subjects. Elevated tone of the pylorus and retarded evacuation from the stomach indicated active hydrochloric acid secretion. Concurrently, bile and pancreas juices were secreted more profusely and intestinal content in the duodenum increased. It was shown that modeled increase of abdominal vein filling stimulates secretion as by fasting stomach so by the liver and pancreas.

  18. Phosphorylation of Serine422 increases the stability and transactivation activities of human Osterix.

    PubMed

    Xu, Yuexin; Yao, Bing; Shi, Kaikai; Lu, Jianlei; Jin, Yucui; Qi, Bing; Li, Hongwei; Pan, Shiyang; Chen, Li; Ma, Changyan

    2015-03-24

    Osterix (Osx) is an essential regulator for osteoblast differentiation and bone formation. Although phosphorylation has been reported to be involved in the regulation of Osx activity, the precise underlying mechanisms remain to be elucidated. Here we identified S422 as a novel phosphorylation site of Osx and demonstrated that GSK-3β interacted and co-localized with Osx. GSK-3β increased the stability and transactivation activity of Osx through phosphorylation of the newly identified site. These findings expanded our understanding of the mechanisms of posttranslational regulation of Osx and the role of GSK-3β in the control of Osx transactivation activity.

  19. Evidence that elevated CO2 levels can indirectly increase rhizosphere denitrifier activity

    NASA Technical Reports Server (NTRS)

    Smart, D. R.; Ritchie, K.; Stark, J. M.; Bugbee, B.

    1997-01-01

    We examined the influence of elevated CO2 concentration on denitrifier enzyme activity in wheat rhizoplanes by using controlled environments and solution culture techniques. Potential denitrification activity was from 3 to 24 times higher on roots that were grown under an elevated CO2 concentration of 1,000 micromoles of CO2 mol-1 than on roots grown under ambient levels of CO2. Nitrogen loss, as determined by a nitrogen mass balance, increased with elevated CO2 levels in the shoot environment and with a high NO3- concentration in the rooting zone. These results indicated that aerial CO2 concentration can play a role in rhizosphere denitrifier activity.

  20. Increased activation in cingulate cortex in conversion disorder: what does it mean?

    PubMed

    van Beilen, M; Vogt, B A; Leenders, K L

    2010-02-15

    Conversion disorder is one of the terms used to describe various psychosomatic neurological symptoms that are thought to originate from a psychological conflict. Psychological stressors can usually be identified but appear to be almost similar to the severity of psychological stress in non-psychosomatic neurological disorders. Recent neuroimaging research provides one rather robust finding of increased activation in the anterior cingulate gyrus. This activation has been explained as a reflection of 'active inhibition' or 'self-monitoring' but its meaning in conversion disorder still remains mysterious. In this paper, current theories are re-examined from a neuroanatomical point of view.

  1. Sucrose increases calcium-dependent protein kinase and phosphatase activities in potato plants.

    PubMed

    Raíces, M; MacIntosh, G C; Ulloa, R M; Gargantini, P R; Vozza, N F; Téllez-Inón, M T

    2003-09-01

    The effect of sucrose on tuber formation, calcium-dependent protein kinase (CDPK) and phosphatase activities was analysed using in vitro cultured potato plants. In short treatments, sucrose induced CDPK and phosphatase activities. In long treatments, sucrose induced tuber formation in the absence of other tuber inducing stimuli. Sorbitol caused a minor increase in CDPK activity and affected plant morphology but did not induce tuber development. The addition of the protein kinase inhibitor Staurosporine precluded sucrose-induced tuberization. Altogether, our results suggest that phosphorylation/dephosphorylation events are involved in sucrose-induced tuber development.

  2. Increased premotor cortex activation in high functioning autism during action observation.

    PubMed

    Perkins, Tom J; Bittar, Richard G; McGillivray, Jane A; Cox, Ivanna I; Stokes, Mark A

    2015-04-01

    The mirror neuron (MN) hypothesis of autism has received considerable attention, but to date has produced inconsistent findings. Using functional MRI, participants with high functioning autism or Asperger's syndrome were compared to typically developing individuals (n=12 in each group). Participants passively observed hand gestures that included waving, pointing, and grasping. Concerning the MN network, both groups activated similar regions including prefrontal, inferior parietal and superior temporal regions, with the autism group demonstrating significantly greater activation in the dorsal premotor cortex. Concerning other regions, participants with autism demonstrated increased activity in the anterior cingulate and medial frontal gyrus, and reduced activation in calcarine, cuneus, and middle temporal gyrus. These results suggest that during observation of hand gestures, frontal cortex activation is affected in autism, which we suggest may be linked to abnormal functioning of the MN system.

  3. Utilizing avidity to improve antifreeze protein activity: a type III antifreeze protein trimer exhibits increased thermal hysteresis activity.

    PubMed

    Can, Özge; Holland, Nolan B

    2013-12-03

    Antifreeze proteins (AFPs) are ice growth inhibitors that allow the survival of several species living at temperatures colder than the freezing point of their bodily fluids. AFP activity is commonly defined in terms of thermal hysteresis, which is the difference observed for the solution freezing and melting temperatures. Increasing the thermal hysteresis activity of these proteins, particularly at low concentrations, is of great interest because of their wide range of potential applications. In this study, we have designed and expressed one-, two-, and three-domain antifreeze proteins to improve thermal hysteresis activity through increased binding avidity. The three-domain type III AFP yielded significantly greater activity than the one- and two-domain proteins, reaching a thermal hysteresis of >1.6 °C at a concentration of <1 mM. To elucidate the basis of this increase, the data were fit to a multidomain protein adsorption model based on the classical Langmuir isotherm. Fits of the data to the modified isotherms yield values for the equilibrium binding constants for the adsorption of AFP to ice and indicate that protein surface coverage is proportional to thermal hysteresis activity.

  4. Improvements in knee biomechanics during walking are associated with increased physical activity after total knee arthroplasty.

    PubMed

    Arnold, John B; Mackintosh, Shylie; Olds, Timothy S; Jones, Sara; Thewlis, Dominic

    2015-12-01

    Total knee arthroplasty (TKA) in people with knee osteoarthritis increases knee-specific and general physical function, but it has not been established if there is a relationship between changes in these elements of functional ability. This study investigated changes and relationships between knee biomechanics during walking, physical activity, and use of time after TKA. Fifteen people awaiting TKA underwent 3D gait analysis before and six months after surgery. Physical activity and use of time were determined in free-living conditions from a high resolution 24-h activity recall. After surgery, participants displayed significant improvements in sagittal plane knee biomechanics and improved their physical activity profiles, standing for 105 more minutes (p=0.001) and performing 64 min more inside chores on average per day (p=0.008). Changes in sagittal plane knee range of motion (ROM) and peak knee flexion positively correlated with changes in total daily energy expenditure, time spent undertaking moderate to vigorous physical activity, inside chores and passive transport (r=0.52-0.66, p=0.005-0.047). Restoration of knee function occurs in parallel and is associated with improvements in physical activity and use of time after TKA. Increased functional knee ROM is required to support improvements in total and context specific physical activity.

  5. Aging of whiskey increases 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity.

    PubMed

    Aoshima, Hitoshi; Tsunoue, Hideaki; Koda, Hirofumi; Kiso, Yoshinobu

    2004-08-11

    1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity of Japanese whiskey after various aging periods in oak barrels was measured to evaluate the antioxidative effects of whiskey. The activity of the whiskey increased with the aging period with high correlation. The activity of various types of whiskey was measured and shown to be correlated to the potentiation of the GABAA receptor response measured in a previous paper. However, the fragrant compounds in the whiskey which potentiated the GABAA receptor response had low DPPH radical scavenging activity, while phenol derivatives had high radical scavenging activity. The whiskey was extracted by pentane. The aqueous part showed the scavenging activity, whereas the pentane part did not. Thus, both the DPPH radical scavenging activity and the potentiation of the GABAA receptor response increased during whiskey aging in oak barrels, but were due to different components. The whiskey protected the H2O2-induced death of E. coli more than ethanol at the same concentration as that of the whiskey. The changes that occurred in the whiskey during aging may be the reason aged whiskies are so highly valued.

  6. Ceramides increase the activity of the secretory phospholipase A2 and alter its fatty acid specificity.

    PubMed Central

    Koumanov, Kamen S; Momchilova, Albena B; Quinn, Peter J; Wolf, Claude

    2002-01-01

    Modulation of human recombinant secretory type II phospholipase A(2) activity by ceramide and cholesterol was investigated using model glycerophospholipid substrates composed of phosphatidylethanolamine and phosphatidylserine dispersed in aqueous medium. Enzyme activity was monitored by measurement of released fatty acids using capillary GC-MS. Fatty acids from the sn-2 position of the phospholipids were hydrolysed by the enzyme in proportion to the relative abundance of the phospholipid in the substrate. Addition of increasing amounts of ceramide to the substrate progressively enhanced phospholipase activity. The increased activity was accomplished largely by preferential hydrolysis of polyunsaturated fatty acids, particularly arachidonic acid, derived from phosphatidylethanolamine. The addition of sphingomyelin to the substrate glycerophospholipids inhibited phospholipase activity but its progressive substitution by ceramide, so as to mimic sphingomyelinase activity, counteracted the inhibition. The presence of cholesterol in dispersions of glycerophospholipid-substrate-containing ceramides suppressed activation of the enzyme resulting from the presence of ceramide. The molecular basis of enzyme modulation was investigated by analysis of the phase structure of the dispersed lipid substrate during temperature scans from 46 to 20 degrees C using small-angle synchrotron X-ray diffraction. These studies indicated that intermediate structures created after ceramide-dependent phase separation of hexagonal and lamellar phases represent the most susceptible form of the substrate for enzyme hydrolysis. PMID:11903045

  7. Comparative Effectiveness of After-School Programs to Increase Physical Activity

    PubMed Central

    Gesell, Sabina B.; Sommer, Evan C.; Lambert, E. Warren; Vides de Andrade, Ana Regina; Davis, Lauren; Beech, Bettina M.; Mitchell, Stephanie J.; Neloms, Stevon; Ryan, Colleen K.

    2013-01-01

    Background. We conducted a comparative effectiveness analysis to evaluate the difference in the amount of physical activity children engaged in when enrolled in a physical activity-enhanced after-school program based in a community recreation center versus a standard school-based after-school program. Methods. The study was a natural experiment with 54 elementary school children attending the community ASP and 37 attending the school-based ASP. Accelerometry was used to measure physical activity. Data were collected at baseline, 6 weeks, and 12 weeks, with 91% retention. Results. At baseline, 43% of the multiethnic sample was overweight/obese, and the mean age was 7.9 years (SD = 1.7). Linear latent growth models suggested that the average difference between the two groups of children at Week 12 was 14.7 percentage points in moderate-vigorous physical activity (P < .001). Cost analysis suggested that children attending traditional school-based ASPs—at an average cost of $17.67 per day—would need an additional daily investment of $1.59 per child for 12 weeks to increase their moderate-vigorous physical activity by a model-implied 14.7 percentage points. Conclusions. A low-cost, alternative after-school program featuring adult-led physical activities in a community recreation center was associated with increased physical activity compared to standard-of-care school-based after-school program. PMID:23984052

  8. Chronic lamotrigine treatment increases rat hippocampal GABA shunt activity and elevates cerebral taurine levels.

    PubMed

    Hassel, B; Taubøll, E; Gjerstad, L

    2001-02-01

    The mechanism of action of the antiepileptic drug lamotrigine has previously been investigated only in acute experiments and is thought to involve inhibition of voltage-dependent sodium channels. However, lamotrigine is effective against more forms of epilepsies than other antiepileptic drugs that also inhibit sodium channels. We investigated whether chronic lamotrigine treatment may affect cerebral amino acid levels. Rats received lamotrigine, 10 mg/kg/day, for 90 days. The hippocampal level of GABA increased 25%, and the activities of glutamate decarboxylase and succinic semialdehyde/GABA transaminase increased 12 and 21% (p< 0.05), respectively, indicating increased GABA turnover. The uptake of GABA and glutamate into proteoliposomes remained unaltered. The level of taurine increased 27% in the hippocampus and 16% in the frontal and parietal cortices. The activities of hexokinase and alpha-ketoglutarate dehydrogenase, remained at control values. Serum lamotrigine was 41.7+/-1.5 microM (mean+/-S.E.M.), which is within the range seen in epileptic patients. Acute experiments with 5, 20 or 100 mg lamotrigine/kg, caused no changes in brain amino acid levels. The results suggest that chronic lamotrigine treatment increases GABAergic activity in the hippocampus. The cerebral increase in taurine, which has neuromodulatory properties, may contribute to the antiepileptic effect of lamotrigine.

  9. No Evidence for Activity Adjustment in Response to Increased Density in Daphnia magna

    PubMed Central

    Sereni, Laura; Einum, Sigurd

    2015-01-01

    Increased population density may lead to a decrease in energy available for growth and reproduction via effects on the activity level of individuals. Whilst this may be of particular importance for organisms that compete for defendable resources and/or have a high frequency of social interactions, it is less obvious how individual activity should covary with population density when food resources are not defendable or direct interactions among individuals are negligible. Based on observations that there is a general negative relationship between population density and metabolism it has been suggested that organisms actively reduce activity under increased density to accommodate an expected decrease in food availability. However, in the absence of direct activity measurements the validity of this hypothesis is unclear. Here we test for such anticipatory adjustments of activity levels in the planktonic cladoceran Daphnia magna Straus, a filter feeder whose food resources are not defendable, meaning that density responses can be evaluated in the absence of direct interactions. We tested for changes in activity in response to two separate density cues, one being the direct physical and visual stimuli resulting from being in the vicinity of conspecifics (‘direct density experiment’), and the other being the detection of olfactory cues in their environment (‘olfactory cue experiment’). Ten genetically distinct clones were used to evaluate the potential for genetic variation in these responses. Our measures of activity were highly repeatable, and there was significant variation in activity among clones. Furthermore, this clonal variation was consistent in the ‘direct density’ and ‘olfactory cue’ experiments. The estimated evolvability of the trait (1.3–3.2%) was within the range typically observed in behavioural traits. However, there was no indication that the activity level of individuals respond to population density, either directly to actual density

  10. Activated factor XI increases the procoagulant activity of the extrinsic pathway by inactivating tissue factor pathway inhibitor

    PubMed Central

    Tucker, Erik I.; Matafonov, Anton; Cheng, Qiufang; Zientek, Keith D.; Gailani, Dave; Gruber, András; McCarty, Owen J. T.

    2015-01-01

    Activation of coagulation factor XI (FXI) may play a role in hemostasis. The primary substrate of activated FXI (FXIa) is FIX, leading to FX activation (FXa) and thrombin generation. However, recent studies suggest the hemostatic role of FXI may not be restricted to the activation of FIX. We explored whether FXI could interact with and inhibit the activity of tissue factor pathway inhibitor (TFPI). TFPI is an essential reversible inhibitor of activated factor X (FXa) and also inhibits the FVIIa-TF complex. We found that FXIa neutralized both endothelium- and platelet-derived TFPI by cleaving the protein between the Kunitz (K) 1 and K2 domains (Lys86/Thr87) and at the active sites of the K2 (Arg107/Gly108) and K3 (Arg199/Ala200) domains. Addition of FXIa to plasma was able to reverse the ability of TFPI to prolong TF-initiated clotting times in FXI- or FIX-deficient plasma, as well as FXa-initiated clotting times in FX-deficient plasma. Treatment of cultured endothelial cells with FXIa increased the generation of FXa and promoted TF-dependent fibrin formation in recalcified plasma. Together, these results suggest that the hemostatic role of FXIa may be attributed not only to activation of FIX but also to promoting the extrinsic pathway of thrombin generation through inactivation of TFPI. PMID:25587039

  11. Potential enzyme activities altered by increased nutrient availability in Arctic tundra soils

    NASA Astrophysics Data System (ADS)

    Koyama, A.; Wallenstein, M. D.; Moore, J. C.; Simpson, R. T.

    2012-12-01

    The Arctic tundra is a biome affected most by global warming predicted in the future. Such warming is expected to increase nutrient availability to soil microbes which, in turn, may accelerate soil organic matter decomposition. We investigated how extra-cellular enzyme activities in soils were affected by increasing nutrient availability in an Arctic tundra ecosystem. Specifically, we measured potential activities of seven enzymes at three profiles (organic, organic/mineral interface, and mineral) of soils which had been fertilized in long- (23 years) and short-terms (six years), assayed at four temperatures. The long-term site had a high fertilization treatment (10g N m-2 year-1 and 5g P m-2 year-1) and control, and the short-term site had a low fertilization treatment (5g N m-2 year-1 and 2.5g P m-2 year-1) in addition to the high fertilization treatment and control. The fertilization treatments significantly altered most of the enzyme activities in both sites. The fertilization treatments increased activities of enzymes hydrolyzing products for C and nitrogen N sources, but decreased phosphatase activities. Such alterations were most pronounced in the organic soils. The fertilization treatments also increased ratios of total enzyme activities involved in hydrolysis for C products to those for N products. This result is consistent with an observation that long-term N and P fertilization decreased soil organic C in the same tundra ecosystem. Altered enzymatic stoichiometry with increased nutrient availability should be considered when modeling biogeochemical cycles in Arctic tundra ecosystems in response to warming predicted in the future.

  12. Ghrelin increases food intake, swimming activity and growth in juvenile brown trout (Salmo trutta).

    PubMed

    Tinoco, Ana B; Näslund, Joacim; Delgado, María J; de Pedro, Nuria; Johnsson, Jörgen I; Jönsson, Elisabeth

    2014-01-30

    Several key functions of ghrelin are well conserved through vertebrate phylogeny. However, some of ghrelin's effects are contradictory and among teleosts only a limited number of species have been used in functional studies on food intake and foraging-related behaviors. Here we investigated the long-term effects of ghrelin on food intake, growth, swimming activity and aggressive contest behavior in one year old wild brown trout (Salmo trutta) using intraperitoneal implants. Food intake and swimming activity were individually recorded starting from day 1, and aggressive behavior was tested at day 11, after ghrelin implantation. Body weight and growth rate were measured from the beginning to the end of the experiment. Triglycerides and lipase activity in muscle and liver; monoaminergic activity in the telencephalon and brainstem; and neuropeptide Y (NPY) mRNA levels in the hypothalamus were analyzed. Ghrelin treatment was found to increase food intake and growth without modifying lipid deposition or lipid metabolism in liver and muscle. Ghrelin treatment led to an increased foraging activity and a trend towards a higher swimming activity. Moreover, ghrelin-treated fish showed a tendency to initiate more conflicts, but this motivation was not reflected in a higher ability to win the conflicts. No changes were observed in monoaminergic activity and NPY mRNA levels in the brain. Ghrelin is therefore suggested to act as an orexigenic hormone regulating behavior in juvenile wild brown trout. These actions are accompanied with an increased growth without the alteration of liver and muscle lipid metabolism and they do not seem to be mediated by changes in brain monoaminergic activity or hypothalamic expression of NPY.

  13. covR Mediated Antibiofilm Activity of 3-Furancarboxaldehyde Increases the Virulence of Group A Streptococcus

    PubMed Central

    Ashwinkumar Subramenium, Ganapathy; Viszwapriya, Dharmaprakash; Iyer, Prasanth Mani; Balamurugan, Krishnaswamy; Karutha Pandian, Shunmugiah

    2015-01-01

    Background Group A streptococcus (GAS, Streptococcus pyogenes), a multi-virulent, exclusive human pathogen responsible for various invasive and non-invasive diseases possesses biofilm forming phenomenon as one of its pathogenic armaments. Recently, antibiofilm agents have gained prime importance, since inhibiting the biofilm formation is expected to reduce development of antibiotic resistance and increase their susceptibility to the host immune cells. Principal Findings The current study demonstrates the antibiofilm activity of 3Furancarboxaldehyde (3FCA), a floral honey derived compound, against GAS biofilm, which was divulged using crystal violet assay, light microscopy, and confocal laser scanning microscopy. The report is extended to study its effect on various aspects of GAS (morphology, virulence, aggregation) at its minimal biofilm inhibitory concentration (132μg/ml). 3FCA was found to alter the growth pattern of GAS in solid and liquid medium and increased the rate of auto-aggregation. Electron microscopy unveiled the increase in extra polymeric substances around cell. Gene expression studies showed down-regulation of covR gene, which is speculated to be the prime target for the antibiofilm activity. Increased hyaluronic acid production and down regulation of srtB gene is attributed to the enhanced rate of auto-aggregation. The virulence genes (srv, mga, luxS and hasA) were also found to be over expressed, which was manifested with the increased susceptibility of the model organism Caenorhabditis elegans to 3FCA treated GAS. The toxicity of 3FCA was ruled out with no adverse effect on C. elegans. Significance Though 3FCA possess antibiofilm activity against GAS, it was also found to increase the virulence of GAS. This study demonstrates that, covR mediated antibiofilm activity may increase the virulence of GAS. This also emphasizes the importance to analyse the acclimatization response and virulence of the pathogen in the presence of antibiofilm compounds

  14. Leptin differentially increases sympathetic nerve activity and its baroreflex regulation in female rats: role of oestrogen.

