Weight Suppression Predicts Time to Remission from Bulimia Nervosa

Science.gov (United States)

Lowe, Michael R.; Berner, Laura A.; Swanson, Sonja A.; Clark, Vicki L.; Eddy, Kamryn T.; Franko, Debra L.; Shaw, Jena A.; Ross, Stephanie; Herzog, David B.

2011-01-01

Objective: To investigate whether, at study entry, (a) weight suppression (WS), the difference between highest past adult weight and current weight, prospectively predicts time to first full remission from bulimia nervosa (BN) over a follow-up period of 8 years, and (b) weight change over time mediates the relationship between WS and time to first…

Suppressing my memories by listening to yours: The effect of socially triggered context-based prediction error on memory.

Science.gov (United States)

Vlasceanu, Madalina; Drach, Rae; Coman, Alin

2018-05-03

The mind is a prediction machine. In most situations, it has expectations as to what might happen. But when predictions are invalidated by experience (i.e., prediction errors), the memories that generate these predictions are suppressed. Here, we explore the effect of prediction error on listeners' memories following social interaction. We find that listening to a speaker recounting experiences similar to one's own triggers prediction errors on the part of the listener that lead to the suppression of her memories. This effect, we show, is sensitive to a perspective-taking manipulation, such that individuals who are instructed to take the perspective of the speaker experience memory suppression, whereas individuals who undergo a low-perspective-taking manipulation fail to show a mnemonic suppression effect. We discuss the relevance of these findings for our understanding of the bidirectional influences between cognition and social contexts, as well as for the real-world situations that involve memory-based predictions.

Bile acids exert negative feedback control on bile acid synthesis in cultured pig hepatocytes by suppression of cholesterol 7α-hydroxylase activity

NARCIS (Netherlands)

Kwekkeboom, J.; Princen, H.M.G.; Voorthuizen, E.M. van; Kempen, H.J.M.

1990-01-01

Feedback regulation of bile acid synthesis by its end products was studied in cultured hepatocytes of young weaned pigs. We previously showed that conversion of exogenous [14C] cholesterol into bile acids was suppressed by addition of bile acids to the culture medium. In the present study, the

Salicylic acid suppresses jasmonic acid signaling downstream of SCFCOI1-JAZ by targeting GCC promoter motifs via transcription factor ORA59

NARCIS (Netherlands)

Does, D. van der; Leon-Reyes, A.; Koornneef, A.; Verk, M.C. van; Rodenburg, N.; Pauwels, L.; Goossens, A.; Körbes, A.P.; Memelink, J.; Ritsema, T.; Wees, S.C.M. van; Pieterse, C.M.J.

2013-01-01

Antagonism between the defense hormones salicylic acid (SA) and jasmonic acid (JA) plays a central role in the modulation of the plant immune signaling network, but the molecular mechanisms underlying this phenomenon are largely unknown. Here, we demonstrate that suppression of the JA pathway by SA

Effect of gastric acid suppressants and prokinetics on peritoneal dialysis-related peritonitis

Science.gov (United States)

Kwon, Ji Eun; Koh, Seong-Joon; Chun, Jaeyoung; Kim, Ji Won; Kim, Byeong Gwan; Lee, Kook Lae; Im, Jong Pil; Kim, Joo Sung; Jung, Hyun Chae

2014-01-01

AIM: To investigate the effect of gastric acid suppressants and prokinetics on peritonitis development in peritoneal dialysis (PD) patients. METHODS: This was a single-center, retrospective study. The medical records of 398 PD patients were collected from January 2000 to September 2012 and analyzed to compare patients with at least one episode of peritonitis (peritonitis group, group A) to patients who never had peritonitis (no peritonitis group, group B). All peritonitis episodes were analyzed to compare peritonitis caused by enteric organisms and peritonitis caused by non-enteric organisms. RESULTS: Among the 120 patients who met the inclusion criteria, 61 patients had at least one episode of peritonitis and 59 patients never experienced peritonitis. Twenty-four of 61 patients (39.3%) in group A and 15 of 59 patients (25.4%) in group B used gastric acid suppressants. Only the use of H2-blocker (H2B) was associated with an increased risk of PD-related peritonitis; the use of proton pump inhibitors, other antacids, and prokinetics was not found to be a significant risk factor for PD-related peritonitis. A total of 81 episodes of peritonitis were divided into enteric peritonitis (EP) or non-enteric peritonitis, depending on the causative organism, and gastric acid suppressants and prokinetics did not increase the risk of EP in PD patients. CONCLUSION: The use of H2B showed a trend for an increased risk of overall PD-related peritonitis, although further studies are required to clarify the effects of drugs on PD-related peritonitis. PMID:25057226

Acid suppression increases rates of Barrett's esophagus and esophageal injury in the presence of duodenal reflux.

LENUS (Irish Health Repository)

2012-01-31

BACKGROUND: The contribution of gastric acid to the toxicity of alkaline duodenal refluxate on the esophageal mucosa is unclear. This study compared the effect of duodenal refluxate when acid was present, decreased by proton pump inhibitors (PPI), or absent. METHODS: We randomized 136 Sprague-Dawley rats into 4 groups: group 1 (n = 33) were controls; group 2 (n = 34) underwent esophagoduodenostomy promoting "combined reflux"; group 3 (n = 34) underwent esophagoduodenostomy and PPI treatment to decrease acid reflux; and group 4, the \\'gastrectomy\\' group (n = 35) underwent esophagoduodenostomy and total gastrectomy to eliminate acid in the refluxate. Esophaguses were examined for inflammatory, Barrett\\'s, and other histologic changes, and expression of proliferative markers Ki-67, proliferating cell nuclear antigen (PCNA), and epidermal growth factor receptor (EGFR). RESULTS: In all reflux groups, the incidence of Barrett\\'s mucosa was greater when acid was suppressed (group C, 62%; group D, 71%) than when not suppressed (group B, 27%; P = 0.004 and P < .001). Erosions were more frequent in the PPI and gastrectomy groups than in the combined reflux group. Edema (wet weight) and ulceration was more frequent in the gastrectomy than in the combined reflux group. Acute inflammatory changes were infrequent in the PPI group (8%) compared with the combined reflux (94%) or gastrectomy (100%) groups, but chronic inflammation persisted in 100% of the PPI group. EGFR levels were greater in the PPI compared with the combined reflux group (P = .04). Ki-67, PCNA, and combined marker scores were greater in the gastrectomy compared with the combined reflux group (P = .006, P = .14, and P < .001). CONCLUSION: Gastric acid suppression in the presence of duodenal refluxate caused increased rates of inflammatory changes, intestinal metaplasia, and molecular proliferative activity. PPIs suppressed acute inflammatory changes only, whereas chronic inflammatory changes persisted.

Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression

International Nuclear Information System (INIS)

Fang, Zhong-Ze; Zhang, Dunfang; Cao, Yun-Feng; Xie, Cen; Lu, Dan; Sun, Dong-Xue; Tanaka, Naoki; Jiang, Changtao; Chen, Qianming; Chen, Yu; Wang, Haina; Gonzalez, Frank J.

2016-01-01

Irinotecan (CPT-11) is a first-line anti-colon cancer drug, however; CPT-11-induced toxicity remains a key factor limiting its clinical application. To search for clues to the mechanism of CPT-11-induced toxicity, metabolomics was applied using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry. Intraperitoneal injection of 50 mg/kg of CPT-11 induced loss of body weight, and intestine toxicity. Changes in gallbladder morphology suggested alterations in bile acid metabolism, as revealed at the molecular level by analysis of the liver, bile, and ileum metabolomes between the vehicle-treated control group and the CPT-11-treated group. Analysis of immune cell populations further showed that CPT-11 treatment significantly decreased the IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes, but not in spleen or mesenteric lymph nodes. In vitro cell culture studies showed that the addition of bile acids deoxycholic acid and taurodeoxycholic acid accelerated the CPT-11-induced suppression of IL-10 secretion by activated CD4 + naive T cells isolated from mouse splenocytes. These results showed that CPT-11 treatment caused metabolic changes in the composition of bile acids that altered CPT-11-induced suppression of IL-10 expression. - Highlights: • CPT-11 is an effective anticancer drug, but induced toxicity limits its application in the clinic. • CPT-11 decreased IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes. • CPT-11 altered the composition of bile acid metabolites, notably DCA and TDCA in liver, bile and intestine. • DCA and TDCA potentiated CPT-11-induced suppression of IL-10 secretion by active CD4 + naive T cells.

Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression

Energy Technology Data Exchange (ETDEWEB)

Fang, Zhong-Ze [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Department of Toxicology, School of Public Health, Tianjin Medical University, Tianjin (China); Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and First Affiliated Hospital of Liaoning Medical University, Dalian (China); Zhang, Dunfang [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu (China); Cao, Yun-Feng [Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and First Affiliated Hospital of Liaoning Medical University, Dalian (China); Xie, Cen [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Lu, Dan [Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin (China); Sun, Dong-Xue; Tanaka, Naoki; Jiang, Changtao [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Chen, Qianming; Chen, Yu [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu (China); Wang, Haina [School of Pharmaceutical Sciences, Shandong University, Jinan (China); Gonzalez, Frank J., E-mail: gonzalef@mail.nih.gov [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States)

2016-01-15

Irinotecan (CPT-11) is a first-line anti-colon cancer drug, however; CPT-11-induced toxicity remains a key factor limiting its clinical application. To search for clues to the mechanism of CPT-11-induced toxicity, metabolomics was applied using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry. Intraperitoneal injection of 50 mg/kg of CPT-11 induced loss of body weight, and intestine toxicity. Changes in gallbladder morphology suggested alterations in bile acid metabolism, as revealed at the molecular level by analysis of the liver, bile, and ileum metabolomes between the vehicle-treated control group and the CPT-11-treated group. Analysis of immune cell populations further showed that CPT-11 treatment significantly decreased the IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes, but not in spleen or mesenteric lymph nodes. In vitro cell culture studies showed that the addition of bile acids deoxycholic acid and taurodeoxycholic acid accelerated the CPT-11-induced suppression of IL-10 secretion by activated CD4{sup +} naive T cells isolated from mouse splenocytes. These results showed that CPT-11 treatment caused metabolic changes in the composition of bile acids that altered CPT-11-induced suppression of IL-10 expression. - Highlights: • CPT-11 is an effective anticancer drug, but induced toxicity limits its application in the clinic. • CPT-11 decreased IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes. • CPT-11 altered the composition of bile acid metabolites, notably DCA and TDCA in liver, bile and intestine. • DCA and TDCA potentiated CPT-11-induced suppression of IL-10 secretion by active CD4{sup +} naive T cells.

Fructose suppresses uric acid excretion to the intestinal lumen as a result of the induction of oxidative stress by NADPH oxidase activation.

Science.gov (United States)

Kaneko, Chihiro; Ogura, Jiro; Sasaki, Shunichi; Okamoto, Keisuke; Kobayashi, Masaki; Kuwayama, Kaori; Narumi, Katsuya; Iseki, Ken

2017-03-01

A high intake of fructose increases the risk for hyperuricemia. It has been reported that long-term fructose consumption suppressed renal uric acid excretion and increased serum uric acid level. However, the effect of single administration of fructose on excretion of uric acid has not been clarified. We used male Wistar rats, which were orally administered fructose (5g/kg). Those rats were used in each experiment at 12h after administration. Single administration of fructose suppressed the function of ileal uric acid excretion and had no effect on the function of renal uric acid excretion. Breast cancer resistance protein (BCRP) predominantly contributes to intestinal excretion of uric acid as an active homodimer. Single administration of fructose decreased BCRP homodimer level in the ileum. Moreover, diphenyleneiodonium (DPI), an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox), recovered the suppression of the function of ileal uric acid excretion and the Bcrp homodimer level in the ileum of rats that received single administration of fructose. Single administration of fructose decreases in BCRP homodimer level, resulting in the suppression the function of ileal uric acid excretion. The suppression of the function of ileal uric acid excretion by single administration of fructose is caused by the activation of Nox. The results of our study provide a new insight into the mechanism of fructose-induced hyperuricemia. Copyright © 2016 Elsevier B.V. All rights reserved.

Use of acid-suppressive therapy before anti-reflux surgery in 2922 patients: a nationwide register-based study in Denmark.

Science.gov (United States)

Lødrup, A; Pottegård, A; Hallas, J; Bytzer, P

2015-07-01

Guidelines recommend that patients with gastro-oesophageal reflux disease are adequately treated with acid-suppressive therapy before undergoing anti-reflux surgery. Little is known of the use of acid-suppressive drugs before anti-reflux surgery. To determine the use of proton pump inhibitors and H2 -receptor antagonists in the year before anti-reflux surgery. A nationwide retrospective study of all patients aged ≥18 undergoing first-time anti-reflux surgery in Denmark during 2000-2012 using data from three different sources: the Danish National Register of Patients, the Danish National Prescription Register, and the Danish Person Register. The study population thus included 2922 patients (median age: 48 years, 55.7% male). The annual proportion of patients redeeming ≥180 DDD of acid-suppressive therapy increased from 17.0% 5 years before anti-reflux surgery to 64.9% 1 year before. The probability for inadequate dosing 1 year before surgery (reflux surgery, as a high proportion of patients receive inadequate dosing of acid-suppressive therapy prior to the operation. © 2015 John Wiley & Sons Ltd.

Reliable gastric tonometry after coronary artery surgery : need for acid secretion suppression despite transient failure of acid secretion

NARCIS (Netherlands)

Bams, JL; Kolkman, JJ; Roukens, MP; Douma, DPN; Loef, BG; Meuwissen, SGM; Groeneveld, ABJ

1998-01-01

Objective:To study the need for suppression of gastric acid secretion for reliable intragastric partial pressure of carbon dioxide (PCO2) tonometry by evaluating the effect of an oral dose of: sodium bicarbonate before and after administration of the H-2-blocker ranitidine to mimic CO2 generation

Reliable gastric tonometry after coronary artery surgery : need for acid secretion suppression despite transient failure of acid secretion

NARCIS (Netherlands)

Bams, JL; Kolkman, JJ; Roukens, MP; Douma, DPN; Loef, BG; Meuwissen, SGM; Groeneveld, ABJ

Objective:To study the need for suppression of gastric acid secretion for reliable intragastric partial pressure of carbon dioxide (PCO2) tonometry by evaluating the effect of an oral dose of: sodium bicarbonate before and after administration of the H-2-blocker ranitidine to mimic CO2 generation

Acid suppressants for managing gastro-oesophageal reflux and gastro-oesophageal reflux disease in infants: a national survey.

Science.gov (United States)

Bell, Jane C; Schneuer, Francisco J; Harrison, Christopher; Trevena, Lyndal; Hiscock, Harriet; Elshaug, Adam G; Nassar, Natasha

2018-02-22

To evaluate the diagnosis and management of reflux and gastro-oesophageal reflux disease (GORD) in infants aged reflux and GORD and their management including prescribing of acid-suppressant medicines (proton pump inhibitors (PPIs) and histamine receptor antagonists (H2RAs)) and counselling, advice or education. Of all infants' visits, 512 (2.7%) included a diagnosis of reflux (n=413, 2.2%) or GORD (n=99, 0.5%). From 2006 to 2016, diagnostic rates decreased for reflux and increased for GORD. Prescribing of acid suppressants occurred in 43.6% visits for reflux and 48.5% visits for GORD, similar to rates of counselling, advice or education (reflux: 38.5%, GORD: 43.4% of visits). Prescribing of PPIs increased (statistically significant only for visits for reflux), while prescribing of H2RAs decreased. Overprescribing of acid suppressants to infants may be occurring. In infants, acid-suppressant medicines are no better than placebo and may have significant negative side effects; however, guidelines are inconsistent. Clear, concise and consistent guidance is needed. GPs and parents need to understand what is normal and limitations of medical therapy. We need a greater understanding of the influences on GP prescribing practices, of parents' knowledge and attitudes and of the pressures on parents of infants with these conditions. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Weight suppression predicts total weight gain and rate of weight gain in outpatients with anorexia nervosa.

Science.gov (United States)

Carter, Frances A; Boden, Joseph M; Jordan, Jennifer; McIntosh, Virginia V W; Bulik, Cynthia M; Joyce, Peter R

2015-11-01

The present study sought to replicate the finding of Wildes and Marcus, Behav Res Ther, 50, 266-274, 2012 that higher levels of weight suppression at pretreatment predict greater total weight gain, faster rate of weight gain, and bulimic symptoms amongst patients admitted with anorexia nervosa. Participants were 56 women with anorexia nervosa diagnosed by using strict or lenient weight criteria, who were participating in a randomized controlled psychotherapy trial (McIntosh et al., Am J Psychiatry, 162, 741-747, 2005). Thirty-five women completed outpatient treatment and post-treatment assessment. Weight suppression was the discrepancy between highest lifetime weight at adult height and weight at pretreatment assessment. Outcome variables were total weight gain, rate of weight gain, and bulimic symptoms in the month prior to post-treatment assessment [assessed using the Eating Disorders Examination (Fairburn et al., Binge-Eating: Nature, Assessment and Treatment. New York: Guilford, 1993)]. Weight suppression was positively associated with total weight gain and rate of weight gain over treatment. Regression models showed that this association could not be explained by covariates (age at onset of anorexia nervosa and treatment modality). Weight suppression was not significantly associated with bulimic symptoms in the month prior to post-treatment assessment, regardless of whether bulimic symptoms were examined as continuous or dichotomous variables. The present study reinforces the previous finding that weight suppression predicts total weight gain and rate of weight gain amongst patients being treated for anorexia nervosa. Methodological issues may explain the failure of the present study to find that weight suppression predicts bulimic symptoms. Weight suppression at pretreatment for anorexia nervosa should be assessed routinely and may inform treatment planning. © 2015 Wiley Periodicals, Inc.

Arrest of chronic acid suppressant drug use after successful Helicobacter pylori eradication in patients with peptic ulcer disease: a six-month follow-up study

NARCIS (Netherlands)

Hurenkamp, G. J.; Grundmeijer, H. G.; van der Ende, A.; Tytgat, G. N.; Assendelft, W. J.; van der Hulst, R. W.

2001-01-01

BACKGROUND: It remains controversial whether successful H. pylori eradication leads to relief of dyspepsia and the subsequent arrest or tapering of acid-suppressant drug therapy, or to an aggravation of acid-related dyspepsia requiring more acid-suppressant drug intake. AIM: To evaluate

Omega-3 free fatty acids suppress macrophage inflammasome activation by inhibiting NF-κB activation and enhancing autophagy.

Directory of Open Access Journals (Sweden)

Yolanda Williams-Bey

Full Text Available The omega-3 (ω3 fatty acid docosahexaenoic acid (DHA can suppress inflammation, specifically IL-1β production through poorly understood molecular mechanisms. Here, we show that DHA reduces macrophage IL-1β production by limiting inflammasome activation. Exposure to DHA reduced IL-1β production by ligands that stimulate the NLRP3, AIM2, and NAIP5/NLRC4 inflammasomes. The inhibition required Free Fatty Acid Receptor (FFAR 4 (also known as GPR120, a G-protein coupled receptor (GPR known to bind DHA. The exposure of cells to DHA recruited the adapter protein β-arrestin1/2 to FFAR4, but not to a related lipid receptor. DHA treatment reduced the initial inflammasome priming step by suppressing the nuclear translocation of NF-κB. DHA also reduced IL-1β levels by enhancing autophagy in the cells. As a consequence macrophages derived from mice lacking the essential autophagy protein ATG7 were partially resistant to suppressive effects of DHA. Thus, DHA suppresses inflammasome activation by two distinct mechanisms, inhibiting the initial priming step and by augmenting autophagy, which limits inflammasome activity.

Tranexamic acid suppresses ultraviolet B eye irradiation-induced melanocyte activation by decreasing the levels of prohormone convertase 2 and alpha-melanocyte-stimulating hormone.

Science.gov (United States)

Hiramoto, Keiichi; Yamate, Yurika; Sugiyama, Daijiro; Takahashi, Yumi; Mafune, Eiichi

2014-12-01

Tranexamic acid (trans-4-aminomethylcyclohexanecarboxylic acid) is a medicinal amino acid used in skin whitening care. This study examined the effects of tranexamic acid on the melanocyte activation of the skin induced by an ultraviolet (UV) B eye irradiation. The eye or ear was locally exposed to UVB at a dose of 1.0 kJ/m(2) using a 20SE sunlamp after covering the remaining body surface with aluminum foil. UVB eye irradiation induced melanocyte activation of the skin, similar to that observed following UVB ear irradiation, which was suppressed by the administration of tranexamic acid treatment. The plasma α-melanocyte-stimulating hormone (α-MSH) content was increased by UVB irradiation of the eye; however, the increase in α-MSH was suppressed by tranexamic acid treatment. In addition, UVB eye irradiation induced the up-regulation of prohormone convertase (PC) 2 in the pituitary gland. Meanwhile, the increase in PC2 induced by UVB eye irradiation was suppressed by tranexamic acid treatment. These results clearly indicate that tranexamic acid decreases the expression of PC2, which cleavages from proopiomelanocortin to α-MSH in the pituitary gland, thereby suppressing melanocyte activation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Activation of peroxisome proliferator-activated receptor-α (PPARα) suppresses postprandial lipidemia through fatty acid oxidation in enterocytes

International Nuclear Information System (INIS)

Kimura, Rino; Takahashi, Nobuyuki; Murota, Kaeko; Yamada, Yuko; Niiya, Saori; Kanzaki, Noriyuki; Murakami, Yoko; Moriyama, Tatsuya; Goto, Tsuyoshi; Kawada, Teruo

2011-01-01

Highlights: → PPARα activation increased mRNA expression levels of fatty acid oxidation-related genes in human intestinal epithelial Caco-2 cells. → PPARα activation also increased oxygen consumption rate and CO 2 production and decreased secretion of triglyceride and ApoB from Caco-2 cells. → Orally administration of bezafibrate increased mRNA expression levels of fatty acid oxidation-related genes and CO 2 production in small intestinal epithelial cells. → Treatment with bezafibrate decreased postprandial serum concentration of triglyceride after oral injection of olive oil in mice. → It suggested that intestinal lipid metabolism regulated by PPARα activation suppresses postprandial lipidemia. -- Abstract: Activation of peroxisome proliferator-activated receptor (PPAR)-α which regulates lipid metabolism in peripheral tissues such as the liver and skeletal muscle, decreases circulating lipid levels, thus improving hyperlipidemia under fasting conditions. Recently, postprandial serum lipid levels have been found to correlate more closely to cardiovascular diseases than fasting levels, although fasting hyperlipidemia is considered an important risk of cardiovascular diseases. However, the effect of PPARα activation on postprandial lipidemia has not been clarified. In this study, we examined the effects of PPARα activation in enterocytes on lipid secretion and postprandial lipidemia. In Caco-2 enterocytes, bezafibrate, a potent PPARα agonist, increased mRNA expression levels of fatty acid oxidation-related genes, such as acyl-CoA oxidase, carnitine palmitoyl transferase, and acyl-CoA synthase, and oxygen consumption rate (OCR) and suppressed secretion levels of both triglycerides and apolipoprotein B into the basolateral side. In vivo experiments revealed that feeding high-fat-diet containing bezafibrate increased mRNA expression levels of fatty acid oxidation-related genes and production of CO 2 and acid soluble metabolites in enterocytes. Moreover

Weight Suppression Predicts Bulimic Symptoms at 20-year Follow-up: The Mediating Role of Drive for Thinness

Science.gov (United States)

Bodell, Lindsay P.; Brown, Tiffany A.; Keel, Pamela K.

2016-01-01

Weight suppression predicts the onset and maintenance of bulimic syndromes. Despite this finding, no study has examined psychological mechanisms contributing to these associations using a longitudinal design. Given societal pressures to be thin and an actual history of higher weight, it is possible that greater weight suppression contributes to increased fear of gaining weight and preoccupation with being thin, which increase vulnerability to eating disorders. The present study investigated whether greater drive for thinness mediates associations between weight suppression and bulimic symptoms over long-term follow-up. Participants were women (n = 1190) and men (n = 509) who completed self-report surveys in college and 10- and 20- years later. Higher weight suppression at baseline predicted higher bulimic symptoms at 20-year follow-up (p symptoms, body mass index, and drive for thinness. Increased drive for thinness at 10-year follow-up mediated this effect. Findings highlight the long-lasting effect of weight suppression on bulimic symptoms and suggest that preoccupation with thinness may help maintain this association. Future studies would benefit from incorporating other hypothesized consequences of weight suppression, including biological factors, into risk models. PMID:27808544

Suppression of sterol 27-hydroxylase mRNA and transcriptional activity by bile acids in cultured rat hepatocytes

NARCIS (Netherlands)

Twisk, J.; Wit, E.C.M. de; Princen, H.M.G.

1995-01-01

In previous work we have demonstrated suppression of cholesterol 7α-hydroxylase by bile acids at the level of mRNA and transcription, resulting in a similar decline in bile acid synthesis in cultured rat hepatocytes. In view of the substantial contribution of the 'alternative' or '27-hydroxylase'

Electrophilic nitro-fatty acids suppress allergic contact dermatitis in mice.

Science.gov (United States)

Mathers, A R; Carey, C D; Killeen, M E; Diaz-Perez, J A; Salvatore, S R; Schopfer, F J; Freeman, B A; Falo, L D

2017-04-01

Reactions between nitric oxide (NO), nitrite (NO2-), and unsaturated fatty acids give rise to electrophilic nitro-fatty acids (NO 2 -FAs), such as nitro oleic acid (OA-NO 2 ) and nitro linoleic acid (LNO 2 ). Endogenous electrophilic fatty acids (EFAs) mediate anti-inflammatory responses by modulating metabolic and inflammatory signal transduction reactions. Hence, there is considerable interest in employing NO 2 -FAs and other EFAs for the prevention and treatment of inflammatory disorders. Thus, we sought to determine whether OA-NO 2 , an exemplary nitro-fatty acid, has the capacity to inhibit cutaneous inflammation. We evaluated the effect of OA-NO 2 on allergic contact dermatitis (ACD) using an established model of contact hypersensitivity in C57Bl/6 mice utilizing 2,4-dinitrofluorobenzene as the hapten. We found that subcutaneous (SC) OA-NO 2 injections administered 18 h prior to sensitization and elicitation suppresses ACD in both preventative and therapeutic models. In vivo SC OA-NO 2 significantly inhibits pathways that lead to inflammatory cell infiltration and the production of inflammatory cytokines in the skin. Moreover, OA-NO 2 is capable of enhancing regulatory T-cell activity. Thus, OA-NO 2 treatment results in anti-inflammatory effects capable of inhibiting ACD by inducing immunosuppressive responses. Overall, these results support the development of OA-NO 2 as a promising therapeutic for ACD and provides new insights into the role of electrophilic fatty acids in the control of cutaneous immune responses potentially relevant to a broad range of allergic and inflammatory skin diseases. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Suppressed hepatic bile acid signalling despite elevated production of primary and secondary bile acids in NAFLD.

Science.gov (United States)

Jiao, Na; Baker, Susan S; Chapa-Rodriguez, Adrian; Liu, Wensheng; Nugent, Colleen A; Tsompana, Maria; Mastrandrea, Lucy; Buck, Michael J; Baker, Robert D; Genco, Robert J; Zhu, Ruixin; Zhu, Lixin

2017-08-03

Bile acids are regulators of lipid and glucose metabolism, and modulate inflammation in the liver and other tissues. Primary bile acids such as cholic acid and chenodeoxycholic acid (CDCA) are produced in the liver, and converted into secondary bile acids such as deoxycholic acid (DCA) and lithocholic acid by gut microbiota. Here we investigated the possible roles of bile acids in non-alcoholic fatty liver disease (NAFLD) pathogenesis and the impact of the gut microbiome on bile acid signalling in NAFLD. Serum bile acid levels and fibroblast growth factor 19 (FGF19), liver gene expression profiles and gut microbiome compositions were determined in patients with NAFLD, high-fat diet-fed rats and their controls. Serum concentrations of primary and secondary bile acids were increased in patients with NAFLD. In per cent, the farnesoid X receptor (FXR) antagonistic DCA was increased, while the agonistic CDCA was decreased in NAFLD. Increased mRNA expression for cytochrome P450 7A1, Na + -taurocholate cotransporting polypeptide and paraoxonase 1, no change in mRNA expression for small heterodimer partner and bile salt export pump, and reduced serum FGF19 were evidence of impaired FXR and fibroblast growth factor receptor 4 (FGFR4)-mediated signalling in NAFLD. Taurine and glycine metabolising bacteria were increased in the gut of patients with NAFLD, reflecting increased secondary bile acid production. Similar changes in liver gene expression and the gut microbiome were observed in high-fat diet-fed rats. The serum bile acid profile, the hepatic gene expression pattern and the gut microbiome composition consistently support an elevated bile acid production in NAFLD. The increased proportion of FXR antagonistic bile acid explains, at least in part, the suppression of hepatic FXR-mediated and FGFR4-mediated signalling. Our study suggests that future NAFLD intervention may target the components of FXR signalling, including the bile acid converting gut microbiome. © Article

The Role of Thought Suppression, Meta-Cognitive Factors and Negative Emotions in Prediction of Substance Dependency Disorder

Directory of Open Access Journals (Sweden)

Omid Saed

2011-08-01

Full Text Available Introduction: This study investigated the role of thought suppression, meta- cognitive factors, and negative emotions in predicting of substance dependency disorder. Method: Subjects were 70 patients with substance dependence disorder and 70 normal individuals (total 140. Substance dependants were selected of outpatient treatment centers and the normal sample was selected of the general population too. Sampling methods in both samples were convenience sampling. All people were assessed by MCQ-30, White Bear Suppression Inventory, and Beck’s Anxiety and Depression Questionnaires. For data analysis, discriminant analysis were used. Results: Negative meta-cognitive beliefs about worry, depression, and thought suppression were the most significant predictors of substance dependence disorder. Conclusion: Through meta-cognitive beliefs, thought suppression and negative emotion (especially depression, substance dependency disorder can be predicted. Based on this model can be used to take a substance dependency disorder prevention approach and psychotherapy approach (based on cognitive and meta-cognitive therapies. In addition, the findings of this research can be applied in clinical and counseling environments to help substance dependant clients.

Assessing the Role of ETHYLENE RESPONSE FACTOR Transcriptional Repressors in Salicylic Acid-Mediated Suppression of Jasmonic Acid-Responsive Genes.

Science.gov (United States)

Caarls, Lotte; Van der Does, Dieuwertje; Hickman, Richard; Jansen, Wouter; Verk, Marcel C Van; Proietti, Silvia; Lorenzo, Oscar; Solano, Roberto; Pieterse, Corné M J; Van Wees, Saskia C M

2017-02-01

Salicylic acid (SA) and jasmonic acid (JA) cross-communicate in the plant immune signaling network to finely regulate induced defenses. In Arabidopsis, SA antagonizes many JA-responsive genes, partly by targeting the ETHYLENE RESPONSE FACTOR (ERF)-type transcriptional activator ORA59. Members of the ERF transcription factor family typically bind to GCC-box motifs in the promoters of JA- and ethylene-responsive genes, thereby positively or negatively regulating their expression. The GCC-box motif is sufficient for SA-mediated suppression of JA-responsive gene expression. Here, we investigated whether SA-induced ERF-type transcriptional repressors, which may compete with JA-induced ERF-type activators for binding at the GCC-box, play a role in SA/JA antagonism. We selected ERFs that are transcriptionally induced by SA and/or possess an EAR transcriptional repressor motif. Several of the 16 ERFs tested suppressed JA-dependent gene expression, as revealed by enhanced JA-induced PDF1.2 or VSP2 expression levels in the corresponding erf mutants, while others were involved in activation of these genes. However, SA could antagonize JA-induced PDF1.2 or VSP2 in all erf mutants, suggesting that the tested ERF transcriptional repressors are not required for SA/JA cross-talk. Moreover, a mutant in the co-repressor TOPLESS, that showed reduction in repression of JA signaling, still displayed SA-mediated antagonism of PDF1.2 and VSP2. Collectively, these results suggest that SA-regulated ERF transcriptional repressors are not essential for antagonism of JA-responsive gene expression by SA. We further show that de novo SA-induced protein synthesis is required for suppression of JA-induced PDF1.2, pointing to SA-stimulated production of an as yet unknown protein that suppresses JA-induced transcription. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Predicting acid dew point with a semi-empirical model

International Nuclear Information System (INIS)

Xiang, Baixiang; Tang, Bin; Wu, Yuxin; Yang, Hairui; Zhang, Man; Lu, Junfu

2016-01-01

Highlights: • The previous semi-empirical models are systematically studied. • An improved thermodynamic correlation is derived. • A semi-empirical prediction model is proposed. • The proposed semi-empirical model is validated. - Abstract: Decreasing the temperature of exhaust flue gas in boilers is one of the most effective ways to further improve the thermal efficiency, electrostatic precipitator efficiency and to decrease the water consumption of desulfurization tower, while, when this temperature is below the acid dew point, the fouling and corrosion will occur on the heating surfaces in the second pass of boilers. So, the knowledge on accurately predicting the acid dew point is essential. By investigating the previous models on acid dew point prediction, an improved thermodynamic correlation formula between the acid dew point and its influencing factors is derived first. And then, a semi-empirical prediction model is proposed, which is validated with the data both in field test and experiment, and comparing with the previous models.

Activation of peroxisome proliferator-activated receptor-{alpha} (PPAR{alpha}) suppresses postprandial lipidemia through fatty acid oxidation in enterocytes

Energy Technology Data Exchange (ETDEWEB)

Kimura, Rino [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Takahashi, Nobuyuki, E-mail: nobu@kais.kyoto-u.ac.jp [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Murota, Kaeko [Department of Life Science, School of Science and Engineering, Kinki University, Osaka 770-8503 (Japan); Yamada, Yuko [Laboratory of Physiological Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Niiya, Saori; Kanzaki, Noriyuki; Murakami, Yoko [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Moriyama, Tatsuya [Department of Applied Cell Biology, Graduate School of Agriculture, Kinki University, Nara 631-8505 (Japan); Goto, Tsuyoshi; Kawada, Teruo [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan)

2011-06-24

Highlights: {yields} PPAR{alpha} activation increased mRNA expression levels of fatty acid oxidation-related genes in human intestinal epithelial Caco-2 cells. {yields} PPAR{alpha} activation also increased oxygen consumption rate and CO{sub 2} production and decreased secretion of triglyceride and ApoB from Caco-2 cells. {yields} Orally administration of bezafibrate increased mRNA expression levels of fatty acid oxidation-related genes and CO{sub 2} production in small intestinal epithelial cells. {yields} Treatment with bezafibrate decreased postprandial serum concentration of triglyceride after oral injection of olive oil in mice. {yields} It suggested that intestinal lipid metabolism regulated by PPAR{alpha} activation suppresses postprandial lipidemia. -- Abstract: Activation of peroxisome proliferator-activated receptor (PPAR)-{alpha} which regulates lipid metabolism in peripheral tissues such as the liver and skeletal muscle, decreases circulating lipid levels, thus improving hyperlipidemia under fasting conditions. Recently, postprandial serum lipid levels have been found to correlate more closely to cardiovascular diseases than fasting levels, although fasting hyperlipidemia is considered an important risk of cardiovascular diseases. However, the effect of PPAR{alpha} activation on postprandial lipidemia has not been clarified. In this study, we examined the effects of PPAR{alpha} activation in enterocytes on lipid secretion and postprandial lipidemia. In Caco-2 enterocytes, bezafibrate, a potent PPAR{alpha} agonist, increased mRNA expression levels of fatty acid oxidation-related genes, such as acyl-CoA oxidase, carnitine palmitoyl transferase, and acyl-CoA synthase, and oxygen consumption rate (OCR) and suppressed secretion levels of both triglycerides and apolipoprotein B into the basolateral side. In vivo experiments revealed that feeding high-fat-diet containing bezafibrate increased mRNA expression levels of fatty acid oxidation-related genes and

Salicylic acid suppresses jasmonic acid signaling downstream of SCFCOI1-JAZ by targeting GCC promoter motifs via transcription factor ORA59.

Science.gov (United States)

Van der Does, Dieuwertje; Leon-Reyes, Antonio; Koornneef, Annemart; Van Verk, Marcel C; Rodenburg, Nicole; Pauwels, Laurens; Goossens, Alain; Körbes, Ana P; Memelink, Johan; Ritsema, Tita; Van Wees, Saskia C M; Pieterse, Corné M J

2013-02-01

Antagonism between the defense hormones salicylic acid (SA) and jasmonic acid (JA) plays a central role in the modulation of the plant immune signaling network, but the molecular mechanisms underlying this phenomenon are largely unknown. Here, we demonstrate that suppression of the JA pathway by SA functions downstream of the E3 ubiquitin-ligase Skip-Cullin-F-box complex SCF(COI1), which targets JASMONATE ZIM-domain transcriptional repressor proteins (JAZs) for proteasome-mediated degradation. In addition, neither the stability nor the JA-induced degradation of JAZs was affected by SA. In silico promoter analysis of the SA/JA crosstalk transcriptome revealed that the 1-kb promoter regions of JA-responsive genes that are suppressed by SA are significantly enriched in the JA-responsive GCC-box motifs. Using GCC:GUS lines carrying four copies of the GCC-box fused to the β-glucuronidase reporter gene, we showed that the GCC-box motif is sufficient for SA-mediated suppression of JA-responsive gene expression. Using plants overexpressing the GCC-box binding APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) transcription factors ERF1 or ORA59, we found that SA strongly reduces the accumulation of ORA59 but not that of ERF1. Collectively, these data indicate that the SA pathway inhibits JA signaling downstream of the SCF(COI1)-JAZ complex by targeting GCC-box motifs in JA-responsive promoters via a negative effect on the transcriptional activator ORA59.

Acidic conditions induce the suppression of CD86 and CD54 expression in THP-1 cells.