    PubMed

    Shi, Zhigang; Brooks, Virginia L

    2015-04-01

    Obesity and hypertension are commonly associated, and activation of the sympathetic nervous system is considered to be a major contributor, at least in part due to the central actions of leptin. However, while leptin increases sympathetic nerve activity (SNA) in males, whether leptin is equally effective in females is unknown. Here, we show that intracerebroventricular (i.c.v.) leptin increases lumbar (LSNA) and renal (RSNA) SNA and baroreflex control of LSNA and RSNA in α-chloralose anaesthetized female rats, but only during pro-oestrus. In contrast, i.c.v. leptin increased basal and baroreflex control of splanchnic SNA (SSNA) and heart rate (HR) in rats in both the pro-oestrus and dioestrus states. The effects of leptin on basal LSNA, RSNA, SSNA and HR were similar in males and pro-oestrus females; however, i.c.v. leptin increased mean arterial pressure (MAP) only in males. Leptin did not alter LSNA or HR in ovariectomized rats, but its effects were normalized with 4 days of oestrogen treatment. Bilateral nanoinjection of SHU9119 into the paraventricular nucleus of the hypothalamus (PVN), to block α-melanocyte-stimulating hormone (α-MSH) type 3 and 4 receptors, decreased LSNA in leptin-treated pro-oestrus but not dioestrus rats. Unlike leptin, i.c.v. insulin infusion increased basal and baroreflex control of LSNA and HR similarly in pro-oestrus and dioestrus rats; these responses did not differ from those in male rats. We conclude that, in female rats, leptin's stimulatory effects on SNA are differentially enhanced by oestrogen, at least in part via an increase in α-MSH activity in the PVN. These data further suggest that the actions of leptin and insulin to increase the activity of various sympathetic nerves occur via different neuronal pathways or cellular mechanisms. These results may explain the poor correlation in females of SNA with adiposity, or of MAP with leptin.

  15. Cocaine increases dopaminergic neuron and motor activity via midbrain α1 adrenergic signaling.

    PubMed

    Goertz, Richard Brandon; Wanat, Matthew J; Gomez, Jorge A; Brown, Zeliene J; Phillips, Paul E M; Paladini, Carlos A

    2015-03-13

    Cocaine reinforcement is mediated by increased extracellular dopamine levels in the forebrain. This neurochemical effect was thought to require inhibition of dopamine reuptake, but cocaine is still reinforcing even in the absence of the dopamine transporter. Here, we demonstrate that the rapid elevation in dopamine levels and motor activity elicited by cocaine involves α1 receptor activation within the ventral midbrain. Activation of α1 receptors increases dopaminergic neuron burst firing by decreasing the calcium-activated potassium channel current (SK), as well as elevates dopaminergic neuron pacemaker firing through modulation of both SK and the hyperpolarization-activated cation currents (Ih). Furthermore, we found that cocaine increases both the pacemaker and burst-firing frequency of rat ventral-midbrain dopaminergic neurons through an α1 adrenergic receptor-dependent mechanism within the ventral tegmental area and substantia nigra pars compacta. These results demonstrate the mechanism underlying the critical role of α1 adrenergic receptors in the regulation of dopamine neurotransmission and behavior by cocaine.

  16. rTMS Induced Tinnitus Relief Is Related to an Increase in Auditory Cortical Alpha Activity

    PubMed Central

    Müller, Nadia; Lorenz, Isabel; Langguth, Berthold; Weisz, Nathan

    2013-01-01

    Chronic tinnitus, the continuous perception of a phantom sound, is a highly prevalent audiological symptom. A promising approach for the treatment of tinnitus is repetitive transcranial magnetic stimulation (rTMS) as this directly affects tinnitus-related brain activity. Several studies indeed show tinnitus relief after rTMS, however effects are moderate and vary strongly across patients. This may be due to a lack of knowledge regarding how rTMS affects oscillatory activity in tinnitus sufferers and which modulations are associated with tinnitus relief. In the present study we examined the effects of five different stimulation protocols (including sham) by measuring tinnitus loudness and tinnitus-related brain activity with Magnetoencephalography before and after rTMS. Changes in oscillatory activity were analysed for the stimulated auditory cortex as well as for the entire brain regarding certain frequency bands of interest (delta, theta, alpha, gamma). In line with the literature the effects of rTMS on tinnitus loudness varied strongly across patients. This variability was also reflected in the rTMS effects on oscillatory activity. Importantly, strong reductions in tinnitus loudness were associated with increases in alpha power in the stimulated auditory cortex, while an unspecific decrease in gamma and alpha power, particularly in left frontal regions, was linked to an increase in tinnitus loudness. The identification of alpha power increase as main correlate for tinnitus reduction sheds further light on the pathophysiology of tinnitus. This will hopefully stimulate the development of more effective therapy approaches. PMID:23390539

  17. Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression

    SciTech Connect

    Liu, Xin-Hua; Yao, Shen; Qiao, Rui-Fang; Levine, Alice C.; Kirschenbaum, Alexander; Pan, Jiangping; Wu, Yong; Qin, Weiping; Bauman, William A.; Cardozo, Christopher P.

    2011-10-14

    Highlights: {yields} Nerve transection increased Notch signaling in paralyzed muscle. {yields} Nandrolone prevented denervation-induced Notch signaling. {yields} Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. {yields} Reduction of denervation-induced Notch signaling by nandrolone is likely through upregulation of Numb. -- Abstract: Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.

  18. Reminiscence Activity and Increased Communication Interaction among Cognitively Disabled Elderly Women.

    ERIC Educational Resources Information Center

    Krupar, Karen R.; Smith, N. Richmond

    Designed as the first phase of a larger project to explore the relationships between the possible impact of reminiscence on memory deterioration in elderly women confined to nursing home environments, a study demonstrated that reminiscence activity is positively correlated with increases in communication interactions. Women were chosen as the…

  19. Increasing Children's Physical Activity: Individual, Social, and Environmental Factors Associated with Walking to and from School

    ERIC Educational Resources Information Center

    Trapp, Georgina S. A.; Giles-Corti, Billie; Christian, Hayley E.; Bulsara, Max; Timperio, Anna F.; McCormack, Gavin R.; Villaneuva, Karen P.

    2012-01-01

    Background. Efforts to increase the prevalence of children's active school transport require evidence to inform the development of comprehensive interventions. This study used a multilevel ecological framework to investigate individual, social, and environmental factors associated with walking to and from school among elementary school-aged…

  20. Text Messaging as a Tool to Increase Physical Activity in College Students

    ERIC Educational Resources Information Center

    Muñoz, Laura R.; La France, Kevin; Dominguez, Daniel; Goei, Kathleen; Herbers, Sharon; Gunter, M. Danielle; Fike, David; Carleton, William; Etnyre, Annette; Richardson, Cynthia; Allwein, David; Rauschhuber, Maureen; Norgan, Gary; Moore, Renée; Marquise, Lisa; Jones, Mary Elaine

    2014-01-01

    The purpose of this study was to assess the effectiveness of text messaging with pedometer intervention for increasing physical activity of college students. Using a two-group prospective randomized intervention-based design, the researchers gave 201 college students pedometers and divided them into intervention and control groups. The…

  1. 78 FR 75905 - Credit for Increasing Research Activities: Intra-Group Gross Receipts

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-13

    ...; ] DEPARTMENT OF TREASURY Internal Revenue Service 26 CFR Part 1 RIN 1545-BE14 Credit for Increasing Research Activities: Intra-Group Gross Receipts AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of... under section 41 of the Internal Revenue Code (Code) relating to the treatment of qualified...

  2. Astute Activities: Increasing Cognitive and Creative Development in the Language Arts Classroom.

    ERIC Educational Resources Information Center

    Bay, Lois Marie Zinke

    Using Mark Twain's "Huckleberry Finn," John Knowles'"A Separate Peace," and Maya Angelou's "I Know Why the Caged Bird Sings," a study examined the effects of Astute Activities--teaching techniques which increase students' cognitive ability and creativity--on student performance in two senior English classes in a small…

  3. Planar fuel cell utilizing nail current collectors for increased active surface area

    DOEpatents

    George, Thomas J.; Meacham, G. B. Kirby

    2002-03-26

    A plurality of nail current collector members are useful in the gas flow passages of an electrochemical device to optimize the active surfaces of the device and to provide structural support. In addition, the thicknesses of cathode and anode layers within the electrochemical device are varied according to current flow through the device to reduce resistance and increase operating efficiency.

  4. Peers Increase Adolescent Risk Taking by Enhancing Activity in the Brain's Reward Circuitry

    ERIC Educational Resources Information Center

    Chein, Jason; Albert, Dustin; O'Brien, Lia; Uckert, Kaitlyn; Steinberg, Laurence

    2011-01-01

    The presence of peers increases risk taking among adolescents but not adults. We posited that the presence of peers may promote adolescent risk taking by sensitizing brain regions associated with the anticipation of potential rewards. Using fMRI, we measured brain activity in adolescents, young adults, and adults as they made decisions in a…

  5. Diabetes promotes DMH-induced colorectal cancer by increasing the activity of glycolytic enzymes in rats.

    PubMed

    Jia, Yanglei; Xu, Gang; Zhou, Wenjing; Wang, Zhenzheng; Meng, Linlin; Zhou, Songnan; Xu, Xia; Yuan, Huiqing; Tian, Keli

    2014-01-01

    The objective of the present study was to investigate the association between diabetes mellitus and colorectal carcinogenesis as well as the possible mechanism involved in this interaction. Diabetes rat models were induced with a low dose of STZ followed by a low dose of DMH to induce colorectal cancer. The formation of ACF in the colon and the incidence, number and size of tumors were measured. The activity of glycolytic enzymes in colonic tissues was also measured. The results demonstrated that both the total number of ACF and the number of foci that contain a different number of crypts were increased in diabetic rats. At the end of the experimental treatment, the incidence, number and size of tumors were also increased in diabetic rats. Overall, these data indicated that diabetes increased the risk of colorectal cancer. The activity of HK and PK in colonic tissues was increased in diabetic rats, whereas the activity of PDH was decreased. In addition, the activities of these enzymes in intratumor were higher than that of in peritumor. These data indicated that the high rate of glycolysis may play a role in colorectal carcinogenesis in diabetic rats.

  6. Ethanol increases p190RhoGAP activity, leading to actin cytoskeleton rearrangements.

    PubMed

    Selva, Javier; Egea, Gustavo

    2011-12-01

    We previously reported that cells chronically exposed to ethanol show alterations in actin cytoskeleton organization and dynamics in primary cultures of newborn rat astrocytes, a well-established in vitro model for foetal alcohol spectrum disorders. These alterations were attributed to a decrease in the cellular levels of active RhoA (RhoA-GTP), which in turn was produced by an increase in the total RhoGAP activity. We here provide evidence that p190RhoGAPs are the main factors responsible for such increase. Thus, in astrocytes chronically exposed to ethanol we observe: (i) an increase in p190A- and p190B-associated RhoGAP activity; (ii) a higher binding of p190A and p190B to RhoA-GTP; (iii) a higher p120RasGAP-p190A RhoGAP complex formation; and (iv) the recruitment of both p190RhoGAPs to the plasma membrane. The simultaneous silencing of both p190 isoforms prevents the actin rearrangements and the total RhoGAP activity increase triggered both by ethanol. Therefore, our data directly points p190RhoGAPs as ethanol-exposure molecular targets on glial cells of the CNS.

  7. Approach run increases preactivation and eccentric phases muscle activity during drop jumps from different drop heights.

    PubMed

    Ruan, Mianfang; Li, Li

    2010-10-01

    The purpose of this study was to investigate the effects of a horizontal approach run and drop height on the activation of lower extremity muscles during drop jumps. Ten participants performed drop jumps from drop heights of 15, 30, 45 and 60cm with zero (standing), one, two, and three approach run steps. The EMG activities of the Gluteus Maximus (GM), Rectus Femoris (RF), Biceps Femoris (BF), Vastus Lateralis (VL), Tibialis Anterior (TA), Gastrocnemius (GA) and Soleus (SO) were recorded, full-wave rectified, and averaged (aEMG) during the preactivation (50ms before touchdown), downward, and push-off phases. Increasing drop height did not enhance the muscle activation level of any examined muscles except GA. During the preactivation phase, the aEMG of all muscles except TA increased with the number of approach run steps. The aEMG of RF, BF, VL, and SO also increased with the number of approach run steps during the downward phase, while no aEMG changes were observed during the push-off phase. These results suggest that a horizontal approach run preceding the drop jump is an effective strategy for increasing the muscle preactivation level, which contributes to a higher level of muscle activity during the eccentric contraction phase and could potentially contribute to the reported higher power output during the concentric contraction phase.

  8. Integrated Health and Physical Education Program to Reduce Media Use and Increase Physical Activity in Youth

    ERIC Educational Resources Information Center

    Clocksin, Brian D.; Wattson, Doris L.; Williams, Daniel P.; Randsell, Lynda

    2009-01-01

    The purpose of this project was to compare an integrated health and physical education curriculum, focused on reducing media use and on increasing physical activity in middle school adolescents, to traditional and nonintegrated health and physical education curricula. Two middle schools' health and physical education classes were assigned to an…

  9. Single-site substitutions improve cold activity and increase thermostability of the dehairing alkaline protease (DHAP).

    PubMed

    Zhao, Hong-Yan; Wu, Li-Ying; Liu, Gang; Feng, Hong

    2016-12-01

    To engineer dehairing alkaline protease (DHAP) variants to improve cold activity and increase thermostability so these variants are suitable for the leather processing industry. Based on previous studies with bacterial alkaline proteases, double-site mutations (W106K/V149I and W106K/M124L) were introduced into the DHAP from Bacillus pumilus. Compared with the wild-type DHAP hydrolytic activity, the double-site variant W106K/V149I showed an increase in specific hydrolytic activity at 15 °C by 2.3-fold toward casein in terms of hydrolytic rate and 2.7-fold toward the synthetic peptide AAPF-pN by means of kcat/Km value. The thermostability of the variant (W106K/V149I) was improved with the half-life at 60 and 70 °C increased by 2.7- and 5.0-fold, respectively, when compared with the thermostability of the wild-type DHAP. Conclusively, an increase in the cold activity and thermostability of a bacterial alkaline protease was achieved by protein engineering.

  10. Cyclic strain increases protease-activated receptor-1 expression in vascular smooth muscle cells

    NASA Technical Reports Server (NTRS)

    Nguyen, K. T.; Frye, S. R.; Eskin, S. G.; Patterson, C.; Runge, M. S.; McIntire, L. V.

    2001-01-01

    Cyclic strain regulates many vascular smooth muscle cell (VSMC) functions through changing gene expression. This study investigated the effects of cyclic strain on protease-activated receptor-1 (PAR-1) expression in VSMCs and the possible signaling pathways involved, on the basis of the hypothesis that cyclic strain would enhance PAR-1 expression, reflecting increased thrombin activity. Uniaxial cyclic strain (1 Hz, 20%) of cells cultured on elastic membranes induced a 2-fold increase in both PAR-1 mRNA and protein levels. Functional activity of PAR-1, as assessed by cell proliferation in response to thrombin, was also increased by cyclic strain. In addition, treatment of cells with antioxidants or an NADPH oxidase inhibitor blocked strain-induced PAR-1 expression. Preincubation of cells with protein kinase inhibitors (staurosporine or Ro 31-8220) enhanced strain-increased PAR-1 expression, whereas inhibitors of NO synthase, tyrosine kinase, and mitogen-activated protein kinases had no effect. Cyclic strain in the presence of basic fibroblast growth factor induced PAR-1 mRNA levels beyond the effect of cyclic strain alone, whereas no additive effect was observed between cyclic strain and platelet-derived growth factor-AB. Our findings that cyclic strain upregulates PAR-1 mRNA expression but that shear stress downregulates this gene in VSMCs provide an opportunity to elucidate signaling differences by which VSMCs respond to different mechanical forces.

  11. Pedometers: A Strategy to Promote Increased Physical Activity among College Students

    ERIC Educational Resources Information Center

    Hackmann, Debra J.; Mintah, Joseph K.

    2010-01-01

    Inactive lifestyle behaviors are predominant in society, especially among the adult population. This study examined the issue of inactivity among college students. A pedometer was used as an intervention strategy, to increase awareness of, and motivate college students to achieve the minimum recommended amount of daily physical activity. A…

  12. Planar fuel cell utilizing nail current collectors for increased active surface area

    SciTech Connect

    George, Thomas J.; Meacham, G.B. Kirby

    1999-11-26

    A plurality of nail current collector members are useful in the gas flow passages of an electrochemical device to optimize the active surfaces of the device and to provide structural support. In addition, the thicknesses of cathode and anode layers within the electrochemical device are varied according to current flow through the device to reduce resistance and increase operating efficiency.

  13. Hemorrhage activates myocardial NFkappaB and increases TNF-alpha in the heart.

    PubMed

    Meldrum, D R; Shenkar, R; Sheridan, B C; Cain, B S; Abraham, E; Harken, A H

    1997-10-01

    The heart is a tumor necrosis factor (TNFalpha) producing organ. Locally (v systemically)-produced TNFalpha likely contributes to myocardial dysfunction via direct suppression of myocardial contractile function, the induction of myocardial apoptosis, and the genesis of cardiac hypertrophy. Although recent studies have demonstrated increased myocardial TNFalpha following endotoxemia, it remains unknown whether shock, in the absence of sepsis, activates myocardial nuclear factor kappa B (NFkappaB, a TNFalpha transcription factor) and/or increases TNFalpha in the heart. To study this, rats were hemorrhaged and resuscitated, after which hearts were harvested and analysed for evidence of NFkappaB activation (electrophoretic mobility shift assay) and assayed for TNFalpha levels. Hemorrhage and resuscitation activated NFkappaB and resulted in a dramatic increase in myocardial TNFalpha. This study constitutes the initial demonstration that hemorrhagic shock activates the signaling mechanisms which culminate in increased myocardial TNFalpha. Indeed, this may have important clinical implications, since hemorrhage is a frequent complication of both iatrogenic and accidental trauma, as well as a potent instigator of multiple organ failure.