Science.gov (United States)

Mitachi, Takafumi; Mezaki, Minori; Yamashita, Kunihiko; Itagaki, Hiroshi

2018-01-01

To evaluate the sensitization potential of chemicals in cosmetics, using non-animal methods, a number of in vitro safety tests have been designed. Current assays are based on the expression of cell surface markers, such as CD86 and CD54, which are associated with the activation of dendritic cells, in skin sensitization tests. However, these markers are influenced by culture conditions through activating danger signals. In this study, we investigated the relationship between extracellular pH and the expression of the skin sensitization test human cell line activation test (h-CLAT) markers CD86 and CD54. We measured expression levels after THP-1 cells were exposed to representative contact allergens, i.e., 2,4-dinitrochlorobenzene and imidazolidinyl urea, under acidic conditions. These conditions were set by exposure to hydrochloric acid, lactic acid, and citric acid. An acidic extracellular pH (6-7) suppressed the augmentation of CD86 and CD54 levels by the sensitizer. Additionally, when the CD86/CD54 expression levels were suppressed, a reduction in the intracellular pH was confirmed. Furthermore, we observed that Na + /H + exchanger 1 (NHE-1), a protein that contributes to the regulation of extracellular/intracellular pH, is involved in CD86 and CD54 expression. These findings suggest that the extracellular/intracellular pH has substantial effects on in vitro skin sensitization markers and should be considered in evaluations of the safety of mixtures and commercial products in the future.

Suppression of gastric acid increases the risk of developing immunoglobulin E-mediated drug hypersensitivity: human diclofenac sensitization and a murine sensitization model.

Science.gov (United States)

Riemer, A B; Gruber, S; Pali-Schöll, I; Kinaciyan, T; Untersmayr, E; Jensen-Jarolim, E

2010-03-01

Hypersensitivity reactions towards non-steroidal anti-inflammatory drugs (NSAID) are common, although true allergies are detectable only in a subgroup of patients. The current study was prompted by a case observation, where a patient experienced generalized urticaria following his second course of diclofenac and proton pump inhibitor medication, and was found to have diclofenac-specific IgE. During recent years, our group has been investigating the importance of gastric digestion in the development of food allergies, demonstrating anti-acid medication as a risk factor for sensitization against food proteins. Here, we aimed to investigate whether the mechanism of food allergy induction described can also be causative in NSAID allergy, using diclofenac as a paradigm. We subjected BALB/c mice to several oral immunization regimens modelled after the patient's medication intake. Diclofenac was applied with or without gastric acid suppression, in various doses, alone or covalently coupled to albumin, a protein abundant in gastric juices. Immune responses were assessed on the antibody level, and functionally examined by in vitro and in vivo crosslinking assays. Only mice receiving albumin-coupled diclofenac under gastric acid suppression developed anti-diclofenac IgG1 and IgE, whereas no immune responses were induced by the drug alone or without gastric acid suppression. Antibody induction was dose dependent with the group receiving the higher dose of the drug showing sustained anti-diclofenac titres. The antibodies induced triggered basophil degranulation in vitro and positive skin tests in vivo. Gastric acid suppression was found to be a causative mechanism in the induction of IgE-mediated diclofenac allergy.

Nucleic acid secondary structure prediction and display.

OpenAIRE

Stüber, K

1986-01-01

A set of programs has been developed for the prediction and display of nucleic acid secondary structures. Information from experimental data can be used to restrict or enforce secondary structural elements. The predictions can be displayed either on normal line printers or on graphic devices like plotters or graphic terminals.

Histone deacetylase inhibitor valproic acid promotes the induction of pluripotency in mouse fibroblasts by suppressing reprogramming-induced senescence stress

Energy Technology Data Exchange (ETDEWEB)

Zhai, Yingying; Chen, Xi; Yu, Dehai [Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061 (China); Stanford University Medical School, Palo Alto Veterans Institute for Research, Palo Alto, CA 94304 (United States); Li, Tao [Stanford University Medical School, Palo Alto Veterans Institute for Research, Palo Alto, CA 94304 (United States); Cui, Jiuwei; Wang, Guanjun [Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061 (China); Hu, Ji-Fan, E-mail: jifan@stanford.edu [Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061 (China); Stanford University Medical School, Palo Alto Veterans Institute for Research, Palo Alto, CA 94304 (United States); Li, Wei, E-mail: jdyylw@163.com [Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061 (China)

2015-09-10

Histone deacetylase inhibitor valproic acid (VPA) has been used to increase the reprogramming efficiency of induced pluripotent stem cell (iPSC) from somatic cells, yet the specific molecular mechanisms underlying this effect is unknown. Here, we demonstrate that reprogramming with lentiviruses carrying the iPSC-inducing factors (Oct4-Sox2-Klf4-cMyc, OSKM) caused senescence in mouse fibroblasts, establishing a stress barrier for cell reprogramming. Administration of VPA protected cells from reprogramming-induced senescent stress. Using an in vitro pre-mature senescence model, we found that VPA treatment increased cell proliferation and inhibited apoptosis through the suppression of the p16/p21 pathway. In addition, VPA also inhibited the G2/M phase blockage derived from the senescence stress. These findings highlight the role of VPA in breaking the cell senescence barrier required for the induction of pluripotency. - Highlights: • Histone deacetylase inhibitor valproic acid enhances iPSC induction. • Valproic acid suppresses reprogramming-induced senescence stress. • Valproic acid downregulates the p16/p21 pathway in reprogramming. • This study demonstrates a new mechanistic role of valproic acid in enhancing reprogramming.

Impact of persistent, frequent regurgitation on quality of life in heartburn responders treated with acid suppression: a multinational primary care study.

Science.gov (United States)

Kahrilas, P J; Howden, C W; Wernersson, B; Denison, H; Nuevo, J; Gisbert, J P

2013-05-01

In gastro-oesophageal reflux disease (GERD), heartburn responds well to acid suppression, but regurgitation is a common cause of incomplete treatment response. To assess the prevalence and burden of persistent, frequent regurgitation in primary care patients with GERD treated with acid suppression. We analysed observational data from 134 sites across six European countries in patients diagnosed with GERD. Within 3 months of the index visit, symptoms were assessed using the Reflux Disease Questionnaire, and their impact on sleep and work productivity with the Quality of Life in Reflux and Dyspepsia questionnaire and the Work Productivity and Activity Impairment Questionnaire, respectively. Patients provided information on concomitant over-the-counter (OTC) GERD medication use. Persistent, frequent (3-7 days/week) regurgitation was reported by 13.2% (153/1156) of GERD patients with no heartburn on acid suppression; the prevalence was very similar for patients with up to 2 days/week of ongoing mild heartburn. Among patients without heartburn, sleep disturbance of any type was reported by 50.7-60.1% with persistent, frequent regurgitation, compared with 38.1-51.1% and 14.4-19.2% of those with less frequent or no regurgitation respectively. Persistent, frequent regurgitation was associated with increased use of OTC medication and more hours of work missed, whether mild, infrequent heartburn was present or not. Frequent regurgitation, which persisted in 12-13% of patients with no or infrequent, mild heartburn on acid suppression, negatively affected sleep and work productivity, and increased use of OTC medication. Persistent, frequent regurgitation is problematic for primary care patients with GERD. © 2013 Blackwell Publishing Ltd.

Ethylene signaling renders the jasmonate response of Arabidopsis insensitive to future suppression by salicylic Acid.

Science.gov (United States)

Leon-Reyes, Antonio; Du, Yujuan; Koornneef, Annemart; Proietti, Silvia; Körbes, Ana P; Memelink, Johan; Pieterse, Corné M J; Ritsema, Tita

2010-02-01

Cross-talk between jasmonate (JA), ethylene (ET), and Salicylic acid (SA) signaling is thought to operate as a mechanism to fine-tune induced defenses that are activated in response to multiple attackers. Here, 43 Arabidopsis genotypes impaired in hormone signaling or defense-related processes were screened for their ability to express SA-mediated suppression of JA-responsive gene expression. Mutant cev1, which displays constitutive expression of JA and ET responses, appeared to be insensitive to SA-mediated suppression of the JA-responsive marker genes PDF1.2 and VSP2. Accordingly, strong activation of JA and ET responses by the necrotrophic pathogens Botrytis cinerea and Alternaria brassicicola prior to SA treatment counteracted the ability of SA to suppress the JA response. Pharmacological assays, mutant analysis, and studies with the ET-signaling inhibitor 1-methylcyclopropene revealed that ET signaling renders the JA response insensitive to subsequent suppression by SA. The APETALA2/ETHYLENE RESPONSE FACTOR transcription factor ORA59, which regulates JA/ET-responsive genes such as PDF1.2, emerged as a potential mediator in this process. Collectively, our results point to a model in which simultaneous induction of the JA and ET pathway renders the plant insensitive to future SA-mediated suppression of JA-dependent defenses, which may prioritize the JA/ET pathway over the SA pathway during multi-attacker interactions.

Distinguishing among potential mechanisms of singleton suppression.

Science.gov (United States)

Gaspelin, Nicholas; Luck, Steven J

2018-04-01

Previous research has revealed that people can suppress salient stimuli that might otherwise capture visual attention. The present study tests between 3 possible mechanisms of visual suppression. According to first-order feature suppression models , items are suppressed on the basis of simple feature values. According to second-order feature suppression models , items are suppressed on the basis of local discontinuities within a given feature dimension. According to global-salience suppression models , items are suppressed on the basis of their dimension-independent salience levels. The current study distinguished among these models by varying the predictability of the singleton color value. If items are suppressed by virtue of salience alone, then it should not matter whether the singleton color is predictable. However, evidence from probe processing and eye movements indicated that suppression is possible only when the color values are predictable. Moreover, the ability to suppress salient items developed gradually as participants gained experience with the feature that defined the salient distractor. These results are consistent with first-order feature suppression models, and are inconsistent with the other models of suppression. In other words, people primarily suppress salient distractors on the basis of their simple features and not on the basis of salience per se. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

GABA predicts visual intelligence.

Science.gov (United States)

Cook, Emily; Hammett, Stephen T; Larsson, Jonas

2016-10-06

Early psychological researchers proposed a link between intelligence and low-level perceptual performance. It was recently suggested that this link is driven by individual variations in the ability to suppress irrelevant information, evidenced by the observation of strong correlations between perceptual surround suppression and cognitive performance. However, the neural mechanisms underlying such a link remain unclear. A candidate mechanism is neural inhibition by gamma-aminobutyric acid (GABA), but direct experimental support for GABA-mediated inhibition underlying suppression is inconsistent. Here we report evidence consistent with a global suppressive mechanism involving GABA underlying the link between sensory performance and intelligence. We measured visual cortical GABA concentration, visuo-spatial intelligence and visual surround suppression in a group of healthy adults. Levels of GABA were strongly predictive of both intelligence and surround suppression, with higher levels of intelligence associated with higher levels of GABA and stronger surround suppression. These results indicate that GABA-mediated neural inhibition may be a key factor determining cognitive performance and suggests a physiological mechanism linking surround suppression and intelligence. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Prostatic acid phosphatase is an ectonucleotidase and suppresses pain by generating adenosine

Science.gov (United States)

Zylka, Mark J.; Sowa, Nathaniel A.; Taylor-Blake, Bonnie; Twomey, Margaret A.; Herrala, Annakaisa; Voikar, Vootele; Vihko, Pirkko

2008-01-01

SUMMARY Thiamine monophosphatase (TMPase, also known as Fluoride-Resistant Acid Phosphatase) is a classic histochemical marker of small-diameter dorsal root ganglia neurons. The molecular identity of TMPase is currently unknown. We found that TMPase is identical to the transmembrane isoform of Prostatic Acid Phosphatase (PAP), an enzyme with unknown molecular and physiological functions. We then found that PAP knockout mice have normal acute pain sensitivity but enhanced sensitivity in chronic inflammatory and neuropathic pain models. In gain-of-function studies, intraspinal injection of PAP protein has potent anti-nociceptive, anti-hyperalgesic and anti-allodynic effects that last longer than the opioid analgesic morphine. PAP suppresses pain by functioning as an ecto-5’-nucleotidase. Specifically, PAP dephosphorylates extracellular adenosine monophosphate (AMP) to adenosine and activates A1-adenosine receptors in dorsal spinal cord. Our studies reveal molecular and physiological functions for PAP in purine nucleotide metabolism and nociception and suggest a novel use for PAP in the treatment of chronic pain. PMID:18940592

Predictive mapping of the acidifying potential for acid sulfate soils

DEFF Research Database (Denmark)

Boman, A; Beucher, Amélie; Mattbäck, S

Developing methods for the predictive mapping of the potential environmental impact from acid sulfate soils is important because recent studies (e.g. Mattbäck et al., under revision) have shown that the environmental hazards (e.g. leaching of acidity) related to acid sulfate soils vary depending...... on their texture (clay, silt, sand etc.). Moreover, acidity correlates, not only with the sulfur content, but also with the electrical conductivity (EC) measured after incubation. Electromagnetic induction (EMI) data collected from an EM38 proximal sensor also enabled the detailed mapping of acid sulfate soils...... over a field (Huang et al., 2014).This study aims at assessing the use of EMI data for the predictive mapping of the acidifying potential in an acid sulfate soil area in western Finland. Different supervised classification modelling techniques, such as Artificial Neural Networks (Beucher et al., 2015...

Evaporation suppression from water reservoirs using floating covers: Lab scale observations and model predictions

Science.gov (United States)

Or, D.; Lehmann, P.; Aminzadeh, M.; Sommer, M.; Wey, H.; Wunderli, H.; Breitenstein, D.

2016-12-01

The competition over dwindling fresh water resources is expected to intensify with projected increase in human population in arid regions, expansion of irrigated land and changes in climate and drought patterns. The volume of water stored in reservoirs would also increase to mitigate seasonal shortages due to rainfall variability and to meet irrigation water needs. By some estimates up to half of the stored water is lost to evaporation thereby exacerbating the water scarcity problem. Recently, there is an upsurge in the use of self-assembling floating covers to suppress evaporation, yet the design, and implementation remain largely empirical. Studies have shown that evaporation suppression is highly nonlinear, as also known from a century of research on gas exchange from plant leaves (that often evaporate as free water surfaces through stomata that are only 1% of leaf area). We report a systematic evaluation of different cover types and external drivers (radiation, wind, wind+radiation) on evaporation suppression and energy balance of a 1.4 m2 basin placed in a wind-tunnel. Surprisingly, evaporation suppression by black and white floating covers (balls and plates) were similar despite significantly different energy balance regimes over the cover surfaces. Moreover, the evaporation suppression efficiency was a simple function of the uncovered area (square root of the uncovered fraction) with linear relations with the covered area in some cases. The thermally decoupled floating covers offer an efficient solution to the evaporation suppression with limited influence of the surface energy balance (water temperature for black and white covers was similar and remained nearly constant). The results will be linked with a predictive evaporation-energy balance model and issues of spatial scales and long exposure times will be studied.

ω-3 Polyunsaturated fatty acids and their cytochrome P450-derived metabolites suppress colorectal tumor development in mice.

Science.gov (United States)

Wang, Weicang; Yang, Jun; Nimiya, Yoshiki; Lee, Kin Sing Stephen; Sanidad, Katherine; Qi, Weipeng; Sukamtoh, Elvira; Park, Yeonhwa; Liu, Zhenhua; Zhang, Guodong

2017-10-01

Many studies have shown that dietary intake of ω-3 polyunsaturated fatty acids (PUFAs) reduces the risks of colorectal cancer; however, the underlying mechanisms are not well understood. Here we used a LC-MS/MS-based lipidomics to explore the role of eicosanoid signaling in the anti-colorectal cancer effects of ω-3 PUFAs. Our results showed that dietary feeding of ω-3 PUFAs-rich diets suppressed growth of MC38 colorectal tumor, and modulated profiles of fatty acids and eicosanoid metabolites in C57BL/6 mice. Notably, we found that dietary feeding of ω-3 PUFAs significantly increased levels of epoxydocosapentaenoic acids (EDPs, metabolites of ω-3 PUFA produced by cytochrome P450 enzymes) in plasma and tumor tissue of the treated mice. We further showed that systematic treatment with EDPs (dose=0.5 mg/kg per day) suppressed MC38 tumor growth in mice, with reduced expressions of pro-oncogenic genes such as C-myc, Axin2, and C-jun in tumor tissues. Together, these results support that formation of EDPs might contribute to the anti-colorectal cancer effects of ω-3 PUFAs. Copyright © 2017 Elsevier Inc. All rights reserved.

Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants in acutely ill adult intensive care patients

DEFF Research Database (Denmark)

Krag, Mette; Perner, Anders; Wetterslev, Jørn

2015-01-01

PURPOSE: To describe the prevalence of, risk factors for, and prognostic importance of gastrointestinal (GI) bleeding and use of acid suppressants in acutely ill adult intensive care patients. METHODS: We included adults without GI bleeding who were acutely admitted to the intensive care unit (IC...

[Effects of sucralfate and acid-suppressive drugs on preventing ventilator- associated pneumonia of mechanically ventilated patients: a meta-analysis].

Science.gov (United States)

He, Hongli; Hu, Shuling; Chen, Qihong; Liu, Ling; Huang, Yingzi; Yang, Yi; Qiu, Haibo

2014-01-01

To evaluate the effect of sucralfate and acid-suppressive drugs on preventing ventilator-associated pneumonia (VAP) in mechanically ventilated patients. All randomized controlled trials (RCTs), which studied the effect of sucralfate and acid-suppressive drugs on the incidence of VAP in mechanically ventilated patients, were searched from PubMed, Embase and the Cochrane Library during January 1966 to March 2013 via manual and computer retrieval. All related data were extracted. Meta analysis was conducted using the statistical software RevMan 5.2 and the quality of the RCTs was strictly evaluated with the methods recommended by the Cochrane Collaboration. A total of 15 RCTs involving 1315 patients in the sucralfate group and 1568 patients in the acid-suppressive drug group were included in this study. The incidence of VAP was significantly reduced in the sucralfate group (RR = 0.81, 95%CI 0.7-0.95, P = 0.008), while no difference was found between the two groups in the incidence of stress-related gastrointestinal bleeding (RR = 0.96, 95%CI 0.59-1.58, P = 0.88). No statistical difference was found in the days on ventilator, duration of ICU stay and ICU mortality in the two groups (all P values > 0.05). In patients with mechanical ventilation, sucralfate could decrease the incidence of VAP, while has no such effect on the stress-related gastrointestinal bleeding, the days on ventilator, duration of ICU stay and ICU mortality.

Salicylic Acid Suppresses Jasmonic Acid Signaling Downstream of SCFCOI1-JAZ by Targeting GCC Promoter Motifs via Transcription Factor ORA59[C][W][OA

Science.gov (United States)

Van der Does, Dieuwertje; Leon-Reyes, Antonio; Koornneef, Annemart; Van Verk, Marcel C.; Rodenburg, Nicole; Pauwels, Laurens; Goossens, Alain; Körbes, Ana P.; Memelink, Johan; Ritsema, Tita; Van Wees, Saskia C.M.; Pieterse, Corné M.J.

2013-01-01

Antagonism between the defense hormones salicylic acid (SA) and jasmonic acid (JA) plays a central role in the modulation of the plant immune signaling network, but the molecular mechanisms underlying this phenomenon are largely unknown. Here, we demonstrate that suppression of the JA pathway by SA functions downstream of the E3 ubiquitin-ligase Skip-Cullin-F-box complex SCFCOI1, which targets JASMONATE ZIM-domain transcriptional repressor proteins (JAZs) for proteasome-mediated degradation. In addition, neither the stability nor the JA-induced degradation of JAZs was affected by SA. In silico promoter analysis of the SA/JA crosstalk transcriptome revealed that the 1-kb promoter regions of JA-responsive genes that are suppressed by SA are significantly enriched in the JA-responsive GCC-box motifs. Using GCC:GUS lines carrying four copies of the GCC-box fused to the β-glucuronidase reporter gene, we showed that the GCC-box motif is sufficient for SA-mediated suppression of JA-responsive gene expression. Using plants overexpressing the GCC-box binding APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) transcription factors ERF1 or ORA59, we found that SA strongly reduces the accumulation of ORA59 but not that of ERF1. Collectively, these data indicate that the SA pathway inhibits JA signaling downstream of the SCFCOI1-JAZ complex by targeting GCC-box motifs in JA-responsive promoters via a negative effect on the transcriptional activator ORA59. PMID:23435661

Ethylene signaling renders the jasmonate response of Arabidopsis insensitive to future suppression by salicylic acid

OpenAIRE

Leon Reyes, H.A.; Du, Y.; Koornneef, A.; Proietti, S.; Körbes, A.P.; Memelink, J.; Pieterse, C.M.J.; Ritsema, T.

2010-01-01

Cross-talk between jasmonate (JA), ethylene (ET), and Salicylic acid (SA) signaling is thought to operate as a mechanism to fine-tune induced defenses that are activated in response to multiple attackers. Here, 43 Arabidopsis genotypes impaired in hormone signaling or defense-related processes were screened for their ability to express SA-mediated suppression of JA-responsive gene expression. Mutant cev1, which displays constitutive expression of JA and ET responses, appeared to be insensitiv...

Prediction of molecular alignment of nucleic acids in aligned media

International Nuclear Information System (INIS)

Wu Bin; Petersen, Michael; Girard, Frederic; Tessari, Marco; Wijmenga, Sybren S.

2006-01-01

We demonstrate - using the data base of all deposited DNA and RNA structures aligned in Pf1-medium and RDC refined - that for nucleic acids in a Pf1-medium the electrostatic alignment tensor can be predicted reliably and accurately via a simple and fast calculation based on the gyration tensor spanned out by the phosphodiester atoms. The rhombicity is well predicted over its full range from 0 to 0.66, while the alignment tensor orientation is predicted correctly for rhombicities up to ca. 0.4, for larger rhombicities it appears to deviate somewhat more than expected based on structural noise and measurement error. This simple analytical approach is based on the Debye-Huckel approximation for the electrostatic interaction potential, valid at distances sufficiently far away from a poly-ionic charged surface, a condition naturally enforced when the charge of alignment medium and solute are of equal sign, as for nucleic acids in a Pf1-phage medium. For the usual salt strengths and nucleic acid sizes, the Debye-Huckel screening length is smaller than the nucleic acid size, but large enough for the collective of Debye-Huckel spheres to encompass the whole molecule. The molecular alignment is then purely electrostatic, but it's functional form is under these conditions similar to that for steric alignment. The proposed analytical expression allows for very fast calculation of the alignment tensor and hence RDCs from the conformation of the nucleic acid molecule. This information provides opportunities for improved structure determination of nucleic acids, including better assessment of dynamics in (multi-domain) nucleic acids and the possibility to incorporate alignment tensor prediction from shape directly into the structure calculation process. The procedures are incorporated into MATLAB scripts, which are available on request

Suppression of pool fires with HRC-125 in a simulated engine nacelle.

Energy Technology Data Exchange (ETDEWEB)

Keyser, David R. (INS, Inc., Lexington Park, MD); Hewson, John C.

2007-06-01

CFD simulations are conducted to predict the distribution of fire suppressant in an engine nacelle and to predict the suppression of pool fires by the application of this suppressant. In the baseline configuration, which is based on an installed system, suppressant is injected through four nozzles at a rate fast enough to suppress all simulated pool fires. Variations that reduce the mass of the suppression system (reducing the impact of the suppression system on meeting mission needs) are considered, including a reduction in the rate of suppressant injection, a reduction in the mass of suppressant and a reduction in the number of nozzles. In general, these variations should work to reduce the effectiveness of the suppression system, but the CFD results point out certain changes that have negligible impact, at least for the range of phenomena considered here. The results are compared with measurements where available. Comparisons with suppressant measurements are reasonable. A series of twenty-three fire suppression tests were conducted to check the predictions. The pre-test predictions were generally successful in identifying the range of successful suppression tests. In two separate cases, each where one nozzle of the suppression system was capped, the simulation results did indicate a failure to suppress for a condition where the tests indicated successful suppression. When the test-suppressant discharge rate was reduced by roughly 25%, the tests were in agreement with the predictions. That is, the simulations predict a failure to suppress slightly before observed in these cases.

Suppression Effects of Betaine-Enriched Spinach on Hyperhomocysteinemia Induced by Guanidinoacetic Acid and Choline Deficiency in Rats

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Yi-Qun Liu

2014-01-01

Full Text Available Betaine is an important natural component of rich food sources, especially spinach. Rats were fed diets with betaine or spinach powder at the same level of betaine for 10 days to investigate the dose-dependent effects of spinach powder supplementation on hyperhomocysteinemia induced by guanidinoacetic acid (GAA addition and choline deprivation. The GAA-induced hyperhomocysteinemia in rats fed 25% casein diet (25C was significantly suppressed by supplementation with betaine or spinach, and it was completely suppressed by taking 11.0% spinach supplementation. The choline deprivation-induced enhancement of plasma homocysteine concentration in rats fed 25% soybean protein diet (25S was markedly suppressed by 3.82% spinach. Supplementation with betaine or spinach partially prevented the effects of GAA on hepatic concentrations of methionine metabolites. The decrease in activity of betaine-homocysteine S-methyltransferase (BHMT and cystathionine β-synthase (CBS in GAA-induced hyperhomocysteinemia was recovered by supplementation with betaine or spinach. Supplementation with betaine or spinach did not affect BHMT activity, whereas it partially restored CBS activity in choline-deprived 25S. The results indicated that betaine or spinach could completely suppress the hyperhomocysteinemia induced by choline deficiency resulting from stimulating the homocysteine removal by both remethylation and cystathionine formation.

Resveratrol suppresses growth of cancer stem-like cells by inhibiting fatty acid synthase.

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Pandey, Puspa R; Okuda, Hiroshi; Watabe, Misako; Pai, Sudha K; Liu, Wen; Kobayashi, Aya; Xing, Fei; Fukuda, Koji; Hirota, Shigeru; Sugai, Tamotsu; Wakabayashi, Go; Koeda, Keisuke; Kashiwaba, Masahiro; Suzuki, Kazuyuki; Chiba, Toshimi; Endo, Masaki; Fujioka, Tomoaki; Tanji, Susumu; Mo, Yin-Yuan; Cao, Deliang; Wilber, Andrew C; Watabe, Kounosuke

2011-11-01

Resveratrol is a natural polyphenolic compound and has been shown to exhibit cardio-protective as well as anti-neoplastic effects on various types of cancers. However, the exact mechanism of its anti-tumor effect is not clearly defined. Resveratrol has been shown to have strong hypolipidemic effect on normal adipocytes and as hyper-lipogenesis is a hallmark of cancer cell physiology, the effect of resveratrol on lipid synthesis in cancer stem-like cells (CD24(-)/CD44(+)/ESA(+)) that were isolated from both ER+ and ER- breast cancer cell lines was examined. The authors found that resveratrol significantly reduced the cell viability and mammosphere formation followed by inducing apoptosis in cancer stem-like cells. This inhibitory effect of resveratrol is accompanied by a significant reduction in lipid synthesis which is caused by the down-regulation of the fatty acid synthase (FAS) gene followed by up-regulation of pro-apoptotic genes, DAPK2 and BNIP3. The activation of apoptotic pathway in the cancer stem-like cells was suppressed by TOFA and by Fumonisin B1, suggesting that resveratrol-induced apoptosis is indeed through the modulation of FAS-mediated cell survival signaling. Importantly, resveratrol was able to significantly suppress the growth of cancer stem-like cells in an animal model of xenograft without showing apparental toxicity. Taken together, the results of this study indicate that resveratrol is capable of inducing apoptosis in the cancer stem-like cells through suppression of lipogenesis by modulating FAS expression, which highlights a novel mechanism of anti-tumor effect of resveratrol.

Predicting nucleic acid binding interfaces from structural models of proteins.

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Dror, Iris; Shazman, Shula; Mukherjee, Srayanta; Zhang, Yang; Glaser, Fabian; Mandel-Gutfreund, Yael

2012-02-01

The function of DNA- and RNA-binding proteins can be inferred from the characterization and accurate prediction of their binding interfaces. However, the main pitfall of various structure-based methods for predicting nucleic acid binding function is that they are all limited to a relatively small number of proteins for which high-resolution three-dimensional structures are available. In this study, we developed a pipeline for extracting functional electrostatic patches from surfaces of protein structural models, obtained using the I-TASSER protein structure predictor. The largest positive patches are extracted from the protein surface using the patchfinder algorithm. We show that functional electrostatic patches extracted from an ensemble of structural models highly overlap the patches extracted from high-resolution structures. Furthermore, by testing our pipeline on a set of 55 known nucleic acid binding proteins for which I-TASSER produces high-quality models, we show that the method accurately identifies the nucleic acids binding interface on structural models of proteins. Employing a combined patch approach we show that patches extracted from an ensemble of models better predicts the real nucleic acid binding interfaces compared with patches extracted from independent models. Overall, these results suggest that combining information from a collection of low-resolution structural models could be a valuable approach for functional annotation. We suggest that our method will be further applicable for predicting other functional surfaces of proteins with unknown structure. Copyright © 2011 Wiley Periodicals, Inc.

The role of Health Insurance Companies in optimising drug prescription in Primary Care; The example of acid suppressing drugs

NARCIS (Netherlands)

Smeets, H.M.

2009-01-01

The use of Acid-suppressing drugs (ASDs) in the Netherlands increases more than 10% annually and of the Dutch population 3.5% uses ASD on a daily basis. However, indications for long term use of ASDs for gastrointestinal complaints are often not evidence based and many patients might be able to stop

Mycophenolic acid suppresses human pterygium and normal tenon fibroblast proliferation in vitro.

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Amer, Radgonde; Rabinowich, Liane; Maftsir, Genia; Puxeddu, Ilaria; Levi-Schaffer, Francesca; Solomon, Abraham

2010-10-01

To investigate whether mycophenolic acid (MPA) exerts antifibrotic effects on pterygium fibroblasts (PFB) with and without stimulation with fibrogenic cytokines, and to compare the efficacy of MPA with mitomycin (MMC) and dexamethasone (DXM) on PFB and tenon fibroblasts (TFB). TFB and PFB were obtained from tissue explants during strabismus or pterygium surgery. Proliferation of subconfluent fibroblasts ± basic fibroblast growth factor (bFGF) (10 ng/ml) was assessed by using the (3H) thymidine-incorporation assay. Cell cultures were incubated with MPA, MMC or DXM. Apoptosis was evaluated by quantifying Annexin V and propidium iodide positive cells with flow cytometry. MPA showed a concentration-dependent inhibition of proliferation of PFB ± bFGF as well as TFB ± bFGF. The antiproliferative effect of MPA was comparable with that of MMC and DXM. Short exposure of PFB to MPA under profibrogenic conditions was significantly inhibitory. No apoptotic effect was found on TFB. MPA suppressed tenon and pterygium fibroblast proliferation in vitro under basal and profibrogenic conditions. It was comparable with MMC under long-term exposure, but MMC was more suppressive under short-term exposure. MPA may be safer than MMC due to a more specific mechanism of action and lack of cytotoxicity. Further investigation is warranted regarding MPA concentrations that will lead to a potent antiproliferative effect in vivo.

High serum uric acid concentration predicts poor survival in patients with breast cancer.

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Yue, Cai-Feng; Feng, Pin-Ning; Yao, Zhen-Rong; Yu, Xue-Gao; Lin, Wen-Bin; Qian, Yuan-Min; Guo, Yun-Miao; Li, Lai-Sheng; Liu, Min

2017-10-01

Uric acid is a product of purine metabolism. Recently, uric acid has gained much attraction in cancer. In this study, we aim to investigate the clinicopathological and prognostic significance of serum uric acid concentration in breast cancer patients. A total of 443 female patients with histopathologically diagnosed breast cancer were included. After a mean follow-up time of 56months, survival was analysed using the Kaplan-Meier method. To further evaluate the prognostic significance of uric acid concentrations, univariate and multivariate Cox regression analyses were applied. Of the clinicopathological parameters, uric acid concentration was associated with age, body mass index, ER status and PR status. Univariate analysis identified that patients with increased uric acid concentration had a significantly inferior overall survival (HR 2.13, 95% CI 1.15-3.94, p=0.016). In multivariate analysis, we found that high uric acid concentration is an independent prognostic factor predicting death, but insufficient to predict local relapse or distant metastasis. Kaplan-Meier analysis indicated that high uric acid concentration is related to the poor overall survival (p=0.013). High uric acid concentration predicts poor survival in patients with breast cancer, and might serve as a potential marker for appropriate management of breast cancer patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Suppression sours sacrifice: emotional and relational costs of suppressing emotions in romantic relationships.

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Impett, Emily A; Kogan, Aleksandr; English, Tammy; John, Oliver; Oveis, Christopher; Gordon, Amie M; Keltner, Dacher

2012-06-01

What happens when people suppress their emotions when they sacrifice for a romantic partner? This multimethod study investigates how suppressing emotions during sacrifice shapes affective and relationship outcomes. In Part 1, dating couples came into the laboratory to discuss important romantic relationship sacrifices. Suppressing emotions was associated with emotional costs for the partner discussing his or her sacrifice. In Part 2, couples participated in a 14-day daily experience study. Within-person increases in emotional suppression during daily sacrifice were associated with decreases in emotional well-being and relationship quality as reported by both members of romantic dyads. In Part 3, suppression predicted decreases in relationship satisfaction and increases in thoughts about breaking up with a romantic partner 3 months later. In the first two parts of the study, authenticity mediated the costly effects of suppression. Implications for research on close relationships and emotion regulation are discussed.

Choice is good, but relevance is excellent: autonomy-enhancing and suppressing teacher behaviours predicting students' engagement in schoolwork.

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Assor, Avi; Kaplan, Haya; Roth, Guy

2002-06-01

This article examines two questions concerning teacher-behaviours that are characterised in Self-Determination Theory (Ryan & Deci, 2000) as autonomy-supportive or suppressive: (1) Can children differentiate among various types of autonomy-enhancing and suppressing teacher behaviours? (2) Which of those types of behaviour are particularly important in predicting feelings toward and engagement in schoolwork? It was hypothesised that teacher behaviours that help students to understand the relevance of schoolwork for their personal interests and goals are particularly important predictors of engagement in schoolwork. Israeli students in grades 3-5 (N = 498) and in grades 6-8 (N = 364) completed questionnaires assessing the variables of interest. Smallest Space Analyses indicated that both children and early adolescents can differentiate among three types of autonomy enhancing teacher behaviours - fostering relevance, allowing criticism, and providing choice - and three types of autonomy suppressing teacher behaviours - suppressing criticism, intruding, and forcing unmeaningful acts. Regression analyses supported the hypothesis concerning the importance of teacher behaviours that clarify the personal relevance of schoolwork. Among the autonomy-suppressing behaviours, 'Criticism-suppression' was the best predictor of feelings and engagement. The findings underscore the active and empathic nature of teachers' role in supporting students' autonomy, and suggest that autonomy-support is important not only for early adolescents but also for children. Discussion of potential determinants of the relative importance of various autonomy-affecting teacher actions suggests that provision of choice should not always be viewed as a major indicator of autonomy support.

Catechol Groups Enable Reactive Oxygen Species Scavenging-Mediated Suppression of PKD-NFkappaB-IL-8 Signaling Pathway by Chlorogenic and Caffeic Acids in Human Intestinal Cells

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Hee Soon Shin

2017-02-01

Full Text Available Chlorogenic acid (CHA and caffeic acid (CA are phenolic compounds found in coffee, which inhibit oxidative stress-induced interleukin (IL-8 production in intestinal epithelial cells, thereby suppressing serious cellular injury and inflammatory intestinal diseases. Therefore, we investigated the anti-inflammatory mechanism of CHA and CA, both of which inhibited hydrogen peroxide (H2O2-induced IL-8 transcriptional activity. They also significantly suppressed nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB transcriptional activity, nuclear translocation of the p65 subunit, and phosphorylation of IκB kinase (IKK. Additionally, upstream of IKK, protein kinase D (PKD was also suppressed. Finally, we found that they scavenged H2O2-induced reactive oxygen species (ROS and the functional moiety responsible for the anti-inflammatory effects of CHA and CA was the catechol group. Therefore, we conclude that the presence of catechol groups in CHA and CA allows scavenging of intracellular ROS, thereby inhibiting H2O2-induced IL-8 production via suppression of PKD-NF-κB signaling in human intestinal epithelial cells.

Acid-suppressive drug use during pregnancy and the risk of atopic dermatitis : A crossover study within the clinical practice research database

NARCIS (Netherlands)

Mulder, Bianca; Hak, Eelko; Schuiling-Veninga, Catharina C.M.; De Vries, Tjalling W.; Jick, Susan S.

2014-01-01

Background: One previous study of our group reported that acid suppressive drug use during pregnancy is associated with an increased risk for the development of atopic dermatitis in children. However, reported associations could have been confounded by unmeasured risk factors. Objectives: The aim of

Interpreting expression data with metabolic flux models: predicting Mycobacterium tuberculosis mycolic acid production.

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Caroline Colijn

2009-08-01

Full Text Available Metabolism is central to cell physiology, and metabolic disturbances play a role in numerous disease states. Despite its importance, the ability to study metabolism at a global scale using genomic technologies is limited. In principle, complete genome sequences describe the range of metabolic reactions that are possible for an organism, but cannot quantitatively describe the behaviour of these reactions. We present a novel method for modeling metabolic states using whole cell measurements of gene expression. Our method, which we call E-Flux (as a combination of flux and expression, extends the technique of Flux Balance Analysis by modeling maximum flux constraints as a function of measured gene expression. In contrast to previous methods for metabolically interpreting gene expression data, E-Flux utilizes a model of the underlying metabolic network to directly predict changes in metabolic flux capacity. We applied E-Flux to Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB. Key components of mycobacterial cell walls are mycolic acids which are targets for several first-line TB drugs. We used E-Flux to predict the impact of 75 different drugs, drug combinations, and nutrient conditions on mycolic acid biosynthesis capacity in M. tuberculosis, using a public compendium of over 400 expression arrays. We tested our method using a model of mycolic acid biosynthesis as well as on a genome-scale model of M. tuberculosis metabolism. Our method correctly predicts seven of the eight known fatty acid inhibitors in this compendium and makes accurate predictions regarding the specificity of these compounds for fatty acid biosynthesis. Our method also predicts a number of additional potential modulators of TB mycolic acid biosynthesis. E-Flux thus provides a promising new approach for algorithmically predicting metabolic state from gene expression data.