  14. Increased Protein Kinase A Activity in the Prkar1a-defective Mouse is Associated with Hyperarousal and Increased Anxiety

    DTIC Science & Technology

    2011-03-09

    Brain , P. F., & Martinez, M. (1999). Effect of predatory stress on sucrose intake and behavior on the plus-maze in male mice . Physiol Behav, 67(2...Extinction in Traumatized Civilians with Posttraumatic Stress Disorder: Relation to Symptom Severity . Biol Psychiatry. Phelps, E. A., & LeDoux, J. E. (2005...showed R1b mice had reduced injury -induced inflammation and pain, without apparent differences in PKA brain activity, likely due to compensatory

  15. Increased Serum Activity of Matrix Metalloproteinase-9 in Patients with Acute Variceal Bleeding

    PubMed Central

    Kwon, Oh Sang; Jung, Hyuk Sang; Bae, Kyung Sook; Jung, Young Kul; Kim, Yeon Suk; Choi, Duck Joo; Kim, Yun Soo

    2012-01-01

    Background/Aims Matrix metalloproteinases (MMP)-2 and -9 can degrade essential components of vascular integrity. The aim of this study was to investigate the association between those MMPs and variceal bleeding (VB). Methods Fifteen controls, 12 patients with acute ulcer bleeding (UB) group, 37 patients with varix (V group), and 35 patients with acute VB group were enrolled. Serum was obtained to measure MMP-2 and -9 activity by zymogram protease assays. Results The activity levels of these compounds were compared with the controls' median value. The median MMP-9 activity was 1.0 in controls, 1.05 in the UB group, 0.43 in the V group, and 0.96 in the VB group. The level of MMP-9 activity was higher in the VB group than in the V group (p<0.001). In the VB group, there was a signifi cant decrease in MMP-9 activity over time after bleeding (p<0.001). The median MMP-2 activity level was 1.0 in controls, 1.01 in the UB group, 1.50 in the V group, and 1.55 in the VB group. The level of MMP-2 activity was similar in the VB and V groups. Conclusions The level of MMP-9 activity increased in association with VB. The role of MMP-9 in the pathogenesis of VB should be verified. PMID:22570756

  16. The TMS Map Scales with Increased Stimulation Intensity and Muscle Activation.

    PubMed

    van de Ruit, Mark; Grey, Michael J

    2016-01-01

    One way to study cortical organisation, or its reorganisation, is to use transcranial magnetic stimulation (TMS) to construct a map of corticospinal excitability. TMS maps are reported to be acquired with a wide variety of stimulation intensities and levels of muscle activation. Whilst MEPs are known to increase both with stimulation intensity and muscle activation, it remains to be established what the effect of these factors is on the map's centre of gravity (COG), area, volume and shape. Therefore, the objective of this study was to systematically examine the effect of stimulation intensity and muscle activation on these four key map outcome measures. In a first experiment, maps were acquired with a stimulation intensity of 110, 120 and 130% of resting threshold. In a second experiment, maps were acquired at rest and at 5, 10, 20 and 40% of maximum voluntary contraction. Map area and map volume increased with both stimulation intensity (P < 0.01) and muscle activation (P < 0.01). Neither the COG nor the map shape changed with either stimulation intensity or muscle activation (P > 0.09 in all cases). This result indicates the map simply scales with stimulation intensity and muscle activation.

  17. aPKC Phosphorylation of HDAC6 Results in Increased Deacetylation Activity

    PubMed Central

    Du, Yifeng; Seibenhener, Michael L.; Yan, Jin; Jiang, Jianxiong; Wooten, Michael C.

    2015-01-01

    The Class II histone deacetylase, HDAC6, has been shown to be involved in cell motility, aggresome formation and mitochondria transport. HDAC6 deacetylase activity regulates α-tubulin acetylation levels and thus plays a critical role in these processes. In turn, HDAC6 activity can be regulated by interaction with various proteins including multiple kinases. Kinase mediated phosphorylation of HDAC6 can lead to either increased or reduced activity. Our previous research has shown that sequestosome1/p62 (SQSTM1/p62) interacts with HDAC6 and regulates its activity. As SQSTM1/p62 is a scaffolding protein known to interact directly with the zeta isoform of Protein Kinase C (PKCζ), we sought to examine if HDAC6 could be a substrate for PKCζ phosphorylation and if so, how its activity might be regulated. Our data demonstrate that HDAC6 is not only present in a protein complex with PKCζ but can also be phosphorylated by PKCζ. We also show that specific phosphorylation of HDAC6 by PKCζ increases HDAC6 deacetylase activity resulting in reduced acetylated tubulin levels. Our findings provide novel insight into the molecular mechanism by which HDAC6, PKCζ and SQSTM1/p62 function together in protein aggregate clearance. These results also highlight a new research direction which may prove fruitful for understanding the underlying cause of several neurodegenerative diseases. PMID:25860570

  18. aPKC phosphorylation of HDAC6 results in increased deacetylation activity.

    PubMed

    Du, Yifeng; Seibenhener, Michael L; Yan, Jin; Jiang, Jianxiong; Wooten, Michael C

    2015-01-01

    The Class II histone deacetylase, HDAC6, has been shown to be involved in cell motility, aggresome formation and mitochondria transport. HDAC6 deacetylase activity regulates α-tubulin acetylation levels and thus plays a critical role in these processes. In turn, HDAC6 activity can be regulated by interaction with various proteins including multiple kinases. Kinase mediated phosphorylation of HDAC6 can lead to either increased or reduced activity. Our previous research has shown that sequestosome1/p62 (SQSTM1/p62) interacts with HDAC6 and regulates its activity. As SQSTM1/p62 is a scaffolding protein known to interact directly with the zeta isoform of Protein Kinase C (PKCζ), we sought to examine if HDAC6 could be a substrate for PKCζ phosphorylation and if so, how its activity might be regulated. Our data demonstrate that HDAC6 is not only present in a protein complex with PKCζ but can also be phosphorylated by PKCζ. We also show that specific phosphorylation of HDAC6 by PKCζ increases HDAC6 deacetylase activity resulting in reduced acetylated tubulin levels. Our findings provide novel insight into the molecular mechanism by which HDAC6, PKCζ and SQSTM1/p62 function together in protein aggregate clearance. These results also highlight a new research direction which may prove fruitful for understanding the underlying cause of several neurodegenerative diseases.

  19. Microbial translocation is associated with increased monocyte activation and dementia in AIDS patients.

    PubMed

    Ancuta, Petronela; Kamat, Anupa; Kunstman, Kevin J; Kim, Eun-Young; Autissier, Patrick; Wurcel, Alysse; Zaman, Tauheed; Stone, David; Mefford, Megan; Morgello, Susan; Singer, Elyse J; Wolinsky, Steven M; Gabuzda, Dana

    2008-06-25

    Elevated plasma lipopolysaccharide (LPS), an indicator of microbial translocation from the gut, is a likely cause of systemic immune activation in chronic HIV infection. LPS induces monocyte activation and trafficking into brain, which are key mechanisms in the pathogenesis of HIV-associated dementia (HAD). To determine whether high LPS levels are associated with increased monocyte activation and HAD, we obtained peripheral blood samples from AIDS patients and examined plasma LPS by Limulus amebocyte lysate (LAL) assay, peripheral blood monocytes by FACS, and soluble markers of monocyte activation by ELISA. Purified monocytes were isolated by FACS sorting, and HIV DNA and RNA levels were quantified by real time PCR. Circulating monocytes expressed high levels of the activation markers CD69 and HLA-DR, and harbored low levels of HIV compared to CD4(+) T-cells. High plasma LPS levels were associated with increased plasma sCD14 and LPS-binding protein (LBP) levels, and low endotoxin core antibody levels. LPS levels were higher in HAD patients compared to control groups, and were associated with HAD independently of plasma viral load and CD4 counts. LPS levels were higher in AIDS patients using intravenous heroin and/or ethanol, or with Hepatitis C virus (HCV) co-infection, compared to control groups. These results suggest a role for elevated LPS levels in driving monocyte activation in AIDS, thereby contributing to the pathogenesis of HAD, and provide evidence that cofactors linked to substance abuse and HCV co-infection influence these processes.

  20. Increased activation of the human cerebellum during pitch discrimination: a positron emission tomography (PET) study.

    PubMed

    Petacchi, Augusto; Kaernbach, Christian; Ratnam, Rama; Bower, James M

    2011-12-01

    Recent years have seen a growing debate concerning the function of the cerebellum. Here we used a pitch discrimination task and PET to test for cerebellar involvement in the active control of sensory data acquisition. Specifically, we predicted greater cerebellar activity during active pitch discrimination compared to passive listening, with the greatest activity when pitch discrimination was most difficult. Ten healthy subjects were trained to discriminate deviant tones presented with a slightly higher pitch than a standard tone, using a Go/No Go paradigm. To ensure that discrimination performance was matched across subjects, individual psychometric curves were assessed beforehand using a two-step psychoacoustic procedure. Subjects were scanned while resting in the absence of any sounds, while passively listening to standard tones, and while detecting deviant tones slightly higher in pitch among these standard tones at four different performance levels. Consistent with our predictions, 1) passive listening alone elicited cerebellar activity (lobule IX), 2) cerebellar activity increased during pitch discrimination as compared to passive listening (crus I and II, lobules VI, VIIB, and VIIIB), and 3) this increase was correlated with the difficulty of the discrimination task (lobules V, VI, and IX). These results complement recent findings showing pitch discrimination deficits in cerebellar patients (Parsons et al., 2009) and further support a role for the cerebellum in sensory data acquisition. The data are discussed in the light of anatomical and physiological evidence functionally connecting auditory system and cerebellum.

  1. Superoxide dismutase and catalase conjugated to polyethylene glycol increases endothelial enzyme activity and oxidant resistance

    SciTech Connect

    Beckman, J.S.; Minor, R.L. Jr.; White, C.W.; Repine, J.E.; Rosen, G.M.; Freeman, B.A.

    1988-05-15

    Covalent conjugation of superoxide dismutase and catalase with polyethylene glycol (PEG) increases the circulatory half-lives of these enzymes from <10 min to 40 h, reduced immunogenicity, and decreases sensitivity to proteolysis. Because PEG has surface active properties and can induce cell fusion, the authors hypothesized that PEG conjugation could enhance cell binding and association of normally membrane-impermeable enzymes. Incubation of cultured porcine aortic endothelial cells with /sup 125/I-PEG-catalase or /sup 125/I-PEG-superoxide dismutase produced a linear, concentration-dependent increase in cellular enzyme activity and radioactivity. Fluorescently labeled PEG-superoxide dismutase incubated with endothelial cells showed a vesicular localization. Mechanical injury to cell monolayers, which is known to stimulate endocytosis, further increased the uptake of fluorescent PEG-superoxide dismutase. Addition of PEG and PEG-conjugated enzymes perturbed the spin-label binding environment, indicative of producing an increase in plasma membrane fluidity. Thus, PEG conjugation to superoxide dismutase and catalase enhances cell association of these enzymes in a manner which increases cellular enzyme activities and provides prolonged protection from partially reduced oxygen species.

  2. Vinculin activators target integrins from within the cell to increase melanoma sensitivity to chemotherapy

    PubMed Central

    Nelson, Elke S.; Folkmann, Andrew W.; Henry, Michael D.; DeMali, Kris A.

    2011-01-01

    Metastatic melanoma is an aggressive skin disease for which there are no effective therapies. Emerging evidence indicates that melanomas can be sensitized to chemotherapy by increasing integrin function. Current integrin therapies work by targeting the extracellular domain, resulting in complete gains or losses of integrin function that lead to mechanism-based toxicities. An attractive alternative approach is to target proteins, such as vinculin, that associate with the integrin cytoplasmic domains and regulate its ligand binding properties. Here we report that a novel reagent, denoted vinculin activating peptide or VAP, increases integrin activity from within the cell, as measured by elevated: (1) numbers of active integrins, (2) adhesion of cells to extracellular matrix ligands, (3) numbers of cell-matrix adhesions, and (4) downstream signaling. These effects are dependent on both integrins and a key regulatory residue A50 in the vinculin head domain. We further show that VAP dramatically increases the sensitivity of melanomas to chemotherapy in clonal growth assays and in vivo mouse models of melanoma. Finally, we demonstrate that the increase in chemosensitivity results from increases in DNA damage-induced apoptosis in a p53-dependent manner. Collectively these findings demonstrate for the first time that integrin function can be manipulated from within the cell and validate integrins as a new therapeutic target for the treatment of chemoresistant melanomas. PMID:21460181

  3. Low Levels of Physical Activity Increase Metabolic Responsiveness to Cold in a Rat (Rattus fuscipes)

    PubMed Central

    Seebacher, Frank; Glanville, Elsa J.

    2010-01-01

    Background Physical activity modulates expression of metabolic genes and may therefore be a prerequisite for metabolic responses to environmental stimuli. However, the extent to which exercise interacts with environmental conditions to modulate metabolism is unresolved. Hence, we tested the hypothesis that even low levels of physical activity are beneficial by improving metabolic responsiveness to temperatures below the thermal neutral zone, thereby increasing the capacity for substrate oxidation and energy expenditure. Methodology/Principal Findings We used wild rats (Rattus fuscipes) to avoid potential effects of breeding on physiological phenotypes. Exercise acclimation (for 30 min/day on 5 days/week for 30 days at 60% of maximal performance) at 22°C increased mRNA concentrations of PGC1α, PPARδ, and NRF-1 in skeletal muscle and brown adipose tissue compared to sedentary animals. Lowering ambient temperature to 12°C caused further increases in relative expression of NRF-1 in skeletal muscle, and of PPARδ of brown adipose tissue. Surprisingly, relative expression of UCP1 increased only when both exercise and cold stimuli were present. Importantly, in sedentary animals cold acclimation (12°C) alone did not change any of the above variables. Similarly, cold alone did not increase maximum capacity for substrate oxidation in mitochondria (cytochrome c oxidase and citrate synthase activities) of either muscle or brown adipose tissue. Animals that exercised regularly had higher exercise induced metabolic rates in colder environments than sedentary rats, and temperature induced metabolic scope was greater in exercised rats. Conclusions/Significance Physical activity is a necessary prerequisite for the expression of transcriptional regulators that influence a broad range of physiological functions from energy metabolism to cardiovascular function and nutrient uptake. A sedentary lifestyle leads to decreased daily energy expenditure because of a lack of direct use

  4. TRPA1 activation by lidocaine in nerve terminals results in glutamate release increase

    SciTech Connect

    Piao, L.-H.; Fujita, Tsugumi; Jiang, C.-Y.; Liu Tao; Yue, H.-Y.; Nakatsuka, Terumasa; Kumamoto, Eiichi

    2009-02-20

    We examined the effects of local anesthetics lidocaine and procaine on glutamatergic spontaneous excitatory transmission in substantia gelatinosa (SG) neurons in adult rat spinal cord slices with whole-cell patch-clamp techniques. Bath-applied lidocaine (1-5 mM) dose-dependently and reversibly increased the frequency but not the amplitude of spontaneous excitatory postsynaptic current (sEPSC) in SG neurons. Lidocaine activity was unaffected by the Na{sup +}-channel blocker, tetrodotoxin, and the TRPV1 antagonist, capsazepine, but was inhibited by the TRP antagonist, ruthenium red. In the same neuron, the TRPA1 agonist, allyl isothiocyanate, and lidocaine both increased sEPSC frequency. In contrast, procaine did not produce presynaptic enhancement. These results indicate that lidocaine activates TRPA1 in nerve terminals presynaptic to SG neurons to increase the spontaneous release of L-glutamate.

  5. TRPA1 activation by lidocaine in nerve terminals results in glutamate release increase.

    PubMed

    Piao, Lian-Hua; Fujita, Tsugumi; Jiang, Chang-Yu; Liu, Tao; Yue, Hai-Yuan; Nakatsuka, Terumasa; Kumamoto, Eiichi

    2009-02-20

    We examined the effects of local anesthetics lidocaine and procaine on glutamatergic spontaneous excitatory transmission in substantia gelatinosa (SG) neurons in adult rat spinal cord slices with whole-cell patch-clamp techniques. Bath-applied lidocaine (1-5 mM) dose-dependently and reversibly increased the frequency but not the amplitude of spontaneous excitatory postsynaptic current (sEPSC) in SG neurons. Lidocaine activity was unaffected by the Na(+)-channel blocker, tetrodotoxin, and the TRPV1 antagonist, capsazepine, but was inhibited by the TRP antagonist, ruthenium red. In the same neuron, the TRPA1 agonist, allyl isothiocyanate, and lidocaine both increased sEPSC frequency. In contrast, procaine did not produce presynaptic enhancement. These results indicate that lidocaine activates TRPA1 in nerve terminals presynaptic to SG neurons to increase the spontaneous release of L-glutamate.

  6. Increased activity in human visual cortex during directed attention in the absence of visual stimulation.

    PubMed

    Kastner, S; Pinsk, M A; De Weerd, P; Desimone, R; Ungerleider, L G

    1999-04-01

    When subjects direct attention to a particular location in a visual scene, responses in the visual cortex to stimuli presented at that location are enhanced, and the suppressive influences of nearby distractors are reduced. What is the top-down signal that modulates the response to an attended versus an unattended stimulus? Here, we demonstrate increased activity related to attention in the absence of visual stimulation in extrastriate cortex when subjects covertly directed attention to a peripheral location expecting the onset of visual stimuli. Frontal and parietal areas showed a stronger signal increase during this expectation than did visual areas. The increased activity in visual cortex in the absence of visual stimulation may reflect a top-down bias of neural signals in favor of the attended location, which derives from a fronto-parietal network.

  7. Increasing total and biologically active chromium in wheat grain and spinach by spraying with chromium salts

    SciTech Connect

    Vicini, F.A.; Ellis, B.G.

    1981-06-01

    Recently, chromium has been shown to be necessary for glucose metabolism in man. But most plant species greatly restrict the uptake of Cr. This study was conducted to determine if both total and biologically active Cr could be increased in wheat grain or spinach by spraying the plants with either Cr/sub 2/(SO/sub 4/)/sub 3/ or Cr-EDTA. Concentrations of Cr in wheat grain were about doubled in a greenhouse experiment by spraying with either Cr source. Biologically active Cr (estimated by extraction with ethanol or NH/sub 4/OH) was increased from about 40 to greater than 50% of total Cr when wheat was sprayed with Cr salts. Total Cr in spinach leaves was increased by as much as 10-fold by spraying, with the sulfate source being more effective than the EDTA.

  8. Theobromine increases NAD⁺/Sirt-1 activity and protects the kidney under diabetic conditions.

    PubMed

    Papadimitriou, Alexandros; Silva, Kamila C; Peixoto, Elisa B M I; Borges, Cynthia M; Lopes de Faria, Jacqueline M; Lopes de Faria, José B

    2015-02-01

    Reduction in sirtuin 1 (Sirt-1) is associated with extracellular matrix (ECM) accumulation in the diabetic kidney. Theobromine may reduce kidney ECM accumulation in diabetic rats. In the current study, we aimed to unravel, under diabetic conditions, the mechanism of kidney ECM accumulation induced by a reduction in Sirt-1 and the effect of theobromine in these events. In vitro, we used immortalized human mesangial cells (iHMCs) exposed to high glucose (HG; 30 mM), with or without small interfering RNA for NOX4 and Sirt-1. In vivo, spontaneously hypertensive rats (SHR) were rendered diabetic by means of streptozotocin and studied after 12 wk. The effects of treatment with theobromine were investigated under both conditions. HG leads to a decrease in Sirt-1 activity and NAD(+) levels in iHMCs. Sirt-1 activity could be reestablished by treatment with NAD(+), silencing NOX4, and poly (ADP-ribose) polymerase-1 (PARP-1) blockade, or with theobromine. HG also leads to a low AMP/ATP ratio, acetylation of SMAD3, and increased collagen IV, which is prevented by theobromine. Sirt-1 or AMPK blockade abolished these effects of theobromine. In diabetic SHR, theobromine prevented increases in albuminuria and kidney collagen IV, reduced AMPK, elevated NADPH oxidase activity and PARP-1, and reduced NAD(+) levels and Sirt-1 activity. These results suggest that in diabetes mellitus, Sirt-1 activity is reduced by PARP-1 activation and NAD(+) depletion due to low AMPK, which increases NOX4 expression, leading to ECM accumulation mediated by transforming growth factor (TGF)-β1 signaling. It is suggested that Sirt-1 activation by theobromine may have therapeutic potential for diabetic nephropathy.

  9. Alpha-Amylase Activity in Blood Increases after Pharmacological, But Not Psychological, Activation of the Adrenergic System

    PubMed Central

    Nater, Urs M.; La Marca, Roberto; Erni, Katja; Ehlert, Ulrike

    2015-01-01

    Background & Aim Alpha-amylase in both blood and saliva has been used as a diagnostic parameter. While studies examining alpha-amylase activity in saliva have shown that it is sensitive to physiological and psychological challenge of the adrenergic system, no challenge studies have attempted to elucidate the role of the adrenergic system in alpha-amylase activity in blood. We set out to examine the impact of psychological and pharmacological challenge on alpha-amylase in blood in two separate studies. Methods In study 1, healthy subjects were examined in a placebo-controlled, double-blind paradigm using yohimbine, an alpha2-adrenergic antagonist. In study 2, subjects were examined in a standardized rest-controlled psychosocial stress protocol. Alpha-amylase activity in blood was repeatedly measured in both studies. Results Results of study 1 showed that alpha-amylase in blood is subject to stronger increases after injection of yohimbine compared to placebo. In study 2, results showed that there was no significant effect of psychological stress compared to rest. Conclusions Alpha-amylase in blood increases after pharmacological activation of the adrenergic pathways suggesting that sympathetic receptors are responsible for these changes. Psychological stress, however, does not seem to have an impact on alpha-amylase in blood. Our findings provide insight into the mechanisms underlying activity changes in alpha-amylase in blood in healthy individuals. PMID:26110636

  10. Aspartic acid aminotransferase activity is increased in actively spiking compared with non-spiking human epileptic cortex.

    PubMed Central

    Kish, S J; Dixon, L M; Sherwin, A L

    1988-01-01

    Increased concentration of the excitatory neurotransmitter aspartic acid in actively spiking human epileptic cerebral cortex was recently described. In order to further characterise changes in the aspartergic system in epileptic brain, the behaviour of aspartic acid aminotransferase (AAT), a key enzyme involved in aspartic acid metabolism has now been examined. Electrocorticography performed during surgery was employed to identify cortical epileptic spike foci in 16 patients undergoing temporal lobectomy for intractable seizures. Patients with spontaneously spiking lateral temporal cortex (n = 8) were compared with a non-spiking control group (n = 8) of patients in whom the epileptic lesions were confined to the hippocampus sparing the temporal convexity. Mean activity of AAT in spiking cortex was significantly elevated by 16-18%, with aspartic acid concentration increased by 28%. Possible explanations for the enhanced AAT activity include increased proliferation of cortical AAT-containing astrocytes at the spiking focus and/or a generalised increase in neuronal or extraneuronal metabolism consequent to the ongoing epileptic discharge. It is suggested that the data provide additional support for a disturbance of central excitatory aspartic acid mechanisms in human epileptic brain. PMID:2898010

  11. Increased digitalis-like activity in human cerebrospinal fluid after expansion of the extracellular fluid volume

    SciTech Connect

    Halperin, J.A.; Martin, A.M.; Malave, S.

    1985-08-12

    The present study was designed to determine whether acute expansion of the extracellular fluid volume influenced the digitalis-like activity of human cerebrospinal fluid (CSF), previously described. Human CSF samples, drawn before and 30 minutes after the intravenous infusion of 1 liter of either saline or glucose solutions, were assayed for digitalis-like activity by inhibition of either the /sup 86/Rb/sup +/ uptake into human erythrocytes or by the activity of a purified Na/sup +/-K/sup +/ ATPase. The CSF inhibitory activity on both systems significantly increased after the infusion of sodium solutions but did not change after the infusion of glucose. These results indicate that the digitalis-like factor of human CSF might be involved in the regulation of the extracellular fluid volume and electrolyte content and thereby in some of the physiological responses to sodium loading. 31 references, 2 figures, 1 table.

  12. Nanocaged enzymes with enhanced catalytic activity and increased stability against protease digestion.

    PubMed

    Zhao, Zhao; Fu, Jinglin; Dhakal, Soma; Johnson-Buck, Alexander; Liu, Minghui; Zhang, Ting; Woodbury, Neal W; Liu, Yan; Walter, Nils G; Yan, Hao

    2016-02-10

    Cells routinely compartmentalize enzymes for enhanced efficiency of their metabolic pathways. Here we report a general approach to construct DNA nanocaged enzymes for enhancing catalytic activity and stability. Nanocaged enzymes are realized by self-assembly into DNA nanocages with well-controlled stoichiometry and architecture that enabled a systematic study of the impact of both encapsulation and proximal polyanionic surfaces on a set of common metabolic enzymes. Activity assays at both bulk and single-molecule levels demonstrate increased substrate turnover numbers for DNA nanocage-encapsulated enzymes. Unexpectedly, we observe a significant inverse correlation between the size of a protein and its activity enhancement. This effect is consistent with a model wherein distal polyanionic surfaces of the nanocage enhance the stability of active enzyme conformations through the action of a strongly bound hydration layer. We further show that DNA nanocages protect encapsulated enzymes against proteases, demonstrating their practical utility in functional biomaterials and biotechnology.

  13. Decreases in Theta and Increases in High Frequency Activity Underlie Associative Memory Encoding

    PubMed Central

    Greenberg, Jeffrey A.; Burke, John F.; Haque, Rafi; Kahana, Michael J.; Zaghloul, Kareem A.

    2015-01-01

    Episodic memory encoding refers to the cognitive process by which items and their associated contexts are stored in memory. To investigate changes directly attributed to the formation of explicit associations, we examined oscillatory power captured through intracranial electroencephalography (iEEG) as 27 neurosurgical patients receiving subdural and depth electrodes for seizure monitoring participated in a paired associates memory task. We examined low (3–8 Hz) and high (45–95 Hz) frequency activity, and found that the successful formation of new associations was accompanied by broad decreases in low frequency activity and a posterior to anterior progression of increases in high frequency activity in the left hemisphere. These data suggest that the observed patterns of activity may reflect the neural mechanisms underlying the formation of novel item-item associations. PMID:25862266

  14. Nanocaged enzymes with enhanced catalytic activity and increased stability against protease digestion

    PubMed Central

    Zhao, Zhao; Fu, Jinglin; Dhakal, Soma; Johnson-Buck, Alexander; Liu, Minghui; Zhang, Ting; Woodbury, Neal W.; Liu, Yan; Walter, Nils G.; Yan, Hao

    2016-01-01

    Cells routinely compartmentalize enzymes for enhanced efficiency of their metabolic pathways. Here we report a general approach to construct DNA nanocaged enzymes for enhancing catalytic activity and stability. Nanocaged enzymes are realized by self-assembly into DNA nanocages with well-controlled stoichiometry and architecture that enabled a systematic study of the impact of both encapsulation and proximal polyanionic surfaces on a set of common metabolic enzymes. Activity assays at both bulk and single-molecule levels demonstrate increased substrate turnover numbers for DNA nanocage-encapsulated enzymes. Unexpectedly, we observe a significant inverse correlation between the size of a protein and its activity enhancement. This effect is consistent with a model wherein distal polyanionic surfaces of the nanocage enhance the stability of active enzyme conformations through the action of a strongly bound hydration layer. We further show that DNA nanocages protect encapsulated enzymes against proteases, demonstrating their practical utility in functional biomaterials and biotechnology. PMID:26861509

  15. Nanocaged enzymes with enhanced catalytic activity and increased stability against protease digestion

    NASA Astrophysics Data System (ADS)

    Zhao, Zhao; Fu, Jinglin; Dhakal, Soma; Johnson-Buck, Alexander; Liu, Minghui; Zhang, Ting; Woodbury, Neal W.; Liu, Yan; Walter, Nils G.; Yan, Hao

    2016-02-01

    Cells routinely compartmentalize enzymes for enhanced efficiency of their metabolic pathways. Here we report a general approach to construct DNA nanocaged enzymes for enhancing catalytic activity and stability. Nanocaged enzymes are realized by self-assembly into DNA nanocages with well-controlled stoichiometry and architecture that enabled a systematic study of the impact of both encapsulation and proximal polyanionic surfaces on a set of common metabolic enzymes. Activity assays at both bulk and single-molecule levels demonstrate increased substrate turnover numbers for DNA nanocage-encapsulated enzymes. Unexpectedly, we observe a significant inverse correlation between the size of a protein and its activity enhancement. This effect is consistent with a model wherein distal polyanionic surfaces of the nanocage enhance the stability of active enzyme conformations through the action of a strongly bound hydration layer. We further show that DNA nanocages protect encapsulated enzymes against proteases, demonstrating their practical utility in functional biomaterials and biotechnology.

  16. Increase in natural killer cell activity following living-related liver transplantation.

    PubMed

    Hirata, M; Kita, Y; Saito, S; Nishimura, M; Ito, M; Mizuta, K; Tanaka, H; Harihara, Y; Kawarasaki, H; Hashizume, K; Makuuchi, M

    1998-01-01

    We monitored the serial changes of natural killer cell (NK) activity in eight recipients of living-related liver transplantation. The HLA types of all eight patients were haplotypically identical with those of their donors. Tacrolimus and methylprednisolone were used for immunosuppression. The NK activity before transplantation was 24.1 +/- 20.2% which is surprisingly low when compared with the value for normal individuals (67.7 +/- 13.2%, P < 0.01) or a liver dysfunction group (49.4 +/- 21.9%, P < 0.05). Serial changes in NK activity revealed a minimum of 6.1 +/- 3.6% 1 week after transplantation, gradually increasing to 49.2 +/- 12.5% at 2 months after transplantation. These results suggest that the diseased liver might play an important role in the suppression of NK activity.

  17. Building a foundation for systems change: increasing access to physical activity programs for older adults.

    PubMed

    Lachenmayr, Sue; Mackenzie, Geraldine

    2004-10-01

    Although 25% of U.S. adults are physically inactive, this percentage increases dramatically for older adults. Organizational change theory guided a state health department in identifying system gaps and developing strategies to expand programming for seniors. A survey of provider agencies in New Jersey assessed (a) capacity for physical activity programs for older adults, (b) accessibility of programs, and (c) barriers to providing programs. One hundred sixty agencies provided physical activity programs to almost 184,000 individuals annually. Fewer than one half of the agencies provided exercise programs for people with disabilities, and only 44% provided in-home programs. Eighty-two percent of program providers wanted to expand programming but cited lack of trained instructors and peer leaders, inadequate facility space, insufficient funding, and limited transportation resources as barriers. Sustaining older adult behavior change requires infrastructure that will ensure access to diverse physical activities. This article provides strategies to expand access to physical activity programs for older adults.

  18. Exogenous Methyl Jasmonate Treatment Increases Glucosinolate Biosynthesis and Quinone Reductase Activity in Kale Leaf Tissue

    PubMed Central

    Ku, Kang-Mo; Jeffery, Elizabeth H.; Juvik, John A.

    2014-01-01

    Methyl jasmonate (MeJA) spray treatments were applied to the kale varieties ‘Dwarf Blue Curled Vates’ and ‘Red Winter’ in replicated field plantings in 2010 and 2011 to investigate alteration of glucosinolate (GS) composition in harvested leaf tissue. Aqueous solutions of 250 µM MeJA were sprayed to saturation on aerial plant tissues four days prior to harvest at commercial maturity. The MeJA treatment significantly increased gluconasturtiin (56%), glucobrassicin (98%), and neoglucobrassicin (150%) concentrations in the apical leaf tissue of these genotypes over two seasons. Induction of quinone reductase (QR) activity, a biomarker for anti-carcinogenesis, was significantly increased by the extracts from the leaf tissue of these two cultivars. Extracts of apical leaf tissues had greater MeJA mediated increases in phenolics, glucosinolate concentrations, GS hydrolysis products, and QR activity than extracts from basal leaf tissue samples. The concentration of the hydrolysis product of glucoraphanin, sulforphane was significantly increased in apical leaf tissue of the cultivar ‘Red Winter’ in both 2010 and 2011. There was interaction between exogenous MeJA treatment and environmental conditions to induce endogenous JA. Correlation analysis revealed that indole-3-carbanol (I3C) generated from the hydrolysis of glucobrassicin significantly correlated with QR activity (r = 0.800, P<0.001). Concentrations required to double the specific QR activity (CD values) of I3C was calculated at 230 µM, which is considerably weaker at induction than other isothiocyanates like sulforphane. To confirm relationships between GS hydrolysis products and QR activity, a range of concentrations of MeJA sprays were applied to kale leaf tissues of both cultivars in 2011. Correlation analysis of these results indicated that sulforaphane, NI3C, neoascorbigen, I3C, and diindolylmethane were all significantly correlated with QR activity. Thus, increased QR activity may be due to

  19. Major increase in endopeptidase activity of human cathepsin B upon removal of occluding loop contacts.

    PubMed

    Nägler, D K; Storer, A C; Portaro, F C; Carmona, E; Juliano, L; Ménard, R

    1997-10-14

    The main feature distinguishing cathepsin B from other cysteine proteases of the papain family is the presence of a large insertion loop, termed the occluding loop, which occupies the S' subsites of the enzyme. The loop is held in place mainly by two contacts with the rest of the enzyme, involving residues His110 and Arg116 on the loop that form salt bridges with Asp22 and Asp224, respectively. The influence of this loop on the endopeptidase activity of cathepsin B has been investigated using site-directed mutagenesis and internally quenched fluorogenic (IQF) substrates. Wild-type cathepsin B displays poor activity against the substrates Abz-AFRSAAQ-EDDnp and Abz-QVVAGA-EDDnp as compared to cathepsin L and papain. Appreciable increases in kcat/KM were observed for cathepsin B containing the single mutations D22A, H110A, R116A, and D224A. The highest activity however is observed for mutants where both loop to enzyme contacts are disrupted. For the triple-mutant D22A/H110A/R116A, an optimum kcat/KM value of 12 x 10(5) M-1 s-1 was obtained for hydrolysis of Abz-AFRSAAQ-EDDnp, which corresponds to a 600-fold increase relative to wild-type cathepsin B and approaches the level of activity observed with cathepsin L or papain. By comparison, the mutations have little effect on the hydrolysis of Cbz-FR-MCA. The influence of the mutations on the pH dependency of activity also indicates that the complexity of pH activity profiles normally observed for cathepsin B is related to the presence of the occluding loop. The major increase in endopeptidase activity is attributed to an increase in loop "flexibility" and suggests that the occluding loop might move when an endopeptidase substrate binds to the enzyme. The possible contribution of these interactions in regulating endopeptidase activity and the implications for cathepsin B activity in physiological or pathological conditions are discussed.

  20. Pulsed Light Stimulation Increases Boundary Preference and Periodicity of Episodic Motor Activity in Drosophila melanogaster

    PubMed Central

    Qiu, Shuang; Xiao, Chengfeng; Robertson, R. Meldrum

    2016-01-01

    There is considerable interest in the therapeutic benefits of long-term sensory stimulation for improving cognitive abilities and motor performance of stroke patients. The rationale is that such stimulation would activate mechanisms of neural plasticity to promote enhanced coordination and associated circuit functions. Experimental approaches to characterize such mechanisms are needed. Drosophila melanogaster is one of the most attractive model organisms to investigate neural mechanisms responsible for stimulation-induced behaviors with its powerful accessibility to genetic analysis. In this study, the effect of chronic sensory stimulation (pulsed light stimulation) on motor activity in w1118 flies was investigated. Flies were exposed to a chronic pulsed light stimulation protocol prior to testing their performance in a standard locomotion assay. Flies responded to pulsed light stimulation with increased boundary preference and travel distance in a circular arena. In addition, pulsed light stimulation increased the power of extracellular electrical activity, leading to the enhancement of periodic electrical activity which was associated with a centrally-generated motor pattern (struggling behavior). In contrast, such periodic events were largely missing in w1118 flies without pulsed light treatment. These data suggest that the sensory stimulation induced a response in motor activity associated with the modifications of electrical activity in the central nervous system (CNS). Finally, without pulsed light treatment, the wild-type genetic background was associated with the occurrence of the periodic activity in wild-type Canton S (CS) flies, and w+ modulated the consistency of periodicity. We conclude that pulsed light stimulation modifies behavioral and electrophysiological activities in w1118 flies. These data provide a foundation for future research on the genetic mechanisms of neural plasticity underlying such behavioral modification. PMID:27684063

  1. PKA and Epac activation mediates cAMP-induced vasorelaxation by increasing endothelial NO production.

    PubMed

    García-Morales, Verónica; Cuíñas, Andrea; Elíes, Jacobo; Campos-Toimil, Manuel

    2014-03-01

    Vascular relaxation induced by 3',5'-cyclic adenosine monophosphate (cAMP) is both endothelium-dependent and endothelium-independent, although the underlying signaling pathways are not fully understood. Aiming to uncover potential mechanisms, we performed contraction-relaxation experiments on endothelium-denuded and intact rat aorta rings and measured NO levels in isolated human endothelial cells using single cell fluorescence imaging. The vasorelaxant effect of forskolin, an adenylyl cyclase activator, was decreased after selective inhibitor of protein kinase A (PKA), a cAMP-activated kinase, or L-NAME, an endothelial nitric oxide synthase (eNOS) inhibitor, only in intact aortic rings. Both selective activation of PKA with 6-Bnz-cAMP and exchange protein directly activated by cAMP (Epac) with 8-pCPT-2'-O-Me-cAMP significantly relaxed phenylephrine-induced contractions. The vasorelaxant effect of the Epac activator, but not that of the PKA activator, was reduced by endothelium removal. Forskolin, dibutyryl cAMP (a cAMP analogue), 6-Bnz-cAMP and 8-pCPT-2'-O-Me-cAMP increased NO levels in endothelial cells and the forskolin effect was significantly inhibited by inactivation of both Epac and PKA, and eNOS inhibition. Our results indicate that the endothelium-dependent component of forskolin/cAMP-induced vasorelaxation is partially mediated by an increase in endothelial NO release due to an enhanced eNOS activity through PKA and Epac activation in endothelial cells.

  2. Shed GP of Ebola Virus Triggers Immune Activation and Increased Vascular Permeability

    PubMed Central

    Escudero-Pérez, Beatriz; Volchkova, Valentina A.; Dolnik, Olga; Lawrence, Philip; Volchkov, Viktor E.

    2014-01-01

    During Ebola virus (EBOV) infection a significant amount of surface glycoprotein GP is shed from infected cells in a soluble form due to cleavage by cellular metalloprotease TACE. Shed GP and non-structural secreted glycoprotein sGP, both expressed from the same GP gene, have been detected in the blood of human patients and experimentally infected animals. In this study we demonstrate that shed GP could play a particular role during EBOV infection. In effect it binds and activates non-infected dendritic cells and macrophages inducing the secretion of pro- and anti-inflammatory cytokines (TNFα, IL1β, IL6, IL8, IL12p40, and IL1-RA, IL10). Activation of these cells by shed GP correlates with the increase in surface expression of co-stimulatory molecules CD40, CD80, CD83 and CD86. Contrary to shed GP, secreted sGP activates neither DC nor macrophages while it could bind DCs. In this study, we show that shed GP activity is likely mediated through cellular toll-like receptor 4 (TLR4) and is dependent on GP glycosylation. Treatment of cells with anti-TLR4 antibody completely abolishes shed GP-induced activation of cells. We also demonstrate that shed GP activity is negated upon addition of mannose-binding sera lectin MBL, a molecule known to interact with sugar arrays present on the surface of different microorganisms. Furthermore, we highlight the ability of shed GP to affect endothelial cell function both directly and indirectly, demonstrating the interplay between shed GP, systemic cytokine release and increased vascular permeability. In conclusion, shed GP released from virus-infected cells could activate non-infected DCs and macrophages causing the massive release of pro- and anti-inflammatory cytokines and effect vascular permeability. These activities could be at the heart of the excessive and dysregulated inflammatory host reactions to infection and thus contribute to high virus pathogenicity. PMID:25412102

  3. Increased glucocerebrosidase (GBA) 2 activity in GBA1 deficient mice brains and in Gaucher leucocytes.

    PubMed

    Burke, Derek G; Rahim, Ahad A; Waddington, Simon N; Karlsson, Stefan; Enquist, Ida; Bhatia, Kailash; Mehta, Atul; Vellodi, Ashok; Heales, Simon

    2013-09-01

    Lysosomal glucocerebrosidase (GBA1) deficiency is causative for Gaucher disease. Not all individuals with GBA1 mutations develop neurological involvement raising the possibility that other factors may provide compensatory protection. One factor may be the activity of the non-lysosomal β-glucosidase (GBA2) which exhibits catalytic activity towards glucosylceramide and is reported to be highly expressed in brain tissue. Here, we assessed brain GBA2 enzymatic activity in wild type, heterozygote and GBA1 deficient mice. Additionally, we determined activity in leucocytes obtained from 13 patients with Gaucher disease, 10 patients with enzymology consistent with heterozygote status and 19 controls. For wild type animals, GBA2 accounted for over 85 % of total brain GBA activity and was significantly elevated in GBA1 deficient mice when compared to heterozygote and wild types (GBA1 deficient; 92.4 ± 5.6, heterozygote; 71.5 ± 2.4, wild type 76.8 ± 5.1 nmol/h/mg protein). For the patient samples, five Gaucher patients had GBA2 leucocyte activities markedly greater than controls. No difference in GBA2 activity was apparent between the control and carrier groups. Undetectable GBA2 activity was identified in four leucocyte preparations; one in the control group, two in the carrier group and one from the Gaucher disease group. Work is now required to ascertain whether GBA2 activity is a disease modifying factor in Gaucher disease and to identify the mechanism(s) responsible for triggering increased GBA2 activity in GBA1 deficiency states.