Pseudoracemic amino acid complexes: blind predictions for flexible two-component crystals.

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Görbitz, Carl Henrik; Dalhus, Bjørn; Day, Graeme M

2010-08-14

Ab initio prediction of the crystal packing in complexes between two flexible molecules is a particularly challenging computational chemistry problem. In this work we present results of single crystal structure determinations as well as theoretical predictions for three 1 ratio 1 complexes between hydrophobic l- and d-amino acids (pseudoracemates), known from previous crystallographic work to form structures with one of two alternative hydrogen bonding arrangements. These are accurately reproduced in the theoretical predictions together with a series of patterns that have never been observed experimentally. In this bewildering forest of potential polymorphs, hydrogen bonding arrangements and molecular conformations, the theoretical predictions succeeded, for all three complexes, in finding the correct hydrogen bonding pattern. For two of the complexes, the calculations also reproduce the exact space group and side chain orientations in the best ranked predicted structure. This includes one complex for which the observed crystal packing clearly contradicted previous experience based on experimental data for a substantial number of related amino acid complexes. The results highlight the significant recent advances that have been made in computational methods for crystal structure prediction.

Suppression of skin inflammation in keratinocytes and acute/chronic disease models by caffeic acid phenethyl ester.

Science.gov (United States)

Lim, Kyung-Min; Bae, SeungJin; Koo, Jung Eun; Kim, Eun-Sun; Bae, Ok-Nam; Lee, Joo Young

2015-04-01

Skin inflammation plays a central role in the pathophysiology and symptoms of diverse chronic skin diseases including atopic dermatitis (AD). In this study, we examined if caffeic acid phenethyl ester (CAPE), a skin-permeable bioactive compound from propolis, was protective against skin inflammation using in vitro cell system and in vivo animal disease models. CAPE suppressed TNF-α-induced NF-κB activation and expression of inflammatory cytokines in human keratinocytes (HaCaT). The potency and efficacy of CAPE were superior to those of a non-phenethyl derivative, caffeic acid. Consistently, topical treatment of CAPE (0.5 %) attenuated 12-O-tetradecanoylphorbol-13-acetate(TPA)-induced skin inflammation on mouse ear as CAPE reduced ear swelling and histologic inflammation scores. CAPE suppressed increased expression of pro-inflammatory molecules such as TNF-α, cyclooxygenase-2 and inducible NO synthase in TPA-stimulated skin. TPA-induced phosphorylation of IκB and ERK was blocked by CAPE suggesting that protective effects of CAPE on skin inflammation is attributed to inhibition of NF-κB activation. Most importantly, in an oxazolone-induced chronic dermatitis model, topical application of CAPE (0.5 and 1 %) was effective in alleviating AD-like symptoms such as increases of trans-epidermal water loss, skin thickening and serum IgE as well as histologic inflammation assessment. Collectively, our results propose CAPE as a promising candidate for a novel topical drug for skin inflammatory diseases.

Use of Acid-Suppressive Drugs in Pregnancy and the Risk of Childhood Asthma : Bidirectional Crossover Study using the General Practice Research Database

NARCIS (Netherlands)

Hak, Eelko; Mulder, Bianca; Schuiling-Veninga, Catharina C. M.; de Vries, Tjalling W.; Jick, Susan S.

Background Recent studies have reported an association between maternal use of gastric acid-suppressive drugs during pregnancy and asthma in the offspring, but the association could have been confounded by unmeasured risk factors. Objective We assessed the association between the use of

Use of Acid-Suppressive Drugs in Pregnancy and the Risk of Childhood Asthma : Bidirectional Crossover Study using the General Practice Research Database

NARCIS (Netherlands)

Hak, Eelko; Mulder, Bianca; Schuiling-Veninga, Catharina C. M.; de Vries, Tjalling W.; Jick, Susan S.

2013-01-01

Background Recent studies have reported an association between maternal use of gastric acid-suppressive drugs during pregnancy and asthma in the offspring, but the association could have been confounded by unmeasured risk factors. Objective We assessed the association between the use of

Gastric ulcer treatment: cure of Helicobacter pylori infection without subsequent acid-suppressive therapy: is it effective?

Science.gov (United States)

van Zanten, Sander Veldhuyzen; van der Knoop, Bloeme

2008-06-01

Whether it is a requirement to continue with anti-secretory therapy following anti-Helicobacter therapy in H. pylori positive gastric ulcers is an important question. As gastric ulcers tend to heal more slowly than duodenal ulcers, may be asymptomatic or only causing mild symptoms and success at curing H. pylori with current fist line therapies is 80% at best, clinicians will likely err on the side of caution and continue acid suppressive therapy to ensure healing of gastric ulcers. This is certainly recommended when dealing with bleeding ulcers.

Anti-IL-17 Antibody Improves Hepatic Steatosis by Suppressing Interleukin-17-Related Fatty Acid Synthesis and Metabolism

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Weidong Shi

2013-01-01

Full Text Available To investigate the relationship between interleukin-17 and proteins involved in fatty acid metabolism with respect to alcoholic liver disease, male ICR mice were randomized into five groups: control, alcoholic liver disease (ALD at 4 weeks, 8 weeks, and 12 weeks, and anti-IL-17 antibody treated ALD. A proteomic approach was adopted to investigate changes in liver proteins between control and ALD groups. The proteomic analysis was performed by two-dimensional difference gel electrophoresis. Spots of interest were subsequently subjected to nanospray ionization tandem mass spectrometry (MS/MS for protein identification. Additionally, expression levels of selected proteins were confirmed by western blot. Transcriptional levels of some selected proteins were determined by RT-PCR. Expression levels of 95 protein spots changed significantly (ratio >1.5, P<0.05 during the development of ALD. Sterol regulatory element-binding protein-lc (SREBP-1c, carbohydrate response element binding protein (ChREBP, enoyl-coenzyme A hydratase (ECHS1, and peroxisome proliferator-activated receptor alpha (PPAR-α were identified by MS/MS among the proteins shown to vary the most; increased IL-17 elevated the transcription of SREBP-1c and ChREBP but suppressed ECHS1 and PPAR-α. The interleukin-17 signaling pathway is involved in ALD development; anti-IL-17 antibody improved hepatic steatosis by suppressing interleukin-17-related fatty acid metabolism.

The relation of weight suppression and BMI to bulimic symptoms.

Science.gov (United States)

Butryn, Meghan L; Juarascio, Adrienne; Lowe, Michael R

2011-11-01

High levels of weight suppression have been associated with greater binge eating and weight gain as well as poorer treatment outcome in bulimia nervosa. This study examined the relationship between weight suppression and bulimia nervosa symptoms and explored how weight suppression might interact with body mass index (BMI) in accounting for level of symptomatology at presentation for treatment. Participants were 64 women with threshold or sub-threshold bulimia nervosa. A clinical interview assessed binge eating and purging. Weight suppression and the interaction between BMI and weight suppression predicted frequency of binge eating such that participants with low BMI and high weight suppression engaged in the most binge eating. High levels of weight suppression also predicted more frequent purging. Additional research is warranted to examine mediators of these relationships. Copyright © 2010 Wiley Periodicals, Inc.

MMS sensitivity of all amino acid-requiring mutants in aspergillus and its suppression by mutations in a single gene.

Science.gov (United States)

Käfer, E

1987-04-01

All available amino acid-requiring mutants of Aspergillus nidulans were found to be hypersensitive to MMS (methyl methanesulfonate) to various degrees. On MMS media, secondary mutations could be selected which suppress this MMS sensitivity but do not affect the requirement. Many such mutations were analyzed and found to be alleles of one gene, smsA (= suppressor of MMS sensitivity), which mapped distal on the right arm of chromosome V. This gene is more likely to be involved in general regulation of amino acid biosynthesis than MMS uptake, since a variety of pathway interactions were clearly modified by smsA suppressors in the absence of MMS.

Jasmonic acid-mediated defense suppresses brassinosteroid-mediated susceptibility to Rice black streaked dwarf virus infection in rice.

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He, Yuqing; Zhang, Hehong; Sun, Zongtao; Li, Junmin; Hong, Gaojie; Zhu, Qisong; Zhou, Xuebiao; MacFarlane, Stuart; Yan, Fei; Chen, Jianping

2017-04-01

Plant hormones play a vital role in plant immune responses. However, in contrast to the relative wealth of information on hormone-mediated immunity in dicot plants, little information is available on monocot-virus defense systems. We used a high-throughput-sequencing approach to compare the global gene expression of Rice black-streaked dwarf virus (RBSDV)-infected rice plants with that of healthy plants. Exogenous hormone applications and transgenic rice were used to test RBSDV infectivity and pathogenicity. Our results revealed that the jasmonic acid (JA) pathway was induced while the brassinosteroid (BR) pathway was suppressed in infected plants. Foliar application of methyl jasmonate (MeJA) or brassinazole (BRZ) resulted in a significant reduction in RBSDV incidence, while epibrassinolide (BL) treatment increased RBSDV infection. Infection studies using coi1-13 and Go mutants demonstrated JA-mediated resistance and BR-mediated susceptibility to RBSDV infection. A mixture of MeJA and BL treatment resulted in a significant reduction in RBSDV infection compared with a single BL treatment. MeJA application efficiently suppressed the expression of BR pathway genes, and this inhibition depended on the JA coreceptor OsCOI1. Collectively, our results reveal that JA-mediated defense can suppress the BR-mediated susceptibility to RBSDV infection. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Poor outcome prediction by burst suppression ratio in adults with post-anoxic coma without hypothermia.

Science.gov (United States)

Yang, Qinglin; Su, Yingying; Hussain, Mohammed; Chen, Weibi; Ye, Hong; Gao, Daiquan; Tian, Fei

2014-05-01

Burst suppression ratio (BSR) is a quantitative electroencephalography (qEEG) parameter. The purpose of our study was to compare the accuracy of BSR when compared to other EEG parameters in predicting poor outcomes in adults who sustained post-anoxic coma while not being subjected to therapeutic hypothermia. EEG was registered and recorded at least once within 7 days of post-anoxic coma onset. Electrodes were placed according to the international 10-20 system, using a 16-channel layout. Each EEG expert scored raw EEG using a grading scale adapted from Young and scored amplitude-integrated electroencephalography tracings, in addition to obtaining qEEG parameters defined as BSR with a defined threshold. Glasgow outcome scales of 1 and 2 at 3 months, determined by two blinded neurologists, were defined as poor outcome. Sixty patients with Glasgow coma scale score of 8 or less after anoxic accident were included. The sensitivity (97.1%), specificity (73.3%), positive predictive value (82.5%), and negative prediction value (95.0%) of BSR in predicting poor outcome were higher than other EEG variables. BSR1 and BSR2 were reliable in predicting death (area under the curve > 0.8, P coma who do not undergo therapeutic hypothermia when compared to other qEEG parameters.

Uric Acid Excretion Predicts Increased Blood Pressure Among American Adolescents of African Descent.

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Mrug, Sylvie; Mrug, Michal; Morris, Anjana Madan; Reynolds, Nina; Patel, Anita; Hill, Danielle C; Feig, Daniel I

2017-04-01

Hyperuricemia predicts the incidence of hypertension in adults and its treatment has blood pressure (BP)-lowering effects in adolescents. To date, no studies have examined the predictive usage of hyperuricemia or urinary uric acid excretion on BP changes in adolescents. Mechanistic models suggest that uric acid impairs both endothelial function and vascular compliance, which would potentially exacerbate a myriad of hypertensive mechanisms, yet little is known about interaction of uric acid and other hypertension risk factors. The primary study was aimed at the effects of stress on BP in adolescents. A community sample of 84 low-income, urban adolescents (50% male, 95% African American, mean age = 13.36 ± 1 years) was recruited from public schools. Youth completed a 12-hour (overnight) urine collection at home and their BP was measured during rest and in response to acute psychosocial stress. Seventy-six of the adolescents participated in a follow-up visit at 1.5 years when their resting BP was reassessed. In this substudy, we assessed the relationship of renal urate excretion and BP reactivity. After adjusting for resting BP levels at baseline and other covariates, higher levels of uric acid excretion predicted greater BP reactivity to acute psychosocial stress and higher resting BP at 18 months. Urinary excretion of uric acid can serve as an alternative, noninvasive measure of serum uric acid levels that are predictive of BP changes. As hyperuricemia-associated hypertension is treatable, urban adolescents may benefit from routine screening for hyperuricemia or high uric acid excretion. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

A Clostridium Group IV Species Dominates and Suppresses a Mixed Culture Fermentation by Tolerance to Medium Chain Fatty Acids Products

Science.gov (United States)

Andersen, Stephen J.; De Groof, Vicky; Khor, Way Cern; Roume, Hugo; Props, Ruben; Coma, Marta; Rabaey, Korneel

2017-01-01

A microbial community is engaged in a complex economy of cooperation and competition for carbon and energy. In engineered systems such as anaerobic digestion and fermentation, these relationships are exploited for conversion of a broad range of substrates into products, such as biogas, ethanol, and carboxylic acids. Medium chain fatty acids (MCFAs), for example, hexanoic acid, are valuable, energy dense microbial fermentation products, however, MCFA tend to exhibit microbial toxicity to a broad range of microorganisms at low concentrations. Here, we operated continuous mixed population MCFA fermentations on biorefinery thin stillage to investigate the community response associated with the production and toxicity of MCFA. In this study, an uncultured species from the Clostridium group IV (related to Clostridium sp. BS-1) became enriched in two independent reactors that produced hexanoic acid (up to 8.1 g L−1), octanoic acid (up to 3.2 g L−1), and trace concentrations of decanoic acid. Decanoic acid is reported here for the first time as a possible product of a Clostridium group IV species. Other significant species in the community, Lactobacillus spp. and Acetobacterium sp., generate intermediates in MCFA production, and their collapse in relative abundance resulted in an overall production decrease. A strong correlation was present between the community composition and both the hexanoic acid concentration (p = 0.026) and total volatile fatty acid concentration (p = 0.003). MCFA suppressed species related to Clostridium sp. CPB-6 and Lactobacillus spp. to a greater extent than others. The proportion of the species related to Clostridium sp. BS-1 over Clostridium sp. CPB-6 had a strong correlation with the concentration of octanoic acid (p = 0.003). The dominance of this species and the increase in MCFA resulted in an overall toxic effect on the mixed community, most significantly on the Lactobacillus spp., which resulted in a decrease in total

Use of acid-suppressive drugs in pregnancy and the risk of childhood asthma : Bidirectional case-crossover study using the general practice research database

NARCIS (Netherlands)

Hak, Eelko; Mulder, Bianca; Schuiling-Veninga, Nynke C. M.; De Vries, Tjalling W.; Jick, Susan S.

2013-01-01

Background: Recent studies have reported an association between maternal use of gastric acid-suppressive drugs during pregnancy and asthma in the offspring, but the association could have been confounded by unmeasured risk factors. Objectives: To assess the association between the use of

Hybrid ATDL-gamma distribution model for predicting area source acid gas concentrations

Energy Technology Data Exchange (ETDEWEB)

Jakeman, A J; Taylor, J A

1985-01-01

An air quality model is developed to predict the distribution of concentrations of acid gas in an urban airshed. The model is hybrid in character, combining reliable features of a deterministic ATDL-based model with statistical distributional approaches. The gamma distribution was identified from a range of distributional models as the best model. The paper shows that the assumptions of a previous hybrid model may be relaxed and presents a methodology for characterizing the uncertainty associated with model predictions. Results are demonstrated for the 98-percentile predictions of 24-h average data over annual periods at six monitoring sites. This percentile relates to the World Health Organization goal for acid gas concentrations.

Why expressive suppression does not pay? Cognitive costs of negative emotion suppression: The mediating role of subjective tense-arousal

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Szczygieł Dorota

2015-09-01

Full Text Available The aim of this paper was to contribute to a broader understanding of the cognitive consequences of expressive suppression. Specifically, we examined whether the deteriorating effect of expressive suppression on cognitive functioning is caused by tense arousal enhanced by suppression. Two experiments were performed in order to test this prediction. In both studies we tested the effect of expressive suppression on working memory, as measured with a backwards digit-span task (Study 1, N = 43 and anagram problem-solving task (Study 2, N = 60. In addition, in Study 2 we tested whether expressive suppression degrades memory of the events that emerged during the period of expressive suppression. Both studies were conducted in a similar design: Participants watched a film clip which evoked negative emotions (i.e. disgust in Study 1 and a combination of sadness and anxiety in Study 2 under the instruction to suppress those negative emotions or (in the control condition to simply watch the film. The results of these experiments lead to three conclusions. First, the results reveal that expressive suppression degrades memory of the events that emerged during the period of expressive suppression and leads to poorer performance on working memory tasks, as measured with a backwards digit-span task and anagram problem-solving task. Second, the results indicate that expressive suppression leads to a significant increase in subjective tense arousal. Third, the results support our prediction that expressive suppression decreases cognitive performance through its effects on subjective tense arousal. The results of the Study 1 show that tense arousal activated during expressive suppression of disgust fully mediates the negative effect of suppression on working memory as measured with a backwards digit-span task. The results of Study 2 reveal that subjective tense arousal elicited while suppressing sadness and anxiety mediates both the effect of suppression on

Absence of gastrointestinal infections in a cohort of patients with Zollinger-Ellison syndrome and other acid hypersecretors receiving long-term acid suppression with lansoprazole

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Worthington Julie

2008-05-01

Full Text Available Abstract Background The relationship between proton pump inhibitor therapy and other acid suppressing medications and the risk of gastrointestinal infections remains controversial. Methods Patients enrolled in a long-term trial of lansoprazole for Zollinger-Ellison syndrome and other acid hypersecretory states had interval histories taken every six months regarding hospitalizations or other intercurrent medical conditions. All medications taken were also reviewed at each visit. In addition, available patients were specifically queried during the study period 2006–2007 regarding the development of any gastrointestinal infections, hospitalizations, and prescriptions for antibiotics. Results Ninety patients were enrolled in our long-term study and 81 were available for review. The median basal gastric pH for the cohort after stabilization on therapy was 2.9 and ranged from 1.1 – 8.4 with a median pentagastrin stimulated gastric pH of 1.60 (range 1.0 – 8.2. No patient developed a clinically significant gastrointestinal infection during the study. The median patient years of follow-up were 6.25 years. Conclusion In a cohort of patients with gastric acid hypersecretion in whom acid secretion status was monitored on lansoprazole, all were free of significant gastrointestinal infections on long-term follow-up. Trial registration NCT00204373

n-3 polyunsaturated fatty acids suppress phosphatidylinositol 4,5-bisphosphate-dependent actin remodelling during CD4+ T-cell activation.

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Hou, Tim Y; Monk, Jennifer M; Fan, Yang-Yi; Barhoumi, Rola; Chen, Yong Q; Rivera, Gonzalo M; McMurray, David N; Chapkin, Robert S

2012-04-01

n-3 PUFA (polyunsaturated fatty acids), i.e. DHA (docosahexaenoic acid), found in fish oil, exhibit anti-inflammatory properties; however, the molecular mechanisms remain unclear. Since PtdIns(4,5)P2 resides in raft domains and DHA can alter the size of rafts, we hypothesized that PtdIns(4,5)P2 and downstream actin remodelling are perturbed by the incorporation of n-3 PUFA into membranes, resulting in suppressed T-cell activation. CD4+ T-cells isolated from Fat-1 transgenic mice (membranes enriched in n-3 PUFA) exhibited a 50% decrease in PtdIns(4,5)P2. Upon activation by plate-bound anti-CD3/anti-CD28 or PMA/ionomycin, Fat-1 CD4+ T-cells failed to metabolize PtdIns(4,5)P2. Furthermore, actin remodelling failed to initiate in Fat-1 CD4+ T-cells upon stimulation; however, the defect was reversed by incubation with exogenous PtdIns(4,5)P2. When Fat-1 CD4+ T-cells were stimulated with anti-CD3/anti-CD28-coated beads, WASP (Wiskott-Aldrich syndrome protein) failed to translocate to the immunological synapse. The suppressive phenotype, consisting of defects in PtdIns(4,5)P2 metabolism and actin remodelling, were recapitulated in CD4+ T-cells isolated from mice fed on a 4% DHA triacylglycerol-enriched diet. Collectively, these data demonstrate that n-3 PUFA, such as DHA, alter PtdIns(4,5)P2 in CD4+ T-cells, thereby suppressing the recruitment of WASP to the immunological synapse, and impairing actin remodelling in CD4+ T-cells.

Hyaluronic Acid Suppresses the Expression of Metalloproteinases in Osteoarthritic Cartilage Stimulated Simultaneously by Interleukin 1β and Mechanical Load.

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Florian Pohlig

Full Text Available In patients with osteoarthritis (OA, intraarticular injection of hyaluronic acid (HA frequently results in reduced pain and improved function for prolonged periods of time, i.e. more than 6 months. However, the mechanisms underlying these effects are not fully understood. Our underlying hypothesis is that HA modifies the enzymatic breakdown of joint tissues.To test this hypothesis, we examined osteochondral cylinders from 12 OA patients. In a bioreactor, these samples were stimulated by interleukin 1β (Il1ß (2 ng/ml plus mechanical load (2.0 Mpa at 0.5 Hz horizontal and 0.1 Hz vertical rotation, thus the experimental setup recapitulated both catabolic and anabolic clues of the OA joint.Upon addition of HA at either 1 or 3 mg/ml, we observed a significant suppression of expression of metalloproteinase (MMP-13. A more detailed analysis based on the Kellgren and Lawrence (K&L OA grade, showed a much greater degree of suppression of MMP-13 expression in grade IV as compared to grade II OA. In contrast to the observed MMP-13 suppression, treatment with HA resulted in a suppression of MMP-1 expression only at 1 mg/ml HA, while MMP-2 expression was not significantly affected by either HA concentration.Together, these data suggest that under concurrent catabolic and anabolic stimulation, HA exhibits a pronounced suppressive effect on MMP-13. In the long-run these findings may benefit the development of treatment strategies aimed at blocking tissue degradation in OA patients.

Detection of bitterness-Suppression using a taste sensor

International Nuclear Information System (INIS)

Iiyama, Satoru; Ezaki, Shu; Toko, Kiyoshi

2008-01-01

We tried to detect the suppression of bitterness with a taste sensor. Quinine hydrochloride, which has a positive charge usually cause large potential change of negatively, charged membranes of the sensor. The potential change was decreased by sour substances such as acetic acid. The decrease of the potential change of response implies a decrease in the intensity of bitterness. Contrary to this, response of the sensor to sodium picrate, which has a negative charge, was diminished by sodium salts of organic acids. As the hydrophobicity of organic acids increased, the suppression of bitterness also increased. The present study is expected to provide a new quantitative technique to measure the strength of bitterness of foods and drugs in place of sensory evaluation. (author)

A garlic extract protects from ultraviolet B (280-320 nm) radiation-induced suppression of contact hypersensitivity

International Nuclear Information System (INIS)

Reeve, V.E.; Bosnic, M.; Rozinova, E.; Boehm-Wilcox, C.

1993-01-01

Lyophilized aged garlic extract has been incorporated at concentrations of 0.1%, 1% and 4% by weight into semi purified powdered diets and fed to hairless mice. Under moderate UVB exposure conditions resulting in 58% suppression of the systemic contact hypersensitivity response in control-fed mice, a dose-responsive protection was observed in the garlic-fed mice; contact hypersensitivity in the UVB-exposed mice fed 4% garlic extract was suppressed by only 19%. If the UVB exposure was replaced by topical application of one of a series of lotions containing increasing concentrations of cis-urocanic acid, a dose-responsive suppression of contact hypersensitivity was demonstrated in control-fed mice (urocanic acid at 25, 50, 100 and 200 micrograms per mouse resulting in 22-46% suppression). Mice fed a diet containing 1% aged garlic extract were partially protected from cis-urocanic acid-induced suppression of contact hypersensitivity, with greater protection from the lower concentrations of urocanic acid. Mice fed a diet containing 4% aged garlic extract were protected from all concentrations of urocanic acid. The results indicate that aged garlic extract contains ingredient(s) that protect from UVB-induced suppression of contact hypersensitivity and suggest that the mechanism of protection is by antagonism of the cis-urocanic acid mediation of this form of immunosuppression

Cis-urocanic acid, a sunlight-induced immunosuppressive factor, activates immune suppression via the 5-HT2A receptor

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Walterscheid, Jeffrey P.; Nghiem, Dat X.; Kazimi, Nasser; Nutt, Leta K.; McConkey, David J.; Norval, Mary; Ullrich, Stephen E.

2006-01-01

Exposure to UV radiation induces skin cancer and suppresses the immune response. To induce immune suppression, the electromagnetic energy of UV radiation must be absorbed by an epidermal photoreceptor and converted into a biologically recognizable signal. Two photoreceptors have been recognized: DNA and trans-urocanic acid (UCA). Trans-UCA is normally found in the outermost layer of skin and isomerizes to the cis isomer upon exposure to UV radiation. Although UCA was identified as a UV photoreceptor years ago, and many have documented its ability to induce immune suppression, its exact mode of action remains elusive. Particularly vexing has been the identity of the molecular pathway by which cis-UCA mediates immune suppression. Here we provide evidence that cis-UCA binds to the serotonin [5-hydroxytryptamine (5-HT)] receptor with relatively high affinity (Kd = 4.6 nM). Anti-cis-UCA antibody precipitates radiolabeled 5-HT, and the binding is inhibited by excess 5-HT and/or excess cis-UCA. Similarly, anti-5-HT antibody precipitates radiolabeled cis-UCA, and the binding is inhibited by excess 5-HT or excess cis-UCA. Calcium mobilization was activated when a mouse fibroblast line, stably transfected with the human 5-HT2A receptor, was treated with cis-UCA. Cis-UCA-induced calcium mobilization was blocked with a selective 5-HT2A receptor antagonist. UV- and cis-UCA-induced immune suppression was blocked by antiserotonin antibodies or by treating the mice with 5-HT2A receptor antagonists. Our findings identify cis-UCA as a serotonin receptor ligand and indicate that the immunosuppressive effects of cis-UCA and UV radiation are mediated by activation of the 5-HT2A receptor. PMID:17085585

Low-Protein Diet Supplemented with Keto Acids Is Associated with Suppression of Small-Solute Peritoneal Transport Rate in Peritoneal Dialysis Patients

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Jiang, Na; Qian, Jiaqi; Lin, Aiwu; Fang, Wei; Zhang, Weiming; Cao, Liou; Wang, Qin; Ni, Zhaohui; Yao, Qiang

2011-01-01

Objective. We investigate whether low-protein diet would show benefits in suppressing peritoneal transport rate in peritoneal dialysis (PD) patients. Methods. This is a supplemented analysis of our previously published trial, which randomized 60 PD patients to receive low- (LP: dietary protein intake of 0.6–0.8 g/kg/d), keto-acid-supplemented low- (sLP: 0.6–0.8 g/kg/d with 0.12 g/kg/d of keto acids), or high- (HP: 1.0–1.2 g/kg/d) protein diet and lasted for one year. In this study, the variat...

RNAi trigger fragment truncation attenuates soybean FAD2-1 transcript suppression and yields intermediate oil phenotypes.

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Wagner, Nicholas; Mroczka, Andrew; Roberts, Peter D; Schreckengost, William; Voelker, Toni

2011-09-01

Suppression of the microsomal ω6 oleate desaturase during the seed development of soybean (Glycine max) with the 420-bp soybean FAD2-1A intron as RNAi trigger shifts the conventional fatty acid composition of soybean oil from 20% oleic and 60% polyunsaturates to one containing greater than 80% oleic acid and less than 10% polyunsaturates. To determine whether RNAi could be attenuated by reducing the trigger fragment length, transgenic plants were generated to express successively shorter 5' or 3' deletion derivatives of the FAD2-1A intron. We observed a gradual reduction in transcript suppression with shorter trigger fragments. Fatty acid composition was less affected with shorter triggers, and triggers less than 60 bp had no phenotypic effect. No trigger sequences conferring significantly higher or lower suppression efficiencies were found, and the primary determinant of suppression effect was sequence length. The observed relationship of transcript suppression with the induced fatty acid phenotype indicates that RNAi is a saturation process and not a step change between suppressed and nonsuppressed states and intermediate suppression states can be achieved. © 2010 Monsanto. Plant Biotechnology Journal © 2010 Society for Experimental Biology and Blackwell Publishing Ltd.

Selective scavenging of intra-mitochondrial superoxide corrects diclofenac-induced mitochondrial dysfunction and gastric injury: A novel gastroprotective mechanism independent of gastric acid suppression.

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Mazumder, Somnath; De, Rudranil; Sarkar, Souvik; Siddiqui, Asim Azhar; Saha, Shubhra Jyoti; Banerjee, Chinmoy; Iqbal, Mohd Shameel; Nag, Shiladitya; Debsharma, Subhashis; Bandyopadhyay, Uday

2016-12-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat multiple inflammatory diseases and pain but severe gastric mucosal damage is the worst outcome of NSAID-therapy. Here we report that mitoTEMPO, a mitochondrially targeted superoxide (O 2 - ) scavenger protected as well as healed gastric injury induced by diclofenac (DCF), the most commonly used NSAID. Common existing therapy against gastric injury involves suppression of gastric acid secretion by proton pump inhibitors and histamine H 2 receptor antagonists; however, dyspepsia, vitamin B12 deficiency and gastric microfloral dysbalance are the major drawbacks of acid suppression. Interestingly, mitoTEMPO did not inhibit gastric acid secretion but offered gastroprotection by preventing DCF-induced generation of O 2 - due to mitochondrial respiratory chain failure and by preventing mitochondrial oxidative stress (MOS)-mediated mitopathology. MitoTEMPO even restored DCF-stimulated reduced fatty acid oxidation, mitochondrial depolarization and bioenergetic crisis in gastric mucosa. MitoTEMPO also prevented the activation of mitochondrial pathway of apoptosis and MOS-mediated proinflammatory signaling through NF-κB by DCF. Furthermore, mitoTEMPO when administered in rats with preformed gastric lesions expedited the healing of gastric injury and the healed stomach exhibited its normal physiology as evident from gastric acid and pepsin secretions under basal or stimulated conditions. Thus, in contrast to the existing antiulcer drugs, mitochondrially targeted O 2 - scavengers like mitoTEMPO may represent a novel class of gastroprotective molecules that does not affect gastric acid secretion and may be used in combination with DCF, keeping its anti-inflammatory action intact, while reducing its gastrodamaging effects. Copyright © 2016 Elsevier Inc. All rights reserved.

Does folic acid supplementation prevent or promote colorectal cancer? Results from model-based predictions.

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Luebeck, E Georg; Moolgavkar, Suresh H; Liu, Amy Y; Boynton, Alanna; Ulrich, Cornelia M

2008-06-01

Folate is essential for nucleotide synthesis, DNA replication, and methyl group supply. Low-folate status has been associated with increased risks of several cancer types, suggesting a chemopreventive role of folate. However, recent findings on giving folic acid to patients with a history of colorectal polyps raise concerns about the efficacy and safety of folate supplementation and the long-term health effects of folate fortification. Results suggest that undetected precursor lesions may progress under folic acid supplementation, consistent with the role of folate role in nucleotide synthesis and cell proliferation. To better understand the possible trade-offs between the protective effects due to decreased mutation rates and possibly concomitant detrimental effects due to increased cell proliferation of folic acid, we used a biologically based mathematical model of colorectal carcinogenesis. We predict changes in cancer risk based on timing of treatment start and the potential effect of folic acid on cell proliferation and mutation rates. Changes in colorectal cancer risk in response to folic acid supplementation are likely a complex function of treatment start, duration, and effect on cell proliferation and mutations rates. Predicted colorectal cancer incidence rates under supplementation are mostly higher than rates without folic acid supplementation unless supplementation is initiated early in life (before age 20 years). To the extent to which this model predicts reality, it indicates that the effect on cancer risk when starting folic acid supplementation late in life is small, yet mostly detrimental. Experimental studies are needed to provide direct evidence for this dual role of folate in colorectal cancer and to validate and improve the model predictions.

Association Between Response to Acid-Suppression Therapy and Efficacy of Antireflux Surgery in Patients With Extraesophageal Reflux.

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Krill, Joseph T; Naik, Rishi D; Higginbotham, Tina; Slaughter, James C; Holzman, Michael D; Francis, David O; Garrett, C Gaelyn; Vaezi, Michael F

2017-05-01

The effectiveness of antireflux surgery (ARS) varies among patients with extraesophageal manifestations of gastroesophageal reflux disease (GERD). By studying a cohort of patients with primary extraesophageal symptoms and abnormal physiologic markers for GERD, we aimed to identify factors associated with positive outcomes from surgery, and compare outcomes to those with typical esophageal manifestations of GERD. We performed a retrospective cohort study to compare adult patients with extraesophageal and typical reflux symptoms who underwent de novo ARS from 2004 through 2012 at a tertiary care center. All 115 patients (79 with typical GERD and 36 with extraesophageal manifestations of GERD) had evidence of abnormal distal esophageal acid exposure based on pH testing or endoscopy. The principle outcome was time to primary symptom recurrence after surgery, based on patient reports of partial or total recurrence of symptoms at follow-up visits. Patients were followed up for a median duration of 66 months (interquartile range, 52-77 mo). The median time to recurrence of symptoms in the overall cohort was 68 months (11.5 months in the extraesophageal cohort vs >132 months in the typical cohort). Symptom recurrence after ARS was associated with having primarily extraesophageal symptoms (adjusted hazard ratio, 2.34; 95% confidence interval, 1.31-4.17) and poor preoperative symptom response to acid-suppression therapy (AST) (hazard ratio, 3.85; 95% confidence interval, 2.05-7.22). Patients with primary extraesophageal symptoms who had a full or partial preoperative AST response experienced lower rates of symptom recurrence compared to patients with poor AST response (P reflux symptoms who had a partial or full symptom response to AST (P acid reflux on pH testing, symptom indices, severity of esophagitis, and hiatal hernia size were not associated with symptom response. In a retrospective study, we found the effectiveness of ARS to be less predictable in patients with

Encapsulation of ferulic acid ethyl ester in caseinate to suppress off-flavor formation in UHT milk.

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Guan, Yongguang; Zhong, Qixin

2017-12-15

Phenolic compounds can principally suppress the off-flavor development in ultrahigh temperature (UHT) treated milk, but little has been studied for lipophilic phenolic compounds that are to be encapsulated for even distribution in milk. The objective of this work was to study physicochemical properties of ferulic acid ethyl ester (FAEE) encapsulated in sodium caseinate and the inhibition of volatile formation after UHT processing. The capsules had an average hydrodynamic diameter of 246.2±10.9nm, a polydispersity index of 0.26±0.01, and a zeta-potential of -31.72±0.74mV. The capsules and the encapsulated FAEE were stable after heating at 138°C for 16min and UV radiation at 365nm for 32h. The encapsulated FAEE at a level of 0.18-1.42mg/mL suppressed the formation of 2-acetyl-2-thiazoline in model UHT milk by 32.8-63.2% after 30-day storage at 30°C. Therefore, FAEE encapsulated in caseinate can be potentially used to improve the quality of UHT milk. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dietary Karaya Saponin and Rhodobacter capsulatus Exert Hypocholesterolemic Effects by Suppression of Hepatic Cholesterol Synthesis and Promotion of Bile Acid Synthesis in Laying Hens

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Sadia Afrose

2010-01-01

Full Text Available This study was conducted to elucidate the mechanism underlying the hypolipidemic action of karaya saponin or Rhodobacter (R. capsulatus. A total of 40 laying hens (20-week-old were assigned into four dietary treatment groups and fed a basal diet (as a control or basal diets supplemented with either karaya saponin, R. capsulatus, or both for 60 days. The level of serum low-density-lipoprotein cholesterol and the levels of cholesterol and triglycerides in the serum, liver, and egg yolk were reduced by all the supplementations (<.05. Liver bile acid concentration and fecal concentrations of cholesterol, triacylglycerol, and bile acid were simultaneously increased by the supplementation of karaya saponin, R. capsulatus, and the combination of karaya saponin and R. capsulatus (<.05. The supplementation of karaya saponin, R. capsulatus, and the combination of karaya saponin and R. capsulatus suppressed the incorporation of 14C from 1-14C-palmitic acid into the fractions of total lipids, phospholipids, triacylglycerol, and cholesterol in the liver in vitro (<.05. These findings suggest that the hypocholesterolemic effects of karaya saponin and R. capsulatus are caused by the suppression of the cholesterol synthesis and the promotion of cholesterol catabolism in the liver.

MODERATING INFLUENCE OF THE DRINKING WATER DISINFECTION BY-PRODUCT DIBROMOACETIC ACID ON A DITHIOCARBAMATE-INDUCED SUPPRESSION OF THE LUTEINIZING HORMONE SURGE IN FEMALE RATS.

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The disinfection by-product dibromoacetic acid (DBA) has been found in female rats to increase circulating concentrations of both estradiol (E2) and estrone (E1). This effect is apparently due, at least in part, to a suppression in hepatic catabolism. The present study investigat...

n – 3 polyunsaturated fatty acids suppress phosphatidylinositol 4,5-bisphosphate-dependent actin remodelling during CD4+ T-cell activation

Science.gov (United States)

Hou, Tim Y.; Monk, Jennifer M.; Fan, Yang-Yi; Barhoumi, Rola; Chen, Yong Q.; Rivera, Gonzalo M.; McMURRAY, David N.; Chapkin, Robert S.

2013-01-01

n – 3 PUFA (polyunsaturated fatty acids), i.e. DHA (docosahexaenoic acid), found in fish oil, exhibit anti-inflammatory properties; however, the molecular mechanisms remain unclear. Since PtdIns(4,5)P2 resides in raft domains and DHA can alter the size of rafts, we hypothesized that PtdIns(4,5)P2 and downstream actin remodelling are perturbed by the incorporation of n – 3 PUFA into membranes, resulting in suppressed T-cell activation. CD4+ T-cells isolated from Fat-1 transgenic mice (membranes enriched in n – 3 PUFA) exhibited a 50% decrease in PtdIns(4,5)P2. Upon activation by plate-bound anti-CD3/anti-CD28 or PMA/ionomycin, Fat-1 CD4+ T-cells failed to metabolize PtdIns(4,5)P2. Furthermore, actin remodelling failed to initiate in Fat-1 CD4+ T-cells upon stimulation; however, the defect was reversed by incubation with exogenous PtdIns(4,5)P2. When Fat-1 CD4+ T-cells were stimulated with anti-CD3/anti-CD28-coated beads, WASP (Wiskott–Aldrich syndrome protein) failed to translocate to the immunological synapse. The suppressive phenotype, consisting of defects in PtdIns(4,5)P2 metabolism and actin remodelling, were recapitulated in CD4+ T-cells isolated from mice fed on a 4% DHA triacylglycerol-enriched diet. Collectively, these data demonstrate that n – 3 PUFA, such as DHA, alter PtdIns(4,5)P2 in CD4+ T-cells, thereby suppressing the recruitment of WASP to the immunological synapse, and impairing actin remodelling in CD4+ T-cells. PMID:22250985

Effect of essential amino acids on enteroids: Methionine deprivation suppresses proliferation and affects differentiation in enteroid stem cells

International Nuclear Information System (INIS)

Saito, Yuki; Iwatsuki, Ken; Hanyu, Hikaru; Maruyama, Natsuki; Aihara, Eitaro; Tadaishi, Miki; Shimizu, Makoto; Kobayashi-Hattori, Kazuo

2017-01-01

We investigated the effects of essential amino acids on intestinal stem cell proliferation and differentiation using murine small intestinal organoids (enteroids) from the jejunum. By selectively removing individual essential amino acids from culture medium, we found that 24 h of methionine (Met) deprivation markedly suppressed cell proliferation in enteroids. This effect was rescued when enteroids cultured in Met deprivation media for 12 h were transferred to complete medium, suggesting that Met plays an important role in enteroid cell proliferation. In addition, mRNA levels of the stem cell marker leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) decreased in enteroids grown in Met deprivation conditions. Consistent with this observation, Met deprivation also attenuated Lgr5-EGFP fluorescence intensity in enteroids. In contrast, Met deprivation enhanced mRNA levels of the enteroendocrine cell marker chromogranin A (ChgA) and markers of K cells, enterochromaffin cells, goblet cells, and Paneth cells. Immunofluorescence experiments demonstrated that Met deprivation led to an increase in the number of ChgA-positive cells. These results suggest that Met deprivation suppresses stem cell proliferation, thereby promoting differentiation. In conclusion, Met is an important nutrient in the maintenance of intestinal stem cells and Met deprivation potentially affects cell differentiation. - Highlights: • Met influences the proliferation of enteroids. • Met plays a crucial role in the maintenance of stem cells. • Met deprivation potentially promotes differentiation into secretory cells.

Suppressed Alpha Oscillations Predict Intelligibility of Speech and its Acoustic Details

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Weisz, Nathan

2012-01-01

Modulations of human alpha oscillations (8–13 Hz) accompany many cognitive processes, but their functional role in auditory perception has proven elusive: Do oscillatory dynamics of alpha reflect acoustic details of the speech signal and are they indicative of comprehension success? Acoustically presented words were degraded in acoustic envelope and spectrum in an orthogonal design, and electroencephalogram responses in the frequency domain were analyzed in 24 participants, who rated word comprehensibility after each trial. First, the alpha power suppression during and after a degraded word depended monotonically on spectral and, to a lesser extent, envelope detail. The magnitude of this alpha suppression exhibited an additional and independent influence on later comprehension ratings. Second, source localization of alpha suppression yielded superior parietal, prefrontal, as well as anterior temporal brain areas. Third, multivariate classification of the time–frequency pattern across participants showed that patterns of late posterior alpha power allowed best for above-chance classification of word intelligibility. Results suggest that both magnitude and topography of late alpha suppression in response to single words can indicate a listener's sensitivity to acoustic features and the ability to comprehend speech under adverse listening conditions. PMID:22100354

Predicting protein amidation sites by orchestrating amino acid sequence features

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Zhao, Shuqiu; Yu, Hua; Gong, Xiujun

2017-08-01

Amidation is the fourth major category of post-translational modifications, which plays an important role in physiological and pathological processes. Identifying amidation sites can help us understanding the amidation and recognizing the original reason of many kinds of diseases. But the traditional experimental methods for predicting amidation sites are often time-consuming and expensive. In this study, we propose a computational method for predicting amidation sites by orchestrating amino acid sequence features. Three kinds of feature extraction methods are used to build a feature vector enabling to capture not only the physicochemical properties but also position related information of the amino acids. An extremely randomized trees algorithm is applied to choose the optimal features to remove redundancy and dependence among components of the feature vector by a supervised fashion. Finally the support vector machine classifier is used to label the amidation sites. When tested on an independent data set, it shows that the proposed method performs better than all the previous ones with the prediction accuracy of 0.962 at the Matthew's correlation coefficient of 0.89 and area under curve of 0.964.

Suppression effects on musical and verbal memory.

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Schendel, Zachary A; Palmer, Caroline

2007-06-01

Three experiments contrasted the effects of articulatory suppression on recognition memory for musical and verbal sequences. In Experiment 1, a standard/comparison task was employed, with digit or note sequences presented visually or auditorily while participants remained silent or produced intermittent verbal suppression (saying "the") or musical suppression (singing "la"). Both suppression types decreased performance by equivalent amounts, as compared with no suppression. Recognition accuracy was lower during suppression for visually presented digits than during that for auditorily presented digits (consistent with phonological loop predictions), whereas accuracy was equivalent for visually presented notes and auditory tones. When visual interference filled the retention interval in Experiment 2, performance with visually presented notes but not digits was impaired. Experiment 3 forced participants to translate visually presented music sequences by presenting comparison sequences auditorily. Suppression effects for visually presented music resembled those for digits only when the recognition task required sensory translation of cues.

Competition-strength-dependent ground suppression in figure-ground perception.

Science.gov (United States)

Salvagio, Elizabeth; Cacciamani, Laura; Peterson, Mary A

2012-07-01

Figure-ground segregation is modeled as inhibitory competition between objects that might be perceived on opposite sides of borders. The winner is the figure; the loser is suppressed, and its location is perceived as shapeless ground. Evidence of ground suppression would support inhibitory competition models and would contribute to explaining why grounds are shapeless near borders shared with figures, yet such evidence is scarce. We manipulated whether competition from potential objects on the ground side of figures was high (i.e., portions of familiar objects were potentially present there) or low (novel objects were potentially present). We predicted that greater competition would produce more ground suppression. The results of two experiments in which suppression was assessed via judgments of the orientation of target bars confirmed this prediction; a third experiment showed that ground suppression is short-lived. Our findings support inhibitory competition models of figure assignment, in particular, and models of visual perception entailing feedback, in general.

METHOD OF SUPPRESSING GASTROINTESTINAL UREASE ACTIVITY

Science.gov (United States)

Visek, W.J.

1963-04-23

This patent shows a method of increasing the growth rate of chicks. Certain diacyl substituted ureas such as alloxan, murexide, and barbituric acid are added to their feed, thereby suppressing gastrointestinal urease activity and thus promoting growth. (AEC)

NEAT-FLEX: Predicting the conformational flexibility of amino acids using neuroevolution of augmenting topologies.

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Grisci, Bruno; Dorn, Márcio

2017-06-01

The development of computational methods to accurately model three-dimensional protein structures from sequences of amino acid residues is becoming increasingly important to the structural biology field. This paper addresses the challenge of predicting the tertiary structure of a given amino acid sequence, which has been reported to belong to the NP-Complete class of problems. We present a new method, namely NEAT-FLEX, based on NeuroEvolution of Augmenting Topologies (NEAT) to extract structural features from (ABS) proteins that are determined experimentally. The proposed method manipulates structural information from the Protein Data Bank (PDB) and predicts the conformational flexibility (FLEX) of residues of a target amino acid sequence. This information may be used in three-dimensional structure prediction approaches as a way to reduce the conformational search space. The proposed method was tested with 24 different amino acid sequences. Evolving neural networks were compared against a traditional error back-propagation algorithm; results show that the proposed method is a powerful way to extract and represent structural information from protein molecules that are determined experimentally.

Mms Sensitivity of All Amino Acid-Requiring Mutants in Aspergillus and Its Suppression by Mutations in a Single Gene

OpenAIRE

Käfer, Etta

1987-01-01

All available amino acid-requiring mutants of Aspergillus nidulans were found to be hypersensitive to MMS (methyl methanesulfonate) to various degrees. On MMS media, secondary mutations could be selected which suppress this MMS sensitivity but do not affect the requirement. Many such mutations were analyzed and found to be alleles of one gene, smsA (= suppressor of MMS sensitivity), which mapped distal on the right arm of chromosome V. This gene is more likely to be involved in general regula...

Caffeic acid phenethyl ester suppresses melanoma tumor growth by inhibiting PI3K/AKT/XIAP pathway.

Science.gov (United States)

Pramanik, Kartick C; Kudugunti, Shashi K; Fofaria, Neel M; Moridani, Majid Y; Srivastava, Sanjay K

2013-09-01

Melanoma is highly metastatic and resistant to chemotherapeutic drugs. Our previous studies have demonstrated that caffeic acid phenethyl ester (CAPE) suppresses the growth of melanoma cells and induces reactive oxygen species generation. However, the exact mechanism of the growth suppressive effects of CAPE was not clear. Here, we determined the potential mechanism of CAPE against melanoma in vivo and in vitro. Administration of 10 mg/kg/day CAPE substantially suppressed the growth of B16F0 tumor xenografts in C57BL/6 mice. Tumors from CAPE-treated mice showed reduced phosphorylation of phosphoinositide 3-kinase, AKT, mammalian target of rapamycin and protein level of X-linked inhibitor of apoptosis protein (XIAP) and enhanced the cleavage of caspase-3 and poly (ADP ribose) polymerase. In order to confirm the in vivo observations, melanoma cells were treated with CAPE. CAPE treatment suppressed the activating phosphorylation of phosphoinositide 3-kinase at Tyr 458, phosphoinositide-dependent kinase-1 at Ser 241, mammalian target of rapamycin at Ser 2448 and AKT at Ser 473 in B16F0 and SK-MEL-28 cells in a concentration and time-dependent study. Furthermore, the expression of XIAP, survivin and BCL-2 was downregulated by CAPE treatment in both cell lines. Significant apoptosis was observed by CAPE treatment as indicated by cleavage of caspase-3 and poly (ADP ribose) polymerase. AKT kinase activity was inhibited by CAPE in a concentration-dependent manner. CAPE treatment increased the nuclear translocation of XIAP, indicating increased apoptosis in melanoma cells. To confirm the involvement of reactive oxygen species in the inhibition of AKT/XIAP pathway, cells were treated with antioxidant N-acetyl-cysteine (NAC) prior to CAPE treatment. Our results indicate that NAC blocked CAPE-mediated AKT/XIAP inhibition and protected the cells from apoptosis. Because AKT regulates XIAP, their interaction was examined by immunoprecipitation studies. Our results show that CAPE

Hepatitis C Virus Frameshift/Alternate Reading Frame Protein Suppresses Interferon Responses Mediated by Pattern Recognition Receptor Retinoic-Acid-Inducible Gene-I.

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Seung Bum Park

Full Text Available Hepatitis C virus (HCV actively evades host interferon (IFN responses but the mechanisms of how it does so are not completely understood. In this study, we present evidence for an HCV factor that contributes to the suppression of retinoic-acid-inducible gene-I (RIG-I-mediated IFN induction. Expression of frameshift/alternate reading frame protein (F/ARFP from HCV -2/+1 frame in Huh7 hepatoma cells suppressed type I IFN responses stimulated by HCV RNA pathogen-associated molecular pattern (PAMP and poly(IC. The suppression occurred independently of other HCV factors; and activation of interferon stimulated genes, TNFα, IFN-λ1, and IFN-λ2/3 was likewise suppressed by HCV F/ARFP. Point mutations in the full-length HCV sequence (JFH1 genotype 2a strain were made to introduce premature termination codons in the -2/+1 reading frame coding for F/ARFP while preserving the original reading frame, which enhanced IFNα and IFNβ induction by HCV. The potentiation of IFN response by the F/ARFP mutations was diminished in Huh7.5 cells, which already have a defective RIG-I, and by decreasing RIG-I expression in Huh7 cells. Furthermore, adding F/ARFP back via trans-complementation suppressed IFN induction in the F/ARFP mutant. The F/ARFP mutants, on the other hand, were not resistant to exogenous IFNα. Finally, HCV-infected human liver samples showed significant F/ARFP antibody reactivity, compared to HCV-uninfected control livers. Therefore, HCV F/ARFP likely cooperates with other viral factors to suppress type I and III IFN induction occurring through the RIG-I signaling pathway. This study identifies a novel mechanism of pattern recognition receptor modulation by HCV and suggests a biological function of the HCV alternate reading frame in the modulation of host innate immunity.

Detailed predictive mapping of acid sulfate soil occurrence using electromagnetic induction data

DEFF Research Database (Denmark)

Beucher, Amélie; Boman, A; Mattbäck, S

impact through the resulting corrosion of concrete and steel infrastructures, or their poor geotechnical qualities. Therefore, mapping acid sulfate soil occurrence constitutes a key step to target the strategic areas for subsequent environmental risk management and mitigation. Conventional mapping (i...... obtained from a EM38 proximal sensor enabled the refined mapping of acid sulfate soils over a field (Huang et al. 2014). The present study aims at developing an efficient and reliable method for the detailed predictive mapping of acid sulfate soil occurrence in a field located in western Finland. Different...

Suppressive effects of Calendula micrantha essential oil and gibberelic acid (PGR) on repro ductive potential of the Mediterranean fruit fly Ceratitis capitata Wied. (Diptera: Tephritidae).

Science.gov (United States)

Hussein, Karam T

2005-08-01

The volatile oil of Calendula micrtantha plant was extracted and the components were identified by Gc/Ms. Adulticidal efficiency of the volatile oil and gibberelic acid "plant growth promoting hormone" as well as their mixture was assessed against the Mediterranean fruit fly Ceratitis capitata. The result showed that the two compounds capable have characteristic resembling to insect juvenile hormones and have suppressive effect on reproductive potential. They induced the significant disturbances in the ovarian protein fraction and the amino acids patterns.

SAAS: Short Amino Acid Sequence - A Promising Protein Secondary Structure Prediction Method of Single Sequence

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Zhou Yuan Wu

2013-07-01

Full Text Available In statistical methods of predicting protein secondary structure, many researchers focus on single amino acid frequencies in α-helices, β-sheets, and so on, or the impact near amino acids on an amino acid forming a secondary structure. But the paper considers a short sequence of amino acids (3, 4, 5 or 6 amino acids as integer, and statistics short sequence's probability forming secondary structure. Also, many researchers select low homologous sequences as statistical database. But this paper select whole PDB database. In this paper we propose a strategy to predict protein secondary structure using simple statistical method. Numerical computation shows that, short amino acids sequence as integer to statistics, which can easy see trend of short sequence forming secondary structure, and it will work well to select large statistical database (whole PDB database without considering homologous, and Q3 accuracy is ca. 74% using this paper proposed simple statistical method, but accuracy of others statistical methods is less than 70%.

Machine learning and hurdle models for improving regional predictions of stream water acid neutralizing capacity

Science.gov (United States)

Nicholas A. Povak; Paul F. Hessburg; Keith M. Reynolds; Timothy J. Sullivan; Todd C. McDonnell; R. Brion Salter

2013-01-01

In many industrialized regions of the world, atmospherically deposited sulfur derived from industrial, nonpoint air pollution sources reduces stream water quality and results in acidic conditions that threaten aquatic resources. Accurate maps of predicted stream water acidity are an essential aid to managers who must identify acid-sensitive streams, potentially...

Supplementing predictive mapping of acid sulfate soil occurrence with Vis-NIR spectroscopy

DEFF Research Database (Denmark)

Beucher, Amélie; Peng, Yi; Knadel, Maria

, including geology, landscape type and terrain parameters. Visible-Near-Infrared (Vis-NIR) spectroscopy constitutes a rapid and cheap alternative to soil analysis, and was successfully utilized for the prediction of soil chemical, physical and biological properties. In particular, the Vis-NIR spectra contain......Releasing acidity and metals into watercourses, acid sulfate soils represent a critical environmental problem worldwide. Identifying the spatial distribution of these soils enables to target the strategic areas for risk management. In Denmark, the occurrence of acid sulfate soils was first studied...... during the 1980’s through conventional mapping (i.e. soil sampling and the subsequent determination of pH at the time of sampling and after incubation, the pyrite content and the acid-neutralizing capacity). Since acid sulfate soils mostly occur in wetlands, the survey specifically targeted these areas...

Chondromalacia patellae: fat-suppressed MR imaging.

Science.gov (United States)

Rose, P M; Demlow, T A; Szumowski, J; Quinn, S F

1994-11-01

To evaluate the accuracy of fat-suppressed magnetic resonance (MR) imaging in diagnosing chondromalacia patellae. Seventy-one patients underwent fat-suppressed MR imaging and arthroscopy of the patellofemoral compartment. Findings were classified as early or advanced chondromalacia or as normal and were correlated with arthroscopic findings. Early and advanced stages of chondromalacia patellae were reliably detected, with positive predictive values of 85% and 92%, respectively. Specificity in early stages was 94% and in late stages was 98%. However, the overall accuracies did not differ substantially from those reported in studies that did not use fat-suppressed imaging. Axial, fat-suppressed MR imaging accurately depicts changes caused by chondromalacia patellae. Early stages can be seen as intrasubstance changes of increased signal intensity. Results of this study suggest a high degree of specificity in excluding both early and advanced changes.

Accurate prediction of the dew points of acidic combustion gases by using an artificial neural network model

International Nuclear Information System (INIS)

ZareNezhad, Bahman; Aminian, Ali

2011-01-01

This paper presents a new approach based on using an artificial neural network (ANN) model for predicting the acid dew points of the combustion gases in process and power plants. The most important acidic combustion gases namely, SO 3 , SO 2 , NO 2 , HCl and HBr are considered in this investigation. Proposed Network is trained using the Levenberg-Marquardt back propagation algorithm and the hyperbolic tangent sigmoid activation function is applied to calculate the output values of the neurons of the hidden layer. According to the network's training, validation and testing results, a three layer neural network with nine neurons in the hidden layer is selected as the best architecture for accurate prediction of the acidic combustion gases dew points over wide ranges of acid and moisture concentrations. The proposed neural network model can have significant application in predicting the condensation temperatures of different acid gases to mitigate the corrosion problems in stacks, pollution control devices and energy recovery systems.

Oropharyngeal flora in patients admitted to the medical intensive care unit: clinical factors and acid suppressive therapy.

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Frandah, Wesam; Colmer-Hamood, Jane; Mojazi Amiri, Hoda; Raj, Rishi; Nugent, Kenneth

2013-05-01

Acid suppression therapy in critically ill patients significantly reduces the incidence of stress ulceration and gastrointestinal (GI) bleeding; however, recent studies suggest that proton pump inhibitors (PPIs) increase the risk of pneumonia. We wanted to test the hypothesis that acid suppressive therapy promotes alteration in the bacterial flora in the GI tract and leads to colonization of the upper airway tract with pathogenic species, potentially forming the biological basis for the observed increased incidence of pneumonia in these patients. This was a prospective observational study on patients (adults 18 years or older) admitted to the medical intensive care unit (MICU) at a tertiary care centre. Exclusion criteria included all patients with a diagnosis of pneumonia at admission, with infection in the upper airway, or with a history of significant dysphagia. Oropharyngeal cultures were obtained on day 1 and days 3 or 4 of admission. We collected data on demographics, clinical information, and severity of the underlying disease using APACHE II scores. There were 110 patients enrolled in the study. The mean age was 49±16 years, 50 were women, and the mean APACHE II score was 9.8 ± 6.5. Twenty per cent of the patients had used a PPI in the month preceding admission. The first oropharyngeal specimen was available in 110 cases; a second specimen at 72-96 h was available in 68 cases. Seventy-five per cent of the patients admitted to the MICU had abnormal flora. In multivariate logistic regression, diabetes mellitus and PPI use were associated with abnormal oral flora on admission. Chronic renal failure and a higher body mass index reduced the frequency of abnormal oral flora on admission. Most critically ill patients admitted to our MICU have abnormal oral flora. Patients with diabetes and a history of recent PPI use are more likely to have abnormal oral flora on admission.

Induction of suppression of delayed type hypersensitivity to herpes simplex virus by epidermal cells exposed to UV-irradiated urocanic acid in vivo

International Nuclear Information System (INIS)

Ross, J.A.; Howie, S.E.; Norval, M.; Maingay, J.P.

1987-01-01

Urocanic acid (UCA), the putative photoreceptor for ultraviolet radiation (UV)-induced suppression, undergoes a UV-dependent trans to cis isomerisation. Epidermal cells from mice painted with UCA, containing a known proportion of the cis-isomer, generate suppression of the delayed type hypersensitivity response to herpes simplex virus type 1 (HSV-1) when transferred to naive syngeneic recipients at the same time and site as infection with HSV-1. One T suppressor cell subset, of phenotype (Thy1+, L3T4+, Ly2-), is induced by the cis-UCA modified epidermal cell transfer. Flow cytometric analysis of the epidermal cells from skin treated with UV or cis-UCA indicates an overall reduction from normal in the number of cells expressing MHC Class II antigens, but no alteration in the number expressing I-J antigens

Prediction of acid dissociation constants of organic compounds using group contribution methods

DEFF Research Database (Denmark)

Zhou, Teng; Jhamb, Spardha; Liang, Xiaodong

2018-01-01

data-points with average absolute error of 0.23; (b) a non-linear GC model for organic compounds using 1622 data-points with average absolute error of 1.18; (c) an artificial neural network (ANN) based GC model for the organic compounds with average absolute error of 0.17. For each of the developed......In this paper, group contribution (GC) property models for the estimation of acid dissociation constants (Ka) of organic compounds are presented. Three GC models are developed to predict the negative logarithm of the acid dissociation constant pKa: (a) a linear GC model for amino acids using 180...

Suppression of the cutaneous immune response following topical application of the prostaglandin PGE2

International Nuclear Information System (INIS)

Rheins, L.A.; Barnes, L.; Amornsiripanitch, S.; Collins, C.E.; Nordlund, J.J.

1987-01-01

UVB irradiation (290-320 nm) and topical applications of arachidonic acid (AA) in mice decrease the number of identifiable Langerhans cells and alter the cutaneous immune response. Application of contact allergens such as dinitrofluorobenzene (DNFB) to irradiated or AA-treated skin induces antigen-specific tolerance. Indomethacin (IM), a cyclooxygenase inhibitor, administered orally to mice prior to UVB irradiation or prior to the topical application of arachidonic acid, abrogates suppression of contact hypersensitivity (CHS) to DNFB. This suggests a byproduct of arachidonic acid generated through the cyclooxygenase pathway may be involved in the immune suppression. Topical application of various prostaglandins (PGE2, PGD2, PGF2 alpha, and CTXA2) did not cause alterations in the population density of the identifiable Ia+ dendritic Langerhans cells. PGE2, but no other tested agent, produced a suppression of the CHS response to DNFB. These observations suggests that of the various prostaglandins, PGE2 might be one of several biochemical signals which mediate the suppression of contact hypersensitivity reactions following ultraviolet radiation exposure. However, the mechanisms by which PGE2 produces its suppressive effects have not been identified

Palmitic acid suppresses apolipoprotein M gene expression via the pathway of PPAR{sub β/δ} in HepG2 cells

Energy Technology Data Exchange (ETDEWEB)

Luo, Guanghua; Shi, Yuanping; Zhang, Jun; Mu, Qinfeng; Qin, Li; Zheng, Lu; Feng, Yuehua [Comprehensive Laboratory, The Third Affiliated Hospital of Soochow University, Changzhou 213003 (China); Berggren-Söderlund, Maria; Nilsson-Ehle, Peter [Division of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, Lund University, S-221 85 Lund (Sweden); Zhang, Xiaoying, E-mail: zhangxy6689996@163.com [Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou 213003 (China); Xu, Ning, E-mail: ning.xu@med.lu.se [Division of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, Lund University, S-221 85 Lund (Sweden)

2014-02-28

Highlights: • Palmitic acid significantly inhibited APOM gene expression in HepG2 cells. • Palmitic acid could obviously increase PPARB/D mRNA levels in HepG2 cells. • PPAR{sub β/δ} antagonist, GSK3787, had no effect on APOM expression. • GSK3787 could reverse the palmitic acid-induced down-regulation of APOM expression. • Palmitic acid induced suppression of APOM expression is mediated via the PPAR{sub β/δ} pathway. - Abstract: It has been demonstrated that apolipoprotein M (APOM) is a vasculoprotective constituent of high density lipoprotein (HDL), which could be related to the anti-atherosclerotic property of HDL. Investigation of regulation of APOM expression is of important for further exploring its pathophysiological function in vivo. Our previous studies indicated that expression of APOM could be regulated by platelet activating factor (PAF), transforming growth factors (TGF), insulin-like growth factor (IGF), leptin, hyperglycemia and etc., in vivo and/or in vitro. In the present study, we demonstrated that palmitic acid could significantly inhibit APOM gene expression in HepG2 cells. Further study indicated neither PI-3 kinase (PI3K) inhibitor LY294002 nor protein kinase C (PKC) inhibitor GFX could abolish palmitic acid induced down-regulation of APOM expression. In contrast, the peroxisome proliferator-activated receptor beta/delta (PPAR{sub β/δ}) antagonist GSK3787 could totally reverse the palmitic acid-induced down-regulation of APOM expression, which clearly demonstrates that down-regulation of APOM expression induced by palmitic acid is mediated via the PPAR{sub β/δ} pathway.

Utilizing knowledge base of amino acids structural neighborhoods to predict protein-protein interaction sites.

Science.gov (United States)

Jelínek, Jan; Škoda, Petr; Hoksza, David

2017-12-06

Protein-protein interactions (PPI) play a key role in an investigation of various biochemical processes, and their identification is thus of great importance. Although computational prediction of which amino acids take part in a PPI has been an active field of research for some time, the quality of in-silico methods is still far from perfect. We have developed a novel prediction method called INSPiRE which benefits from a knowledge base built from data available in Protein Data Bank. All proteins involved in PPIs were converted into labeled graphs with nodes corresponding to amino acids and edges to pairs of neighboring amino acids. A structural neighborhood of each node was then encoded into a bit string and stored in the knowledge base. When predicting PPIs, INSPiRE labels amino acids of unknown proteins as interface or non-interface based on how often their structural neighborhood appears as interface or non-interface in the knowledge base. We evaluated INSPiRE's behavior with respect to different types and sizes of the structural neighborhood. Furthermore, we examined the suitability of several different features for labeling the nodes. Our evaluations showed that INSPiRE clearly outperforms existing methods with respect to Matthews correlation coefficient. In this paper we introduce a new knowledge-based method for identification of protein-protein interaction sites called INSPiRE. Its knowledge base utilizes structural patterns of known interaction sites in the Protein Data Bank which are then used for PPI prediction. Extensive experiments on several well-established datasets show that INSPiRE significantly surpasses existing PPI approaches.

AA-PMe, a novel asiatic acid derivative, induces apoptosis and suppresses proliferation, migration, and invasion of gastric cancer cells.

Science.gov (United States)

Jing, Yue; Wang, Gang; Ge, Ying; Xu, Minjie; Tang, Shuainan; Gong, Zhunan

2016-01-01

Asiatic acid (AA; 2α,3β,23-trihydroxyurs-12-ene-28-oic acid) is widely used for medicinal purposes in many Asian countries due to its various bioactivities. A series of AA derivatives has been synthesized in attempts to improve its therapeutic potencies. Herein we investigated the anti-tumor activities of N-(2α,3β,23-acetoxyurs-12-en-28-oyl)-l-proline methyl ester (AA-PMe), a novel AA derivative. AA-PMe exhibited a stronger anti-cancer activity than its parent compound AA. AA-PMe inhibited the proliferation of SGC7901 and HGC27 human gastric cancer cells in a dose-dependent manner but had no significant toxicity in human gastric mucosa epithelial cells (GES-1). AA-PMe induced cell cycle arrest in G0/G1 phase and blocked G1-S transition, which correlated well with marked decreases in levels of cyclin D1, cyclin-dependent kinase CKD4, and phosphorylated retinoblastoma protein, and increase in cyclin-dependent kinase inhibitor P15. Further, AA-PMe induced apoptosis of human gastric cancer cells by affecting Bcl-2, Bax, c-Myc, and caspase-3. Moreover, AA-PMe suppressed the migration and invasion of human gastric cancer cells (SGC7901 and HGC27) cells by downregulating the expression of MMP-2 and MMP-9. Overall, this study investigated the potential anti-cancer activities of AA-PMe including inducing apoptosis and suppressing proliferation, migration and invasion of gastric cancer cells, as well as the underlying mechanisms, suggesting that AA-PMe is a promising anti-cancer drug candidate in gastric cancer therapy.

Airborne Precursors Predict Maternal Serum Perfluoroalkyl Acid Concentrations.

Science.gov (United States)

Makey, Colleen M; Webster, Thomas F; Martin, Jonathan W; Shoeib, Mahiba; Harner, Tom; Dix-Cooper, Linda; Webster, Glenys M

2017-07-05

Human exposure to persistent perfluoroalkyl acids (PFAAs), including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorooctanesulfonate (PFOS), can occur directly from contaminated food, water, air, and dust. However, precursors to PFAAs (PreFAAs), such as dipolyfluoroalkyl phosphates (diPAPs), fluorotelomer alcohols (FTOHs), perfluorooctyl sulfonamides (FOSAs), and sulfonamidoethanols (FOSEs), which can be biotransformed to PFAAs, may also be a source of exposure. PFAAs were analyzed in 50 maternal sera samples collected in 2007-2008 from participants in Vancouver, Canada, while PFAAs and PreFAAs were measured in matching samples of residential bedroom air collected by passive sampler and in sieved vacuum dust (<150 μm). Concentrations of PreFAAs were higher than for PFAAs in air and dust. Positive associations were discovered between airborne 10:2 FTOH and serum PFOA and PFNA and between airborne MeFOSE and serum PFOS. On average, serum PFOS concentrations were 2.3 ng/mL (95%CI: 0.40, 4.3) higher in participants with airborne MeFOSE concentrations in the highest tertile relative to the lowest tertile. Among all PFAAs, only PFNA in air and vacuum dust predicted serum PFNA. Results suggest that airborne PFAA precursors were a source of PFOA, PFNA, and PFOS exposure in this population.

Effects of rare sugar D-allulose on acid production and probiotic activities of dairy lactic acid bacteria.

Science.gov (United States)

Kimoto-Nira, H; Moriya, N; Hayakawa, S; Kuramasu, K; Ohmori, H; Yamasaki, S; Ogawa, M

2017-07-01

It has recently been reported that the rare sugar d-allulose has beneficial effects, including the suppression of postprandial blood glucose elevation in humans, and can be substituted for sucrose as a low-calorie food ingredient. To examine the applications of d-allulose in the dairy industry, we investigated the effects of d-allulose on the acid production of 8 strains of yogurt starter (Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus thermophilus) and 4 strains of lactococci, including potential probiotic candidates derived from dairy products. Acid production by 2 L. delbrueckii ssp. bulgaricus yogurt starter strains in milk was suppressed by d-allulose, but this phenomenon was also observed in some strains with another sugar (xylose), a sugar alcohol (sorbitol), or both. In contrast, among the dairy probiotic candidates, Lactococcus lactis H61, which has beneficial effects for human skin when drunk as part of fermented milk, was the only strain that showed suppression of acid production in the presence of d-allulose. Strain H61 did not metabolize d-allulose. We did not observe suppression of acid production by strain H61 with the addition of xylose or sorbitol, and xylose and sorbitol were not metabolized by strain H61. The acid production of strain H61 after culture in a constituted medium (tryptone-yeast extract-glucose broth) was also suppressed with the addition of d-allulose, but growth efficiency and sugar fermentation style were not altered. Probiotic activities-such as the angiotensin-converting enzyme inhibitory activity of H61-fermented milk and the superoxide dismutase activity of H61 cells grown in tryptone-yeast extract-glucose broth-were not affected by d-allulose. d-Allulose may suppress acid production in certain lactic acid bacteria without altering their probiotic activity. It may be useful for developing new probiotic dairy products from probiotic strains such as Lactococcus lactis H61. Copyright © 2017 American Dairy Science

Modeling and prediction of retardance in citric acid coated ferrofluid using artificial neural network

International Nuclear Information System (INIS)

Lin, Jing-Fung; Sheu, Jer-Jia

2016-01-01

Citric acid coated (citrate-stabilized) magnetite (Fe 3 O 4 ) magnetic nanoparticles have been conducted and applied in the biomedical fields. Using Taguchi-based measured retardances as the training data, an artificial neural network (ANN) model was developed for the prediction of retardance in citric acid (CA) coated ferrofluid (FF). According to the ANN simulation results in the training stage, the correlation coefficient between predicted retardances and measured retardances was found to be as high as 0.9999998. Based on the well-trained ANN model, the predicted retardance at excellent program from Taguchi method showed less error of 2.17% compared with a multiple regression (MR) analysis of statistical significance. Meanwhile, the parameter analysis at excellent program by the ANN model had the guiding significance to find out a possible program for the maximum retardance. It was concluded that the proposed ANN model had high ability for the prediction of retardance in CA coated FF. - Highlights: • The feedforward ANN is applied for modeling of retardance in CA coated FFs. • ANN can predict the retardance at excellent program with acceptable error to MR. • The proposed ANN has high ability for the prediction of retardance.

Efflux inhibitor suppresses Streptococcus mutans virulence properties.

Science.gov (United States)

Zeng, Huihui; Liu, Jia; Ling, Junqi

2017-04-01

It is well established that efflux pumps play important roles in bacterial pathogenicity and efflux inhibitors (EIs) have been proved to be effective in suppressing bacterial virulence properties. However, little is known regarding the EI of Streptococcus mutans, a well-known caries-inducing bacterium. In this study, we identified the EI of S. mutans through ethidium bromide efflux assay and investigated how EI affected S. mutans virulence regarding the cariogenicity and stress response. Results indicated that reserpine, the identified EI, suppressed acid tolerance, mutacin production and transformation efficiency of S. mutans, and modified biofilm architecture and extracellular polysaccharide distribution. Suppressed glycosyltransferase activity was also noted after reserpine exposure. The data from quantitative real-time-PCR demonstrated that reserpine significantly altered the expression profile of quorum-sensing and virulence-associated genes. These findings suggest that reserpine represents a promising adjunct anticariogenic agent in that it suppresses virulence properties of S. mutans. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Spatial Patterns and Temperature Predictions of Tuna Fatty Acids: Tracing Essential Nutrients and Changes in Primary Producers.

Directory of Open Access Journals (Sweden)

Heidi R Pethybridge

Full Text Available Fatty acids are among the least understood nutrients in marine environments, despite their profile as key energy components of food webs and that they are essential to all life forms. Presented here is a novel approach to predict the spatial-temporal distributions of fatty acids in marine resources using generalized additive mixed models. Fatty acid tracers (FAT of key primary producers, nutritional condition indices and concentrations of two essential long-chain (≥C20 omega-3 fatty acids (EFA measured in muscle of albacore tuna, Thunnus alalunga, sampled in the south-west Pacific Ocean were response variables. Predictive variables were: location, time, sea surface temperature (SST and chlorophyll-a (Chla, and phytoplankton biomass at time of catch and curved fork length. The best model fit for all fatty acid parameters included fish length and SST. The first oceanographic contour maps of EFA and FAT (FATscapes were produced and demonstrated clear geographical gradients in the study region. Predicted changes in all fatty acid parameters reflected shifts in the size-structure of dominant primary producers. Model projections show that the supply and availability of EFA are likely to be negatively affected by increases in SST especially in temperate waters where a 12% reduction in both total fatty acid content and EFA proportions are predicted. Such changes will have large implications for the availability of energy and associated health benefits to high-order consumers. Results convey new concerns on impacts of projected climate change on fish-derived EFA in marine systems.

Prediction of protein modification sites of pyrrolidone carboxylic acid using mRMR feature selection and analysis.

Directory of Open Access Journals (Sweden)

Lu-Lu Zheng

Full Text Available Pyrrolidone carboxylic acid (PCA is formed during a common post-translational modification (PTM of extracellular and multi-pass membrane proteins. In this study, we developed a new predictor to predict the modification sites of PCA based on maximum relevance minimum redundancy (mRMR and incremental feature selection (IFS. We incorporated 727 features that belonged to 7 kinds of protein properties to predict the modification sites, including sequence conservation, residual disorder, amino acid factor, secondary structure and solvent accessibility, gain/loss of amino acid during evolution, propensity of amino acid to be conserved at protein-protein interface and protein surface, and deviation of side chain carbon atom number. Among these 727 features, 244 features were selected by mRMR and IFS as the optimized features for the prediction, with which the prediction model achieved a maximum of MCC of 0.7812. Feature analysis showed that all feature types contributed to the modification process. Further site-specific feature analysis showed that the features derived from PCA's surrounding sites contributed more to the determination of PCA sites than other sites. The detailed feature analysis in this paper might provide important clues for understanding the mechanism of the PCA formation and guide relevant experimental validations.

Prediction of beta-turns from amino acid sequences using the residue-coupled model.