  4. Increased lactate/pyruvate ratio augments blood flow in physiologically activated human brain

    NASA Astrophysics Data System (ADS)

    Mintun, Mark A.; Vlassenko, Andrei G.; Rundle, Melissa M.; Raichle, Marcus E.

    2004-01-01

    The factors regulating cerebral blood flow (CBF) changes in physiological activation remain the subject of great interest and debate. Recent experimental studies suggest that an increase in cytosolic NADH mediates increased blood flow in the working brain. Lactate injection should elevate NADH levels by increasing the lactate/pyruvate ratio, which is in near equilibrium with the NADH/NAD+ ratio. We studied CBF responses to bolus lactate injection at rest and in visual stimulation by using positron-emission tomography in seven healthy volunteers. Bolus lactate injection augmented the CBF response to visual stimulation by 38-53% in regions of the visual cortex but had no effect on the resting CBF or the whole-brain CBF. These lactate-induced CBF increases correlated with elevations in plasma lactate/pyruvate ratios and in plasma lactate levels but not with plasma pyruvate levels. Our observations support the hypothesis that an increase in the NADH/NAD+ ratio activates signaling pathways to selectively increase CBF in the physiologically stimulated brain regions.

  5. Restraint stress increases hemichannel activity in hippocampal glial cells and neurons.

    PubMed

    Orellana, Juan A; Moraga-Amaro, Rodrigo; Díaz-Galarce, Raúl; Rojas, Sebastián; Maturana, Carola J; Stehberg, Jimmy; Sáez, Juan C

    2015-01-01

    Stress affects brain areas involved in learning and emotional responses, which may contribute in the development of cognitive deficits associated with major depression. These effects have been linked to glial cell activation, glutamate release and changes in neuronal plasticity and survival including atrophy of hippocampal apical dendrites, loss of synapses and neuronal death. Under neuro-inflammatory conditions, we recently unveiled a sequential activation of glial cells that release ATP and glutamate via hemichannels inducing neuronal death due to activation of neuronal NMDA/P2X7 receptors and pannexin1 hemichannels. In the present work, we studied if stress-induced glia activation is associated to changes in hemichannel activity. To this end, we compared hemichannel activity of brain cells after acute or chronic restraint stress in mice. Dye uptake experiments in hippocampal slices revealed that acute stress induces opening of both Cx43 and Panx1 hemichannels in astrocytes, which were further increased by chronic stress; whereas enhanced Panx1 hemichannel activity was detected in microglia and neurons after acute/chronic and chronic stress, respectively. Moreover, inhibition of NMDA/P2X7 receptors reduced the chronic stress-induced hemichannel opening, whereas blockade of Cx43 and Panx1 hemichannels fully reduced ATP and glutamate release in hippocampal slices from stressed mice. Thus, we propose that gliotransmitter release through hemichannels may participate in the pathogenesis of stress-associated psychiatric disorders and possibly depression.

  6. Restraint stress increases hemichannel activity in hippocampal glial cells and neurons

    PubMed Central

    Orellana, Juan A.; Moraga-Amaro, Rodrigo; Díaz-Galarce, Raúl; Rojas, Sebastián; Maturana, Carola J.; Stehberg, Jimmy; Sáez, Juan C.

    2015-01-01

    Stress affects brain areas involved in learning and emotional responses, which may contribute in the development of cognitive deficits associated with major depression. These effects have been linked to glial cell activation, glutamate release and changes in neuronal plasticity and survival including atrophy of hippocampal apical dendrites, loss of synapses and neuronal death. Under neuro-inflammatory conditions, we recently unveiled a sequential activation of glial cells that release ATP and glutamate via hemichannels inducing neuronal death due to activation of neuronal NMDA/P2X7 receptors and pannexin1 hemichannels. In the present work, we studied if stress-induced glia activation is associated to changes in hemichannel activity. To this end, we compared hemichannel activity of brain cells after acute or chronic restraint stress in mice. Dye uptake experiments in hippocampal slices revealed that acute stress induces opening of both Cx43 and Panx1 hemichannels in astrocytes, which were further increased by chronic stress; whereas enhanced Panx1 hemichannel activity was detected in microglia and neurons after acute/chronic and chronic stress, respectively. Moreover, inhibition of NMDA/P2X7 receptors reduced the chronic stress-induced hemichannel opening, whereas blockade of Cx43 and Panx1 hemichannels fully reduced ATP and glutamate release in hippocampal slices from stressed mice. Thus, we propose that gliotransmitter release through hemichannels may participate in the pathogenesis of stress-associated psychiatric disorders and possibly depression. PMID:25883550

  7. Increased levels of peroxisomal active oxygen-related enzymes in copper-tolerant pea plants

    SciTech Connect

    Palma, J.M.; Gomez, M.; Yanez, J.; Del Rio, L.A.

    1987-10-01

    The effect in vivo of high nutrient levels of copper (240 micromolar) on the activity of different metalloenzymes containing Cu, Mn, Fe, and Zn, distributed in chloroplasts, peroxisomes, and mitochondria, was studied in leaves of two varieties of Pisum sativum L. plants with different sensitivity to copper. The metalloenzymes studied were: cytochrome c oxidase, Mn-superoxide dismutase (Mn-SOD) and Cu,Zn-superoxide dismutase I (Cu,Zn-SOD I), for mitochondria; catalase and Mn-SOD, for peroxisomes; and isozyme Cu,Zn-SOD II for chloroplasts. The activity of mitochondrial SOD isozymes (Mn-SOD and Cu,Zn-SOD I) was very similar in Cu-tolerant and Cu-sensitive plants, whereas cytochrome c oxidase was lower in Cu-sensitive plants. Chloroplastid Cu,Zn-SOD activity was the same in the two plant varieties. In contrast, the peroxisomal Mn-SOD activity was considerably higher in Cu-tolerant than in Cu-sensitive plants, and the activity of catalase was also increased in peroxisomes of Cu-tolerant plants. The higher activities of these peroxisomal active oxygen-related enzymes in Cu-tolerant plants suggest the involvement of reactive oxygen intermediates (O/sub 2//sup -/, OH) in the mechanism of Cu lethality, and also imply a function for peroxisomal Mn-SOD in the molecular mechanisms of plant tolerance to Cu in Pisum sativum L.

  8. PKCθ-Mediated PDK1 Phosphorylation Enhances T Cell Activation by Increasing PDK1 Stability

    PubMed Central

    Kang, Jung-Ah; Choi, Hyunwoo; Yang, Taewoo; Cho, Steve K.; Park, Zee-Yong; Park, Sung-Gyoo

    2017-01-01

    PDK1 is essential for T cell receptor (TCR)-mediated activation of NF-κB, and PDK1-induced phosphorylation of PKCθ is important for TCR-induced NF-κB activation. However, inverse regulation of PDK1 by PKCθ during T cell activation has not been investigated. In this study, we found that PKCθ is involved in human PDK1 phosphorylation and that its kinase activity is crucial for human PDK1 phosphorylation. Mass spectrometry analysis of wild-type PKCθ or of kinase-inactive form of PKCθ revealed that PKCθ induced phosphorylation of human PDK1 at Ser-64. This PKCθ-induced PDK1 phosphorylation positively regulated T cell activation and TCR-induced NF-κB activation. Moreover, phosphorylation of human PDK1 at Ser-64 increased the stability of human PDK1 protein. These results suggest that Ser-64 is an important phosphorylation site that is part of a positive feedback loop for human PDK1-PKCθ-mediated T cell activation. PMID:28152304

  9. Endothelial STAT3 Activation Increases Vascular Leakage Through Downregulating Tight Junction Proteins: Implications for Diabetic Retinopathy.

    PubMed

    Yun, Jang-Hyuk; Park, Sung Wook; Kim, Kyung-Jin; Bae, Jong-Sup; Lee, Eun Hui; Paek, Sun Ha; Kim, Seung U; Ye, Sangkyu; Kim, Jeong-Hun; Cho, Chung-Hyun

    2017-05-01

    Vascular inflammation is characteristic feature of diabetic retinopathy. In diabetic retina, a variety of the pro-inflammatory cytokines are elevated and involved in endothelial dysfunction. STAT3 transcription factor has been implicated in mediating cytokine signaling during vascular inflammation. However, whether and how STAT3 is involved in the direct regulation of the endothelial permeability is currently undefined. Our studies revealed that IL-6-induced STAT3 activation increases retinal endothelial permeability and vascular leakage in retinas of mice through the reduced expression of the tight junction proteins ZO-1 and occludin. In a co-culture model with microglia and endothelial cells under a high glucose condition, the microglia-derived IL-6 induced STAT3 activation in the retinal endothelial cells, leading to increasing endothelial permeability. In addition, IL-6-induced STAT3 activation was independent of ROS generation in the retinal endothelial cells. Moreover, we demonstrated that STAT3 activation downregulates the ZO-1 and occludin levels and increases the endothelial permeability through the induction of VEGF production in retinal endothelial cells. These results suggest the potential importance of IL-6/STAT3 signaling in regulating endothelial permeability and provide a therapeutic target to prevent the pathology of diabetic retinopathy. J. Cell. Physiol. 232: 1123-1134, 2017. © 2016 Wiley Periodicals, Inc.

  10. Amplification of the groESL operon in Pseudomonas putida increases siderophore gene promoter activity.

    PubMed

    Venturi, V; Wolfs, K; Leong, J; Weisbeek, P J

    1994-10-17

    Pseudobactin 358 is the yellow-green fluorescent siderophore [microbial iron(III) transport agent] produced by Pseudomonas putida WCS358 under iron-limiting conditions. The genes encoding pseudobactin 358 biosynthesis are iron-regulated at the level of transcription. In this study, the molecular characterization is reported of a cosmid clone of WCS358 DNA that can stimulate, in an iron-dependent manner, the activity of a WCS358 siderophore gene promoter in the heterologous Pseudomonas strain A225. The functional region in the clone was identified by subcloning, transposon mutagenesis and DNA sequencing as the groESL operon of strain WCS358. This increase in promoter activity was not observed when the groESL genes of strain WCS358 were integrated via a transposon vector into the genome of Pseudomonas A225, indicating that multiple copies of the operon are necessary for the increase in siderophore gene promoter activity. Amplification of the Escherichia coli and WCS358 groESL genes also increased iron-regulated promoter activity in the parent strain WCS358. The groESL operon codes for the chaperone proteins GroES and GroEL, which are responsible for mediating the folding and assembly of many proteins.

  11. Prenatal Iron Deficiency in Guinea Pigs Increases Locomotor Activity but Does Not Influence Learning and Memory

    PubMed Central

    Fiset, Catherine; Rioux, France M.; Surette, Marc E.; Fiset, Sylvain

    2015-01-01

    The objective of the current study was to determine whether prenatal iron deficiency induced during gestation in guinea pigs affected locomotor activity and learning and memory processes in the progeny. Dams were fed either iron-deficient anemic or iron-sufficient diets throughout gestation and lactation. After weaning, all pups were fed an iron-sufficient diet. On postnatal day 24 and 40, the pups’ locomotor activity was observed within an open-field test, and from postnatal day 25 to 40, their learning and memory processes were assessed within a Morris Water Maze. The behavioural and cognitive tests revealed that the iron deficient pup group had increased locomotor activity, but solely on postnatal day 40, and that there were no group differences in the Morris Water Maze. In the general discussion, we propose that prenatal iron deficiency induces an increase in nervousness due to anxiety in the progeny, which, in the current study, resulted in an increase of locomotor activity. PMID:26186713

  12. Mechanism of allopurinol-mediated increase in enzyme activity in man

    PubMed Central

    Beardmore, Thomas D.; Cashman, Jay S.; Kelley, William N.

    1972-01-01

    Allopurinol therapy in man interferes with pyrimidine biosynthesis de novo by inhibition of one or both of the two enzymes, orotate phosphoribosyltransferase (OPRT) and orotidylic decarboxylase (ODC), responsible for the conversion of orotic acid to uridine-5′-monophosphate. Inhibition of this pathway in vivo is followed in 1-3 wk by an increase in the activity of both of these enzymes in erythrocytes and of ODC in circulating leukocytes. This drug-mediated increase in enzyme activity in erythrocytes could not be attributed to enzyme stabilization or induction in vivo but appeared to be due to enzyme “activation.” “Activation” of the OPRT enzyme was directly demonstrated in erythrocytes studied in vitro after incubation with oxipurinol, and to a lesser extent, with allopurinol. No evidence for “activation” of the ODC enzyme was demonstrated in vitro. This response to allopurinol therapy provides an excellent model for examining the mechanism of increased enzyme activity in response to drug administration. PMID:5032526

  13. Prolonged daily light exposure increases body fat mass through attenuation of brown adipose tissue activity.

    PubMed

    Kooijman, Sander; van den Berg, Rosa; Ramkisoensing, Ashna; Boon, Mariëtte R; Kuipers, Eline N; Loef, Marieke; Zonneveld, Tom C M; Lucassen, Eliane A; Sips, Hetty C M; Chatzispyrou, Iliana A; Houtkooper, Riekelt H; Meijer, Johanna H; Coomans, Claudia P; Biermasz, Nienke R; Rensen, Patrick C N

    2015-05-26

    Disruption of circadian rhythmicity is associated with obesity and related disorders, including type 2 diabetes and cardiovascular disease. Specifically, prolonged artificial light exposure associates with obesity in humans, although the underlying mechanism is unclear. Here, we report that increasing the daily hours of light exposure increases body adiposity through attenuation of brown adipose tissue (BAT) activity, a major contributor of energy expenditure. Mice exposed to a prolonged day length of 16- and 24-h light, compared with regular 12-h light, showed increased adiposity without affecting food intake or locomotor activity. Mechanistically, we demonstrated that prolonged day length decreases sympathetic input into BAT and reduces β3-adrenergic intracellular signaling. Concomitantly, prolonging day length decreased the uptake of fatty acids from triglyceride-rich lipoproteins, as well as of glucose from plasma selectively by BAT. We conclude that impaired BAT activity is an important mediator in the association between disturbed circadian rhythm and adiposity, and anticipate that activation of BAT may overcome the adverse metabolic consequences of disturbed circadian rhythmicity.

  14. Prolonged daily light exposure increases body fat mass through attenuation of brown adipose tissue activity

    PubMed Central

    Kooijman, Sander; van den Berg, Rosa; Ramkisoensing, Ashna; Boon, Mariëtte R.; Kuipers, Eline N.; Loef, Marieke; Zonneveld, Tom C. M.; Lucassen, Eliane A.; Sips, Hetty C. M.; Chatzispyrou, Iliana A.; Houtkooper, Riekelt H.; Meijer, Johanna H.; Coomans, Claudia P.; Biermasz, Nienke R.; Rensen, Patrick C. N.

    2015-01-01

    Disruption of circadian rhythmicity is associated with obesity and related disorders, including type 2 diabetes and cardiovascular disease. Specifically, prolonged artificial light exposure associates with obesity in humans, although the underlying mechanism is unclear. Here, we report that increasing the daily hours of light exposure increases body adiposity through attenuation of brown adipose tissue (BAT) activity, a major contributor of energy expenditure. Mice exposed to a prolonged day length of 16- and 24-h light, compared with regular 12-h light, showed increased adiposity without affecting food intake or locomotor activity. Mechanistically, we demonstrated that prolonged day length decreases sympathetic input into BAT and reduces β3-adrenergic intracellular signaling. Concomitantly, prolonging day length decreased the uptake of fatty acids from triglyceride-rich lipoproteins, as well as of glucose from plasma selectively by BAT. We conclude that impaired BAT activity is an important mediator in the association between disturbed circadian rhythm and adiposity, and anticipate that activation of BAT may overcome the adverse metabolic consequences of disturbed circadian rhythmicity. PMID:25964318

  15. A physiological increase in insulin suppresses gluconeogenic gene activation in fetal sheep with sustained hypoglycemia.

    PubMed

    Thorn, Stephanie R; Sekar, Satya M; Lavezzi, Jinny R; O'Meara, Meghan C; Brown, Laura D; Hay, William W; Rozance, Paul J

    2012-10-15

    Reduced maternal glucose supply to the fetus and resulting fetal hypoglycemia and hypoinsulinemia activate fetal glucose production as a means to maintain cellular glucose uptake. However, this early activation of fetal glucose production may be accompanied by hepatic insulin resistance. We tested the capacity of a physiological increase in insulin to suppress fetal hepatic gluconeogenic gene activation following sustained hypoglycemia to determine whether hepatic insulin sensitivity is maintained. Control fetuses (CON), hypoglycemic fetuses induced by maternal insulin infusion for 8 wk (HG), and 8 wk HG fetuses that received an isoglycemic insulin infusion for the final 7 days (HG+INS) were studied. Glucose and insulin concentrations were 60% lower in HG compared with CON fetuses. Insulin was 50% higher in HG+INS compared with CON and four-fold higher compared with HG fetuses. Expression of the hepatic gluconeogenic genes, PCK1, G6PC, FBP1, GLUT2, and PGC1A was increased in the HG and reduced in the HG+INS liver. Expression of the insulin-regulated glycolytic and lipogenic genes, PFKL and FAS, was increased in the HG+INS liver. Total FOXO1 protein expression, a gluconeogenic activator, was 60% higher in the HG liver. Despite low glucose, insulin, and IGF1 concentrations, phosphorylation of AKT and ERK was higher in the HG liver. Thus, a physiological increase in fetal insulin is sufficient for suppression of gluconeogenic genes and activation of glycolytic and lipogenic genes in the HG fetal liver. These results demonstrate that fetuses exposed to sustained hypoglycemia have maintained hepatic insulin action in contrast to fetuses exposed to placental insufficiency.

  16. Increasing Level of Leisure Physical Activity Could Reduce the Risk of Hip Fracture in Older Women

    PubMed Central

    Rong, Ke; Liu, Xiao-yu; Wu, Xu-hua; Li, Xiao-liu; Xia, Qing-quan; Chen, Jiong; Yin, Xiao-fan

    2016-01-01

    Abstract We carried out the study to investigate and quantitatively assess the potential association between current level of physical activity and the risk of osteoporosis hip fracture in older women. Relevant publications before October 2015 were identified using the PubMed and Ovid searching tools. A dose–response meta-analysis was carried out to combine and analysis results. Fourteen prospective studies were included in the meta-analysis. A general analysis of 9 studies showed a significant inverse relationship between increasing level of physical activity and risk of hip fracture in older women [relative risk (RR) = 0.93, 95% confidence interval (95% CI): 0.91–0.96]. The result of a sensitivity analysis was consistent with the general analysis (RR = 0.94, 95% CI: 0.93–0.96). The association between increasing level of physical activity and risk of wrist fracture was not statistically significant in a general analysis of three studies (RR = 1.004, 95% CI: 0.98–1.03). A potential direct association between increasing level of physical activity and risk of wrist fracture was observed after removing 1 study with the greatest weight (RR = 1.01, 95% CI: 1.00–1.03). No significant publication bias was observed in our analysis. Our results show that increasing level of physical activity within an appropriate range may reduce the risk of hip fracture but not the risk of wrist fracture in older women. PMID:26986111

  17. Tear fluid hyperosmolality increases nerve impulse activity of cold thermoreceptor endings of the cornea.

    PubMed

    Parra, Andres; Gonzalez-Gonzalez, Omar; Gallar, Juana; Belmonte, Carlos

    2014-08-01

    Dry eye disease (DED) is a multifactorial disorder affecting the composition and volume of tears. DED causes ocular surface dryness, cooling, and hyperosmolality, leading ultimately to corneal epithelium damage and reduced visual performance. Ocular discomfort is the main clinical symptom in DED. However, the peripheral neural source of such unpleasant sensations is still unclear. We analyzed in excised, superfused mouse eyes, the effect of NaCl-induced hyperosmolality (325-1005 mOsm·kg(-1)) on corneal cold thermoreceptor and polymodal nociceptor nerve terminal impulse (NTI) activity. Osmolality elevations at basal corneal temperature (33.6°C) linearly increased the ongoing NTI frequency of cold thermoreceptors, at a mean rate of 0.34 imp·s(-1)/10 mOsm. This frequency increase became significant with osmolality values greater than 340 mOsm. Comparison of cold thermoreceptor activity increase induced by a dynamic temperature reduction of 1.8°C under iso- and hyperosmolal (360-mOsm) conditions provided evidence that more than 50% of the increased firing response was attributable to hyperosmolality. Comparatively, activation of corneal polymodal nociceptor endings by hyperosmolal solutions started with values of 600 mOsm and greater. Sensitization of polymodal nociceptors by continuous perfusion with an "inflammatory soup" (bradykinin, histamine, prostaglandin E2 [PGE2], serotonin, and adenosine triphosphate [ATP]) did not enhance their activation by hyperosmolal solutions. High osmolality also altered the firing pattern and shape of cold and polymodal NTIs, possibly reflecting disturbances in local membrane currents. Results strongly suggest that tear osmolality elevations in the range observed in DED predominantly excite cold thermoreceptors, supporting the hypothesis that dryness sensations experienced by these patients are due, at least in part, to an augmented activity of corneal cold thermoreceptors.