Science.gov (United States)

Guruprasad, K; Shukla, S

2003-04-01

We evaluated the prediction of beta-turns from amino acid sequences using the residue-coupled model with an enlarged representative protein data set selected from the Protein Data Bank. Our results show that the probability values derived from a data set comprising 425 protein chains yielded an overall beta-turn prediction accuracy 68.74%, compared with 94.7% reported earlier on a data set of 30 proteins using the same method. However, we noted that the overall beta-turn prediction accuracy using probability values derived from the 30-protein data set reduces to 40.74% when tested on the data set comprising 425 protein chains. In contrast, using probability values derived from the 425 data set used in this analysis, the overall beta-turn prediction accuracy yielded consistent results when tested on either the 30-protein data set (64.62%) used earlier or a more recent representative data set comprising 619 protein chains (64.66%) or on a jackknife data set comprising 476 representative protein chains (63.38%). We therefore recommend the use of probability values derived from the 425 representative protein chains data set reported here, which gives more realistic and consistent predictions of beta-turns from amino acid sequences.

Obeticholic acid, a selective farnesoid X receptor agonist, regulates bile acid homeostasis in sandwich-cultured human hepatocytes.

Science.gov (United States)

Zhang, Yuanyuan; Jackson, Jonathan P; St Claire, Robert L; Freeman, Kimberly; Brouwer, Kenneth R; Edwards, Jeffrey E

2017-08-01

Farnesoid X receptor (FXR) is a master regulator of bile acid homeostasis through transcriptional regulation of genes involved in bile acid synthesis and cellular membrane transport. Impairment of bile acid efflux due to cholangiopathies results in chronic cholestasis leading to abnormal elevation of intrahepatic and systemic bile acid levels. Obeticholic acid (OCA) is a potent and selective FXR agonist that is 100-fold more potent than the endogenous ligand chenodeoxycholic acid (CDCA). The effects of OCA on genes involved in bile acid homeostasis were investigated using sandwich-cultured human hepatocytes. Gene expression was determined by measuring mRNA levels. OCA dose-dependently increased fibroblast growth factor-19 (FGF-19) and small heterodimer partner (SHP) which, in turn, suppress mRNA levels of cholesterol 7-alpha-hydroxylase (CYP7A1), the rate-limiting enzyme for de novo synthesis of bile acids. Consistent with CYP7A1 suppression, total bile acid content was decreased by OCA (1 μmol/L) to 42.7 ± 20.5% relative to control. In addition to suppressing de novo bile acids synthesis, OCA significantly increased the mRNA levels of transporters involved in bile acid homeostasis. The bile salt excretory pump (BSEP), a canalicular efflux transporter, increased by 6.4 ± 0.8-fold, and the basolateral efflux heterodimer transporters, organic solute transporter α (OST α ) and OST β increased by 6.4 ± 0.2-fold and 42.9 ± 7.9-fold, respectively. The upregulation of BSEP and OST α and OST β, by OCA reduced the intracellular concentrations of d 8 -TCA, a model bile acid, to 39.6 ± 8.9% relative to control. These data demonstrate that OCA does suppress bile acid synthesis and reduce hepatocellular bile acid levels, supporting the use of OCA to treat bile acid-induced toxicity observed in cholestatic diseases. © 2017 Intercept Pharmaceuticals. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and

The effect of titrated fentanyl on suppressed cough reflex in healthy adult volunteers.

Science.gov (United States)

Kelly, H E; Shaw, G M; Brett, C N; Greenwood, F M; Huckabee, M L

2016-05-01

Cough suppression is part of the pharmacodynamic profile of opioids. We investigated the impact of clinical doses of fentanyl on suppressing the cough reflex. Thirteen volunteers received 2 μg.kg(-1) of fentanyl in a divided administration protocol. Three minutes after each administration and at 10 min intervals during washout, suppressed cough reflex testing with nebulised citric acid was performed and compared with fentanyl effect-site concentration. Mean (SD) citric acid concentration provoking cough increased from 0.5 (0.28) mol.l(-1) at baseline to 1.2 (0.50) mol.l(-1) after 2 μg.kg(-1) of fentanyl (p = 0.01). Mean (SD) fentanyl effect-site concentration after the final dose of fentanyl was 1.89 (0.05) ng.ml(-1) . A strong positive correlation was found between suppressed cough reflex thresholds and fentanyl effect-site concentrations during both fentanyl administration and washout phases of the study (r(2) = 0.79, p = 0.01). The mean (SD) length of time for return of suppressed cough response was 44.6 (18.8) min. Clinically relevant doses of fentanyl produced cough reflex suppression in healthy volunteers. © 2016 The Association of Anaesthetists of Great Britain and Ireland.

Amino acid sequences of predicted proteins and their annotation for 95 organism species. - Gclust Server | LSDB Archive [Life Science Database Archive metadata

Lifescience Database Archive (English)

Full Text Available List Contact us Gclust Server Amino acid sequences of predicted proteins and their annotation for 95 organis...m species. Data detail Data name Amino acid sequences of predicted proteins and their annotation for 95 orga...nism species. DOI 10.18908/lsdba.nbdc00464-001 Description of data contents Amino acid sequences of predicted proteins...Database Description Download License Update History of This Database Site Policy | Contact Us Amino acid sequences of predicted prot...eins and their annotation for 95 organism species. - Gclust Server | LSDB Archive ...

Repetition Suppression in the Left Inferior Frontal Gyrus Predicts Tone Learning Performance.

Science.gov (United States)

Asaridou, Salomi S; Takashima, Atsuko; Dediu, Dan; Hagoort, Peter; McQueen, James M

2016-06-01

Do individuals differ in how efficiently they process non-native sounds? To what extent do these differences relate to individual variability in sound-learning aptitude? We addressed these questions by assessing the sound-learning abilities of Dutch native speakers as they were trained on non-native tone contrasts. We used fMRI repetition suppression to the non-native tones to measure participants' neuronal processing efficiency before and after training. Although all participants improved in tone identification with training, there was large individual variability in learning performance. A repetition suppression effect to tone was found in the bilateral inferior frontal gyri (IFGs) before training. No whole-brain effect was found after training; a region-of-interest analysis, however, showed that, after training, repetition suppression to tone in the left IFG correlated positively with learning. That is, individuals who were better in learning the non-native tones showed larger repetition suppression in this area. Crucially, this was true even before training. These findings add to existing evidence that the left IFG plays an important role in sound learning and indicate that individual differences in learning aptitude stem from differences in the neuronal efficiency with which non-native sounds are processed. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Suppress to feel and remember less: Neural correlates of explicit and implicit emotional suppression on perception and memory.

Science.gov (United States)

Katsumi, Yuta; Dolcos, Sanda

2018-02-09

Available evidence suggests that emotion regulation can modulate both immediate (emotional experience) and long-term (episodic memory) effects of emotion, and that both explicit and implicit forms may be effective. However, neural mechanisms by which explicit and implicit emotional suppression affect these phenomena remain unclear, particularly regarding their effects on memory. In this study, participants rated the emotional content of negative and neutral images, following explicit (verbal instructions) or implicit (priming) induction of emotional suppression goals, during functional magnetic resonance imaging. Participants' memory for the images was tested one week later. Behaviorally, explicit suppression reduced emotional ratings of negative images, whereas both explicit and implicit suppression reduced subsequent memory. At the neural level, the engagement of explicit suppression was uniquely associated with decreased activity in the amygdala (AMY), during emotional ratings, and in the AMY and inferior frontal gyrus (IFG), during successful encoding. Although both explicit and implicit suppression diminished functional connectivity between these regions and the hippocampus (HC) linked to successful encoding, explicit suppression was uniquely associated with interference with AMY-HC interactions, which no longer predicted subsequent memory for the explicitly-suppressed items. Overall, these findings advance our understanding of the common and dissociable mechanisms of explicit and implicit emotional suppression on perception and memory, and suggest their impact on both bottom-up and top-down mechanisms involved in emotion-cognition interactions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Rodlike Supramolecular Nanoassemblies of Degradable Poly(Aspartic Acid) Derivatives and Hydroxyl-Rich Polycations for Effective Delivery of Versatile Tumor-Suppressive ncRNAs.

Science.gov (United States)

Song, Hai-Qing; Pan, Wenting; Li, Rui-Quan; Yu, Bingran; Liu, Wenjuan; Yang, Ming; Xu, Fu-Jian

2018-03-01

The delivery of tumor-suppressive noncoding RNAs (ncRNAs) including short ncRNAs (i.e., miRNAs) and long ncRNAs (lncRNAs) is put forward to treat tumors. In this work, novel rodlike supramolecular nanoassemblies (CNC @CB[8] @ PGEA) of degradable poly(aspartic acid) (PAsp) derivatives-grafted cellulose nanocrystals (CNCs) and hydroxyl-rich polycations (ethanolamine-functionalized poly(glycidyl methacrylate), PGEA) are proposed via typical cucurbit[8]uril (CB[8])-based host-guest interactions for delivery of different ncRNAs to treat hepatocellular carcinoma (HCC). Spindly CNCs, one kind of natural polysaccharide nanoparticles, possess good biocompatibility and unique physico-chemical properties. PGEA with abundant hydroxyl groups is one promising gene carrier with low cytotoxicity. PAsp can benefit the disassembly and degradability of nanoassemblies within cells. CNC @ CB[8]@PGEA combines the different unique properties of CNC, PGEA, and PAsp. CNC @ CB[8] @ PGEA effectively complexes the expression constructs of miR-101 (plasmid pc3.0-miR-101) and lncRNA MEG3 (plasmid pc3.0-MEG3). CNC @ CB[8] @ PGEA produces much better transfection performances than PGEA-containing assembly units. In addition, the codelivery system of CNC @ CB[8] @ PGEA/(pc3.0-MEG3+pc3.0-miR-101) nanocomplexes demonstrates better efficacy in suppressing HCC than CNC @ CB[8] @ PGEA/pc3.0-MEG3 or CNC @ CB[8] @ PGEA/pc3.0-miR-101 nanocomplexes alone. Such rodlike supramolecular nanoassemblies will provide a promising means to produce efficient delivery vectors of versatile tumor-suppressive nucleic acids. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Prediction of valid acidity in intact apples with Fourier transform near infrared spectroscopy.

Science.gov (United States)

Liu, Yan-De; Ying, Yi-Bin; Fu, Xia-Ping

2005-03-01

To develop nondestructive acidity prediction for intact Fuji apples, the potential of Fourier transform near infrared (FT-NIR) method with fiber optics in interactance mode was investigated. Interactance in the 800 nm to 2619 nm region was measured for intact apples, harvested from early to late maturity stages. Spectral data were analyzed by two multivariate calibration techniques including partial least squares (PLS) and principal component regression (PCR) methods. A total of 120 Fuji apples were tested and 80 of them were used to form a calibration data set. The influences of different data preprocessing and spectra treatments were also quantified. Calibration models based on smoothing spectra were slightly worse than that based on derivative spectra, and the best result was obtained when the segment length was 5 nm and the gap size was 10 points. Depending on data preprocessing and PLS method, the best prediction model yielded correlation coefficient of determination (r2) of 0.759, low root mean square error of prediction (RMSEP) of 0.0677, low root mean square error of calibration (RMSEC) of 0.0562. The results indicated the feasibility of FT-NIR spectral analysis for predicting apple valid acidity in a nondestructive way.

Foam suppression in overloaded manure-based biogas reactors using antifoaming agents

DEFF Research Database (Denmark)

Kougias, Panagiotis; Boe, Kanokwan; Tsapekos, Panagiotis

2014-01-01

Foam control is an imperative need in biogas plants, as foaming is a major operational problem. In the present study, the effect of oils (rapeseed oil, oleic acid, and octanoic acid) and tributylphosphate on foam reduction and process performance in batch and continuous manure-based biogas reactors...... was investigated. The compounds were tested in dosages of 0.05%, 0.1% and 0.5% v/vfeed. The results showed that rapeseed oil was most efficient to suppress foam at the dosage of 0.05% and 0.1% v/vfeed, while octanoic acid was most efficient to suppress foam at dosage of 0.5% v/vfeed. Moreover, the addition...... of rapeseed oil also increased methane yield. In contrast, tributylphosphate, which was very efficient antifoam, was found to be inhibitory to the biogas process. © 2013 Elsevier Ltd....

Tipping the balance: Sclerotinia sclerotiorum secreted oxalic acid suppresses host defenses by manipulating the host redox environment.

Directory of Open Access Journals (Sweden)

Brett Williams

2011-06-01

Full Text Available Sclerotinia sclerotiorum is a necrotrophic ascomycete fungus with an extremely broad host range. This pathogen produces the non-specific phytotoxin and key pathogenicity factor, oxalic acid (OA. Our recent work indicated that this fungus and more specifically OA, can induce apoptotic-like programmed cell death (PCD in plant hosts, this induction of PCD and disease requires generation of reactive oxygen species (ROS in the host, a process triggered by fungal secreted OA. Conversely, during the initial stages of infection, OA also dampens the plant oxidative burst, an early host response generally associated with plant defense. This scenario presents a challenge regarding the mechanistic details of OA function; as OA both suppresses and induces host ROS during the compatible interaction. In the present study we generated transgenic plants expressing a redox-regulated GFP reporter. Results show that initially, Sclerotinia (via OA generates a reducing environment in host cells that suppress host defense responses including the oxidative burst and callose deposition, akin to compatible biotrophic pathogens. Once infection is established however, this necrotroph induces the generation of plant ROS leading to PCD of host tissue, the result of which is of direct benefit to the pathogen. In contrast, a non-pathogenic OA-deficient mutant failed to alter host redox status. The mutant produced hypersensitive response-like features following host inoculation, including ROS induction, callose formation, restricted growth and cell death. These results indicate active recognition of the mutant and further point to suppression of defenses by the wild type necrotrophic fungus. Chemical reduction of host cells with dithiothreitol (DTT or potassium oxalate (KOA restored the ability of this mutant to cause disease. Thus, Sclerotinia uses a novel strategy involving regulation of host redox status to establish infection. These results address a long-standing issue

Analysis of a simplified normalized covariance measure based on binary weighting functions for predicting the intelligibility of noise-suppressed speech.

Science.gov (United States)

Chen, Fei; Loizou, Philipos C

2010-12-01

The normalized covariance measure (NCM) has been shown previously to predict reliably the intelligibility of noise-suppressed speech containing non-linear distortions. This study analyzes a simplified NCM measure that requires only a small number of bands (not necessarily contiguous) and uses simple binary (1 or 0) weighting functions. The rationale behind the use of a small number of bands is to account for the fact that the spectral information contained in contiguous or nearby bands is correlated and redundant. The modified NCM measure was evaluated with speech intelligibility scores obtained by normal-hearing listeners in 72 noisy conditions involving noise-suppressed speech corrupted by four different types of maskers (car, babble, train, and street interferences). High correlation (r = 0.8) was obtained with the modified NCM measure even when only one band was used. Further analysis revealed a masker-specific pattern of correlations when only one band was used, and bands with low correlation signified the corresponding envelopes that have been severely distorted by the noise-suppression algorithm and/or the masker. Correlation improved to r = 0.84 when only two disjoint bands (centered at 325 and 1874 Hz) were used. Even further improvements in correlation (r = 0.85) were obtained when three or four lower-frequency (<700 Hz) bands were selected.

Ursodeoxycholic acid suppresses eosinophilic airway inflammation by inhibiting the function of dendritic cells through the nuclear farnesoid X receptor.

Science.gov (United States)

Willart, M A M; van Nimwegen, M; Grefhorst, A; Hammad, H; Moons, L; Hoogsteden, H C; Lambrecht, B N; Kleinjan, A

2012-12-01

Ursodeoxycholic acid (UDCA) is the only known beneficial bile acid with immunomodulatory properties. Ursodeoxycholic acid prevents eosinophilic degranulation and reduces eosinophil counts in primary biliary cirrhosis. It is unknown whether UDCA would also modulate eosinophilic inflammation outside the gastrointestinal (GI) tract, such as eosinophilic airway inflammation seen in asthma. The working mechanism for its immunomodulatory effect is unknown. The immunosuppressive features of UDCA were studied in vivo, in mice, in an ovalbumin (OVA)-driven eosinophilic airway inflammation model. To study the mechanism of action of UDCA, we analyzed the effect of UDCA on eosinophils, T cells, and dendritic cell (DCs). DC function was studied in greater detail, focussing on migration and T-cell stimulatory strength in vivo and interaction with T cells in vitro as measured by time-lapse image analysis. Finally, we studied the capacity of UDCA to influence DC/T cell interaction. Ursodeoxycholic acid treatment of OVA-sensitized mice prior to OVA aerosol challenge significantly reduced eosinophilic airway inflammation compared with control animals. DCs expressed the farnesoid X receptor for UDCA. Ursodeoxycholic acid strongly promoted interleukin (IL)-12 production and enhanced the migration in DCs. The time of interaction between DCs and T cells was sharply reduced in vitro by UDCA treatment of the DCs resulting in a remarkable T-cell cytokine production. Ursodeoxycholic acid-treated DCs have less capacity than saline-treated DCs to induce eosinophilic inflammation in vivo in Balb/c mice. Ursodeoxycholic acid has the potency to suppress eosinophilic inflammation outside the GI tract. This potential comprises to alter critical function of DCs, in essence, the effect of UDCA on DCs through the modulation of the DC/T cell interaction. © 2012 John Wiley & Sons A/S.

Quantum-mechanical suppression of bremsstrahlung

Energy Technology Data Exchange (ETDEWEB)

Becker-Szendy, R.; Keller, L.; Niemi, G.; Perl, M.; Rochester, L. [Stanford Univ., CA (United States); Anthony, P. [Stanford Univ., CA (United States)]|[Lawrence Livermore National Lab., CA (United States); Bosted, P. [American Univ., Washington, DC (United States); Cavalli-Sforza, M.; Kelley, L.; Klein, S. [Univ. of California, Santa Cruz, CA (United States)] [and others

1994-12-01

The authors have studied quantum-mechanical suppression of bremsstrahlung of low-energy 1-500 MeV photons from high-energy 25 GeV electrons. They have measured the LPM effect, where multiple scattering of the radiating electron destroys coherence required for the emission of low-energy photons, and the dielectric effect, where the emitted photon traveling in the radiator medium interferes with itself. For the experiment, the collaboration developed a novel method of extracting a parasitic low-intensity high-energy electron beam into the fixed target area during normal SLC operation of the accelerator. The results agree quantitatively with Migdal`s calculation of the LPM effect. Surface effects, for which there is no satisfactory theoretical prediction, are visible at low photon energies. For very thin targets, the suppression disappears, as expected. Preliminary results on dielectric suppression of bremsstrahlung are in qualitative agreement with the expectation.

Characterization of the ecological role of genes mediating acid resistance in Lactobacillus reuteri during colonization of the gastrointestinal tract.

Science.gov (United States)

Krumbeck, Janina A; Marsteller, Nathan L; Frese, Steven A; Peterson, Daniel A; Ramer-Tait, Amanda E; Hutkins, Robert W; Walter, Jens

2016-07-01

Rodent-derived strains of Lactobacillus reuteri densely colonize the forestomach of mice and possess several genes whose predicted functions constitute adaptations towards an acidic environment. The objective of this study was to systematically determine which genes of L. reuteri 100-23 contribute to tolerance towards host gastric acid secretion. Genes predicted to be involved in acid resistance were inactivated, and their contribution to survival under acidic conditions was confirmed in model gastric juice. Fitness of five mutants that showed impaired in vitro acid resistance were then compared through competition experiments in ex-germ-free mice that were either treated with omeprazole, a proton-pump inhibitor that suppresses acid secretion in the stomach, or left untreated. This analysis revealed that the urease cluster was the predominant factor in mediating resistance to gastric acid production. Population levels of the mutant, which were substantially decreased in untreated mice, were almost completely restored through omeprazole, demonstrating that urease production in L. reuteri is mainly devoted to overcome gastric acid. The findings provide novel information on the mechanisms by which L. reuteri colonizes its gastric niche and demonstrate that in silico gene predictions and in vitro tests have limitations for predicting the ecological functions of colonization factors in bacterial symbionts. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

AA-PMe, a novel asiatic acid derivative, induces apoptosis and suppresses proliferation, migration, and invasion of gastric cancer cells

Science.gov (United States)

Jing, Yue; Wang, Gang; Ge, Ying; Xu, Minjie; Tang, Shuainan; Gong, Zhunan

2016-01-01

Asiatic acid (AA; 2α,3β,23-trihydroxyurs-12-ene-28-oic acid) is widely used for medicinal purposes in many Asian countries due to its various bioactivities. A series of AA derivatives has been synthesized in attempts to improve its therapeutic potencies. Herein we investigated the anti-tumor activities of N-(2α,3β,23-acetoxyurs-12-en-28-oyl)-l-proline methyl ester (AA-PMe), a novel AA derivative. AA-PMe exhibited a stronger anti-cancer activity than its parent compound AA. AA-PMe inhibited the proliferation of SGC7901 and HGC27 human gastric cancer cells in a dose-dependent manner but had no significant toxicity in human gastric mucosa epithelial cells (GES-1). AA-PMe induced cell cycle arrest in G0/G1 phase and blocked G1-S transition, which correlated well with marked decreases in levels of cyclin D1, cyclin-dependent kinase CKD4, and phosphorylated retinoblastoma protein, and increase in cyclin-dependent kinase inhibitor P15. Further, AA-PMe induced apoptosis of human gastric cancer cells by affecting Bcl-2, Bax, c-Myc, and caspase-3. Moreover, AA-PMe suppressed the migration and invasion of human gastric cancer cells (SGC7901 and HGC27) cells by downregulating the expression of MMP-2 and MMP-9. Overall, this study investigated the potential anti-cancer activities of AA-PMe including inducing apoptosis and suppressing proliferation, migration and invasion of gastric cancer cells, as well as the underlying mechanisms, suggesting that AA-PMe is a promising anti-cancer drug candidate in gastric cancer therapy. PMID:27073325

Deconstructing Interocular Suppression: Attention and Divisive Normalization.

Directory of Open Access Journals (Sweden)

Hsin-Hung Li

2015-10-01

Full Text Available In interocular suppression, a suprathreshold monocular target can be rendered invisible by a salient competitor stimulus presented in the other eye. Despite decades of research on interocular suppression and related phenomena (e.g., binocular rivalry, flash suppression, continuous flash suppression, the neural processing underlying interocular suppression is still unknown. We developed and tested a computational model of interocular suppression. The model included two processes that contributed to the strength of interocular suppression: divisive normalization and attentional modulation. According to the model, the salient competitor induced a stimulus-driven attentional modulation selective for the location and orientation of the competitor, thereby increasing the gain of neural responses to the competitor and reducing the gain of neural responses to the target. Additional suppression was induced by divisive normalization in the model, similar to other forms of visual masking. To test the model, we conducted psychophysics experiments in which both the size and the eye-of-origin of the competitor were manipulated. For small and medium competitors, behavioral performance was consonant with a change in the response gain of neurons that responded to the target. But large competitors induced a contrast-gain change, even when the competitor was split between the two eyes. The model correctly predicted these results and outperformed an alternative model in which the attentional modulation was eye specific. We conclude that both stimulus-driven attention (selective for location and feature and divisive normalization contribute to interocular suppression.

Deconstructing Interocular Suppression: Attention and Divisive Normalization.

Science.gov (United States)

Li, Hsin-Hung; Carrasco, Marisa; Heeger, David J

2015-10-01

In interocular suppression, a suprathreshold monocular target can be rendered invisible by a salient competitor stimulus presented in the other eye. Despite decades of research on interocular suppression and related phenomena (e.g., binocular rivalry, flash suppression, continuous flash suppression), the neural processing underlying interocular suppression is still unknown. We developed and tested a computational model of interocular suppression. The model included two processes that contributed to the strength of interocular suppression: divisive normalization and attentional modulation. According to the model, the salient competitor induced a stimulus-driven attentional modulation selective for the location and orientation of the competitor, thereby increasing the gain of neural responses to the competitor and reducing the gain of neural responses to the target. Additional suppression was induced by divisive normalization in the model, similar to other forms of visual masking. To test the model, we conducted psychophysics experiments in which both the size and the eye-of-origin of the competitor were manipulated. For small and medium competitors, behavioral performance was consonant with a change in the response gain of neurons that responded to the target. But large competitors induced a contrast-gain change, even when the competitor was split between the two eyes. The model correctly predicted these results and outperformed an alternative model in which the attentional modulation was eye specific. We conclude that both stimulus-driven attention (selective for location and feature) and divisive normalization contribute to interocular suppression.

Low-protein diet supplemented with keto acids is associated with suppression of small-solute peritoneal transport rate in peritoneal dialysis patients.

Science.gov (United States)

Jiang, Na; Qian, Jiaqi; Lin, Aiwu; Fang, Wei; Zhang, Weiming; Cao, Liou; Wang, Qin; Ni, Zhaohui; Yao, Qiang

2011-01-01

Objective. We investigate whether low-protein diet would show benefits in suppressing peritoneal transport rate in peritoneal dialysis (PD) patients. Methods. This is a supplemented analysis of our previously published trial, which randomized 60 PD patients to receive low- (LP: dietary protein intake of 0.6-0.8 g/kg/d), keto-acid-supplemented low- (sLP: 0.6-0.8 g/kg/d with 0.12 g/kg/d of keto acids), or high- (HP: 1.0-1.2 g/kg/d) protein diet and lasted for one year. In this study, the variations of peritoneal transport rate were assessed. Results. While baseline D/P(cr) (dialysate-to-plasma concentration ratio for creatinine at 4 hour) and D/D0(glu) (dialysate glucose at 4 hour to baseline dialysate glucose concentration ratio) were similar, D/P(cr) in group sLP was lower, and D/D0(glu) was higher than those in the other two groups (P diet with keto acids may benefit PD patients by maintaining peritoneum at a lower transport rate.

Predicting sorption of organic acids to a wide range of carbonized sorbents

Science.gov (United States)

Sigmund, Gabriel; Kah, Melanie; Sun, Huichao; Hofmann, Thilo

2016-04-01

Many contaminants and infochemicals are organic acids that undergo dissociation under environmental conditions. The sorption of dissociated anions to biochar and other carbonized sorbents is typically lower than that of neutral species. It is driven by complex processes that are not yet fully understood. It is known that predictive approaches developed for neutral compounds are unlikely to be suitable for organic acids, due to the effects of dissociation on sorption. Previous studies on the sorption of organic acids to soils have demonstrated that log Dow, which describes the decrease in hydrophobicity of acids upon dissociation, is a useful alternative to log Kow. The aim of the present study was to adapt a log Dow based approach to describe the sorption of organic acids to carbonized sorbents. Batch experiments were performed with a series of 9 sorbents (i.e., carbonized wood shavings, pig manure, and sewage sludge, carbon nanotubes and activated carbon), and four acids commonly used for pesticidal and biocidal purposes (i.e., 2,4-D, MCPA, 2,4-DB, and triclosan). Sorbents were comprehensively characterized, including by N2 and CO2 physisorption, Fourier transform infrared spectroscopy, and elemental analysis. The wide range of sorbents considered allows (i) discussing the mechanisms driving the sorption of neutral and anionic species to biochar, and (ii) their dependency on sorbate and sorbent properties. Results showed that the sorption of the four acids was influenced by factors that are usually not considered for neutral compounds (i.e., pH, ionic strength). Dissociation affected the sorption of the four compounds, and sorption of the anions ranged over five orders of magnitude, thus substantially contributing to sorption in some cases. For prediction purposes, most of the variation in sorption to carbonized sorbents (89%) could be well described with a two-parameter regression equation including log Dow and sorbent specific surface area. The proposed model

Identification of predictor parameters to determine agro-industrial compost suppressiveness against Fusarium oxysporum and Phytophthora capsici diseases in muskmelon and pepper seedlings.

Science.gov (United States)

Blaya, Josefa; Lloret, Eva; Ros, Margarita; Pascual, Jose Antonio

2015-05-01

The lack of reliable prediction tools for evaluation of the level and specificity of compost suppressiveness limits its application. In our study, different chemical, biological and microbiological parameters were used to evaluate their potential use as a predictor parameter for the suppressive effect of composts against Fusarium oxysporum f. sp. melonis (FOM) and Phytophthora capsici (P. capsici) in muskmelon and pepper seedlings respectively. Composts were obtained from artichoke sludge, chopped vineyard pruning waste and various agro-industrial wastes (C1: blanched artichokes; C2: garlic waste; C3: dry olive cake). Compost C3 proved to offer the highest level of resistance against FOM, and compost C2 the highest level of resistance against P. capsici. Analysis of phospholipid fatty acids isolated from compost revealed that the three composts showed different microbial community structures. Protease, NAGase and chitinase activities were significantly higher in compost C3, as was dehydrogenase activity in compost C2. The use of specific parameters such as general (dehydrogenase activity) and specific enzymatic activities (protease, NAGase and chitinase activities) may be useful to predict compost suppressiveness against both pathogens. The selection of raw materials for agro-industrial composts is important in controlling Fusarium wilt and Phytophthora root rot. © 2014 Society of Chemical Industry.

Studies on Synthesis of Electrochemically Exfoliated Functionalized Graphene and Polylactic Acid/Ferric Phytate Functionalized Graphene Nanocomposites as New Fire Hazard Suppression Materials.

Science.gov (United States)

Feng, Xiaming; Wang, Xin; Cai, Wei; Qiu, Shuilai; Hu, Yuan; Liew, Kim Meow

2016-09-28

Practical application of functionalized graphene in polymeric nanocomposites is hampered by the lack of cost-effective and eco-friendly methods for its production. Here, we reported a facile and green electrochemical approach for preparing ferric phytate functionalized graphene (f-GNS) by simultaneously utilizing biobased phytic acid as electrolyte and modifier for the first time. Due to the presence of phytic acid, electrochemical exfoliation leads to low oxidized graphene sheets (a C/O ratio of 14.8) that are tens of micrometers large. Successful functionalization of graphene was confirmed by the appearance of phosphorus and iron peaks in the X-ray photoelectron spectrum. Further, high-performance polylactic acid/f-GNS nanocomposites are readily fabricated by a convenient masterbatch strategy. Notably, inclusion of well-dispersed f-GNS resulted in dramatic suppression on fire hazards of polylactic acid in terms of reduced peak heat-release rate (decreased by 40%), low CO yield, and formation of a high graphitized protective char layer. Moreover, obviously improvements in crystallization rate and thermal conductivities of polylactic acid nanocomposites were observed, highlighting its promising potential in practical application. This novel strategy toward the simultaneous exfoliation and functionalization for graphene demonstrates a simple yet very effective approach for fabricating graphene-based flame retardants.

Antisense-mediated suppression of C-hordein biosynthesis in the barley grain results in correlated changes in the transcriptome, protein profile, and amino acid composition

DEFF Research Database (Denmark)

Hansen, Mette; Lange, Marianne; Friis, Carsten

2007-01-01

Antisense- or RNAi-mediated suppression of the biosynthesis of nutritionally inferior storage proteins is a promising strategy for improving the amino acid profile of seeds. However, the potential pleiotropic effects of this on interconnected pathways and the agronomic quality traits need...... to be addressed. In the current study, a transcriptomic analysis of an antisense C-hordein line of barley was performed, using a grain-specific cDNA array. The C-hordein antisense line is characterized by marked changes in storage protein and amino acid profiles, while the seed weight is within the normal range...... and no external morphological irregularities were observed. The results of the transcriptome analysis showed excellent correlation with data on changes in the relative proportions of storage proteins and amino acid composition. The antisense line had a lower C-hordein level and down-regulated transcript encoding...

Fast computational methods for predicting protein structure from primary amino acid sequence

Science.gov (United States)

Agarwal, Pratul Kumar [Knoxville, TN

2011-07-19

The present invention provides a method utilizing primary amino acid sequence of a protein, energy minimization, molecular dynamics and protein vibrational modes to predict three-dimensional structure of a protein. The present invention also determines possible intermediates in the protein folding pathway. The present invention has important applications to the design of novel drugs as well as protein engineering. The present invention predicts the three-dimensional structure of a protein independent of size of the protein, overcoming a significant limitation in the prior art.

Animal model of acid-reflux esophagitis: pathogenic roles of acid/pepsin, prostaglandins, and amino acids.

Science.gov (United States)

Takeuchi, Koji; Nagahama, Kenji

2014-01-01

Esophagitis was induced in rats within 3 h by ligating both the pylorus and transitional region between the forestomach and glandular portion under ether anesthesia. This esophageal injury was prevented by the administration of acid suppressants and antipepsin drug and aggravated by exogenous pepsin. Damage was also aggravated by pretreatment with indomethacin and the selective COX-1 but not COX-2 inhibitor, whereas PGE2 showed a biphasic effect depending on the dose; a protection at low doses, and an aggravation at high doses, with both being mediated by EP1 receptors. Various amino acids also affected this esophagitis in different ways; L-alanine and L-glutamine had a deleterious effect, while L-arginine and glycine were highly protective, both due to yet unidentified mechanisms. It is assumed that acid/pepsin plays a major pathogenic role in this model of esophagitis; PGs derived from COX-1 are involved in mucosal defense of the esophagus; and some amino acids are protective against esophagitis. These findings also suggest a novel therapeutic approach in the treatment of esophagitis, in addition to acid suppressant therapy. The model introduced may be useful to test the protective effects of drugs on esophagitis and investigate the mucosal defense mechanism in the esophagus.

Predicting HLA class I non-permissive amino acid residues substitutions.

Directory of Open Access Journals (Sweden)

T Andrew Binkowski

Full Text Available Prediction of peptide binding to human leukocyte antigen (HLA molecules is essential to a wide range of clinical entities from vaccine design to stem cell transplant compatibility. Here we present a new structure-based methodology that applies robust computational tools to model peptide-HLA (p-HLA binding interactions. The method leverages the structural conservation observed in p-HLA complexes to significantly reduce the search space and calculate the system's binding free energy. This approach is benchmarked against existing p-HLA complexes and the prediction performance is measured against a library of experimentally validated peptides. The effect on binding activity across a large set of high-affinity peptides is used to investigate amino acid mismatches reported as high-risk factors in hematopoietic stem cell transplantation.

Sugar and acid content of Citrus prediction modeling using FT-IR fingerprinting in combination with multivariate statistical analysis.

Science.gov (United States)

Song, Seung Yeob; Lee, Young Koung; Kim, In-Jung

2016-01-01

A high-throughput screening system for Citrus lines were established with higher sugar and acid contents using Fourier transform infrared (FT-IR) spectroscopy in combination with multivariate analysis. FT-IR spectra confirmed typical spectral differences between the frequency regions of 950-1100 cm(-1), 1300-1500 cm(-1), and 1500-1700 cm(-1). Principal component analysis (PCA) and subsequent partial least square-discriminant analysis (PLS-DA) were able to discriminate five Citrus lines into three separate clusters corresponding to their taxonomic relationships. The quantitative predictive modeling of sugar and acid contents from Citrus fruits was established using partial least square regression algorithms from FT-IR spectra. The regression coefficients (R(2)) between predicted values and estimated sugar and acid content values were 0.99. These results demonstrate that by using FT-IR spectra and applying quantitative prediction modeling to Citrus sugar and acid contents, excellent Citrus lines can be early detected with greater accuracy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Near-infrared reflectance spectroscopy for predicting amino acids content in intact processed animal proteins.

Science.gov (United States)

De la Haba, Maria José; Garrido-Varo, Ana; Guerrero-Ginel, José Emilio; Pérez-Marín, Dolores C

2006-10-04

Near-infrared calibrations were developed for the instantaneous prediction of amino acids composition of processed animal proteins (PAPs). Two sample presentation modes were compared (ground vs intact) for demonstrating the viability of the analysis in the intact form, avoiding the need for milling. Modified partial least-squares (MPLS) equations for the prediction of amino acids in PAPs were developed using the same set of samples (N = 92 PAPs) analyzed in ground and intact form and in three cups differing in the optical window size. The standard error for cross validation (SECV) and the coefficient of determination (1-VR) values yielded with the calibrations developed using the samples analyzed in the intact form showed similar or even better accuracy than those obtained with finely ground samples. The excellent predictive ability (1-VR > 0.90; CV marketing of these important protein feed ingredients, alleviating the costs and time associated with the routine quality controls.

Accurate prediction of the toxicity of benzoic acid compounds in mice via oral without using any computer codes

International Nuclear Information System (INIS)

Keshavarz, Mohammad Hossein; Gharagheizi, Farhad; Shokrolahi, Arash; Zakinejad, Sajjad

2012-01-01

Highlights: ► A novel method is introduced for desk calculation of toxicity of benzoic acid derivatives. ► There is no need to use QSAR and QSTR methods, which are based on computer codes. ► The predicted results of 58 compounds are more reliable than those predicted by QSTR method. ► The present method gives good predictions for further 324 benzoic acid compounds. - Abstract: Most of benzoic acid derivatives are toxic, which may cause serious public health and environmental problems. Two novel simple and reliable models are introduced for desk calculations of the toxicity of benzoic acid compounds in mice via oral LD 50 with more reliance on their answers as one could attach to the more complex outputs. They require only elemental composition and molecular fragments without using any computer codes. The first model is based on only the number of carbon and hydrogen atoms, which can be improved by several molecular fragments in the second model. For 57 benzoic compounds, where the computed results of quantitative structure–toxicity relationship (QSTR) were recently reported, the predicted results of two simple models of present method are more reliable than QSTR computations. The present simple method is also tested with further 324 benzoic acid compounds including complex molecular structures, which confirm good forecasting ability of the second model.

A precise form of divisive suppression supports population coding in the primary visual cortex.

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MacEvoy, Sean P; Tucker, Thomas R; Fitzpatrick, David

2009-05-01

The responses of neurons in the primary visual cortex (V1) to an optimally oriented grating are suppressed when a non-optimal grating is superimposed. Although cross-orientation suppression is thought to reflect mechanisms that maintain a distributed code for orientation, the effect of superimposed gratings on V1 population responses is unknown. Using intrinsic signal optical imaging, we found that patterns of tree shrew V1 activity evoked by superimposed equal-contrast gratings were predicted by the averages of patterns evoked by individual component gratings. This prediction held across contrasts, for summed sinusoidal gratings or nonsumming square-wave gratings, and was evident in single-unit extracellular recordings. Intracellular recordings revealed consistent levels of suppression throughout the time course of subthreshold responses. These results indicate that divisive suppression powerfully governs population responses to multiple orientations. Moreover, the specific form of suppression that we observed appears to support independent population codes for stimulus orientation and strength and calls for a reassessment of mechanisms that underlie cross-orientation suppression.