  18. Acute and chronic caffeine administration increases physical activity in sedentary adults.

    PubMed

    Schrader, Patrick; Panek, Leah M; Temple, Jennifer L

    2013-06-01

    Caffeine is a commonly used stimulant thought to have ergogenic properties. Most studies on the ergogenic effects of caffeine have been conducted in athletes. The purpose of this study was to test the hypothesis that caffeine reduces ratings of perceived exertion and increases liking of physical activity in sedentary adults. Participants completed treadmill walking at 60% to 70% of their maximal heart rate at baseline and for 6 subsequent visits, during which half of the participants were given caffeine (3 mg/kg) and half given placebo in a sports drink vehicle. To investigate the potential synergistic effects of acute and chronic caffeine on self-determined exercise duration, participants were rerandomized to either the same or different condition for the last visit, creating 4 chronic/acute treatment groups (placebo/placebo, placebo/caffeine, caffeine/placebo, caffeine/caffeine). Participants rated how much they liked the activity and perceived exertion at each visit. There was a main effect of time on liking of physical activity, with liking increasing over time and an interaction of sex and caffeine treatment on liking, with liking of activity increasing in female participants treated with caffeine, but not with placebo. There was no effect of caffeine on ratings of perceived exertion. Individuals who received caffeine on the final test day exercised for significantly longer than those who received placebo. These data suggest that repeated exposure to physical activity significantly increases liking of exercise and reduces ratings of perceived exertion and that caffeine does little to further modify these effects.

  19. Magnesium ions increase the activity of Bacillus deramificans pullulanase expressed by Brevibacillus choshinensis.

    PubMed

    Zou, Chun; Duan, Xuguo; Wu, Jing

    2016-08-01

    Addition of MgCl2 to the culture medium has been found to dramatically increase the activity of Bacillus deramificans pullulanase expressed by Brevibacillus choshinensis. The specific activity of the pullulanase obtained from medium supplemented with MgCl2 was also higher than that obtained in culture medium without added magnesium ions. In this work, the mechanism of this increase was studied. When cultured in medium without added magnesium ions, B. choshinensis mainly produced a thermolabile, inactive form of pullulanase. The addition of magnesium ions led to the production of a thermostable, active form of pullulanase. Circular dichroism assays revealed considerable differences in secondary structure between the active and inactive pullulanase forms. Transmission electron microscopy suggested that magnesium ion addition inhibits the shedding of cell wall protein (HWP) layers from the cell surface. Quantitative real-time PCR showed that magnesium ion addition represses transcription of HWP. Because the pullulanase gene and HWP have identical promoters, pullulanase gene transcription was also inhibited. These results suggest that when pullulanase is expressed slowly, it tends to fold into an active form.

  20. Does increased physical activity in school affect children's executive function and aerobic fitness?

    PubMed

    Kvalø, S E; Bru, E; Brønnick, K; Dyrstad, S M

    2017-02-16

    This study seeks to explore whether increased PA in school affects children's executive function and aerobic fitness. The "Active school" study was a 10-month randomized controlled trial. The sample included 449 children (10-11 years old) in five intervention and four control schools. The weekly interventions were 2×45 minutes physically active academic lessons, 5×10 minutes physically active breaks, and 5×10 minutes physically active homework. Aerobic fitness was measured using a 10-minute interval running test. Executive function was tested using four cognitive tests (Stroop, verbal fluency, digit span, and Trail Making). A composite score for executive function was computed and used in analyses. Mixed ANCOVA repeated measures were performed to analyze changes in scores for aerobic fitness and executive function. Analysis showed a tendency for a time×group interaction on executive function, but the results were non-significant F(1, 344)=3.64, P=.057. There was no significant time×group interaction for aerobic fitness. Results indicate that increased physical activity in school might improve children's executive function, even without improvement in aerobic fitness, but a longer intervention period may be required to find significant effects.

  1. The effectiveness of interventions to increase physical activity. A systematic review.

    PubMed

    Kahn, Emily B; Ramsey, Leigh T; Brownson, Ross C; Heath, Gregory W; Howze, Elizabeth H; Powell, Kenneth E; Stone, Elaine J; Rajab, Mummy W; Corso, Phaedra

    2002-05-01

    The Guide to Community Preventive Service's methods for systematic reviews were used to evaluate the effectiveness of various approaches to increasing physical activity: informational, behavioral and social, and environmental and policy approaches. Changes in physical activity behavior and aerobic capacity were used to assess effectiveness. Two informational interventions ("point-of-decision" prompts to encourage stair use and community-wide campaigns) were effective, as were three behavioral and social interventions (school-based physical education, social support in community settings, and individually-adapted health behavior change) and one environmental and policy intervention (creation of or enhanced access to places for physical activity combined with informational outreach activities). Additional information about applicability, other effects, and barriers to implementation are provided for these interventions. Evidence is insufficient to assess a number of interventions: classroom-based health education focused on information provision, and family-based social support (because of inconsistent findings); mass media campaigns and college-based health education and physical education (because of an insufficient number of studies); and classroom-based health education focused on reducing television viewing and video game playing (because of insufficient evidence of an increase in physical activity). These recommendations should serve the needs of researchers, planners, and other public health decision makers.

  2. High phosphorylase activity is correlated with increased potato minituber formation and starch content during extended clinorotation

    NASA Astrophysics Data System (ADS)

    Nedukha, O. M.; Schnyukova, E. I.; Leach, J. E.

    2003-05-01

    The major purpose of these experiments were to investigate growth of potato storage organs and starch synthesis in minitubers at slow horizontal clinorotation (2 rpm), which partly mimics microgravity, and a secondary goal was to study the activity and localization of phosphorylase (EC 2.4.1.1) in storage parenchyma under these conditions. Miniplants of Solanum tuberosum L. (cv Adreta) were grown in culture for 30 days for both the vertical control and the horizontal clinorotation. During long-term clinorotation, an acceleration of minituber formation, and an increase of amyloplast number and size in storage parenchyma cells, as well as increased starch content, was observed in the minitubers. The differences among cytochemical reaction intensity, activity of phosphorylase, and carbohydrate content in storage parenchyma cells of minitubers grown in a horizontal clinostat were established by electron-cytochemical and biochemical methods. It is shown that high phosphorylase activity is correlated with increased starch content during extended clinorotation. The results demonstrate the increase in carbohydrate metabolism and possible accelerated growth of storage organs under the influence of microgravity, as mimicked by clinorotation; therefore, clinorotation can be used as a basis for future studies on mechanisms of starch synthesis under microgravity.

  3. Calpain expression in lymphoid cells. Increased mRNA and protein levels after cell activation.

    PubMed

    Deshpande, R V; Goust, J M; Chakrabarti, A K; Barbosa, E; Hogan, E L; Banik, N L

    1995-02-10

    Although calpain is ubiquitously present in human tissues and is thought to play a role in demyelination, its activity is very low in resting normal lymphocytes. To determine the nature of calpain expression at the mRNA and protein levels in human lymphoid cells, we studied human T lymphocytic, B lymphocytic, and monocytic lines as well as peripheral blood mononuclear cells. Stimulation of cells with the phorbol ester phorbol myristate acetate and the calcium ionophore A23187 resulted in increased calpain mRNA and protein expression. Calpain mRNA expression is also increased in human T cells stimulated with anti-CD3. A dissociation between the increases of RNA and protein suggested that calpain could be released from the cells; the subsequent experiments showed its presence in the extracellular environment. 5,6-Dichloro-1b-D-ribofuranosylbenzimidazole, a reversible inhibitor of mRNA synthesis, reduced calpain mRNA levels by 50-67% and protein levels by 72-91%. Its removal resulted in resumption of both calpain mRNA and protein synthesis. Cycloheximide, a translational inhibitor, reduced calpain protein levels by 77-81% and calpain mRNA levels by 96% in activated THP-1 cells. Interferon-gamma induced calpain mRNA and protein in U-937 and THP-1 cells. Dexamethasone increased mRNA expression in THP-1 cells. Our results indicate that activation of lymphoid cells results in de novo synthesis and secretion of calpain.

  4. Activation of PI3Kγ/Akt pathway increases cardiomyocyte HMGB1 expression in diabetic environment

    PubMed Central

    Song, Jia; Liu, Qian; Tang, Han; Tao, Aibin; Wang, Hao; Kao, Raymond; Rui, Tao

    2016-01-01

    Background The high mobility group box 1 (HMGB1) protein mediates the cardiomyocyte–cardiac fibroblast interaction that contributes to induction of myocardial fibrosis in diabetes mellitus (DM). In the present study, we aim to investigate the intracellular signaling pathway that leads to cardiomyocyte HMGB1 expression under a diabetic environment. Results HMGB1 expression is increased in high concentration of glucose (HG)-conditioned cardiomyocytes. Challenging cardiomyocytes with HG also increased PI3Kγ and Akt phosphorylation. Inhibition of PI3Kγ (CRISPR/Cas9 knockout plasmid or AS605240) prevented HG-induced Akt phosphorylation and HMGB1 expression by the cardiomyocytes. In addition, inhibition of Akt (Akt1/2/3 siRNA or A6730) attenuated HG-induced HMGB1 production. Finally, challenging cardiomyocytes with HG resulted in increased reactive oxygen species (ROS) production. Treatment of cardiomyocytes with an antioxidant (Mitotempo) abolished HG-induced PI3Kγ and Akt activation, as well as HMGB1 production. Materials and Methods Isolated rat cardiomyocytes were cultured with a high concentration of glucose. Cardiomyocyte phosphatidylinositol 3-kinase gamma (PI3Kγ) and Akt activation were determined by Western blot. Cardiomyocyte HMGB1 production was evaluated with Western blot and enzyme-linked immunosorbent assay (ELISA), while cardiomyocyte oxidative stress was determined with a DCFDA fluorescence probe. Conclusions Our results suggest that the cardiomyocytes incur an oxidative stress under diabetic condition, which subsequently activates the PI3Kγ/Akt cell-signaling pathway and further increases HMGB1 expression. PMID:27821807

  5. Carnitine Palmitoyltransferase 1 Increases Lipolysis, UCP1 Protein Expression and Mitochondrial Activity in Brown Adipocytes

    PubMed Central

    Calderon-Dominguez, María; Sebastián, David; Fucho, Raquel; Weber, Minéia; Mir, Joan F.; García-Casarrubios, Ester; Obregón, María Jesús; Zorzano, Antonio; Valverde, Ángela M.; Serra, Dolors

    2016-01-01

    The discovery of active brown adipose tissue (BAT) in adult humans and the fact that it is reduced in obese and diabetic patients have put a spotlight on this tissue as a key player in obesity-induced metabolic disorders. BAT regulates energy expenditure through thermogenesis; therefore, harnessing its thermogenic fat-burning power is an attractive therapeutic approach. We aimed to enhance BAT thermogenesis by increasing its fatty acid oxidation (FAO) rate. Thus, we expressed carnitine palmitoyltransferase 1AM (CPT1AM), a permanently active mutant form of CPT1A (the rate-limiting enzyme in FAO), in a rat brown adipocyte (rBA) cell line through adenoviral infection. We found that CPT1AM-expressing rBA have increased FAO, lipolysis, UCP1 protein levels and mitochondrial activity. Additionally, enhanced FAO reduced the palmitate-induced increase in triglyceride content and the expression of obese and inflammatory markers. Thus, CPT1AM-expressing rBA had enhanced fat-burning capacity and improved lipid-induced derangements. This indicates that CPT1AM-mediated increase in brown adipocytes FAO may be a new approach to the treatment of obesity-induced disorders. PMID:27438137

  6. Process Evaluation of an Intervention to Increase Child Activity Levels in Afterschool Programs

    PubMed Central

    Weaver, R. Glenn; Saunders, Ruth; Webster, Collin; Beets, Michael W.

    2014-01-01

    Background Identifying effective strategies in Afterschool programs (ASPs) to increase children's moderate-to-vigorous physical activity (MVPA) in the ASP setting is crucial. This study describes the process evaluation outcomes from an intervention to reduce child sedentary time and increase MVPA in ASPs. Methods Four ASPs participated in a quasi-experimental single-group pre-post study targeting child sedentary time and MVPA. The strategies implemented to help ASPs meet Physical Activity Standards consisted of detailed schedules, professional development trainings, on-site booster sessions, and technical assistance. Process evaluation related to staff behaviors was collected via systematic observation to identify the interventions impact on the physical and social environment of the ASP. Random-effects regression models examined the impact of the intervention on boys/girls observed sedentary behavior, MVPA, and changes in staff behaviors. Results Increases in MVPA and reductions in sedentary behavior were observed during enrichment, academics, organized and free-play physical activities (PA). Corresponding changes in staff behaviors were observed during these ASP contexts. For example, staff reduced child idle-time during organized PA (38.9%-1.8%) and provided energizers more often during enrichment (0.2%-11.5%). Conclusions This study identified changes in staff behavior during ASP contexts that led to increases in child MVPA and decreases in child sedentary behavior. PMID:24836999

  7. Prolactin increases hepatic Na+/taurocholate co-transport activity and messenger RNA post partum.

    PubMed Central

    Ganguly, T C; Liu, Y; Hyde, J F; Hagenbuch, B; Meier, P J; Vore, M

    1994-01-01

    We have shown that Na+/taurocholate co-transport activity is decreased in pregnancy, but rebounds post partum relative to non-pregnant controls, and that activity can be increased by treatment with ovine prolactin [Ganguly, Hyde and Vore (1993) J. Pharmacol. Exp. Ther. 267, 82-87]. To determine the basis for these effects, Na+/taurocholate co-transport was determined in purified basolateral liver plasma-membrane (bLPM) vesicles and compared with steady-state mRNA levels encoding the Na+/taurocholate-co-transporting polypeptide (Ntcp) in non-pregnant controls, pregnant rats (19-20 days pregnant), rats post partum (48 h post partum) and rats post partum treated with bromocriptine to inhibit prolactin secretion. Na+/taurocholate co-transport activity (nmol/5 s per mg of protein) in bLPM was decreased from 10.4 +/- 1.8 in non-pregnant controls to 7.9 +/- 0.6 in bLPM in pregnant rats, but rebounded to 17.5 +/- 1.3 post partum; treatment of rats post partum with bromocriptine to inhibit prolactin secretion decreased activity to 14.1 +/- 0.9. Northern and slot-blot analyses revealed similar changes in mRNA for Ntcp, so that a positive correlation was observed between Na+/taurocholate co-transport activity and Ntcp mRNA. Furthermore, treatment of ovariectomized rats with ovine prolactin increased Ntcp mRNA 10-fold compared with solvent-treated controls, consistent with the 2-fold increase in Vmax, for Na+/taurocholate co-transport in isolated hepatocytes. These data are the first to demonstrate endogenous physiological regulation by prolactin of Ntcp mRNA in parallel with Na+/taurocholate co-transport activity. Images Figure 2 PMID:7945260

  8. INCREASE IN ACTIVATED PROTEIN C MEDIATES ACUTE TRAUMATIC COAGULOPATHY IN MICE

    PubMed Central

    Chesebro, Brian B.; Rahn, Pamela; Carles, Michel; Esmon, Charles T.; Xu, Jun; Brohi, Karim; Frith, Daniel; Pittet, Jean-François; Cohen, Mitchell J.

    2013-01-01

    In severely injured and hypoperfused trauma patients, endogenous acute coagulopathy (EAC) is associated with an increased morbidity and mortality. Recent human data correlate this coagulopathy with activation of the protein C pathway. To examine the mechanistic role of protein C in the development of EAC, we used a mouse model of trauma and hemorrhagic shock, characterized by the combination of tissue injury and severe metabolic acidosis. Mice were subjected to one of four treatment groups: 1) C, control; 2) T, trauma (laparotomy); 3) H, hemorrhage (MAP, 35 mmHg × 60 min); 4) TH, trauma + hemorrhage. After 60 min, blood was drawn for analysis. Compared with C mice, the TH mice had a significantly elevated activated partial thromboplastin time (23.3 vs. 34.5 s) and significantly increased levels of activated protein C (aPC; 2.30 vs. 13.58 ng/mL). In contrast, T and H mice did not develop an elevated activated partial thromboplastin time or increased aPC. Selective inhibition of the anticoagulant property of aPC prevented the coagulopathy seen in response to trauma/hemorrhage (23.5 vs. 38.6 s [inhibitory vs. control monoclonal antibody]) with no impact on survival during the shock period. However, complete blockade of both the anticoagulant and cytoprotective functions of aPC caused 100% mortality within 45 min of shock, with histopathology evidence of pulmonary thrombosis and perivascular hemorrhage. These results indicate that our unique mouse model of T/H shock mimics our previous observations in trauma patients and demonstrates that EAC is mediated by the activation of the protein C pathway. In addition, the cytoprotective effect of protein C activation seems to be necessary for survival of the initial shock injury. PMID:19333141

  9. Progesterone increases the activity of glutamate transporter type 3 expressed in Xenopus oocytes.

    PubMed

    Son, Ilsoon; Shin, Hyun-Jung; Ryu, Jung-Hee; Kim, Hae-Kyoung; Do, Sang-Hwan; Zuo, Zhiyi

    2013-09-05

    Progesterone is an important sex hormone for pregnancy and also has neuroprotective and anticonvulsant effects. It is well-known that full-term parturients become more susceptible to volatile anesthetics. Glutamate transporters are important for preventing neurotoxicity and anesthetic action in the central nervous system. We investigated the effects of progesterone on the activity of glutamate transporter type 3 (EAAT3), the major neuronal EAAT. EAAT3 was expressed in Xenopus laevis oocytes by injecting its mRNA. Oocytes were incubated with diluted progesterone for 72 h. Two-electrode voltage clamping was used to measure membrane currents before, during, and after applying 30 μML-glutamate. Progesterone (1-100 nM) significantly increased EAAT3 activity in a dose-dependent manner. Our kinetic study showed that the Vmax was increased in the progesterone group compared with that in the control group (2.7 ± 0.2 vs. 3.6 ± 0.2μC for control group vs. progesterone group; n=18-23; P<0.05), however, Km was unaltered (46.7 ± 10.2μM vs. 55.9 ± 10.5μM for control group vs. progesterone group; n=18-23; P>0.05). Phorbol-12-myristate-13-acetate, a protein kinase C (PKC) activator, did not change progesterone-enhanced EAAT3 activity. Inhibitors of PKC or phosphatidylinositol 3-kinase (PI3K) abolished the progesterone-induced increases in EAAT3 activity. Our results suggest that progesterone enhances EAAT3 activity and that PKC and PI3K are involved in mediating these effects. These effects of progesterone may contribute to its anticonvulsant and anesthesia-related properties.