Smiling on the Inside: The Social Benefits of Suppressing Positive Emotions in Outperformance Situations.

Science.gov (United States)

Schall, Marina; Martiny, Sarah E; Goetz, Thomas; Hall, Nathan C

2016-05-01

Although expressing positive emotions is typically socially rewarded, in the present work, we predicted that people suppress positive emotions and thereby experience social benefits when outperformed others are present. We tested our predictions in three experimental studies with high school students. In Studies 1 and 2, we manipulated the type of social situation (outperformance vs. non-outperformance) and assessed suppression of positive emotions. In both studies, individuals reported suppressing positive emotions more in outperformance situations than in non-outperformance situations. In Study 3, we manipulated the social situation (outperformance vs. non-outperformance) as well as the videotaped person's expression of positive emotions (suppression vs. expression). The findings showed that when outperforming others, individuals were indeed evaluated more positively when they suppressed rather than expressed their positive emotions, and demonstrate the importance of the specific social situation with respect to the effects of suppression. © 2016 by the Society for Personality and Social Psychology, Inc.

Quantum Chemical Prediction of Equilibrium Acidities of Ureas, Deltamides, Squaramides, and Croconamides.

Science.gov (United States)

Ho, Junming; Zwicker, Vincent E; Yuen, Karen K Y; Jolliffe, Katrina A

2017-10-06

Robust quantum chemical methods are employed to predict the pK a 's of several families of dual hydrogen-bonding organocatalysts/anion receptors, including deltamides and croconamides as well as their thio derivatives. The average accuracy of these predictions is ∼1 pK a unit and allows for a comparison of the acidity between classes of receptors and for quantitative studies of substituent effects. These computational insights further explain the relationship between pK a and chloride anion affinity of these receptors that will be important for designing future anion receptors and organocatalysts.

Predicting taxonomic and functional structure of microbial communities in acid mine drainage.

Science.gov (United States)

Kuang, Jialiang; Huang, Linan; He, Zhili; Chen, Linxing; Hua, Zhengshuang; Jia, Pu; Li, Shengjin; Liu, Jun; Li, Jintian; Zhou, Jizhong; Shu, Wensheng

2016-06-01

Predicting the dynamics of community composition and functional attributes responding to environmental changes is an essential goal in community ecology but remains a major challenge, particularly in microbial ecology. Here, by targeting a model system with low species richness, we explore the spatial distribution of taxonomic and functional structure of 40 acid mine drainage (AMD) microbial communities across Southeast China profiled by 16S ribosomal RNA pyrosequencing and a comprehensive microarray (GeoChip). Similar environmentally dependent patterns of dominant microbial lineages and key functional genes were observed regardless of the large-scale geographical isolation. Functional and phylogenetic β-diversities were significantly correlated, whereas functional metabolic potentials were strongly influenced by environmental conditions and community taxonomic structure. Using advanced modeling approaches based on artificial neural networks, we successfully predicted the taxonomic and functional dynamics with significantly higher prediction accuracies of metabolic potentials (average Bray-Curtis similarity 87.8) as compared with relative microbial abundances (similarity 66.8), implying that natural AMD microbial assemblages may be better predicted at the functional genes level rather than at taxonomic level. Furthermore, relative metabolic potentials of genes involved in many key ecological functions (for example, nitrogen and phosphate utilization, metals resistance and stress response) were extrapolated to increase under more acidic and metal-rich conditions, indicating a critical strategy of stress adaptation in these extraordinary communities. Collectively, our findings indicate that natural selection rather than geographic distance has a more crucial role in shaping the taxonomic and functional patterns of AMD microbial community that readily predicted by modeling methods and suggest that the model-based approach is essential to better understand natural

PENAMBAHAN BAKTERI ASAM LAKTAT TERENKAPSULASI UNTUK MENEKAN PERTUMBUHAN BAKTERI PATOGEN PADA PROSES PRODUKSI TAPIOKA [Addition of Encapsulated Lactic Acid Bacteria to Suppress the Growth of Pathogenic Bacteria during Tapioca Production

Directory of Open Access Journals (Sweden)

Glisina Dwinoor Rembulan

2015-07-01

Full Text Available Lactic acid bacteria (LAB produce organic acids and active compounds which can inhibit the growth of pathogenic bacteria. Lactic acid bacteria potentially can be introduced to inhibit pathogenic bacteria in the tapioca production at the extraction stage, especially during the settling process since there is possibility of starch slurry to be contaminated by pathogenic bacteria from water. The objectives of this research were to design a solid starter of LAB through encapsulation by using modified starch includes sour cassava starch, lintnerized cassava starch and nanocrystalline starch, utilize the starter for suppressing the growth of pathogenic bacteria in the production process of tapioca and characterize the functional properties of tapioca. The encapsulation of lactic acid bacteria was conducted by freeze drying at a temperature of -50°C for 48 hours. The viability of LAB after freeze drying with sour cassava starch matrix was 92% of the liquid starter, with lintnerized cassava starch matrix was 93%, while that with nanocrystalline matrix was 96%. After application of the LAB culture during settling process for tapioca extraction and the tapioca was stored at room temperature for 6 months, it was shown that E. coli, Salmonella and Shigella were  detected in the native tapioca starch (without treatment while the starch added with lactic acid bacteria starter was not absent for the pathogenic bacteria. The addition of lactic acid bacteria in extraction process can suppress the growth of pathogenic bacteria in tapioca. The results showed that lintnerized cassava starch matrix is the best matrix because after 6 months it still contained lactic acid bacteria as compared to liquid starter and that encapsulated with other matrixes.

Suppression of CCR impacts metabolite profile and cell wall composition in Pinus radiata tracheary elements.

Science.gov (United States)

Wagner, Armin; Tobimatsu, Yuki; Goeminne, Geert; Phillips, Lorelle; Flint, Heather; Steward, Diane; Torr, Kirk; Donaldson, Lloyd; Boerjan, Wout; Ralph, John

2013-01-01

Suppression of the lignin-related gene cinnamoyl-CoA reductase (CCR) in the Pinus radiata tracheary element (TE) system impacted both the metabolite profile and the cell wall matrix in CCR-RNAi lines. UPLC-MS/MS-based metabolite profiling identified elevated levels of p-coumaroyl hexose, caffeic acid hexoside and ferulic acid hexoside in CCR-RNAi lines, indicating a redirection of metabolite flow within phenylpropanoid metabolism. Dilignols derived from coniferyl alcohol such as G(8-5)G, G(8-O-4)G and isodihydrodehydrodiconiferyl alcohol (IDDDC) were substantially depleted, providing evidence for CCR's involvement in coniferyl alcohol biosynthesis. Severe CCR suppression almost halved lignin content in TEs based on a depletion of both H-type and G-type lignin, providing evidence for CCR's involvement in the biosynthesis of both lignin types. 2D-NMR studies revealed minor changes in the H:G-ratio and consequently a largely unchanged interunit linkage distribution in the lignin polymer. However, unusual cell wall components including ferulate and unsaturated fatty acids were identified in TEs by thioacidolysis, pyrolysis-GC/MS and/or 2D-NMR in CCR-RNAi lines, providing new insights into the consequences of CCR suppression in pine. Interestingly, CCR suppression substantially promoted pyrolytic breakdown of cell wall polysaccharides, a phenotype most likely caused by the incorporation of acidic compounds into the cell wall matrix in CCR-RNAi lines.

4-Hydroxyphenylacetic Acid Attenuated Inflammation and Edema via Suppressing HIF-1α in Seawater Aspiration-Induced Lung Injury in Rats

Science.gov (United States)

Liu, Zhongyang; Xi, Ronggang; Zhang, Zhiran; Li, Wangping; Liu, Yan; Jin, Faguang; Wang, Xiaobo

2014-01-01

4-Hydroxyphenylacetic acid (4-HPA) is an active component of Chinese herb Aster tataricus which had been widely used in China for the treatment of pulmonary diseases. The aim of this study is to investigate the effect of 4-HPA on seawater aspiration-induced lung injury. Pulmonary inflammation and edema were assessed by enzyme-linked immunosorbent assay (ELISA), bronchoalveolar lavage fluid (BALF) white cell count, Evans blue dye analysis, wet to dry weight ratios, and histology study. Hypoxia-inducible factor-1α (HIF-1α) siRNA and permeability assay were used to study the effect of 4-HPA on the production of inflammatory cytokines and monolayer permeability in vitro. The results showed that 4-HPA reduced seawater instillation-induced mortality in rats. In lung tissues, 4-HPA attenuated hypoxia, inflammation, vascular leak, and edema, and decreased HIF-1α protein level. In primary rat alveolar epithelial cells (AEC), 4-HPA decreased hypertonicity- and hypoxia-induced HIF-1α protein levels through inhibiting the activations of protein translational regulators and via promoting HIF-1α protein degradation. In addition, 4-HPA lowered inflammatory cytokines levels through suppressing hypertonicity- and hypoxia-induced HIF-1α in NR8383 macrophages. Moreover, 4-HPA decreased monolayer permeability through suppressing hypertonicity and hypoxia-induced HIF-1α, which was mediated by inhibiting vascular endothelial growth factor (VEGF) in rat lung microvascular endothelial cell line (RLMVEC). In conclusion, 4-HPA attenuated inflammation and edema through suppressing hypertonic and hypoxic induction of HIF-1α in seawater aspiration-induced lung injury in rats. PMID:25050781

Uric acid predicts mortality and ischaemic stroke in subjects with diastolic dysfunction: the Tromsø Study 1994-2013.

Science.gov (United States)

Norvik, Jon V; Schirmer, Henrik; Ytrehus, Kirsti; Storhaug, Hilde M; Jenssen, Trond G; Eriksen, Bjørn O; Mathiesen, Ellisiv B; Løchen, Maja-Lisa; Wilsgaard, Tom; Solbu, Marit D

2017-05-01

To investigate whether serum uric acid predicts adverse outcomes in persons with indices of diastolic dysfunction in a general population. We performed a prospective cohort study among 1460 women and 1480 men from 1994 to 2013. Endpoints were all-cause mortality, incident myocardial infarction, and incident ischaemic stroke. We stratified the analyses by echocardiographic markers of diastolic dysfunction, and uric acid was the independent variable of interest. Hazard ratios (HR) were estimated per 59 μmol/L increase in baseline uric acid. Multivariable adjusted Cox proportional hazards models showed that uric acid predicted all-cause mortality in subjects with E/A ratio 1.5 (HR 1.51, 95% CI 1.09-2.09, P for interaction between E/A ratio category and uric acid = 0.02). Elevated uric acid increased mortality risk in persons with E-wave deceleration time 220 ms (HR 1.46, 95% CI 1.01-2.12 and HR 1.13, 95% CI 1.02-1.26, respectively; P for interaction = 0.04). Furthermore, in participants with isovolumetric relaxation time ≤60 ms, mortality risk was higher with increasing uric acid (HR 4.98, 95% CI 2.02-12.26, P for interaction = 0.004). Finally, elevated uric acid predicted ischaemic stroke in subjects with severely enlarged left atria (HR 1.62, 95% CI 1.03-2.53, P for interaction = 0.047). Increased uric acid was associated with higher all-cause mortality risk in subjects with echocardiographic indices of diastolic dysfunction, and with higher ischaemic stroke risk in persons with severely enlarged left atria.

Simulation of Axial Combustion Instability Development and Suppression in Solid Rocket Motors

Directory of Open Access Journals (Sweden)

David R. Greatrix

2009-03-01

Full Text Available In the design of solid-propellant rocket motors, the ability to understand and predict the expected behaviour of a given motor under unsteady conditions is important. Research towards predicting, quantifying, and ultimately suppressing undesirable strong transient axial combustion instability symptoms necessitates a comprehensive numerical model for internal ballistic simulation under dynamic flow and combustion conditions. An updated numerical model incorporating recent developments in predicting negative and positive erosive burning, and transient, frequency-dependent combustion response, in conjunction with pressure-dependent and acceleration-dependent burning, is applied to the investigation of instability-related behaviour in a small cylindrical-grain motor. Pertinent key factors, like the initial pressure disturbance magnitude and the propellant's net surface heat release, are evaluated with respect to their influence on the production of instability symptoms. Two traditional suppression techniques, axial transitions in grain geometry and inert particle loading, are in turn evaluated with respect to suppressing these axial instability symptoms.

Endogenous fatty acid ethanolamides suppress nicotine-induced activation of mesolimbic dopamine neurons through nuclear receptors.

Science.gov (United States)

Melis, Miriam; Pillolla, Giuliano; Luchicchi, Antonio; Muntoni, Anna Lisa; Yasar, Sevil; Goldberg, Steven R; Pistis, Marco

2008-12-17

Nicotine stimulates the activity of mesolimbic dopamine neurons, which is believed to mediate the rewarding and addictive properties of tobacco use. Accumulating evidence suggests that the endocannabinoid system might play a major role in neuronal mechanisms underlying the rewarding properties of drugs of abuse, including nicotine. Here, we investigated the modulation of nicotine effects by the endocannabinoid system on dopamine neurons in the ventral tegmental area with electrophysiological techniques in vivo and in vitro. We discovered that pharmacological inhibition of fatty acid amide hydrolase (FAAH), the enzyme that catabolizes fatty acid ethanolamides, among which the endocannabinoid anandamide (AEA) is the best known, suppressed nicotine-induced excitation of dopamine cells. Importantly, this effect was mimicked by the administration of the FAAH substrates oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), but not methanandamide, the hydrolysis resistant analog of AEA. OEA and PEA are naturally occurring lipid signaling molecules structurally related to AEA, but devoid of affinity for cannabinoid receptors. They blocked the effects of nicotine by activation of the peroxisome proliferator-activated receptor-alpha (PPAR-alpha), a nuclear receptor transcription factor involved in several aspects of lipid metabolism and energy balance. Activation of PPAR-alpha triggered a nongenomic stimulation of tyrosine kinases, which might lead to phosphorylation and negative regulation of neuronal nicotinic acetylcholine receptors. These data indicate for the first time that the anorexic lipids OEA and PEA possess neuromodulatory properties as endogenous ligands of PPAR-alpha in the brain and provide a potential new target for the treatment of nicotine addiction.

Topical acetylsalicylic, salicylic acid and indomethacin suppress pain from experimental tissue acidosis in human skin.

Science.gov (United States)

Steen, K H; Reeh, P W; Kreysel, H W

1995-09-01

Topically applied acetylsalicylic acid (ASA), salicylic acid (SA) and indomethacin were tested in an experimental pain model that provides direct nociceptor excitation through cutaneous tissue acidosis. In 30 volunteers, sustained burning pain was produced in the palmar forearm through a continuous intradermal pressure infusion of a phosphate-buffered isotonic solution (pH 5.2). In 5 different, double-blind, randomized cross-over studies with 6 volunteers each, the flow rate of the syringe pump was individually adjusted to result in constant pain ratings of around 20% (50% in study 4) on a visual analog scale (VAS). The painful skin area was then covered with either placebo or the drugs which had been dissolved in diethylether. In the first study on 6 volunteers, ASA (60 mg/ml) or lactose (placebo) in diethylether (10 ml) was applied, using both arms at 3-day intervals. Both treatments resulted in sudden and profound pain relief due to the cooling effect of the evaporating ether. With lactose, however, the mean pain rating was restored close to the baseline within 6-8 min while, with ASA, it remained significantly depressed for the rest of the observation period (another 20 min). This deep analgesia was not accompanied by a loss of tactile sensation. The further studies served to show that indomethacin (4.5 mg/ml) and SA (60 mg/ml) were equally effective as ASA (each 92-96% pain reduction) and that the antinociceptive effects were due to local but not systemic actions, since ASA and SA dis not reach measurable plasma levels up to 3 h after topical applications. With a higher flow rate of acid buffer producing more intense pain (VAS 50%). ASA and SA were still able to significantly reduce the ratings by 90% or 84%, respectively. On the other hand, by increasing the flow rate by a factor of 2 on average, during the period of fully developed drug effect it was possible to overcome the pain suppression, which suggests a competitive mechanism of (acetyl-) salicylic

Resveratrol suppresses ethanol stress in winery and bottom brewery yeast by affecting superoxide dismutase, lipid peroxidation and fatty acid profile.

Science.gov (United States)

Gharwalova, Lucia; Sigler, Karel; Dolezalova, Jana; Masak, Jan; Rezanka, Tomas; Kolouchova, Irena

2017-11-03

Mid-exponential cultures of two traditional biotechnological yeast species, winery Saccharomyces cerevisiae and the less ethanol tolerant bottom-fermenting brewery Saccharomyces pastorianus, were exposed to different concentrations of added ethanol (3, 5 and 8%) The degree of ethanol-induced cell stress was assessed by measuring the cellular activity of superoxide dismutase (SOD), level of lipid peroxidation products, changes in cell lipid content and fatty acid profile. The resveratrol as an antioxidant was found to decrease the ethanol-induced rise of SOD activity and suppress the ethanol-induced decrease in cell lipids. A lower resveratrol concentration (0.5 mg/l) even reduced the extent of lipid peroxidation in cells. Resveratrol also alleviated ethanol-induced changes in cell lipid composition in both species by strongly enhancing the proportion of saturated fatty acids and contributing thereby to membrane stabilization. Lower resveratrol concentrations could thus diminish the negative effects of ethanol stress on yeast cells and improve their physiological state. These effects may be utilized to enhance yeast vitality in high-ethanol-producing fermentations or to increase the number of yeast generations in brewery.

The antagonistic regulation of abscisic acid-inhibited root growth by brassinosteroids is partially mediated via direct suppression of ABSCISIC ACID INSENSITIVE 5 expression by BRASSINAZOLE RESISTANT 1.

Science.gov (United States)

Yang, Xiaorui; Bai, Yang; Shang, Jianxiu; Xin, Ruijiao; Tang, Wenqiang

2016-09-01

Brassinosteroids (BRs) and abscisic acid (ABA) are plant hormones that antagonistically regulate many aspects of plant growth and development; however, the mechanisms that regulate the crosstalk of these two hormones are still not well understood. BRs regulate plant growth and development by activating BRASSINAZOLE RESISTANT 1 (BZR1) family transcription factors. Here we show that the crosstalk between BRs and ABA signalling is partially mediated by BZR1 regulated gene expression. bzr1-1D is a dominant mutant with enhanced BR signalling; our results showed that bzr1-1D mutant is less sensitive to ABA-inhibited primary root growth. By RNA sequencing, a subset of BZR1 regulated ABA-responsive root genes were identified. Of these genes, the expression of a major ABA signalling component ABA INSENSITIVE 5 (ABI5) was found to be suppressed by BR and by BZR1. Additional evidences showed that BZR1 could bind strongly with several G-box cis-elements in the promoter of ABI5, suppress the expression of ABI5 and make plants less sensitive to ABA. Our study demonstrated that ABI5 is a direct target gene of BZR1, and modulating the expression of ABI5 by BZR1 plays important roles in regulating the crosstalk between the BR and ABA signalling pathways. © 2016 John Wiley & Sons Ltd.

The EPED pedestal model and edge localized mode-suppressed regimes: Studies of quiescent H-mode and development of a model for edge localized mode suppression via resonant magnetic perturbations

Energy Technology Data Exchange (ETDEWEB)

Snyder, P. B.; Osborne, T. H.; Burrell, K. H.; Groebner, R. J.; Leonard, A. W.; Wade, M. R. [General Atomics, P.O. Box 85608, San Diego, California 92186-5608 (United States); Nazikian, R. [Princeton Plasma Physics Laboratory, Princeton, New Jersey (United States); Orlov, D. M. [University of California-San Diego, San Diego, California 92093 (United States); Schmitz, O. [Institut fuer Plasmaphysik, Forschungszentrum Juelich GmbH, Association FZJ-EURATOM, Juelich (Germany); Wilson, H. R. [York Plasma Institute, Department of Physics, University of York, Heslington, York YO10 5DD (United Kingdom)

2012-05-15

The EPED model predicts the H-mode pedestal height and width based upon two fundamental and calculable constraints: (1) onset of non-local peeling-ballooning modes at low to intermediate mode number, (2) onset of nearly local kinetic ballooning modes at high mode number. We present detailed tests of the EPED model in discharges with edge localized modes (ELMs), employing new high resolution measurements, and finding good quantitative agreement across a range of parameters. The EPED model is then applied for the first time to quiescent H-mode (QH), finding a similar level of agreement between predicted and observed pedestal height and width, and suggesting that the model can be used to predict the critical density for QH-mode operation. Finally, the model is applied toward understanding the suppression of ELMs with 3D resonant magnetic perturbations (RMP). Combining EPED with plasma response physics, a new working model for RMP ELM suppression is developed. We propose that ELMs are suppressed when a 'wall' associated with the RMP blocks the inward penetration of the edge transport barrier. A calculation of the required location of this 'wall' with EPED is consistent with observed profile changes during RMP ELM suppression and offers an explanation for the observed dependence on safety factor (q{sub 95}).

Accuracy of serum uric acid as a predictive test for maternal complications in pre-eclampsia: Bivariate meta-analysis and decision analysis

NARCIS (Netherlands)

Koopmans, Corine M.; van Pampus, Maria G.; Groen, Henk; Aarnoudse, Jan G.; van den Berg, Paul P.; Mol, Ben W. J.

2009-01-01

The aim of this study is to determine the accuracy and clinical value of serum uric acid in predicting maternal complications in women with pre-eclampsia. An existing meta-analysis on the subject was updated. The accuracy of serum uric acid for the prediction of maternal complications was assessed

Accuracy of serum uric acid as a predictive test for maternal complications in pre-eclampsia : Bivariate meta-analysis and decision analysis

NARCIS (Netherlands)

Koopmans, C.M.; van Pampus, Maria; Groen, H.; Aarnoudse, J.G.; van den Berg, P.P.; Mol, B.W.J.

The aim of this study is to determine the accuracy and clinical value of serum uric acid in predicting maternal complications in women with pre-eclampsia. An existing meta-analysis on the subject was updated. The accuracy of serum uric acid for the prediction of maternal complications was assessed

Tumour–stromal interactions in acid-mediated invasion: A mathematical model

KAUST Repository

Martin, Natasha K.

2010-12-01

It is well established that the tumour microenvironment can both promote and suppress tumour growth and invasion, however, most mathematical models of invasion view the normal tissue as inhibiting tumour progression via immune modulation or spatial constraint. In particular, the production of acid by tumour cells and the subsequent creation of a low extracellular pH environment has been explored in several \\'acid-mediated tumour invasion\\' models where the acidic environment facilitates normal cell death and permits tumour invasion. In this paper, we extend the acid-invasion model developed by Gatenby and Gawlinski (1996) to include both the competitive and cooperative interactions between tumour and normal cells, by incorporating the influence of extracellular matrix and protease production at the tumour-stroma interface. Our model predicts an optimal level of tumour acidity which produces both cell death and matrix degradation. Additionally, very aggressive tumours prevent protease production and matrix degradation by excessive normal cell destruction, leading to an acellular (but matrix filled) gap between the tumour and normal tissue, a feature seen in encapsulated tumours. These results suggest, counterintuitively, that increasing tumour acidity may, in some cases, prevent tumour invasion.

Gallic acid reduces cell viability, proliferation, invasion and angiogenesis in human cervical cancer cells

Science.gov (United States)

ZHAO, BING; HU, MENGCAI

2013-01-01

Gallic acid is a trihydroxybenzoic acid, also known as 3,4,5-trihydroxybenzoic acid, which is present in plants worldwide, including Chinese medicinal herbs. Gallic acid has been shown to have cytotoxic effects in certain cancer cells, without damaging normal cells. The objective of the present study was to determine whether gallic acid is able to inhibit human cervical cancer cell viability, proliferation and invasion and suppress cervical cancer cell-mediated angiogenesis. Treatment of HeLa and HTB-35 human cancer cells with gallic acid decreased cell viability in a dose-dependent manner. BrdU proliferation and tube formation assays indicated that gallic acid significantly decreased human cervical cancer cell proliferation and tube formation in human umbilical vein endothelial cells, respectively. Additionally, gallic acid decreased HeLa and HTB-35 cell invasion in vitro. Western blot analysis demonstrated that the expression of ADAM17, EGFR, p-Akt and p-Erk was suppressed by gallic acid in the HeLa and HTB-35 cell lines. These data indicate that the suppression of ADAM17 and the downregulation of the EGFR, Akt/p-Akt and Erk/p-Erk signaling pathways may contribute to the suppression of cancer progression by Gallic acid. Gallic acid may be a valuable candidate for the treatment of cervical cancer. PMID:24843386

A possible correlation between performance IQ, visuomotor adaptation ability and mu suppression.

Science.gov (United States)

Anwar, Muhammad Nabeel; Navid, Muhammad Samran; Khan, Mushtaq; Kitajo, Keiichi

2015-04-07

Psychometric, anatomical and functional brain studies suggest that individuals differ in the way that they perceive and analyze information and strategically control and execute movements. Inter-individual differences are also observed in neural correlates of specific and general cognitive ability. As a result, some individuals perceive and adapt to environmental conditions and perform motor activities better than others. The aim of this study was to identify a common factor that predicts adaptation of a reaching movement to a visual perturbation and suppression of movement-related brain activity (mu rhythms). Twenty-eight participants participated in two different experiments designed to evaluate visuomotor adaptation and mu suppression ability. Performance intelligence quotient (IQ) was assessed using the revised Wechsler Adult Intelligence Scale. Performance IQ predicted adaptation index of visuomotor performance (r=0.43, p=0.02) and suppression of mu rhythms (r=-0.59; pIQ were faster at adapting to a visuomotor perturbation and better at suppressing mu activity than participants with low performance IQ. We found a possible link between performance IQ and mu suppression, and performance IQ and the initial rate of adaptation. Individuals with high performance IQ were better in suppressing mu rhythms and were quicker at associating motor command and required movement than individuals with low performance IQ. Copyright © 2015 Elsevier B.V. All rights reserved.

Low-Protein Diet Supplemented with Keto Acids Is Associated with Suppression of Small-Solute Peritoneal Transport Rate in Peritoneal Dialysis Patients

Directory of Open Access Journals (Sweden)

Na Jiang

2011-01-01

Full Text Available Objective. We investigate whether low-protein diet would show benefits in suppressing peritoneal transport rate in peritoneal dialysis (PD patients. Methods. This is a supplemented analysis of our previously published trial, which randomized 60 PD patients to receive low- (LP: dietary protein intake of 0.6–0.8 g/kg/d, keto-acid-supplemented low- (sLP: 0.6–0.8 g/kg/d with 0.12 g/kg/d of keto acids, or high- (HP: 1.0–1.2 g/kg/d protein diet and lasted for one year. In this study, the variations of peritoneal transport rate were assessed. Results. While baseline D/Pcr (dialysate-to-plasma concentration ratio for creatinine at 4 hour and D/D0glu (dialysate glucose at 4 hour to baseline dialysate glucose concentration ratio were similar, D/Pcr in group sLP was lower, and D/D0glu was higher than those in the other two groups (P<0.05 at 12th month. D/D0glu increased (P<0.05, and D/Pcr tended to decrease, (P=0.071 in group sLP. Conclusions. Low-protein diet with keto acids may benefit PD patients by maintaining peritoneum at a lower transport rate.

Symptomless endophytic fungi suppress endogenous levels of salicylic acid and interact with the jasmonate-dependent indirect defense traits of their host, lima bean (Phaseolus lunatus).

Science.gov (United States)

Navarro-Meléndez, Ariana L; Heil, Martin

2014-07-01

Symptomless ‘type II’ fungal endophytes colonize their plant host horizontally and exert diverse effects on its resistance phenotype. Here, we used wild Lima bean (Phaseolus lunatus) plants that were experimentally colonized with one of three strains of natural endophytes (Bartalinia pondoensis, Fusarium sp., or Cochliobolus lunatus) to investigate the effects of fungal colonization on the endogenous levels of salicylic acid (SA) and jasmonic acid (JA) and on two JA-dependent indirect defense traits. Colonization with Fusarium sp. enhanced JA levels in intact leaves, whereas B. pondoensis suppressed the induction of endogenous JA in mechanically damaged leaves. Endogenous SA levels in intact leaves were significantly decreased by all strains and B. pondoensis and Fusarium sp. decreased SA levels after mechanical damage. Colonization with Fusarium sp. or C. lunatus enhanced the number of detectable volatile organic compounds (VOCs) emitted from intact leaves, and all three strains enhanced the relative amount of several VOCs emitted from intact leaves as well as the number of detectable VOCs emitted from slightly damaged leaves. All three strains completely suppressed the induced secretion of extrafloral nectar (EFN) after the exogenous application of JA. Symptomless endophytes interact in complex and strain-specific ways with the endogenous levels of SA and JA and with the defense traits that are controlled by these hormones. These interactions can occur both upstream and downstream of the defense hormones.

Pretransplantation recipient regulatory T cell suppressive function predicts delayed and slow graft function after kidney transplantation.

Science.gov (United States)

Nguyen, Minh-Tri J P; Fryml, Elise; Sahakian, Sossy K; Liu, Shuqing; Michel, Rene P; Lipman, Mark L; Mucsi, Istvan; Cantarovich, Marcelo; Tchervenkov, Jean I; Paraskevas, Steven

2014-10-15

Delayed graft function (DGF) and slow graft function (SGF) are a continuous spectrum of ischemia-reperfusion-related acute kidney injury (AKI) that increases the risk for acute rejection and graft loss after kidney transplantation. Regulatory T cells (Tregs) are critical in transplant tolerance and attenuate murine AKI. In this prospective observational cohort study, we evaluated whether pretransplantation peripheral blood recipient Treg frequency and suppressive function are predictors of DGF and SGF after kidney transplantation. Deceased donor kidney transplant recipients (n=53) were divided into AKI (n=37; DGF, n=10; SGF, n=27) and immediate graft function (n=16) groups. Pretransplantation peripheral blood CD4CD25FoxP3 Treg frequency was quantified by flow cytometry. Regulatory T-cell suppressive function was measured by suppression of autologous effector T-cell proliferation by Treg in co-culture. Pretransplantation Treg suppressive function, but not frequency, was decreased in AKI recipients (Paccounting for the effects of cold ischemic time and donor age, Treg suppressive function discriminated DGF from immediate graft function recipients in multinomial logistic regression (odds ratio, 0.77; Pfunction is a potential independent pretransplantation predictor of DGF and SGF.

Gallic acid-capped gold nanoparticles inhibit EGF-induced MMP-9 expression through suppression of p300 stabilization and NFκB/c-Jun activation in breast cancer MDA-MB-231 cells

International Nuclear Information System (INIS)

Chen, Ying-Jung; Lee, Yuan-Chin; Huang, Chia-Hui; Chang, Long-Sen

2016-01-01

Triple-negative breast cancers (TNBCs) are highly invasive and have a higher rate of distant metastasis. Matrix metalloproteinase-9 (MMP-9) plays a crucial role in EGF/EGFR-mediated malignant progression and metastasis of TNBCs. Various studies have revealed that treatment with gallic acid down-regulates MMP-9 expression in cancer cells, and that conjugation of phytochemical compounds with gold nanoparticles (AuNPs) increases the anti-tumor activity of the phytochemical compounds. Thus, the effect of gallic acid-capped AuNPs (GA-AuNPs) on MMP-9 expression in EGF-treated TNBC MDA-MB-231 cells was analyzed in the present study. The so-called green synthesis of AuNPs by means of gallic acid was performed at pH 10, and the resulting GA-AuNPs had spherical shape with an average diameter of approximately 50 nm. GA-AuNPs notably suppressed migration and invasion of EGF-treated cells, and inhibited EGF-induced MMP-9 up-regulation. GA-AuNPs abrogated EGF-induced Akt/p65 and ERK/c-Jun phosphorylation, leading to down-regulation of MMP-9 mRNA and protein expression in EGF-treated cells. Meanwhile, EGF-induced p300 stabilization was found to be involved in MMP-9 expression, whereas GA-AuNPs inhibited the EGF-promoted stability of the p300 protein. Although GA-AuNPs and gallic acid suppressed EGF-induced MMP-9 up-regulation via the same signaling pathway, the effective concentration of gallic acid was approximately 100-fold higher than that of GA-AuNPs for inhibition of MMP-9 expression in EGF-treated cells to a similar extent. Collectively, our data indicate that, in comparison with gallic acid, GA-AuNPs have a superior ability to inhibit EGF/EGFR-mediated MMP-9 expression in TNBC MDA-MB-231 cells. Our findings also point to a way to improve the anti-tumor activity of gallic acid. - Highlights: • Gallic acid-capped gold nanoparticles inhibit EGF-induced MMP-9 expression. • EGF-induced MMP-9 expression via p300 stabilization and NFκB/c-Jun activation. • Gallic acid

Gallic acid-capped gold nanoparticles inhibit EGF-induced MMP-9 expression through suppression of p300 stabilization and NFκB/c-Jun activation in breast cancer MDA-MB-231 cells

Energy Technology Data Exchange (ETDEWEB)

Chen, Ying-Jung; Lee, Yuan-Chin; Huang, Chia-Hui [Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan (China); Chang, Long-Sen, E-mail: lschang@mail.nsysu.edu.tw [Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan (China); Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China)

2016-11-01

Triple-negative breast cancers (TNBCs) are highly invasive and have a higher rate of distant metastasis. Matrix metalloproteinase-9 (MMP-9) plays a crucial role in EGF/EGFR-mediated malignant progression and metastasis of TNBCs. Various studies have revealed that treatment with gallic acid down-regulates MMP-9 expression in cancer cells, and that conjugation of phytochemical compounds with gold nanoparticles (AuNPs) increases the anti-tumor activity of the phytochemical compounds. Thus, the effect of gallic acid-capped AuNPs (GA-AuNPs) on MMP-9 expression in EGF-treated TNBC MDA-MB-231 cells was analyzed in the present study. The so-called green synthesis of AuNPs by means of gallic acid was performed at pH 10, and the resulting GA-AuNPs had spherical shape with an average diameter of approximately 50 nm. GA-AuNPs notably suppressed migration and invasion of EGF-treated cells, and inhibited EGF-induced MMP-9 up-regulation. GA-AuNPs abrogated EGF-induced Akt/p65 and ERK/c-Jun phosphorylation, leading to down-regulation of MMP-9 mRNA and protein expression in EGF-treated cells. Meanwhile, EGF-induced p300 stabilization was found to be involved in MMP-9 expression, whereas GA-AuNPs inhibited the EGF-promoted stability of the p300 protein. Although GA-AuNPs and gallic acid suppressed EGF-induced MMP-9 up-regulation via the same signaling pathway, the effective concentration of gallic acid was approximately 100-fold higher than that of GA-AuNPs for inhibition of MMP-9 expression in EGF-treated cells to a similar extent. Collectively, our data indicate that, in comparison with gallic acid, GA-AuNPs have a superior ability to inhibit EGF/EGFR-mediated MMP-9 expression in TNBC MDA-MB-231 cells. Our findings also point to a way to improve the anti-tumor activity of gallic acid. - Highlights: • Gallic acid-capped gold nanoparticles inhibit EGF-induced MMP-9 expression. • EGF-induced MMP-9 expression via p300 stabilization and NFκB/c-Jun activation. • Gallic acid

Re-Evaluation of Acid-Base Prediction Rules in Patients with Chronic Respiratory Acidosis

Directory of Open Access Journals (Sweden)

Tereza Martinu

2003-01-01

Full Text Available RATIONALE: The prediction rules for the evaluation of the acid-base status in patients with chronic respiratory acidosis, derived primarily from an experimental canine model, suggest that complete compensation should not occur. This appears to contradict frequent observations of normal or near-normal pH levels in patients with chronic hypercapnia.

Suppressive mechanisms in visual motion processing: From perception to intelligence.

Science.gov (United States)

Tadin, Duje

2015-10-01

Perception operates on an immense amount of incoming information that greatly exceeds the brain's processing capacity. Because of this fundamental limitation, the ability to suppress irrelevant information is a key determinant of perceptual efficiency. Here, I will review a series of studies investigating suppressive mechanisms in visual motion processing, namely perceptual suppression of large, background-like motions. These spatial suppression mechanisms are adaptive, operating only when sensory inputs are sufficiently robust to guarantee visibility. Converging correlational and causal evidence links these behavioral results with inhibitory center-surround mechanisms, namely those in cortical area MT. Spatial suppression is abnormally weak in several special populations, including the elderly and individuals with schizophrenia-a deficit that is evidenced by better-than-normal direction discriminations of large moving stimuli. Theoretical work shows that this abnormal weakening of spatial suppression should result in motion segregation deficits, but direct behavioral support of this hypothesis is lacking. Finally, I will argue that the ability to suppress information is a fundamental neural process that applies not only to perception but also to cognition in general. Supporting this argument, I will discuss recent research that shows individual differences in spatial suppression of motion signals strongly predict individual variations in IQ scores. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Omega-3 polyunsaturated Fatty acids suppress the cystic lesion formation of peritoneal endometriosis in transgenic mouse models.