  10. Transient increase in phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol trisphosphate during activation of human neutrophils

    SciTech Connect

    Traynor-Kaplan, A.E.; Thompson, B.L.; Harris, A.L.; Taylor, P.; Omann, G.M.; Sklar, L.A. )

    1989-09-15

    We recently showed that phosphatidylinositol trisphosphate (PIP3) was present in a unique lipid fraction generated in neutrophils during activation. Here, we demonstrate that the band containing this fraction isolated from thin layer chromatography consists primarily of PIP3 and that only small amounts of radiolabeled PIP3 exist prior to activation. In addition, high performance liquid chromatography of deacylated phospholipids from stimulated cells reveals an increase in a fraction eluting ahead of glycerophosphoinositol 4,5-P2. After removal of the glycerol we found that it coeluted with inositol 1,3,4-P3 when resubjected to high performance liquid chromatography. Thus, we have detected a second, novel form of phosphatidylinositol bisphosphate in activated neutrophils, PI-(3,4)P2. The elevation of PIP3 through the formyl peptide receptor is blocked by pretreatment with pertussis toxin, implicating mediation of the increase in PIP3 by a guanosine triphosphate-binding (G) protein. The rise in PIP3 is not secondary to calcium elevation. Buffering the rise in intracellular calcium did not diminish the increase in PIP3. The elevation of PIP3 appears to occur during activation with physiological agonists, its level varying with the degree of activation. Leukotriene B4, which elicits many of the same responses as stimulation of the formyl peptide receptor but with minimal oxidant production, stimulates a much attenuated rise in PIP3. Isoproterenol, which inhibits oxidant production also reduces the rise in PIP3. Hence formation of PI(3,4)P2 and PIP3 (presumed to be PI(3,4,5)P3) correlates closely with the early events of neutrophil activation.

  11. Increased calcium/calmodulin-dependent protein kinase II activity by morphine-sensitization in rat hippocampus.

    PubMed

    Kadivar, Mehdi; Farahmandfar, Maryam; Ranjbar, Faezeh Esmaeli; Zarrindast, Mohammad-Reza

    2014-07-01

    Repeated exposure to drugs of abuse, such as morphine, elicits a progressive enhancement of drug-induced behavioral responses, a phenomenon termed behavioral sensitization. These changes in behavior may reflect long-lasting changes in some of the important molecules involved in memory processing such as calcium/calmodulin-dependent protein kinase II (CaMKII). In the present study, we investigated the effect of morphine sensitization on mRNA expression of α and β isoforms and activity of CaMKII in the hippocampus of male rats. Animals were treated for 3 days with saline or morphine (20mg/kg) and following a washout period of 5 days, a challenge dose of morphine (5mg/kg) were administered. The results indicate that morphine administration in pre-treated animals produces behavioral sensitization, as determined by significant increase in locomotion and oral stereotypy behavior. In addition, repeated morphine treatment increased mRNA expression of both α and β isoforms of CaMKII in the hippocampus. The present study also showed that induction of morphine sensitization significantly increased both Ca2+/calmodulin-independent and Ca2+/calmodulin-dependent activities of CaMK II in the rat hippocampus. However, acute administration of morphine (5mg/kg) did not alter either α and β CaMKII mRNA expression or CaMKII activity in the hippocampus. The stimulation effects of morphine sensitization on mRNA expression and activity of CaMKII were completely abolished by administration of naloxone, 30min prior to s.c. injections of morphine (20mg/kg/day×3 days). Our data demonstrated that induction of morphine sensitization could effectively modulate the activity and the mRNA expression of CaMKII in the hippocampus and this effect of morphine was exerted by the activation of opioid receptors.

  12. Postnatal Chick Choroids Exhibit Increased Retinaldehyde Dehydrogenase Activity During Recovery From Form Deprivation Induced Myopia

    PubMed Central

    Harper, Angelica R.; Wang, Xiang; Moiseyev, Gennadiy; Ma, Jian-Xing; Summers, Jody A.

    2016-01-01

    Purpose Increases in retinaldehyde dehydrogenase 2 (RALDH2) transcript in the chick choroid suggest that RALDH2 may be responsible for increases observed in all-trans-retinoic acid (atRA) synthesis during recovery from myopic defocus. The purpose of the present study was to examine RALDH2 protein expression, RALDH activity, and distribution of RALDH2 cells in control and recovering chick ocular tissues. Methods Myopia was induced in White Leghorn chicks for 10 days, followed by up to 15 days of unrestricted vision (recovery). Expression of RALDH isoforms in chick ocular tissues was evaluated by Western blot. Catalytic activity of RALDH was measured in choroidal cytosol fractions using an in vitro atRA synthesis assay together with HPLC quantification of synthesized atRA. Distribution of RALDH2 cells throughout the choroid was evaluated by immunohistochemistry. Results RALDH2 was expressed predominately in the chick choroid (P < 0.001) and increased after 24 hours and 4 days of recovery (76%, 74%, and 165%, respectively; P < 0.05). Activity of RALDH was detected solely in the choroid and was elevated at 3 and 7 days of recovery compared to controls (70% and 48%, respectively; P < 0.05). The number of RALDH2 immunopositive cells in recovering choroids was increased at 24 hours and 4 to 15 days of recovery (P < 0.05) and were concentrated toward the RPE side compared to controls. Conclusions The results of this study suggest that RALDH2 is the major RALDH isoform in the chick choroid and is responsible for the increased RALDH activity seen during recovery. PMID:27654415

  13. Acrolein activates matrix metalloproteinases by increasing reactive oxygen species in macrophages

    SciTech Connect

    O'Toole, Timothy E. Zheng Yuting; Hellmann, Jason; Conklin, Daniel J.; Barski, Oleg; Bhatnagar, Aruni

    2009-04-15

    Acrolein is a ubiquitous component of environmental pollutants such as automobile exhaust, cigarette, wood, and coal smoke. It is also a natural constituent of several foods and is generated endogenously during inflammation or oxidation of unsaturated lipids. Because increased inflammation and episodic exposure to acrolein-rich pollutants such as traffic emissions or cigarette smoke have been linked to acute myocardial infarction, we examined the effects of acrolein on matrix metalloproteinases (MMPs), which destabilize atherosclerotic plaques. Our studies show that exposure to acrolein resulted in the secretion of MMP-9 from differentiated THP-1 macrophages. Acrolein-treatment of macrophages also led to an increase in reactive oxygen species (ROS), free intracellular calcium ([Ca{sup 2+}]{sub i}), and xanthine oxidase (XO) activity. ROS production was prevented by allopurinol, but not by rotenone or apocynin and by buffering changes in [Ca{sup 2+}]{sub I} with BAPTA-AM. The increase in MMP production was abolished by pre-treatment with the antioxidants Tiron and N-acetyl cysteine (NAC) or with the xanthine oxidase inhibitors allopurinol or oxypurinol. Finally, MMP activity was significantly stimulated in aortic sections from apoE-null mice containing advanced atherosclerotic lesions after exposure to acrolein ex vivo. These observations suggest that acrolein exposure results in MMP secretion from macrophages via a mechanism that involves an increase in [Ca{sup 2+}]{sub I}, leading to xanthine oxidase activation and an increase in ROS production. ROS-dependent activation of MMPs by acrolein could destabilize atherosclerotic lesions during brief episodes of inflammation or pollutant exposure.

  14. Relaxin increases sympathetic nerve activity and activates spinally projecting neurons in the paraventricular nucleus of nonpregnant, but not pregnant, rats

    PubMed Central

    Coldren, K. Max; Brown, Randall; Hasser, Eileen M.

    2015-01-01

    Pregnancy is characterized by increased blood volume and baseline sympathetic nerve activity (SNA), vasodilation, and tachycardia. Relaxin (RLX), an ovarian hormone elevated in pregnancy, activates forebrain sites involved in control of blood volume and SNA through ANG II-dependent mechanisms and contributes to adaptations during pregnancy. In anesthetized, arterial baroreceptor-denervated nonpregnant (NP) rats, RLX microinjected into the subfornical organ (SFO; 0.77 pmol in 50 nl) produced sustained increases in lumbar SNA (8 ± 3%) and mean arterial pressure (MAP; 26 ± 4 mmHg). Low-dose intracarotid artery infusion of RLX (155 pmol·ml−1·h−1; 1.5 h) had minor transient effects on AP and activated neurons [increased Fos-immunoreactivity (IR)] in the SFO and in spinally projecting (19 ± 2%) and arginine-vasopressin (AVP)-IR (21 ± 5%) cells in the paraventricular nucleus of the hypothalamus of NP, but not pregnant (P), rats. However, mRNA for RLX and ANG II type 1a receptors in the SFO was preserved in pregnancy. RLX receptor-IR is present in the region of the SFO in NP and P rats and is localized in astrocytes, the major source of angiotensinogen in the SFO. These data provide an anatomical substrate for a role of RLX in the resetting of AVP secretion and increased baseline SNA in pregnancy. Since RLX and ANG II receptor expression was preserved in the SFO of P rats, we speculate that the lack of response to exogenous RLX may be due to maximal activation by elevated endogenous levels of RLX in near-term pregnancy. PMID:26400184

  15. EGFR Activation Increases Parathyroid Hyperplasia and Calcitriol Resistance in Kidney Disease

    PubMed Central

    Arcidiacono, Maria Vittoria; Sato, Tetsuhiko; Alvarez-Hernandez, Daniel; Yang, Jing; Tokumoto, Masanori; Gonzalez-Suarez, Ignacio; Lu, Yan; Tominaga, Yoshihiro; Cannata-Andia, Jorge; Slatopolsky, Eduardo; Dusso, Adriana S.

    2008-01-01

    Calcitriol, acting through vitamin D receptors (VDR) in the parathyroid, suppresses parathyroid hormone synthesis and cell proliferation. In secondary hyperparathyroidism (SH), VDR content is reduced as hyperplasia becomes more severe, limiting the efficacy of calcitriol. In a rat model of SH, activation of the EGF receptor (EGFR) by TGF-α is required for the development of parathyroid hyperplasia, but the relationship between EGFR activation and reduced VDR content is unknown. With the use of the same rat model, it was found that pharmacologic inhibition of EGFR activation with erlotinib prevented the upregulation of parathyroid TGF-α, the progression of growth, and the reduction of VDR. Increased TGF-α/EGFR activation induced the synthesis of liver-enriched inhibitory protein, a potent mitogen and the dominant negative isoform of the transcription factor CCAAT enhancer binding protein-β, in human hyperplastic parathyroid glands and in the human epidermoid carcinoma cell line A431, which mimics hyperplastic parathyroid cells. Increases in liver-enriched inhibitory protein directly correlated with proliferating activity and, in A431 cells, reduced VDR expression by antagonizing CCAAT enhancer binding protein-β transactivation of the VDR gene. Similarly, in nodular hyperplasia, which is the most severe form of SH and the most resistant to calcitriol therapy, higher TGF-α activation of the EGFR was associated with an 80% reduction in VDR mRNA levels. Thus, in SH, EGFR activation is the cause of both hyperplastic growth and VDR reduction and therefore influences the efficacy of therapy with calcitriol. PMID:18216322

  16. Meta-analysis of internet-delivered interventions to increase physical activity levels

    PubMed Central

    2012-01-01

    Many internet-delivered physical activity behaviour change programs have been developed and evaluated. However, further evidence is required to ascertain the overall effectiveness of such interventions. The objective of the present review was to evaluate the effectiveness of internet-delivered interventions to increase physical activity, whilst also examining the effect of intervention moderators. A systematic search strategy identified relevant studies published in the English-language from Pubmed, Proquest, Scopus, PsychINFO, CINHAL, and Sport Discuss (January 1990 – June 2011). Eligible studies were required to include an internet-delivered intervention, target an adult population, measure and target physical activity as an outcome variable, and include a comparison group that did not receive internet-delivered materials. Studies were coded independently by two investigators. Overall effect sizes were combined based on the fixed effect model. Homogeneity and subsequent exploratory moderator analysis was undertaken. A total of 34 articles were identified for inclusion. The overall mean effect of internet-delivered interventions on physical activity was d = 0.14 (p = 0.00). Fixed-effect analysis revealed significant heterogeneity across studies (Q = 73.75; p = 0.00). Moderating variables such as larger sample size, screening for baseline physical activity levels and the inclusion of educational components significantly increased intervention effectiveness. Results of the meta-analysis support the delivery of internet-delivered interventions in producing positive changes in physical activity, however effect sizes were small. The ability of internet-delivered interventions to produce meaningful change in long-term physical activity remains unclear. PMID:22546283

  17. CMKLR1 activation ex vivo does not increase proportionally to serum total chemerin in obese humans

    PubMed Central

    Toulany, Jay; Parlee, Sebastian D; Sinal, Christopher J; Slayter, Kathryn; McNeil, Shelly

    2016-01-01

    Prochemerin is the inactive precursor of the adipokine chemerin. Proteolytic processing is obligatory for the conversion of prochemerin into active chemerin and subsequent regulation of cellular processes via the chemokine-like receptor 1 (CMKLR1). Elevated plasma or serum chemerin concentrations and differential processing of prochemerin have been reported in obese humans. The impact of these changes on CMKLR1 signalling in humans is unknown. The objective of this pilot study was to develop a cellular bioassay to measure CMKLR1 activation by chemerin present in human serum and to characterise how obesity modifies serum activation of CMKLR1 under fasted and fed conditions. Blood samples were collected from control (N = 4, BMI 20–25) and obese (N = 4, BMI >30) female subjects after an overnight fast (n = 2) and at regular intervals (n = 7) following consumption of breakfast over a period of 6 h. A cellular CMKLR1-luminescent reporter assay and a pan-chemerin ELISA were used to determine CMKLR1 activation and total chemerin concentrations, respectively. Serum total chemerin concentration (averaged across all samples) was higher in obese vs control subjects (17.9 ± 1.8 vs 10.9 ± 0.5 nM, P < 0.05), but serum activation of CMKLR1 was similar in both groups. The CMKLR1 activation/total chemerin ratio was lower in obese vs control subjects (0.33 ± 0.04 vs 0.58 ± 0.05, P < 0.05). After breakfast, serum total chemerin or CMKLR1 activation did not differ from baseline values. In conclusion, the unexpected observation that obese serum activation of CMKLR1 did not match increased total chemerin concentrations suggests impaired processing to and/or enhanced degradation of active chemerin in serum of obese humans. PMID:27881447

  18. Serotonin activates catecholamine neurons in the solitary tract nucleus by increasing spontaneous glutamate inputs.

    PubMed

    Cui, Ran Ji; Roberts, Brandon L; Zhao, Huan; Zhu, Mingyan; Appleyard, Suzanne M

    2012-11-14

    Serotonin (5-HT) is a critical neurotransmitter in the control of autonomic functions. 5-HT(3) receptors participate in vagal afferent feedback to decrease food intake and regulate cardiovascular reflexes; however, the phenotype of the solitary tract nucleus (NTS) neurons involved is not known. A(2)/C(2) catecholamine (CA) neurons in the NTS are directly activated by visceral afferents and are important for the control of food intake and cardiovascular function, making them good candidates to respond to and mediate the effects of serotonin at the level of the NTS. This study examines serotonin's effects on NTS-CA neurons using patch-clamp techniques and transgenic mice expressing an enhanced green fluorescent protein driven by the tyrosine hydroxylase (TH) promoter (TH-EGFP) to identify catecholamine neurons. Serotonin increased the frequency of spontaneous glutamate excitatory postsynaptic currents (sEPSCs) in >90% of NTS-TH-EGFP neurons, an effect blocked by the 5-HT(3) receptor antagonist ondansetron and mimicked by the 5-HT(3) receptor agonists SR5227 and mCPBG. In contrast, 5-HT(3) receptor agonists increased sEPSCs on a minority (<30%) of non-TH neurons. 5-HT(3) receptor agonists increased the frequency, but not the amplitude, of mini-EPSCs, suggesting that their actions are presynaptic. 5-HT(3) receptor agonists increased the firing rate of TH-EGFP neurons, an effect dependent on the increased spontaneous glutamate inputs as it was blocked by the ionotropic glutamate antagonist NBQX, but independent of visceral afferent activation. These results demonstrate a cellular mechanism by which serotonin activates NTS-TH neurons and suggest a pathway by which it can increase catecholamine release in target regions to modulate food intake, motivation, stress, and cardiovascular function.

  19. Serotonin Activates Catecholamine Neurons in the Solitary Tract Nucleus by Increasing Spontaneous Glutamate Inputs

    PubMed Central

    Cui, Ran Ji; Roberts, Brandon L.; Zhao, Huan; Zhu, Mingyan

    2012-01-01

    Serotonin (5-HT) is a critical neurotransmitter in the control of autonomic functions. 5-HT3 receptors participate in vagal afferent feedback to decrease food intake and regulate cardiovascular reflexes; however, the phenotype of the solitary tract nucleus (NTS) neurons involved is not known. A2/C2 catecholamine (CA) neurons in the NTS are directly activated by visceral afferents and are important for the control of food intake and cardiovascular function, making them good candidates to respond to and mediate the effects of serotonin at the level of the NTS. This study examines serotonin's effects on NTS-CA neurons using patch-clamp techniques and transgenic mice expressing an enhanced green fluorescent protein driven by the tyrosine hydroxylase (TH) promoter (TH-EGFP) to identify catecholamine neurons. Serotonin increased the frequency of spontaneous glutamate excitatory postsynaptic currents (sEPSCs) in >90% of NTS-TH-EGFP neurons, an effect blocked by the 5-HT3 receptor antagonist ondansetron and mimicked by the 5-HT3 receptor agonists SR5227 and mCPBG. In contrast, 5-HT3 receptor agonists increased sEPSCs on a minority (<30%) of non-TH neurons. 5-HT3 receptor agonists increased the frequency, but not the amplitude, of mini-EPSCs, suggesting that their actions are presynaptic. 5-HT3 receptor agonists increased the firing rate of TH-EGFP neurons, an effect dependent on the increased spontaneous glutamate inputs as it was blocked by the ionotropic glutamate antagonist NBQX, but independent of visceral afferent activation. These results demonstrate a cellular mechanism by which serotonin activates NTS-TH neurons and suggest a pathway by which it can increase catecholamine release in target regions to modulate food intake, motivation, stress, and cardiovascular function. PMID:23152635

  20. Mechanisms of Increased Particle and VOC Emissions during DPF Active Regeneration and Practical Emissions Considering Regeneration.

    PubMed

    Yamada, Hiroyuki; Inomata, Satoshi; Tanimoto, Hiroshi

    2017-03-07

    Mechanisms involved in increased particle and volatile organic compound (VOC) emissions during active and parked active regenerations of a diesel particulate filter (DPF) were investigated using heavy-duty trucks equipped with both a urea selective catalytic reduction system and a DPF (SCR + DPF) and a DPF-only. Particle emissions increased in the later part of the regeneration period but the mechanisms were different above and below 23 nm. Particles above 23 nm were emitted due to the lower filtering efficiency of the DPF because of the decreasing amount of soot trapped during regeneration. Small particles below 23 nm were thought to be mainly sulfuric acid particles produced from SO2 trapped by the catalyst, being released and oxidized during regeneration. Contrary to the particle emissions, VOCs increased in the earlier part of the regeneration period. The mean molecular weights of the VOCs increased gradually as the regeneration proceeded. To evaluate "practical emissions" in which increased emissions during the regeneration were considered, a Regeneration Correction Factor (RCF), which is the average emission during one cycle of regeneration/emission in normal operation, was adopted. The RCFs of PM and VOCs were 1.1-1.5, and those of PNs were as high as 3-140, although they were estimated from a limited number of observations.

  1. Frontostriatal activity and connectivity increase during proactive inhibition across adolescence and early adulthood.

    PubMed

    Vink, Matthijs; Zandbelt, Bram B; Gladwin, Thomas; Hillegers, Manon; Hoogendam, Janna Marie; van den Wildenberg, Wery P M; Du Plessis, Stefan; Kahn, René S

    2014-09-01

    During adolescence, functional and structural changes in the brain facilitate the transition from childhood to adulthood. Because the cortex and the striatum mature at different rates, temporary imbalances in the frontostriatal network occur. Here, we investigate the development of the subcortical and cortical components of the frontostriatal network from early adolescence to early adulthood in 60 subjects in a cross-sectional design, using functional MRI and a stop-signal task measuring two forms of inhibitory control: reactive inhibition (outright stopping) and proactive inhibition (anticipation of stopping). During development, reactive inhibition improved: older subjects were faster in reactive inhibition. In the brain, this was paralleled by an increase in motor cortex suppression. The level of proactive inhibition increased, with older subjects slowing down responding more than younger subjects when anticipating a stop-signal. Activation increased in the right striatum, right ventral and dorsal inferior frontal gyrus, and supplementary motor area. Moreover, functional connectivity during proactive inhibition increased between striatum and frontal regions with age. In conclusion, we demonstrate that developmental improvements in proactive inhibition are paralleled by increases in activation and functional connectivity of the frontostriatal network. These data serve as a stepping stone to investigate abnormal development of the frontostriatal network in disorders such as schizophrenia and attention-deficit hyperactivity disorder.