Directory of Open Access Journals (Sweden)

Kensuke Tomio

Full Text Available Omega-3 polyunsaturated fatty acids (omega-3 PUFAs play a role in controlling pathological inflammatory reactions. Endometriosis is characterized by the presence of endometrial tissue on the peritoneum and an exaggerated inflammatory environment around ectopic tissues. Here peritoneal endometriosis was reproduced using a mouse model in which murine endometrial fragments were inoculated into the peritoneal cavity of mice. Fat-1 mice, in which omega-6 can be converted to omega-3 PUFAs, or wild type mice, in which it cannot, were used for the endometriosis model to address the actions of omega-3 PUFAs on the development of endometriotic lesions. The number and weight of cystic endometriotic lesions in fat-1 mice two weeks after inoculation were significantly less than half to those of controls. Mediator lipidomics revealed that cystic endometriotic lesions and peritoneal fluids were abundant in 12/15-hydroxyeicosapentaenoic acid (12/15-HEPE, derived from eicosapentaenoic acid (EPA, and their amount in fat-1 mice was significantly larger than that in controls. 12/15-Lipoxygenase (12/15-LOX-knockout (KO and control mice with or without EPA administration were assessed for the endometriosis model. EPA administration decreased the number of lesions in controls but not in 12/15-LOX-KO mice. The peritoneal fluids in EPA-fed 12/15-LOX-KO mice contained reduced levels of EPA metabolites such as 12/15-HEPE and EPA-derived resolvin E3 even after EPA administration. cDNA microarrays of endometriotic lesions revealed that Interleukin-6 (IL-6 expression in fat-1 mice was significantly lower than that in controls. These results suggest that both endogenous and exogenous EPA-derived PUFAs protect against the development of endometriosis through their anti-inflammatory effects and, in particular, the 12/15-LOX-pathway products of EPA may be key mediators to suppress endometriosis.

Omega-3 polyunsaturated Fatty acids suppress the cystic lesion formation of peritoneal endometriosis in transgenic mouse models.

Science.gov (United States)

Tomio, Kensuke; Kawana, Kei; Taguchi, Ayumi; Isobe, Yosuke; Iwamoto, Ryo; Yamashita, Aki; Kojima, Satoko; Mori, Mayuyo; Nagamatsu, Takeshi; Arimoto, Takahide; Oda, Katsutoshi; Osuga, Yutaka; Taketani, Yuji; Kang, Jing X; Arai, Hiroyuki; Arita, Makoto; Kozuma, Shiro; Fujii, Tomoyuki

2013-01-01

Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) play a role in controlling pathological inflammatory reactions. Endometriosis is characterized by the presence of endometrial tissue on the peritoneum and an exaggerated inflammatory environment around ectopic tissues. Here peritoneal endometriosis was reproduced using a mouse model in which murine endometrial fragments were inoculated into the peritoneal cavity of mice. Fat-1 mice, in which omega-6 can be converted to omega-3 PUFAs, or wild type mice, in which it cannot, were used for the endometriosis model to address the actions of omega-3 PUFAs on the development of endometriotic lesions. The number and weight of cystic endometriotic lesions in fat-1 mice two weeks after inoculation were significantly less than half to those of controls. Mediator lipidomics revealed that cystic endometriotic lesions and peritoneal fluids were abundant in 12/15-hydroxyeicosapentaenoic acid (12/15-HEPE), derived from eicosapentaenoic acid (EPA), and their amount in fat-1 mice was significantly larger than that in controls. 12/15-Lipoxygenase (12/15-LOX)-knockout (KO) and control mice with or without EPA administration were assessed for the endometriosis model. EPA administration decreased the number of lesions in controls but not in 12/15-LOX-KO mice. The peritoneal fluids in EPA-fed 12/15-LOX-KO mice contained reduced levels of EPA metabolites such as 12/15-HEPE and EPA-derived resolvin E3 even after EPA administration. cDNA microarrays of endometriotic lesions revealed that Interleukin-6 (IL-6) expression in fat-1 mice was significantly lower than that in controls. These results suggest that both endogenous and exogenous EPA-derived PUFAs protect against the development of endometriosis through their anti-inflammatory effects and, in particular, the 12/15-LOX-pathway products of EPA may be key mediators to suppress endometriosis.

Histamine H2 Receptor-Mediated Suppression of Intestinal Inflammation by Probiotic Lactobacillus reuteri.

Science.gov (United States)

Gao, Chunxu; Major, Angela; Rendon, David; Lugo, Monica; Jackson, Vanessa; Shi, Zhongcheng; Mori-Akiyama, Yuko; Versalovic, James

2015-12-15

Probiotics and commensal intestinal microbes suppress mammalian cytokine production and intestinal inflammation in various experimental model systems. Limited information exists regarding potential mechanisms of probiotic-mediated immunomodulation in vivo. In this report, we demonstrate that specific probiotic strains of Lactobacillus reuteri suppress intestinal inflammation in a trinitrobenzene sulfonic acid (TNBS)-induced mouse colitis model. Only strains that possess the hdc gene cluster, including the histidine decarboxylase and histidine-histamine antiporter genes, can suppress colitis and mucosal cytokine (interleukin-6 [IL-6] and IL-1β in the colon) gene expression. Suppression of acute colitis in mice was documented by diminished weight loss, colonic injury, serum amyloid A (SAA) protein concentrations, and reduced uptake of [(18)F]fluorodeoxyglucose ([(18)F]FDG) in the colon by positron emission tomography (PET). The ability of probiotic L. reuteri to suppress colitis depends on the presence of a bacterial histidine decarboxylase gene(s) in the intestinal microbiome, consumption of a histidine-containing diet, and signaling via the histamine H2 receptor (H2R). Collectively, luminal conversion of l-histidine to histamine by hdc(+) L. reuteri activates H2R, and H2R signaling results in suppression of acute inflammation within the mouse colon. Probiotics are microorganisms that when administered in adequate amounts confer beneficial effects on the host. Supplementation with probiotic strains was shown to suppress intestinal inflammation in patients with inflammatory bowel disease and in rodent colitis models. However, the mechanisms of probiosis are not clear. Our current studies suggest that supplementation with hdc(+) L. reuteri, which can convert l-histidine to histamine in the gut, resulted in suppression of colonic inflammation. These findings link luminal conversion of dietary components (amino acid metabolism) by gut microbes and probiotic

A study of LPM suppression of bremsstrahlung at 25 GeV

International Nuclear Information System (INIS)

Anthony, P.; Becker-Szendy, R.; Bosted, P.

1993-03-01

We are making an accurate measurement of the LPM suppression of bremsstrahlung with 25 GeV electrons. By using a 120 pulses per second beam, a precise BGO calorimeter, and spectrometer to tag the outgoing electrons, we are able to make an accurate measurement of the bremsstrahlung photons in the 0-400 MeV region, where the Bethe Heitler and LPM predictions differ. We are taking data with targets made of carbon, uranium, tungsten and iron, with thicknesses in the 2% to 6% X 0 range. In addition, we are taking data with two very thin gold targets. The latter have thicknesses that are comparable to or less than the LPM formation zone length, and so should not exhibit LPM suppression. We are also studying photons of a few MeV in energy, to test the closely related longitudinal density effect predicted by Ter-Mikaelian in which very low energy photon emission is suppressed due to dielectric effects of the medium

Repetition suppression and multi-voxel pattern similarity differentially track implicit and explicit visual memory.

Science.gov (United States)

Ward, Emily J; Chun, Marvin M; Kuhl, Brice A

2013-09-11

Repeated exposure to a visual stimulus is associated with corresponding reductions in neural activity, particularly within visual cortical areas. It has been argued that this phenomenon of repetition suppression is related to increases in processing fluency or implicit memory. However, repetition of a visual stimulus can also be considered in terms of the similarity of the pattern of neural activity elicited at each exposure--a measure that has recently been linked to explicit memory. Despite the popularity of each of these measures, direct comparisons between the two have been limited, and the extent to which they differentially (or similarly) relate to behavioral measures of memory has not been clearly established. In the present study, we compared repetition suppression and pattern similarity as predictors of both implicit and explicit memory. Using functional magnetic resonance imaging, we scanned 20 participants while they viewed and categorized repeated presentations of scenes. Repetition priming (facilitated categorization across repetitions) was used as a measure of implicit memory, and subsequent scene recognition was used as a measure of explicit memory. We found that repetition priming was predicted by repetition suppression in prefrontal, parietal, and occipitotemporal regions; however, repetition priming was not predicted by pattern similarity. In contrast, subsequent explicit memory was predicted by pattern similarity (across repetitions) in some of the same occipitotemporal regions that exhibited a relationship between priming and repetition suppression; however, explicit memory was not related to repetition suppression. This striking double dissociation indicates that repetition suppression and pattern similarity differentially track implicit and explicit learning.

Impact of regurgitation on health-related quality of life in gastro-oesophageal reflux disease before and after short-term potent acid suppression therapy.

Science.gov (United States)

Kahrilas, Peter J; Jonsson, Andreas; Denison, Hans; Wernersson, Börje; Hughes, Nesta; Howden, Colin W

2014-05-01

Limited data exist on the impact of regurgitation on health-related quality of life (HRQOL) in gastro-oesophageal reflux disease (GORD). We assessed the relationship between regurgitation frequency and HRQOL before and after acid suppression therapy in GORD. We used data from two randomised trials of AZD0865 25-75 mg/day versus esomeprazole 20 or 40 mg/day in non-erosive reflux disease (NERD) (n=1415) or reflux oesophagitis (RO) (n=1460). The Reflux Disease Questionnaire was used to select patients with frequent and intense heartburn for inclusion and to assess treatment response. The Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire was used to assess HRQOL. At baseline, 93% of patients in both the NERD and RO groups experienced regurgitation. Mean QOLRAD scores were similar for NERD and RO at baseline and at week 4 and disclosed decremental HRQOL with increasing frequency of regurgitation; a clinically relevant difference of >0.5 in mean QOLRAD scores was seen with regurgitation ≥4 days/week versus <4 days/week. The prevalence of frequent, persistent regurgitation (≥4 days/week) at week 4 among heartburn responders (≤1 day/week of mild heartburn) was 28% in NERD and 23% in RO. QOLRAD scores were higher among heartburn responders. There was a similar pattern of impact related to regurgitation frequency in heartburn responders compared with the group as a whole. Frequent regurgitation was associated with a clinically relevant, incremental decline in HRQOL beyond that associated with heartburn before and after potent acid suppression in both NERD and RO. NCT00206284 and NCT00206245.

Thought suppression, impaired regulation of urges, and Addiction-Stroop predict affect-modulated cue-reactivity among alcohol dependent adults.

Science.gov (United States)

Garland, Eric L; Carter, Kristin; Ropes, Katie; Howard, Matthew O

2012-01-01

Abstinent alcohol dependent individuals commonly employ thought suppression to cope with stress and intrusive cognitions about alcohol. This strategy may inadvertently bias attention towards alcohol-related stimuli while depleting neurocognitive resources needed to regulate urges, manifested as decreased heart rate variability (HRV) responsivity to alcohol cues. The present study tested the hypothesis that trait and state thought suppression, impaired regulation of urges, and alcohol attentional bias as measured by the Addiction-Stroop would have significant effects on the HRV responsivity of 58 adults in residential treatment for alcohol dependence (mean age=39.6 ± 9.4, 81% female) who participated in an affect-modulated cue-reactivity protocol. Regression analyses controlling for age, level of pre-treatment alcohol consumption, and baseline HRV indicated that higher levels of trait thought suppression, impaired regulation of alcohol urges, and attentional fixation on alcohol cues were associated with lower HRV responsivity during stress-primed alcohol cue-exposure. Moreover, there was a significant state × trait suppression interaction on HRV cue-responsivity, such that alcohol dependent persons reporting high levels of state and trait suppression exhibited less HRV during cue-exposure than persons reporting low levels of state and trait suppression. Results suggest that chronic thought suppression taxes regulatory resources reflected in reduced HRV responsivity, an effect that is particularly evident when high trait suppressors engage in intensive suppression of drinking-related thoughts under conditions of stress. Treatment approaches that offer effective alternatives to the maladaptive strategy of suppressing alcohol urges may be crucial for relapse prevention. Copyright © 2011 Elsevier B.V. All rights reserved.

Hemoglobin levels do not predict biochemical outcome for localized prostate cancer treated with neoadjuvant androgen-suppression therapy and external-beam radiotherapy

International Nuclear Information System (INIS)

Pai, Howard Huaihan; Ludgate, Charles; Pickles, Tom; Paltiel, Chuck M.Sc.; Agranovich, Alex; Berthelet, Eric; Duncan, Graeme; Kim-Sing, Charmaine; Kwan, Winkle; Lim, Jan; Liu, Mitchell; Tyldesley, Scott

2006-01-01

Purpose: To investigate whether hemoglobin (Hb) levels affect outcome in men with localized prostate adenocarcinoma (LPA) treated with neoadjuvant androgen-suppression therapy (NAST) and external-beam radiotherapy (EBRT). Methods and Materials: A total of 563 men with LPA treated with NAST (median: 5.3 months) and EBRT who had Hb levels during treatment were retrospectively reviewed. Patient, tumor, and treatment variables, including the following Hb variables, were subjected to univariate and multivariable analyses to identify factors that predict biochemical control (bNED) and overall survival (OS): pre-EBRT Hb, Hb nadir during EBRT, and change in Hb from pre-EBRT to nadir during EBRT. Results: Median PSA follow-up was 4.25 years. Forty-nine percent of men were anemic during EBRT, with a median Hb of 13.4 g/dL, and 68% experienced a decline in Hb from pre-EBRT to during EBRT of median 0.6 g/dL. Five-year Nadir + 2 bNED and OS rates were similar for anemic and nonanemic patients during EBRT. High percent-positive biopsies, PSA and Gleason score, and use of AA monotherapy predicted worse bNED. High stage and age predicted worse OS. Hb variables were not predictive of bNED or OS. Conclusions: Anemia is a common side effect of NAST and is usually mild. Hb levels, however, do not predict biochemical control or survival

Increased production of free fatty acids in Aspergillus oryzae by disruption of a predicted acyl-CoA synthetase gene.

Science.gov (United States)

Tamano, Koichi; Bruno, Kenneth S; Koike, Hideaki; Ishii, Tomoko; Miura, Ai; Umemura, Myco; Culley, David E; Baker, Scott E; Machida, Masayuki

2015-04-01

Fatty acids are attractive molecules as source materials for the production of biodiesel fuel. Previously, we attained a 2.4-fold increase in fatty acid production by increasing the expression of fatty acid synthesis-related genes in Aspergillus oryzae. In this study, we achieved an additional increase in the production of fatty acids by disrupting a predicted acyl-CoA synthetase gene in A. oryzae. The A. oryzae genome is predicted to encode six acyl-CoA synthetase genes and disruption of AO090011000642, one of the six genes, resulted in a 9.2-fold higher accumulation (corresponding to an increased production of 0.23 mmol/g dry cell weight) of intracellular fatty acid in comparison to the wild-type strain. Furthermore, by introducing a niaD marker from Aspergillus nidulans to the disruptant, as well as changing the concentration of nitrogen in the culture medium from 10 to 350 mM, fatty acid productivity reached 0.54 mmol/g dry cell weight. Analysis of the relative composition of the major intracellular free fatty acids caused by disruption of AO090011000642 in comparison to the wild-type strain showed an increase in stearic acid (7 to 26 %), decrease in linoleic acid (50 to 27 %), and no significant changes in palmitic or oleic acid (each around 20-25 %).

Amino acid assisted dehalogenation of carbon tetrachloride by green rust

DEFF Research Database (Denmark)

Yin, Weizhao; Strobel, Bjarne W.; Hansen, Hans Chr. Bruun

2017-01-01

that reduce the formation of toxic by-products such as chloroform (CF). In this study, carbon tetrachloride (CT) dehalogenation by the chloride form of GR (GRCl) was tested in presence of glycine (GLY) and other selected amino acids. GLY, alanine (ALA) or serine (SER) all resulted in remarkable suppression...... of CF formation with only ~ 10% of CF recovery while sarcosine (SAR) showed insignificant effects. For two non-amino acid buffers, TRIS had little effect while HEPES resulted in a 40 times lower rate constant compared to experiments where no buffer was added. The FeII complexing properties of the amino...... acids and buffers caused variable extents of GRCl dissolution which was linearly correlated with CF suppression and dehalogenation rate. We hypothesize that the CF suppression seen for amino acids is caused by stabilization of carbene intermediates via the carbonyl group. Different effects on CF...

Self-initiated actions result in suppressed auditory but amplified visual evoked components in healthy participants.

Science.gov (United States)

Mifsud, Nathan G; Oestreich, Lena K L; Jack, Bradley N; Ford, Judith M; Roach, Brian J; Mathalon, Daniel H; Whitford, Thomas J

2016-05-01

Self-suppression refers to the phenomenon that sensations initiated by our own movements are typically less salient, and elicit an attenuated neural response, compared to sensations resulting from changes in the external world. Evidence for self-suppression is provided by previous ERP studies in the auditory modality, which have found that healthy participants typically exhibit a reduced auditory N1 component when auditory stimuli are self-initiated as opposed to externally initiated. However, the literature investigating self-suppression in the visual modality is sparse, with mixed findings and experimental protocols. An EEG study was conducted to expand our understanding of self-suppression across different sensory modalities. Healthy participants experienced either an auditory (tone) or visual (pattern-reversal) stimulus following a willed button press (self-initiated), a random interval (externally initiated, unpredictable onset), or a visual countdown (externally initiated, predictable onset-to match the intrinsic predictability of self-initiated stimuli), while EEG was continuously recorded. Reduced N1 amplitudes for self- versus externally initiated tones indicated that self-suppression occurred in the auditory domain. In contrast, the visual N145 component was amplified for self- versus externally initiated pattern reversals. Externally initiated conditions did not differ as a function of their predictability. These findings highlight a difference in sensory processing of self-initiated stimuli across modalities, and may have implications for clinical disorders that are ostensibly associated with abnormal self-suppression. © 2016 Society for Psychophysiological Research.

Trans-Fatty Acids Aggravate Obesity, Insulin Resistance and Hepatic Steatosis in C57BL/6 Mice, Possibly by Suppressing the IRS1 Dependent Pathway.

Science.gov (United States)

Zhao, Xiaona; Shen, Cheng; Zhu, Hong; Wang, Cong; Liu, Xiangwei; Sun, Xiaolei; Han, Shasha; Wang, Peng; Dong, Zhen; Ma, Xin; Hu, Kai; Sun, Aijun; Ge, Junbo

2016-05-30

Trans-fatty acid consumption has been reported as a risk factor for metabolic disorders and targeted organ damages. Nonetheless, little is known about the roles and mechanisms of trans-fatty acids in obesity, insulin resistance (IR) and hepatic steatosis. Adult C57BL/6 male mice were fed with four different diets for 20 weeks: normal diet (ND), high fat diet (HFD), low trans-fatty acids diet (LTD) and high trans-fatty acid diet (HTD). The diet-induced metabolic disorders were assessed by evaluating body weight, glucose tolerance test, hepatic steatosis and plasma lipid profiles post 20-week diet. Histological (H&E, Oil-Red-O) staining and western blot analysis were employed to assess liver steatosis and potential signaling pathways. After 20-weeks of diet, the body weights of the four groups were 29.61 ± 1.89 g (ND), 39.04 ± 4.27 g (HFD), 34.09 ± 2.62 g (LTD) and 43.78 ± 4.27 g (HTD) (p steatosis compared with HFD group possibly through regulating adipose triglyceride lipase. The group consuming the HTD also exhibited significantly reduced levels of IRS1, phosphor-PKC and phosphor-AKT. These results support our hypothesis that consumption of a diet high in trans-fatty acids induces higher rates of obesity, IR and hepatic steatosis in male C57BL/6 mice, possibly by suppressing the IRS1dependent pathway.

Application of infrared portable sensor technology for predicting perceived astringency of acidic whey protein beverages.

Science.gov (United States)

Wang, Ting; Tan, Siow-Ying; Mutilangi, William; Plans, Marcal; Rodriguez-Saona, Luis

2016-12-01

Formulating whey protein beverages at acidic pH provides better clarity but the beverages typically develop an unpleasant and astringent flavor. Our aim was to evaluate the application of infrared spectroscopy and chemometrics in predicting astringency of acidic whey protein beverages. Whey protein isolate (WPI), whey protein concentrate (WPC), and whey protein hydrolysate (WPH) from different manufacturers were used to formulate beverages at pH ranging from 2.2 to 3.9. Trained panelists using the spectrum method of descriptive analysis tested the beverages providing astringency scores. A portable Fourier transform infrared spectroscopy attenuated total reflectance spectrometer was used for spectra collection that was analyzed by multivariate regression analysis (partial least squares regression) to build calibration models with the sensory astringency scores. Beverage astringency scores fluctuated from 1.9 to 5.2 units and were explained by pH, protein type (WPC, WPI, or WPH), source (manufacturer), and their interactions, revealing the complexity of astringency development in acidic whey protein beverages. The WPC and WPH beverages showed an increase in astringency as the pH of the solution was lowered, but no relationship was found for WPI beverages. The partial least squares regression analysis showed strong relationship between the reference astringency scores and the infrared predicted values (correlation coefficient >0.94), giving standard error of cross-validation ranging from 0.08 to 0.12 units, depending on whey protein type. Major absorption bands explaining astringency scores were associated with carboxylic groups and amide regions of proteins. The portable infrared technique allowed rapid prediction of astringency of acidic whey protein beverages, providing the industry a novel tool for monitoring sensory characteristics of whey-containing beverages. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Gallic acid-capped gold nanoparticles inhibit EGF-induced MMP-9 expression through suppression of p300 stabilization and NFκB/c-Jun activation in breast cancer MDA-MB-231 cells.

Science.gov (United States)

Chen, Ying-Jung; Lee, Yuan-Chin; Huang, Chia-Hui; Chang, Long-Sen

2016-11-01

Triple-negative breast cancers (TNBCs) are highly invasive and have a higher rate of distant metastasis. Matrix metalloproteinase-9 (MMP-9) plays a crucial role in EGF/EGFR-mediated malignant progression and metastasis of TNBCs. Various studies have revealed that treatment with gallic acid down-regulates MMP-9 expression in cancer cells, and that conjugation of phytochemical compounds with gold nanoparticles (AuNPs) increases the anti-tumor activity of the phytochemical compounds. Thus, the effect of gallic acid-capped AuNPs (GA-AuNPs) on MMP-9 expression in EGF-treated TNBC MDA-MB-231 cells was analyzed in the present study. The so-called green synthesis of AuNPs by means of gallic acid was performed at pH10, and the resulting GA-AuNPs had spherical shape with an average diameter of approximately 50nm. GA-AuNPs notably suppressed migration and invasion of EGF-treated cells, and inhibited EGF-induced MMP-9 up-regulation. GA-AuNPs abrogated EGF-induced Akt/p65 and ERK/c-Jun phosphorylation, leading to down-regulation of MMP-9 mRNA and protein expression in EGF-treated cells. Meanwhile, EGF-induced p300 stabilization was found to be involved in MMP-9 expression, whereas GA-AuNPs inhibited the EGF-promoted stability of the p300 protein. Although GA-AuNPs and gallic acid suppressed EGF-induced MMP-9 up-regulation via the same signaling pathway, the effective concentration of gallic acid was approximately 100-fold higher than that of GA-AuNPs for inhibition of MMP-9 expression in EGF-treated cells to a similar extent. Collectively, our data indicate that, in comparison with gallic acid, GA-AuNPs have a superior ability to inhibit EGF/EGFR-mediated MMP-9 expression in TNBC MDA-MB-231 cells. Our findings also point to a way to improve the anti-tumor activity of gallic acid. Copyright © 2016 Elsevier Inc. All rights reserved.

Rosmarinic acid inhibits inflammation and angiogenesis of hepatocellular carcinoma by suppression of NF-κB signaling in H22 tumor-bearing mice

Directory of Open Access Journals (Sweden)

Wen Cao

2016-10-01

Full Text Available The aim of this study was to explore the anti-tumor effect and therapeutic potential of rosmarinic acid (RA in the treatment of hepatocellular carcinoma (HCC. RA at 75, 150 and 300 mg/kg was given to H22 tumor-bearing mice by intragastric administration once daily for 10 consecutive days. Levels of inflammatory and angiogenic factors, including interleukin-1β (IL-1β, interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α, vascular endothelial growth factor (VEGF, and transforming growth factor-β (TGF-β were measured by enzyme linked immunosorbent assays (ELISA. Protein levels of phosphorylated NF-κB p65 and p65 were detected by western blot. mRNA level of NF-κB p65 was analyzed by qRT-PCR. The results showed that RA could effectively suppress tumor growth with fewer toxic effects by regulating the secretion of cytokines associated with inflammation and angiogenesis, and suppressing the expression of NF-κB p65 in the xenograft microenvironment. Our findings unveil the possible anti-tumor mechanisms of RA and support RA as a potential drug for the treatment of HCC.

Hyaluronic acid levels predict risk of hepatic encephalopathy and liver-related death in HIV/viral hepatitis coinfected patients

DEFF Research Database (Denmark)

Peters, Lars; Mocroft, Amanda; Soriano, Vincent

2013-01-01

Whereas it is well established that various soluble biomarkers can predict level of liver fibrosis, their ability to predict liver-related clinical outcomes is less clearly established, in particular among HIV/viral hepatitis co-infected persons. We investigated plasma hyaluronic acid's (HA......) ability to predict risk of liver-related events (LRE; hepatic coma or liver-related death) in the EuroSIDA study....

Evaluation of Suppressiveness of Soils Exhibiting Soil-Borne Disease Suppression after Long-Term Application of Organic Amendments by the Co-cultivation Method of Pathogenic Fusarium oxysporum and Indigenous Soil Microorganisms.

Science.gov (United States)

Mitsuboshi, Masahiro; Kioka, Yuuzou; Noguchi, Katsunori; Asakawa, Susumu

2018-03-29

Preventive measures against soil-borne diseases need to be implemented before cultivation because very few countermeasures are available after the development of diseases. Some soils suppress soil-borne diseases despite the presence of a high population density of pathogens. If the suppressiveness of soil against soil-borne diseases may be predicted and diagnosed for crop fields, it may be possible to reduce the labor and cost associated with excessive disinfection practices. We herein evaluated the suppressiveness of soils in fields with the long-term application of organic amendments by examining the growth of pathogenic Fusarium oxysporum co-cultivated with indigenous soil microorganisms on agar plates. Soils treated with coffee residue compost or rapeseed meal showed suppressiveness against spinach wilt disease by F. oxysporum f. sp. spinaciae or spinach wilt and lettuce root rot diseases by F. oxysporum f. sp. spinaciae and F. oxysporum f. sp. lactucae, respectively, and the growth of pathogenic Fusarium spp. on agar plates was suppressed when co-cultured with microorganisms in a suspension from these soils before crop cultivation. These results indicate the potential of the growth degree of pathogenic F. oxysporum estimated by this method as a diagnostic indicator of the suppressiveness of soil associated with the inhabiting microorganisms. A correlation was found between the incidence of spinach wilt disease in spinach and the growth degree of F. oxysporum f. sp. spinaciae by this co-cultivation method, indicating that suppressiveness induced by organic amendment applications against F. oxysporum f. sp. spinaciae is evaluable by this method. The co-cultivation method may be useful for predicting and diagnosing suppressiveness against soil-borne diseases.

SNBRFinder: A Sequence-Based Hybrid Algorithm for Enhanced Prediction of Nucleic Acid-Binding Residues.

Directory of Open Access Journals (Sweden)

Xiaoxia Yang

Full Text Available Protein-nucleic acid interactions are central to various fundamental biological processes. Automated methods capable of reliably identifying DNA- and RNA-binding residues in protein sequence are assuming ever-increasing importance. The majority of current algorithms rely on feature-based prediction, but their accuracy remains to be further improved. Here we propose a sequence-based hybrid algorithm SNBRFinder (Sequence-based Nucleic acid-Binding Residue Finder by merging a feature predictor SNBRFinderF and a template predictor SNBRFinderT. SNBRFinderF was established using the support vector machine whose inputs include sequence profile and other complementary sequence descriptors, while SNBRFinderT was implemented with the sequence alignment algorithm based on profile hidden Markov models to capture the weakly homologous template of query sequence. Experimental results show that SNBRFinderF was clearly superior to the commonly used sequence profile-based predictor and SNBRFinderT can achieve comparable performance to the structure-based template methods. Leveraging the complementary relationship between these two predictors, SNBRFinder reasonably improved the performance of both DNA- and RNA-binding residue predictions. More importantly, the sequence-based hybrid prediction reached competitive performance relative to our previous structure-based counterpart. Our extensive and stringent comparisons show that SNBRFinder has obvious advantages over the existing sequence-based prediction algorithms. The value of our algorithm is highlighted by establishing an easy-to-use web server that is freely accessible at http://ibi.hzau.edu.cn/SNBRFinder.

SNBRFinder: A Sequence-Based Hybrid Algorithm for Enhanced Prediction of Nucleic Acid-Binding Residues.

Science.gov (United States)

Yang, Xiaoxia; Wang, Jia; Sun, Jun; Liu, Rong

2015-01-01

Protein-nucleic acid interactions are central to various fundamental biological processes. Automated methods capable of reliably identifying DNA- and RNA-binding residues in protein sequence are assuming ever-increasing importance. The majority of current algorithms rely on feature-based prediction, but their accuracy remains to be further improved. Here we propose a sequence-based hybrid algorithm SNBRFinder (Sequence-based Nucleic acid-Binding Residue Finder) by merging a feature predictor SNBRFinderF and a template predictor SNBRFinderT. SNBRFinderF was established using the support vector machine whose inputs include sequence profile and other complementary sequence descriptors, while SNBRFinderT was implemented with the sequence alignment algorithm based on profile hidden Markov models to capture the weakly homologous template of query sequence. Experimental results show that SNBRFinderF was clearly superior to the commonly used sequence profile-based predictor and SNBRFinderT can achieve comparable performance to the structure-based template methods. Leveraging the complementary relationship between these two predictors, SNBRFinder reasonably improved the performance of both DNA- and RNA-binding residue predictions. More importantly, the sequence-based hybrid prediction reached competitive performance relative to our previous structure-based counterpart. Our extensive and stringent comparisons show that SNBRFinder has obvious advantages over the existing sequence-based prediction algorithms. The value of our algorithm is highlighted by establishing an easy-to-use web server that is freely accessible at http://ibi.hzau.edu.cn/SNBRFinder.

SAAMBE: Webserver to Predict the Charge of Binding Free Energy Caused by Amino Acids Mutations.

Science.gov (United States)

Petukh, Marharyta; Dai, Luogeng; Alexov, Emil

2016-04-12

Predicting the effect of amino acid substitutions on protein-protein affinity (typically evaluated via the change of protein binding free energy) is important for both understanding the disease-causing mechanism of missense mutations and guiding protein engineering. In addition, researchers are also interested in understanding which energy components are mostly affected by the mutation and how the mutation affects the overall structure of the corresponding protein. Here we report a webserver, the Single Amino Acid Mutation based change in Binding free Energy (SAAMBE) webserver, which addresses the demand for tools for predicting the change of protein binding free energy. SAAMBE is an easy to use webserver, which only requires that a coordinate file be inputted and the user is provided with various, but easy to navigate, options. The user specifies the mutation position, wild type residue and type of mutation to be made. The server predicts the binding free energy change, the changes of the corresponding energy components and provides the energy minimized 3D structure of the wild type and mutant proteins for download. The SAAMBE protocol performance was tested by benchmarking the predictions against over 1300 experimentally determined changes of binding free energy and a Pearson correlation coefficient of 0.62 was obtained. How the predictions can be used for discriminating disease-causing from harmless mutations is discussed. The webserver can be accessed via http://compbio.clemson.edu/saambe_webserver/.

Suppression of glycosaminoglycan synthesis by articular cartilage, but not of hyaluronic acid synthesis by synovium, after exposure to radiation

International Nuclear Information System (INIS)

Hugenberg, S.T.; Myers, S.L.; Brandt, K.D.

1989-01-01

We recently found that injection of 2 mCi of yttrium 90 (90Y; approximately 23,000 rads) into normal canine knees stimulated glycosaminoglycan (GAG) synthesis by femoral condylar cartilage. The present investigation was conducted to determine whether radiation affects cartilage metabolism directly. Rates of GAG synthesis and degradation in normal canine articular cartilage were studied following irradiation. Cultured synovium from the same knees was treated similarly, to determine the effects of irradiation on hyaluronic acid synthesis. Twenty-four hours after exposure to 1,000 rads, 10,000 rads, or 50,000 rads, 35S-GAG synthesis by the cartilage was 93%, 69%, and 37%, respectively, of that in control, nonirradiated cartilage. The effect was not rapidly reversible: 120 hours after exposure to 50,000 rads, GAG synthesis remained at only 28% of the control level. Autoradiography showed marked suppression of 35S uptake by chondrocytes after irradiation. Cartilage GAG degradation was also increased following irradiation: 4 hours and 8 hours after exposure to 50,000 rads, the cartilage GAG concentration was only 66% and 54%, respectively, of that at time 0, while corresponding values for control, nonirradiated cartilage were 90% and 87%. In contrast to its effects on cartilage GAG metabolism, radiation at these levels had no effect on synovial hyaluronic acid synthesis

Suppression of glycosaminoglycan synthesis by articular cartilage, but not of hyaluronic acid synthesis by synovium, after exposure to radiation

Energy Technology Data Exchange (ETDEWEB)

Hugenberg, S.T.; Myers, S.L.; Brandt, K.D.

1989-04-01

We recently found that injection of 2 mCi of yttrium 90 (90Y; approximately 23,000 rads) into normal canine knees stimulated glycosaminoglycan (GAG) synthesis by femoral condylar cartilage. The present investigation was conducted to determine whether radiation affects cartilage metabolism directly. Rates of GAG synthesis and degradation in normal canine articular cartilage were studied following irradiation. Cultured synovium from the same knees was treated similarly, to determine the effects of irradiation on hyaluronic acid synthesis. Twenty-four hours after exposure to 1,000 rads, 10,000 rads, or 50,000 rads, 35S-GAG synthesis by the cartilage was 93%, 69%, and 37%, respectively, of that in control, nonirradiated cartilage. The effect was not rapidly reversible: 120 hours after exposure to 50,000 rads, GAG synthesis remained at only 28% of the control level. Autoradiography showed marked suppression of 35S uptake by chondrocytes after irradiation. Cartilage GAG degradation was also increased following irradiation: 4 hours and 8 hours after exposure to 50,000 rads, the cartilage GAG concentration was only 66% and 54%, respectively, of that at time 0, while corresponding values for control, nonirradiated cartilage were 90% and 87%. In contrast to its effects on cartilage GAG metabolism, radiation at these levels had no effect on synovial hyaluronic acid synthesis.

Styrene maleic acid-encapsulated RL71 micelles suppress tumor growth in a murine xenograft model of triple negative breast cancer.

Science.gov (United States)

Martey, Orleans; Nimick, Mhairi; Taurin, Sebastien; Sundararajan, Vignesh; Greish, Khaled; Rosengren, Rhonda J

2017-01-01

Patients with triple negative breast cancer have a poor prognosis due in part to the lack of targeted therapies. In the search for novel drugs, our laboratory has developed a second-generation curcumin derivative, 3,5-bis(3,4,5-trimethoxybenzylidene)-1-methylpiperidine-4-one (RL71), that exhibits potent in vitro cytotoxicity. To improve the clinical potential of this drug, we have encapsulated it in styrene maleic acid (SMA) micelles. SMA-RL71 showed improved biodistribution, and drug accumulation in the tumor increased 16-fold compared to control. SMA-RL71 (10 mg/kg, intravenously, two times a week for 2 weeks) also significantly suppressed tumor growth compared to control in a xenograft model of triple negative breast cancer. Free RL71 was unable to alter tumor growth. Tumors from SMA-RL71-treated mice showed a decrease in angiogenesis and an increase in apoptosis. The drug treatment also modulated various cell signaling proteins including the epidermal growth factor receptor, with the mechanisms for tumor suppression consistent with previous work with RL71 in vitro. The nanoformulation was also nontoxic as shown by normal levels of plasma markers for liver and kidney injury following weekly administration of SMA-RL71 (10 mg/kg) for 90 days. Thus, we report clinical potential following encapsulation of a novel curcumin derivative, RL71, in SMA micelles.

Antagonism between salicylic and abscisic acid reflects early host-pathogen conflict and moulds plant defence responses.

Science.gov (United States)

de Torres Zabala, Marta; Bennett, Mark H; Truman, William H; Grant, Murray R

2009-08-01

The importance of phytohormone balance is increasingly recognized as central to the outcome of plant-pathogen interactions. Recently it has been demonstrated that abscisic acid signalling pathways are utilized by the bacterial phytopathogen Pseudomonas syringae to promote pathogenesis. In this study, we examined the dynamics, inter-relationship and impact of three key acidic phytohormones, salicylic acid, abscisic acid and jasmonic acid, and the bacterial virulence factor, coronatine, during progression of P. syringae infection of Arabidopsis thaliana. We show that levels of SA and ABA, but not JA, appear to play important early roles in determining the outcome of the infection process. SA is required in order to mount a full innate immune responses, while bacterial effectors act rapidly to activate ABA biosynthesis. ABA suppresses inducible innate immune responses by down-regulating SA biosynthesis and SA-mediated defences. Mutant analyses indicated that endogenous ABA levels represent an important reservoir that is necessary for effector suppression of plant-inducible innate defence responses and SA synthesis prior to subsequent pathogen-induced increases in ABA. Enhanced susceptibility due to loss of SA-mediated basal resistance is epistatically dominant over acquired resistance due to ABA deficiency, although ABA also contributes to symptom development. We conclude that pathogen-modulated ABA signalling rapidly antagonizes SA-mediated defences. We predict that hormonal perturbations, either induced or as a result of environmental stress, have a marked impact on pathological outcomes, and we provide a mechanistic basis for understanding priming events in plant defence.