  2. Increases in Physical Activity Result in Diminishing Increments in Daily Energy Expenditure in Mice.

    PubMed

    O'Neal, Timothy J; Friend, Danielle M; Guo, Juen; Hall, Kevin D; Kravitz, Alexxai V

    2017-02-06

    Exercise is a common component of weight loss strategies, yet exercise programs are associated with surprisingly small changes in body weight [1-4]. This may be due in part to compensatory adaptations, in which calories expended during exercise are counteracted by decreases in other aspects of energy expenditure [1, 5-10]. Here we examined the relationship between a rodent model of voluntary exercise- wheel running- and total daily energy expenditure. Use of a running wheel for 3 to 7 days increased daily energy expenditure, resulting in a caloric deficit of ∼1 kcal/day; however, total daily energy expenditure remained stable after the first week of wheel access, despite further increases in wheel use. We hypothesized that compensatory mechanisms accounted for the lack of increase in daily energy expenditure after the first week. Supporting this idea, we observed a decrease in off-wheel ambulation when mice were using the wheels, indicating behavioral compensation. Finally, we asked whether individual variation in wheel use within a group of mice would be associated with different levels of daily energy expenditure. Despite a large variation in wheel running, we did not observe a significant relationship between the amount of daily wheel running and total daily energy expenditure or energy intake across mice. Together, our experiments support a model in which the transition from sedentary to light activity is associated with an increase in daily energy expenditure, but further increases in physical activity produce diminishingly small increments in daily energy expenditure.

  3. Children with High Functioning Autism show increased prefrontal and temporal cortex activity during error monitoring

    PubMed Central

    Goldberg, Melissa C.; Spinelli, Simona; Joel, Suresh; Pekar, James J.; Denckla, Martha B.; Mostofsky, Stewart H.

    2010-01-01

    Evidence exists for deficits in error monitoring in autism. These deficits may be particularly important because they may contribute to excessive perseveration and repetitive behavior in autism. We examined the neural correlates of error monitoring using fMRI in 8–12-year-old children with high-functioning autism (HFA, n=11) and typically developing children (TD, n=15) during performance of a Go/No-Go task by comparing the neural correlates of commission errors versus correct response inhibition trials. Compared to TD children, children with HFA showed increased BOLD fMRI signal in the anterior medial prefrontal cortex (amPFC) and the left superior temporal gyrus (STempG) during commission error (versus correct inhibition) trials. A follow-up region-of-interest analysis also showed increased BOLD signal in the right insula in HFA compared to TD controls. Our findings of increased amPFC and STempG activity in HFA, together with the increased activity in the insula, suggest a greater attention towards the internally-driven emotional state associated with making an error in children with HFA. Since error monitoring occurs across different cognitive tasks throughout daily life, an increased emotional reaction to errors may have important consequences for early learning processes. PMID:21151713

  4. Focused campaign increases activity among participants in Nature's Notebook, a citizen science project

    USGS Publications Warehouse

    Crimmins, Theresa M.; Weltzin, Jake F.; Rosemartin, Alyssa H.; Surina, Echo M.; Marsh, Lee; Denny, Ellen G.

    2014-01-01

    Citizen science projects, which engage non-professional scientists in one or more stages of scientific research, have been gaining popularity; yet maintaining participants’ activity level over time remains a challenge. The objective of this study was to evaluate the potential for a short-term, focused campaign to increase participant activity in a national-scale citizen science program. The campaign that we implemented was designed to answer a compelling scientific question. We invited participants in the phenology-observing program, Nature’s Notebook, to track trees throughout the spring of 2012, to ascertain whether the season arrived as early as the anomalous spring of 2010. Consisting of a series of six electronic newsletters and costing our office slightly more than 1 week of staff resources, our effort was successful; compared with previous years, the number of observations collected in the region where the campaign was run increased by 184%, the number of participants submitting observations increased by 116%, and the number of trees registered increased by 110%. In comparison, these respective metrics grew by 25, 55, and 44%, over previous years, in the southeastern quadrant of the United States, where no such campaign was carried out. The campaign approach we describe here is a model that could be adapted by a wide variety of programs to increase engagement and thereby positively influence participant retention.

  5. Endolymphatic Sac Tumor Showing Increased Activity on 68Ga DOTATATE PET/CT.

    PubMed

    Papadakis, Georgios Z; Millo, Corina; Sadowski, Samira M; Bagci, Ulas; Patronas, Nicholas J

    2016-10-01

    Endolymphatic sac tumors (ELSTs) are rare tumors arising from the epithelium of the endolymphatic sac and duct that can be either sporadic or associated with von Hippel-Lindau (VHL) disease. We report a case of a VHL patient with histologically proven residual ELST who underwent Ga DOTATATE PET/CT showing increased activity (SUVmax, 6.29) by the ELST. The presented case of a VHL-associated ELST with increased Ga DOTATATE uptake indicates cell-surface expression of somatostatin receptors by this tumor, suggesting the potential application of somatostatin receptor imaging using Ga DOTA-conjugated peptides in the workup and management of these patients.

  6. Carbonic anhydrase II increases the activity of the human electrogenic Na+/HCO3- cotransporter.

    PubMed

    Becker, Holger M; Deitmer, Joachim W

    2007-05-04

    Several acid/base-coupled membrane transporters, such as the electrogenic sodium-bicarbonate cotransporter (NBCe1), have been shown to bind to different carbonic anhydrase isoforms to create a "transport metabolon." We have expressed NBCe1 derived from human kidney in oocytes of Xenopus leavis and determined its transport activity by recording the membrane current in voltage clamp, and the cytosolic H(+) and Na(+) concentrations using ion-selective microelectrodes. When carbonic anhydrase isoform II (CAII) had been injected into oocytes, the membrane current and the rate of cytosolic Na(+) rise, indicative for NBCe1 activity, increased significantly with the amount of injected CAII (2-200 ng). The CAII inhibitor ethoxyzolamide reversed the effects of CAII on the NBCe1 activity. Co-expressing wild-type CAII or NH(2)-terminal mutant CAII together with NBCe1 provided similar results, whereas co-expressing the catalytically inactive CAII mutant V143Y had no effect on NBCe1 activity. Mass spectrometric analysis and the rate of cytosolic H(+) change following addition of CO(2)/HCO(3)(-) confirmed the catalytic activity of injected and expressed CAII in oocytes. Our results show that the transport capacity of NBCe1 is enhanced by the catalytic activity of CAII, in line with the notion that CAII forms a transport metabolon with NBCe1.

  7. The hyperactive syndrome: metanalysis of genetic alterations, pharmacological treatments and brain lesions which increase locomotor activity.

    PubMed

    Viggiano, Davide

    2008-12-01

    The large number of transgenic mice realized thus far with different purposes allows addressing new questions, such as which animals, over the entire set of transgenic animals, show a specific behavioural abnormality. In the present study, we have used a metanalytical approach to organize a database of genetic modifications, brain lesions and pharmacological interventions that increase locomotor activity in animal models. To further understand the resulting data set, we have organized a second database of the alterations (genetic, pharmacological or brain lesions) that reduce locomotor activity. Using this approach, we estimated that 1.56% of the genes in the genome yield to hyperactivity and 0.75% of genes produce hypoactivity when altered. These genes have been classified into genes for neurotransmitter systems, hormonal, metabolic systems, ion channels, structural proteins, transcription factors, second messengers and growth factors. Finally, two additional classes included animals with neurodegeneration and inner ear abnormalities. The analysis of the database revealed several unexpected findings. First, the genes that, when mutated, induce hyperactive behaviour do not pertain to a single neurotransmitter system. In fact, alterations in most neurotransmitter systems can give rise to a hyperactive phenotype. In contrast, fewer changes can decrease locomotor activity. Specifically, genetic and pharmacological alterations that enhance the dopamine, orexin, histamine, cannabinoids systems or that antagonize the cholinergic system induce an increase in locomotor activity. Similarly, imbalances in the two main neurotransmitters of the nervous system, GABA and glutamate usually result in hyperactive behaviour. It is remarkable that no genetic alterations pertaining to the GABA system have been reported to reduce locomotor behaviour. Other neurotransmitters, such as norepinephrine and serotonin, have a more complex influence. For instance, a decrease in norepinephrine

  8. AMPK activation promotes lipid droplet dispersion on detyrosinated microtubules to increase mitochondrial fatty acid oxidation

    PubMed Central

    Herms, Albert; Bosch, Marta; Reddy, Babu J.N.; Schieber, Nicole L.; Fajardo, Alba; Rupérez, Celia; Fernández-Vidal, Andrea; Ferguson, Charles; Rentero, Carles; Tebar, Francesc; Enrich, Carlos; Parton, Robert G.; Gross, Steven P.; Pol, Albert

    2015-01-01

    Lipid droplets (LDs) are intracellular organelles that provide fatty acids (FAs) to cellular processes including synthesis of membranes and production of metabolic energy. While known to move bidirectionally along microtubules (MTs), the role of LD motion and whether it facilitates interaction with other organelles are unclear. Here we show that during nutrient starvation, LDs and mitochondria relocate on detyrosinated MT from the cell centre to adopt a dispersed distribution. In the cell periphery, LD–mitochondria interactions increase and LDs efficiently supply FAs for mitochondrial beta-oxidation. This cellular adaptation requires the activation of the energy sensor AMPK, which in response to starvation simultaneously increases LD motion, reorganizes the network of detyrosinated MTs and activates mitochondria. In conclusion, we describe the existence of a specialized cellular network connecting the cellular energetic status and MT dynamics to coordinate the functioning of LDs and mitochondria during nutrient scarcity. PMID:26013497

  9. Spectral Analysis of the Signals Associated with Increased Activity in Popocatepetl Volcano April 2012

    NASA Astrophysics Data System (ADS)

    Cuenca, J.

    2013-05-01

    After several decades of being inactive in 1994 had a strong reactivation. Since then he has had long periods where volcanic activity including increased growth and destruction of a dome. In April 2012 Popocatepetl Volcano activity showed an increase in the emission of gas and ash, and Vulcanian type explosions. As a result the National Center for Disaster Prevention (CENAPRED) raised the yellow phase from 2 to 3. Spectrally analyzes seismic activity characteristic of the types of events (explosions, LP, Type-B and tremors) that provides information of the source processes that cause it, despite sustained change reflected by the complexity of the volcanic apparatus, through of: 1) the spectral content of the process provides the source, 2) the spectral ratio H / V, its associated amplification and dominant frequencies, 3) time frequency analysis showing the variation in frequency, 4) the particle motion to analyze its retrograde or prograde acting in a volcanic complex medium. The calculation of H / V was performed by each hour using windows with duration of 80 seconds in the broadband seismic station "Canario" (PPPB). The predominant frequencies of H / V are around 1.4-1.8 Hz to 2.1-2.6 Hz and amplifications from 2.3 to 6.9 times. Analysis of H / V of 48 hours (days 16 and April 17) for the case of 1.4-1.8 Hz was observed: (1) From 0-9 hours there is no amplification. (2) The seismic amplification increases from 10 to 11 hours. (3) A first crisis reaches a maximum at 13 hours with about 6 times of amplification. (4) From 14 to 15 hours there is a strong relaxation of the activity. (5) The activity begins to increase from 16 to 23 hours where it reaches its maximum amplification of almost 7 times. (6) The following two hours and is kept exceeding 6 times of amplification. (7) Then is followed by a decrease to 4 hours on the day 17, from which is maintained at a level variable. (8) At 18 hours of the day 17 grows the amplification at 6.2 times, which conforms a

  10. Reduced peroxisomal citrate synthase activity increases substrate availability for polyhydroxyalkanoate biosynthesis in plant peroxisomes.

    PubMed

    Tilbrook, Kimberley; Poirier, Yves; Gebbie, Leigh; Schenk, Peer M; McQualter, Richard B; Brumbley, Stevens M

    2014-10-01

    Polyhydroxyalkanoates (PHAs) are bacterial carbon storage polymers used as renewable, biodegradable plastics. PHA production in plants may be a way to reduce industrial PHA production costs. We recently demonstrated a promising level of peroxisomal PHA production in the high biomass crop species sugarcane. However, further production strategies are needed to boost PHA accumulation closer to commercial targets. Through exogenous fatty acid feeding of Arabidopsis thaliana plants that contain peroxisome-targeted PhaA, PhaB and PhaC enzymes from Cupriavidus necator, we show here that the availability of substrates derived from the β-oxidation cycle limits peroxisomal polyhydroxybutyrate (PHB) biosynthesis. Knockdown of peroxisomal citrate synthase activity using artificial microRNA increased PHB production levels approximately threefold. This work demonstrates that reduction of peroxisomal citrate synthase activity may be a valid metabolic engineering strategy for increasing PHA production in other plant species.

  11. Severe Impingement of Lumbar Disc Replacements Increases the Functional Biological Activity of Polyethylene Wear Debris

    PubMed Central

    Baxter, Ryan M.; MacDonald, Daniel W.; Kurtz, Steven M.; Steinbeck, Marla J.

    2013-01-01

    Background: Wear, oxidation, and particularly rim impingement damage of ultra-high molecular weight polyethylene total disc replacement components have been observed following surgical revision. However, neither in vitro testing nor retrieval-based evidence has shown the effect(s) of impingement on the characteristics of polyethylene wear debris. Thus, we sought to determine (1) differences in polyethylene particle size, shape, number, or biological activity that correspond to mild or severe rim impingement and (2) in an analysis of all total disc replacements, regardless of impingement classification, whether there are correlations between the extent of regional damage and the characteristics of polyethylene wear debris. Methods: The extent of dome and rim damage was characterized for eleven retrieved polyethylene cores obtained at revision surgery after an average duration of implantation of 9.7 years (range, 4.6 to 16.1 years). Polyethylene wear debris was isolated from periprosthetic tissues with use of nitric acid and was imaged with use of environmental scanning electron microscopy. Subsequently, particle size, shape, number, biological activity, and chronic inflammation scores were determined. Results: Grouping of particles by size ranges that represented high biological relevance (<0.1 to 1-μm particles), intermediate biological relevance (1 to 10-μm particles), and low biological relevance (>10-μm particles) revealed an increased volume fraction of particles in the <0.1 to 1-μm and 1 to 10-μm size ranges in the mild-impingement cohort as compared with the severe-impingement cohort. The increased volume fractions resulted in a higher specific biological activity per unit particle volume in the mild-impingement cohort than in the severe-impingement cohort. However, functional biological activity, which is normalized by particle volume (mm3/g of tissue), was significantly higher in the severe-impingement cohort. This increase was due to a larger volume

  12. Inhibitory effects of the dietary flavonoid quercetin on the enzyme activity of zinc(II)-dependent yeast alcohol dehydrogenase: Spectroscopic and molecular docking studies.

    PubMed

    Bhuiya, Sutanwi; Haque, Lucy; Pradhan, Ankur Bikash; Das, Suman

    2017-02-01

    A multispectroscopic exploration was employed to investigate the interaction between the metallo-enzyme alcohol dehydrogenase (ADH) from yeast with bioflavonoid quercetin (QTN). Here, we have characterized the complex formation between QTN and Zn(2+) in aqueous solution and then examined the effect of such complex formation on the enzymatic activity of a zinc(II)-dependent enzyme alcohol dehydrogenase from yeast. We have observed an inhibition of enzymatic activity of ADH in presence of QTN. Enzyme inhibition kinetic experiments revealed QTN as a non-competitive inhibitor of yeast ADH. Perturbation of Circular dichroic (CD) spectrum of ADH in presence of QTN is observed due to the structural changes of ADH on complexation with the above flavonoid. Our results indicate a conformational change of ADH due to removal of Zn(2+) present in the enzyme by QTN. This was further established by molecular modeling study which shows that the flavonoid binds to the Zn(2+) ion which maintains the tertiary structure of the metallo-enzyme. So, QTN abstracts only half of the Zn(2+) ions present in the enzyme i.e. one Zn(2+) ion per monomer. From the present study, the structural alteration and loss of enzymatic activity of ADH are attributed to the complex formation between QTN and Zn(2+).

  13. Increased Brain Activation for Dual Tasking with 70-Days Head-Down Bed Rest

    PubMed Central

    Yuan, Peng; Koppelmans, Vincent; Reuter-Lorenz, Patricia A.; De Dios, Yiri E.; Gadd, Nichole E.; Wood, Scott J.; Riascos, Roy; Kofman, Igor S.; Bloomberg, Jacob J.; Mulavara, Ajitkumar P.; Seidler, Rachael D.

    2016-01-01

    Head-down tilt bed rest (HDBR) has been used as a spaceflight analog to simulate the effects of microgravity exposure on human physiology, sensorimotor function, and cognition on Earth. Previous studies have reported that concurrent performance of motor and cognitive tasks can be impaired during space missions. Understanding the consequences of HDBR for neural control of dual tasking may possibly provide insight into neural efficiency during spaceflight. In the current study, we evaluated how dual task performance and the underlying brain activation changed as a function of HDBR. Eighteen healthy men participated in this study. They remained continuously in the 6° head-down tilt position for 70 days. Functional MRI for bimanual finger tapping was acquired during both single task and dual task conditions, and repeated at 7 time points pre-, during- and post-HDBR. Another 12 healthy males participated as controls who did not undergo HDBR. A widely distributed network involving the frontal, parietal, cingulate, temporal, and occipital cortices exhibited increased activation for dual tasking and increased activation differences between dual and single task conditions during HDBR relative to pre- or post-HDBR. This HDBR-related brain activation increase for dual tasking implies that more neurocognitive control is needed for dual task execution during HDBR compared to pre- and post-HDBR. We observed a positive correlation between pre-to-post HDBR changes in dual-task cost of reaction time and pre-to-post HDBR change in dual-task cost of brain activation in several cerebral and cerebellar regions. These findings could be predictive of changes in dual task processing during spaceflight. PMID:27601982

  14. Methylphenidate treatment increases Na(+), K (+)-ATPase activity in the cerebrum of young and adult rats.

    PubMed

    Scherer, Emilene B S; Matté, Cristiane; Ferreira, Andréa G K; Gomes, Karin M; Comim, Clarissa M; Mattos, Cristiane; Quevedo, João; Streck, Emilio L; Wyse, Angela T S

    2009-12-01

    Methylphenidate is a central nervous system stimulant used for the treatment of attention-deficit hyperactivity disorder. Na(+), K(+)-ATPase is a membrane-bound enzyme necessary to maintain neuronal excitability. Considering that methylphenidate effects on central nervous system metabolism are poorly known and that Na(+), K(+)-ATPase is essential to normal brain function, the purpose of this study was to evaluate the effect of this drug on Na(+), K(+)-ATPase activity in the cerebrum of young and adult rats. For acute administration, a single injection of methylphenidate (1.0, 2.0, or 10.0 mg/Kg) or saline was given to rats on postnatal day 25 or postnatal day 60, in the young and adult groups, respectively. For chronic administration, methylphenidate (1.0, 2.0, or 10.0 mg/Kg) or saline injections were given to young rats starting at postnatal day 25 once daily for 28 days. In adult rats, the same regimen was performed starting at postnatal day 60. Our results showed that acute methylphenidate administration increased Na(+), K(+)-ATPase activity in hippocampus, prefrontal cortex, and striatum of young and adult rats. In young rats, chronic administration of methylphenidate also enhanced Na(+), K(+)-ATPase activity in hippocampus and prefrontal cortex, but not in striatum. When tested in adult rats, Na(+), K(+)-ATPase activity was increased in all cerebral structures studied. The present findings suggest that increased Na(+), K(+)-ATPase activity may be associated with neuronal excitability caused by methylphenidate.

  15. Increased Low- and High-Frequency Oscillatory Activity in the Prefrontal Cortex of Fibromyalgia Patients

    PubMed Central

    Lim, Manyoel; Kim, June Sic; Kim, Dajung J.; Chung, Chun Kee

    2016-01-01

    Recent human neuroimaging studies have suggested that fibromyalgia (FM), a chronic widespread pain disorder, exhibits altered thalamic structure and function. Since the thalamus has extensive reciprocal connection with the cortex, structural and functional thalamic alterations in FM might be linked to aberrant thalamocortical oscillation. This study investigated the presence of abnormal brain rhythmicity in low- and high-frequency bands during resting state in patients with FM and their relationship to clinical pain symptom. Spontaneous magnetoencephalography (MEG) activity was recorded in 18 females w