Ascorbic acid suppresses endotoxemia and NF-κB signaling cascade in alcoholic liver fibrosis in guinea pigs: A mechanistic approach

Energy Technology Data Exchange (ETDEWEB)

Abhilash, P.A.; Harikrishnan, R.; Indira, M., E-mail: indiramadambath@gmail.com

2014-01-15

Alcohol consumption increases the small intestinal bacterial overgrowth (SIBO) and intestinal permeability of endotoxin. The endotoxin mediated inflammatory signaling plays a major role in alcoholic liver fibrosis. We evaluated the effect of ascorbic acid (AA), silymarin and alcohol abstention on the alcohol induced endotoxemia and NF-κB activation cascade pathway in guinea pigs (Cavia porcellus). Guinea pigs were administered ethanol at a daily dose of 4 g/kg b.wt for 90 days. After 90 days, ethanol administration was stopped. The ethanol treated animals were divided into abstention, silymarin (250 mg/kg b.wt) and AA (250 mg/kg b.wt) supplemented groups and maintained for 30 days. The SIBO, intestinal permeability and endotoxin were significantly increased in the ethanol group. The mRNA expressions of intestinal proteins claudin, occludin and zona occludens-1 were significantly decreased in ethanol group. The mRNA levels of inflammatory receptors, activity of IKKβ and the protein expressions of phospho-IκBα, NF-κB, TNF-α, TGF-β{sub 1} and IL-6 were also altered in ethanol group. The expressions of fibrosis markers α-SMA, α{sub 1} (I) collagen and sirius red staining in the liver revealed the induction of fibrosis. But the supplementation of AA could induce greater reduction of ethanol induced SIBO, intestinal barrier defects, NF-κB activation and liver fibrosis than silymarin. The possible mechanism may be the inhibitory effect of AA on SIBO, intestinal barrier defect and IKKβ, which decreased the activation of NF-κB and synthesis of cytokines. This might have led to suppression of HSCs activation and liver fibrosis. - Highlights: • Alcohol increases intestinal bacterial overgrowth and permeability of endotoxin. • Endotoxin mediated inflammation plays a major role in alcoholic liver fibrosis. • Ascorbic acid reduces endotoxemia, NF-κB activation and proinflammatory cytokines. • AA's action is by inhibition of SIBO, IKKβ and alteration of

Conjugated docosahexaenoic acid suppresses KPL-1 human breast cancer cell growth in vitro and in vivo: potential mechanisms of action

International Nuclear Information System (INIS)

Tsujita-Kyutoku, Miki; Ogawa, Yutaka; Tsubura, Airo; Yuri, Takashi; Danbara, Naoyuki; Senzaki, Hideto; Kiyozuka, Yasuhiko; Uehara, Norihisa; Takada, Hideho; Hada, Takahiko; Miyazawa, Teruo

2004-01-01

The present study was conducted to examine the effect of conjugated docosahexaenoic acid (CDHA) on cell growth, cell cycle progression, mode of cell death, and expression of cell cycle regulatory and/or apoptosis-related proteins in KPL-1 human breast cancer cell line. This effect of CDHA was compared with that of docosahexaenoic acid (DHA). KPL-1 cell growth was assessed by colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; cell cycle progression and mode of cell death were examined by flow cytometry; and levels of expression of p53, p21 Cip1/Waf1 , cyclin D 1 , Bax, and Bcl-2 proteins were examined by Western blotting analysis. In vivo tumor growth was examined by injecting KPL-1 cells subcutaneously into the area of the right thoracic mammary fat pad of female athymic mice fed a CDHA diet. CDHA inhibited KPL-1 cells more effectively than did DHA (50% inhibitory concentration for 72 hours: 97 μmol/l and 270 μmol/l, respectively). With both CDHA and DHA growth inhibition was due to apoptosis, as indicated by the appearance of a sub-G 1 fraction. The apoptosis cascade involved downregulation of Bcl-2 protein; Bax expression was unchanged. Cell cycle progression was due to G 0 /G 1 arrest, which involved increased expression of p53 and p21 Cip1/Waf1 , and decreased expression of cyclin D 1 . CDHA modulated cell cycle regulatory proteins and apoptosis-related proteins in a manner similar to that of parent DHA. In the athymic mouse system 1.0% dietary CDHA, but not 0.2%, significantly suppressed growth of KPL-1 tumor cells; CDHA tended to decrease regional lymph node metastasis in a dose dependent manner. CDHA inhibited growth of KPL-1 human breast cancer cells in vitro more effectively than did DHA. The mechanisms of action involved modulation of apoptosis cascade and cell cycle progression. Dietary CDHA at 1.0% suppressed KPL-1 cell growth in the athymic mouse system

Simultaneous Determination of Chelating Agents by Ion-Suppression and Ion-Pair Chromatography in Wastewater

International Nuclear Information System (INIS)

Dodi, Alain; Bouscarel, Maelle

2008-01-01

This article describes two methods for analysing chelating agents found in nuclear waste. First, ion-suppression chromatography using an anion exchange stationary phase and mobile phase consisting of a nitric acid solution and pure water gradient. UV detection was performed at 330 nm after the reaction with a post-column reagent composed of iron nitrate in perchloric acid. Secondly, ion-pair chromatography with a mobile phase consisting of a mixture of nitric acid, tetra-butyl-ammonium hydrogeno-sulphate, tetra-butyl-ammonium hydroxide and iron chloride. A reversed-phase material was used as a stationary phase and detection was performed by direct measurement of the UV absorption at 260 nm. The quantification limits were lower for ion-pair chromatography than for ion-suppression chromatography. Both methods were easy to implement and allow a multi-element separation in less than 30 min with low detection limits. (authors)

Simultaneous Determination of Chelating Agents by Ion-Suppression and Ion-Pair Chromatography in Wastewater

Energy Technology Data Exchange (ETDEWEB)

Dodi, Alain; Bouscarel, Maelle [Commissariat a l' energie atomique - C.E.A, Centre d' Etude de Cadarache, Laboratoire d' Analyses Radiochimiques et Chimiques, St Paul lez Durance (France)

2008-07-01

This article describes two methods for analysing chelating agents found in nuclear waste. First, ion-suppression chromatography using an anion exchange stationary phase and mobile phase consisting of a nitric acid solution and pure water gradient. UV detection was performed at 330 nm after the reaction with a post-column reagent composed of iron nitrate in perchloric acid. Secondly, ion-pair chromatography with a mobile phase consisting of a mixture of nitric acid, tetra-butyl-ammonium hydrogeno-sulphate, tetra-butyl-ammonium hydroxide and iron chloride. A reversed-phase material was used as a stationary phase and detection was performed by direct measurement of the UV absorption at 260 nm. The quantification limits were lower for ion-pair chromatography than for ion-suppression chromatography. Both methods were easy to implement and allow a multi-element separation in less than 30 min with low detection limits. (authors)

Iso-α-acids, bitter components of beer, prevent obesity-induced cognitive decline.

Science.gov (United States)

Ayabe, Tatsuhiro; Ohya, Rena; Kondo, Keiji; Ano, Yasuhisa

2018-03-19

Dementia and cognitive decline have become worldwide public health problems, and it was recently reported that life-style related diseases and obesity are key risk factors in dementia. Iso-α-acids, hop-derived bitter components of beer, have been reported to have various physiological functions via activation of peroxisome proliferator-activated receptor γ. In this report, we demonstrated that daily intake of iso-α-acids suppresses inflammations in the hippocampus and improves cognitive decline induced by high fat diet (HFD). Body weight, epididymal fat weight, and plasma triglyceride levels were increased in HFD-fed mice, and significantly decreased in iso-α-acids supplemented HFD-fed mice. HFD feeding enhances the production of inflammatory cytokines and chemokines, such as TNF-α, which was significantly suppressed by iso-α-acids administration. HFD-induced neuroinflammation caused lipid peroxidation, neuronal loss, and atrophy in hippocampus, and those were not observed in iso-α-acids-treated mice. Furthermore, iso-α-acids intake significantly improved cognitive decline induced by HFD-feeding. Iso-α-acids are food derived components that suppressing both lipid accumulation and brain inflammation, thus iso-α-acids might be beneficial for the risk of dementia increased by obesity and lifestyle-related diseases.

Overnight Dexamethasone Suppression Test in the Diagnosis of Cushing's Disease

Directory of Open Access Journals (Sweden)

Fatemeh Esfahanian

2010-08-01

Full Text Available Realizing the cause of Cushing's Syndrome (CS is one of the most challenging processes in clinical endocrinology. The long high dose dexamethasone suppression test (standard test is costly and need an extended inpatient stay. In this study we want to show the clinical utility of the overnight 8 mg dexamethasone suppression test (DST for differential diagnosis of CS in a referral center. Retrospectively from 2002-2005 we selected the patients of endocrinology ward in Imam hospital who were admitted with the diagnosis of Cushing syndrome and had 8 mg DST (modified test along with classic DST. In modified test a decrease in an 8 AM serum cortisol level of 50% or more is thought to indicate suppression and we compared the results of modified test with standard test. This test had been done on 42 patients: 10 male (23% and 32 female (76%. The mean age of patients was 31.39 (15-63, 32 with proven pituitary Cushing's disease, 7 with primary adrnal tumors and 3 with ectopic ACTH syndrome. The standard test according to 50% suppression of UFC had 90.62% sensitivity, and according to 90% suppression had 43.75% sensitivity. The sensitivity of this test was 71.85% for serum cortisol suppression. The modified test (8 mg overnight DST had 78% sensitivity. All of these tests had 100% specificity for the diagnosis of Cushing's disease. The positive predictive vale (PPV of all of these tests was 100%. The negative predictive value (NPV of modified test for the diagnosis of Cushing's disease was 58.82%. In standard test the NPV of serum cortisol was 52.6%, UFC 50% had 76.9% NPV and UFC 90% had 35.7% NPV. The results of serum cortisol suppression in modified test is better than standard test. Although 50% suppression of UFC in standard test had greater sensitivity than modified test, collecting of urine is difficult, time consuming and needing hospitalization, so we advice modified test that is much simpler and more convenient instead of standard test in the first

FolC2-mediated folate metabolism contributes to suppression of inflammation by probiotic Lactobacillus reuteri.

Science.gov (United States)

Thomas, Carissa M; Saulnier, Delphine M A; Spinler, Jennifer K; Hemarajata, Peera; Gao, Chunxu; Jones, Sara E; Grimm, Ashley; Balderas, Miriam A; Burstein, Matthew D; Morra, Christina; Roeth, Daniel; Kalkum, Markus; Versalovic, James

2016-10-01

Bacterial-derived compounds from the intestinal microbiome modulate host mucosal immunity. Identification and mechanistic studies of these compounds provide insights into host-microbial mutualism. Specific Lactobacillus reuteri strains suppress production of the proinflammatory cytokine, tumor necrosis factor (TNF), and are protective in a mouse model of colitis. Human-derived L. reuteri strain ATCC PTA 6475 suppresses intestinal inflammation and produces 5,10-methenyltetrahydrofolic acid polyglutamates. Insertional mutagenesis identified the bifunctional dihydrofolate synthase/folylpolyglutamate synthase type 2 (folC2) gene as essential for 5,10-methenyltetrahydrofolic acid polyglutamate biosynthesis, as well as for suppression of TNF production by activated human monocytes, and for the anti-inflammatory effect of L. reuteri 6475 in a trinitrobenzene sulfonic acid-induced mouse model of acute colitis. In contrast, folC encodes the enzyme responsible for folate polyglutamylation but does not impact TNF suppression by L. reuteri. Comparative transcriptomics between wild-type and mutant L. reuteri strains revealed additional genes involved in immunomodulation, including previously identified hdc genes involved in histidine to histamine conversion. The folC2 mutant yielded diminished hdc gene cluster expression and diminished histamine production, suggesting a link between folate and histadine/histamine metabolism. The identification of genes and gene networks regulating production of bacterial-derived immunoregulatory molecules may lead to improved anti-inflammatory strategies for digestive diseases. © 2016 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Prediction of the acid generating potential of coal mining spoils

International Nuclear Information System (INIS)

Monterroso, C.; Macias, F.

1998-01-01

The sulfide oxidation impact on mined land reclamation makes it necessary for mine spoils to be classified according to their acidifying potential. In this paper predictions were made of the acid generating potential of sulfide-containing spoils from the Puentes lignite mine (Galicia, NW Spain), and the limits of sulfur contents allowable for their storage in aerobic conditions, were established. Using samples of fresh spoils, analyses were made of the content and speciation of sulfur, pH was measured after oxidation of the sample with H 2 O 2 (pH of oxidation = pH OX ), and titration of the oxidation extract with 0.1N NaOH to pH = 7 was carried out (Net Acid Production = NAP). The total sulfur content (S T ) varied between 3%, with pyritic-S being the most common form (> 80%). pH OX varied between 1.6 and 6.4 and NAP between 1.2 and 85.0 Kg-CaCO 3 t -1 . A high correlation was found between the NAP and the S T (r-0.98, p T > 0.15% cause high risks of mine-soil acidification, and create the need for large doses of CaCO 3 to be used on final surface of the mine dump. Use of fly ash, produced from the combustion of lignite, as an alternative to commercial lime is more effective in the control of acidity generated by spoils with high S T . 20 refs., 5 figs., 1 tab

Nuclear suppression of J/Ψ: From RHIC to the LHC

International Nuclear Information System (INIS)

Kopeliovich, B.Z.; Potashnikova, I.K.; Schmidt, Ivan

2011-01-01

A parameter-free calculation for J/Ψ suppression in pA collisions, based on the dipole description, is confronted with the new data from the PHENIX experiment. Achieving good agreement, we employed this model predicting the contribution of initial state interactions (ISI) to J/Ψ suppression in AA collisions. Such a transition from pA to AA is not straightforward, since involves specific effects of double color filtering and boosting of the saturation scale. Relying on this refined ISI contribution, we updated the previous analysis of RHIC data on J/Ψ production in Cu-Cu and Au-Au collisions at √(s)=200 GeV, and determined the transport coefficient of the created dense medium at q-hat 0 =0.6 GeV 2 /fm. Nuclear effects for J/Ψ production at the LHC are predicted using the transport coefficient q-hat 0 =0.8 GeV 2 /fm, extracted from data on suppression of high-p T hadrons in central lead-lead collisions at √(s)=2.76 TeV. Our analysis covers only direct J/Ψ production, while data may also include the feed-down from decay of heavier states and B-mesons.

Emotion suppression, emotional eating, and eating behavior among parent-adolescent dyads.

Science.gov (United States)

Ferrer, Rebecca A; Green, Paige A; Oh, April Y; Hennessy, Erin; Dwyer, Laura A

2017-10-01

Emotion suppression may lead to ironic increases in emotional experience. More important, suppression is a transactional process, creating stress and disrupting interactions for the suppressor and those in social interactions with individuals who are suppressing emotion. However, no research has examined the behavioral consequences of emotion suppression in close relationships. We examine the possibility that emotion suppression will predict eating behaviors as a secondary emotion regulatory strategy among 1,556 parent-adolescent dyads (N = 3,112), consistent with evidence suggesting that suppression influences eating at the individual-level. Actor-partner interdependence models and structural equation modeling demonstrate that one's own emotion suppression was associated with emotional eating; greater consumption of hedonic-low nutrient, high energy dense-foods; and lower consumption of fruits and vegetables (actor effects). One's partner's emotion suppression was also independently associated with one's own emotional eating; lower consumption of fruits and vegetables; and greater consumption of hedonic foods (partner effects), although this association was most consistent for adolescents' suppression and parents' eating (compared with the converse). These analyses suggest that dyadic emotion regulatory processes have implications on eating behavior. Moreover, analyses suggest that emotion suppression has potential implications on eating behaviors of others within close relationships with a suppressor, consistent with the notion that emotion regulation is a transactional process. These findings suggest that interventions to improve eating habits of parents and their adolescent children should consider dyadic emotion regulatory processes. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Error-dependent modulation of speech-induced auditory suppression for pitch-shifted voice feedback

Directory of Open Access Journals (Sweden)

Larson Charles R

2011-06-01

Full Text Available Abstract Background The motor-driven predictions about expected sensory feedback (efference copies have been proposed to play an important role in recognition of sensory consequences of self-produced motor actions. In the auditory system, this effect was suggested to result in suppression of sensory neural responses to self-produced voices that are predicted by the efference copies during vocal production in comparison with passive listening to the playback of the identical self-vocalizations. In the present study, event-related potentials (ERPs were recorded in response to upward pitch shift stimuli (PSS with five different magnitudes (0, +50, +100, +200 and +400 cents at voice onset during active vocal production and passive listening to the playback. Results Results indicated that the suppression of the N1 component during vocal production was largest for unaltered voice feedback (PSS: 0 cents, became smaller as the magnitude of PSS increased to 200 cents, and was almost completely eliminated in response to 400 cents stimuli. Conclusions Findings of the present study suggest that the brain utilizes the motor predictions (efference copies to determine the source of incoming stimuli and maximally suppresses the auditory responses to unaltered feedback of self-vocalizations. The reduction of suppression for 50, 100 and 200 cents and its elimination for 400 cents pitch-shifted voice auditory feedback support the idea that motor-driven suppression of voice feedback leads to distinctly different sensory neural processing of self vs. non-self vocalizations. This characteristic may enable the audio-vocal system to more effectively detect and correct for unexpected errors in the feedback of self-produced voice pitch compared with externally-generated sounds.

Error-dependent modulation of speech-induced auditory suppression for pitch-shifted voice feedback.

Science.gov (United States)

Behroozmand, Roozbeh; Larson, Charles R

2011-06-06

The motor-driven predictions about expected sensory feedback (efference copies) have been proposed to play an important role in recognition of sensory consequences of self-produced motor actions. In the auditory system, this effect was suggested to result in suppression of sensory neural responses to self-produced voices that are predicted by the efference copies during vocal production in comparison with passive listening to the playback of the identical self-vocalizations. In the present study, event-related potentials (ERPs) were recorded in response to upward pitch shift stimuli (PSS) with five different magnitudes (0, +50, +100, +200 and +400 cents) at voice onset during active vocal production and passive listening to the playback. Results indicated that the suppression of the N1 component during vocal production was largest for unaltered voice feedback (PSS: 0 cents), became smaller as the magnitude of PSS increased to 200 cents, and was almost completely eliminated in response to 400 cents stimuli. Findings of the present study suggest that the brain utilizes the motor predictions (efference copies) to determine the source of incoming stimuli and maximally suppresses the auditory responses to unaltered feedback of self-vocalizations. The reduction of suppression for 50, 100 and 200 cents and its elimination for 400 cents pitch-shifted voice auditory feedback support the idea that motor-driven suppression of voice feedback leads to distinctly different sensory neural processing of self vs. non-self vocalizations. This characteristic may enable the audio-vocal system to more effectively detect and correct for unexpected errors in the feedback of self-produced voice pitch compared with externally-generated sounds.

RBscore&NBench: a high-level web server for nucleic acid binding residues prediction with a large-scale benchmarking database.

Science.gov (United States)

Miao, Zhichao; Westhof, Eric

2016-07-08

RBscore&NBench combines a web server, RBscore and a database, NBench. RBscore predicts RNA-/DNA-binding residues in proteins and visualizes the prediction scores and features on protein structures. The scoring scheme of RBscore directly links feature values to nucleic acid binding probabilities and illustrates the nucleic acid binding energy funnel on the protein surface. To avoid dataset, binding site definition and assessment metric biases, we compared RBscore with 18 web servers and 3 stand-alone programs on 41 datasets, which demonstrated the high and stable accuracy of RBscore. A comprehensive comparison led us to develop a benchmark database named NBench. The web server is available on: http://ahsoka.u-strasbg.fr/rbscorenbench/. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Quantitative milk genomics: estimation of variance components and prediction of fatty acids in bovine milk

DEFF Research Database (Denmark)

Krag, Kristian

The composition of bovine milk fat, used for human consumption, is far from the recommendations for human fat nutrition. The aim of this PhD was to describe the variance components and prediction probabilities of individual fatty acids (FA) in bovine milk, and to evaluate the possibilities...

Inhibition of Hyaluronic Acid Synthesis Suppresses Angiogenesis in Developing Endometriotic Lesions.

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Carla N Olivares

Full Text Available The development and long-term survival of endometriotic lesions is crucially dependent on an adequate vascularization. Hyaluronic acid (HA through its receptor CD44 has been described to be involved in the process of angiogenesis.To study the effect of HA synthesis inhibition using non-toxic doses of 4-methylumbelliferone (4-MU on endometriosis-related angiogenesis.The cytotoxicity of different in vitro doses of 4-MU on endothelial cells was firstly tested by means of a lactate dehydrogenase assay. The anti-angiogenic action of non-cytotoxic doses of 4-MU was then assessed by a rat aortic ring assay. In addition, endometriotic lesions were induced in dorsal skinfold chambers of female BALB/c mice, which were daily treated with an intraperitoneal injection of 0.9% NaCl (vehicle group; n = 6, 20 mg/kg 4-MU (n = 8 or 80 mg/kg 4-MU (n = 7 throughout an observation period of 14 days. The effect of 4-MU on their vascularization, survival and growth were studied by intravital fluorescence microscopy, histology and immunohistochemistry.Non-cytotoxic doses of 4-MU effectively inhibited vascular sprout formation in the rat aortic ring assay. Endometriotic lesions in dorsal skinfold chambers of 4-MU-treated mice dose-dependently exhibited a significantly smaller vascularized area and lower functional microvessel density when compared to vehicle-treated controls. Histological analyses revealed a downregulation of HA expression in 4-MU-treated lesions. This was associated with a reduced density of CD31-positive microvessels within the lesions. In contrast, numbers of PCNA-positive proliferating and cleaved caspase-3-positive apoptotic cells did not differ between 4-MU-treated and control lesions.The present study demonstrates for the first time that targeting the synthesis of HA suppresses angiogenesis in developing endometriotic lesions. Further studies have to clarify now whether in the future this anti-angiogenic effect can be used beneficially for the

Prediction of the ageing of commercial lager beer during storage based on the degradation of iso-α-acids.

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Blanco, Carlos A; Nimubona, Dieudonné; Caballero, Isabel

2014-08-01

Iso-α-acids and their chemically modified variants are responsible for the bitterness of beer and play a disproportionately large role in the final quality of beer. The current study was undertaken to predict the degradation of commercial lager beers related to changes in the concentration of trans-iso-α-acids during storage by using high-pressure liquid chromatography. In the analysed beers the concentration of isohumulone (average concentration 28 mg L(-1)) was greater than that of isocohumulone (20 mg L(-1)) and isoadhumulone (10 mg L(-1)). The kinetic parameters, activation energy and rate constant, of the trans-iso-α-acids were calculated. In the case of dark beers, the activation energy for the degradation of trans-isocohumulones was found to be higher than for trans-isohumulones and trans-isoadhumulones, whereas in pale and alcohol-free beers activation energies for the degradation of the three trans isomers were similar. The loss of iso-α-acids can be calculated using the activation energy of the degradation of trans-iso-α-acids and the temperature profile of the accelerated ageing. The results obtained in the investigation can be used in the beer industry to predict the alteration of the bitterness of beer during storage. © 2013 Society of Chemical Industry.

Subjective duration distortions mirror neural repetition suppression.

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Pariyadath, Vani; Eagleman, David M

2012-01-01

Subjective duration is strongly influenced by repetition and novelty, such that an oddball stimulus in a stream of repeated stimuli appears to last longer in duration in comparison. We hypothesize that this duration illusion, called the temporal oddball effect, is a result of the difference in expectation between the oddball and the repeated stimuli. Specifically, we conjecture that the repeated stimuli contract in duration as a result of increased predictability; these duration contractions, we suggest, result from decreased neural response amplitude with repetition, known as repetition suppression. Participants viewed trials consisting of lines presented at a particular orientation (standard stimuli) followed by a line presented at a different orientation (oddball stimulus). We found that the size of the oddball effect correlates with the number of repetitions of the standard stimulus as well as the amount of deviance from the oddball stimulus; both of these results are consistent with a repetition suppression hypothesis. Further, we find that the temporal oddball effect is sensitive to experimental context--that is, the size of the oddball effect for a particular experimental trial is influenced by the range of duration distortions seen in preceding trials. Our data suggest that the repetition-related duration contractions causing the oddball effect are a result of neural repetition suppression. More generally, subjective duration may reflect the prediction error associated with a stimulus and, consequently, the efficiency of encoding that stimulus. Additionally, we emphasize that experimental context effects need to be taken into consideration when designing duration-related tasks.

Subjective duration distortions mirror neural repetition suppression.

Directory of Open Access Journals (Sweden)

Vani Pariyadath

Full Text Available Subjective duration is strongly influenced by repetition and novelty, such that an oddball stimulus in a stream of repeated stimuli appears to last longer in duration in comparison. We hypothesize that this duration illusion, called the temporal oddball effect, is a result of the difference in expectation between the oddball and the repeated stimuli. Specifically, we conjecture that the repeated stimuli contract in duration as a result of increased predictability; these duration contractions, we suggest, result from decreased neural response amplitude with repetition, known as repetition suppression.Participants viewed trials consisting of lines presented at a particular orientation (standard stimuli followed by a line presented at a different orientation (oddball stimulus. We found that the size of the oddball effect correlates with the number of repetitions of the standard stimulus as well as the amount of deviance from the oddball stimulus; both of these results are consistent with a repetition suppression hypothesis. Further, we find that the temporal oddball effect is sensitive to experimental context--that is, the size of the oddball effect for a particular experimental trial is influenced by the range of duration distortions seen in preceding trials.Our data suggest that the repetition-related duration contractions causing the oddball effect are a result of neural repetition suppression. More generally, subjective duration may reflect the prediction error associated with a stimulus and, consequently, the efficiency of encoding that stimulus. Additionally, we emphasize that experimental context effects need to be taken into consideration when designing duration-related tasks.

Stimulus-dependent suppression of chaos in recurrent neural networks

International Nuclear Information System (INIS)

Rajan, Kanaka; Abbott, L. F.; Sompolinsky, Haim

2010-01-01

Neuronal activity arises from an interaction between ongoing firing generated spontaneously by neural circuits and responses driven by external stimuli. Using mean-field analysis, we ask how a neural network that intrinsically generates chaotic patterns of activity can remain sensitive to extrinsic input. We find that inputs not only drive network responses, but they also actively suppress ongoing activity, ultimately leading to a phase transition in which chaos is completely eliminated. The critical input intensity at the phase transition is a nonmonotonic function of stimulus frequency, revealing a 'resonant' frequency at which the input is most effective at suppressing chaos even though the power spectrum of the spontaneous activity peaks at zero and falls exponentially. A prediction of our analysis is that the variance of neural responses should be most strongly suppressed at frequencies matching the range over which many sensory systems operate.

Nickel Inhibits Mitochondrial Fatty Acid Oxidation

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Uppala, Radha; McKinney, Richard W.; Brant, Kelly A.; Fabisiak, James P.; Goetzman, Eric S.

2015-01-01

Nickel exposure is associated with changes in cellular energy metabolism which may contribute to its carcinogenic properties. Here, we demonstrate that nickel strongly represses mitochondrial fatty acid oxidation—the pathway by which fatty acids are catabolized for energy—in both primary human lung fibroblasts and mouse embryonic fibroblasts. At the concentrations used, nickel suppresses fatty acid oxidation without globally suppressing mitochondrial function as evidenced by increased glucose oxidation to CO2. Pre-treatment with L-carnitine, previously shown to prevent nickel-induced mitochondrial dysfunction in neuroblastoma cells, did not prevent the inhibition of fatty acid oxidation. The effect of nickel on fatty acid oxidation occurred only with prolonged exposure (>5 hr), suggesting that direct inhibition of the active sites of metabolic enzymes is not the mechanism of action. Nickel is a known hypoxia-mimetic that activates hypoxia inducible factor-1α (HIF1α). Nickel-induced inhibition of fatty acid oxidation was blunted in HIF1α knockout fibroblasts, implicating HIF1α as one contributor to the mechanism. Additionally, nickel down-regulated the protein levels of the key fatty acid oxidation enzyme very long-chain acyl-CoA dehydrogenase (VLCAD) in a dose-dependent fashion. In conclusion, inhibition of fatty acid oxidation by nickel, concurrent with increased glucose metabolism, represents a form of metabolic reprogramming that may contribute to nickel-induced carcinogenesis. PMID:26051273

Plasma uric acid and tumor volume are highly predictive of outcome in nasopharyngeal carcinoma patients receiving intensity modulated radiotherapy

International Nuclear Information System (INIS)

Lin, Hui; Lin, Huan-Xin; Ge, Nan; Wang, Hong-Zhi; Sun, Rui; Hu, Wei-Han

2013-01-01

The combined predictive value of plasma uric acid and primary tumor volume in nasopharyngeal carcinoma (NPC) patients receiving intensity modulated radiation therapy (IMRT) has not yet been determined. In this retrospective study, plasma uric acid level was measured after treatment in 130 histologically-proven NPC patients treated with IMRT. Tumor volume was calculated from treatment planning CT scans. Overall (OS), progression-free (PFS) and distant metastasis-free (DMFS) survival were compared using Kaplan-Meier analysis and the log rank test, and Cox multivariate and univariate regression models were created. Patients with a small tumor volume (<27 mL) had a significantly better DMFS, PFS and OS than patients with a large tumor volume. Patients with a high post-treatment plasma uric acid level (>301 μmol/L) had a better DMFS, PFS and OS than patients with a low post-treatment plasma uric acid level. Patients with a small tumor volume and high post-treatment plasma uric acid level had a favorable prognosis compared to patients with a large tumor volume and low post-treatment plasma uric acid level (7-year overall OS, 100% vs. 48.7%, P <0.001 and PFS, 100% vs. 69.5%, P <0.001). Post-treatment plasma uric acid level and pre-treatment tumor volume have predictive value for outcome in NPC patients receiving IMRT. NPC patients with a large tumor volume and low post-treatment plasma uric acid level may benefit from additional aggressive treatment after IMRT

Prediction of intramuscular fat content and major fatty acid groups of lamb M. longissimus lumborum using Raman spectroscopy.

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Fowler, Stephanie M; Ponnampalam, Eric N; Schmidt, Heinar; Wynn, Peter; Hopkins, David L

2015-12-01

A hand held Raman spectroscopic device was used to predict intramuscular fat (IMF) levels and the major fatty acid (FA) groups of fresh intact ovine M. longissimus lumborum (LL). IMF levels were determined using the Soxhlet method, while FA analysis was conducted using a rapid (KOH in water, methanol and sulphuric acid in water) extraction procedure. IMF levels and FA values were regressed against Raman spectra using partial least squares regression and against each other using linear regression. The results indicate that there is potential to predict PUFA (R(2)=0.93) and MUFA (R(2)=0.54) as well as SFA values that had been adjusted for IMF content (R(2)=0.54). However, this potential was significantly reduced when correlations between predicted and observed values were determined by cross validation (R(2)cv=0.21-0.00). Overall, the prediction of major FA groups using Raman spectra was more precise (relative reductions in error of 0.3-40.8%) compared to the null models. Copyright © 2015 Elsevier Ltd. All rights reserved.

Antagonism between abscisic acid and gibberellins is partially mediated by ascorbic acid during seed germination in rice.

Science.gov (United States)

Ye, Nenghui; Zhang, Jianhua

2012-05-01

The antagonism between abscisic acid (ABA) and gibberellin (GA) plays a key role in controlling seed germination, but the mechanism of antagonism during this process is not known. In the associated study, we investigated the relationship among ABA, reactive oxygen species (ROS), ascorbic acid (ASC) and GA during rice seed germination. ROS production is reduced by ABA, which hence results in decreasing ASC accumulation during imbibition. GA accumulation was also suppressed by a reduced ROS and ASC level, whereas application of exogenous ASC can partially rescue seed germination from ABA treatment. Further results show that production of ASC, which acts as a substrate in GA biosynthesis, was significantly inhibited by lycorine which thus suppressed the accumulation of GA. Consequently, expression of GA biosynthesis genes was suppressed by the low levels of ROS and ASC in ABA-treated seeds. These studies reveal a new role for ASC in mediating the antagonism between ABA and GA during seed germination in rice.

Complex suppression patterns distinguish between major energy loss effects in Quark–Gluon Plasma

Energy Technology Data Exchange (ETDEWEB)

Djordjevic, Magdalena, E-mail: magda@ipb.ac.rs

2016-12-10

Interactions of high momentum partons with Quark–Gluon Plasma created in relativistic heavy-ion collisions provide an excellent tomography tool for this new form of matter. Recent measurements for charged hadrons and unidentified jets at the LHC show an unexpected flattening of the suppression curves at high momentum, exhibited when either momentum or the collision centrality is changed. Furthermore, a limited data available for B probes indicate a qualitatively different pattern, as nearly the same flattening is exhibited for the curves corresponding to two opposite momentum ranges. We here show that the experimentally measured suppression curves are well reproduced by our theoretical predictions, and that the complex suppression patterns are due to an interplay of collisional, radiative energy loss and the dead-cone effect. Furthermore, for B mesons, we predict that the uniform flattening of the suppression indicated by the limited dataset is in fact valid across the entire span of the momentum ranges, which will be tested by the upcoming experiments. Overall, the study presented here, provides a rare opportunity for pQCD theory to qualitatively distinguish between the major energy loss mechanisms at the same (nonintuitive) dataset.

Serum uric acid level predicts adverse outcomes after myocardial revascularization or cardiac valve surgery.

Science.gov (United States)

Lazzeroni, Davide; Bini, Matteo; Camaiora, Umberto; Castiglioni, Paolo; Moderato, Luca; Bosi, Davide; Geroldi, Simone; Ugolotti, Pietro T; Brambilla, Lorenzo; Brambilla, Valerio; Coruzzi, Paolo

2018-01-01

Background High levels of serum uric acid have been associated with adverse outcomes in cardiovascular diseases such as myocardial infarction and heart failure. The aim of the current study was to evaluate the prognostic role of serum uric acid levels in patients undergoing cardiac rehabilitation after myocardial revascularization and/or cardiac valve surgery. Design We performed an observational prospective cohort study. Methods The study included 1440 patients with available serum uric acid levels, prospectively followed for 50 ± 17 months. Mean age was 67 ± 11 years; 781 patients (54%) underwent myocardial revascularization, 474 (33%) cardiac valve surgery and 185 (13%) valve-plus-coronary artery by-pass graft surgery. The primary endpoints were overall and cardiovascular mortality while secondary end-points were combined major adverse cardiac and cerebrovascular events. Results Serum uric acid level mean values were 286 ± 95 µmol/l and elevated serum uric acid levels (≥360 µmol/l or 6 mg/dl) were found in 275 patients (19%). Overall mortality (hazard ratio = 2.1; 95% confidence interval: 1.5-3.0; p uric acid levels, even after adjustment for age, gender, arterial hypertension, diabetes, glomerular filtration rate, atrial fibrillation and medical therapy. Moreover, strong positive correlations between serum uric acid level and probability of overall mortality ( p uric acid levels predict mortality and adverse cardiovascular outcome in patients undergoing myocardial revascularization and/or cardiac valve surgery even after the adjustment for age, gender, arterial hypertension, diabetes, glomerular filtration rate and medical therapy.

Immediate acid-suppressing effects of ranitidine hydrochloride and rabeprazole sodium following initial administration and reintroduction: A randomized, cross-over study using wireless pH monitoring capsules.

Science.gov (United States)

Ono, Shouko; Kato, Mototsugu; Ono, Yuji; Imai, Aki; Yoshida, Takeshi; Shimizu, Yuichi; Asaka, Masahiro

2009-04-01

Histamine 2 receptor antagonists and proton-pump inhibitors, drugs that are widely used for the treatment of acid-related diseases, have different clinical characteristics. The objective of this study was to compare the acid-suppressing effects of ranitidine hydrochloride and those of rabeprazole sodium at the first administration and re-administration after withdrawal. The study was designed as an open-label, randomized, two-way cross-over trial. Seven Helicobacter pylori-negative healthy volunteers were enrolled in this study. Ranitidine hydrochloride (300 mg/day) or rabeprazole sodium (20 mg/day) was administered from days 1 to 7 and from days 11 to 13. The percentage of time with gastric pH sodium maintained a potent and stable effect from days 2 to 7 (ranitidine vs rabeprazole: P hydrochloride was attenuated after day 4. In addition, the effect of ranitidine hydrochloride at re-administration was attenuated (days 11, 12, and 13 vs pre-administration: not significant). In view of our observations, we expect symptoms associated with gastric acidity to be more adequately controlled with rabeprazole sodium in the short term when compared to ranitidine hydrochloride.

Molecular mechanism of intracellular lipid accumulation: Suppressive effect of PycnogenolR in liver cells

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Shoichiro Ikuyama

2013-09-01

Full Text Available ABSTRACTCells are physiologically ready to accumulate lipids such as triacylglycerides in the cytoplasm.Five classes of perilipin (PLIN family proteins are known to be involved in the process of intracellular lipid accumulation. PLIN2 is expressed ubiquitously including adipocytes, hepatocytes and macrophages. Over-expression of PLIN2 is demonstrated in the lesions of fatty liver diseases and atherosclerosis. Suppression of PLIN2 expression prevents from developing these pathological conditions in animal models, suggesting that PLIN2 could be a therapeutic target molecule for excessive intracellular lipid accumulation which leads to various metabolic derangements. The PLIN2 gene promoter has two important cis-acting elements in close proximity:AP-1 element which mediates inflammatory signals and PPRE which mediates free fatty acid effect. In NMuLi mouse liver cells, FFA such as oleic acid requires both functional AP-1 and PPRE simultaneously to stimulate the promoter activity, indicating the presence of intimate interaction of inflammatory and metabolic signals on this gene. PycnogenolR, French maritime pine bark extracts, suppressed the oleic acid-induced PLIN2 expression and lipid accumulation in NMuLi cells. We found that PycnogenolR did not suppress the PLIN2 promoter activity or AP-1 binding to DNA. Instead, PycnogenolRfacilitates the PLIN2 mRNA degradation, leading to suppression of lipid accumulation. This effect seems to be independent of antioxidant effect of PycnogenolR.We raise the idea that PLIN2 is a putative target molecule for prevention of pathological condition induced by excessive lipid accumulation, and this class of natural compounds could be putative therapeutic modalities.Key words: PycnogenolR, lipid droplet, perilipin, fatty liver disease

The multiple facets of Peto's paradox: a life-history model for the evolution of cancer suppression.

Science.gov (United States)

Brown, Joel S; Cunningham, Jessica J; Gatenby, Robert A

2015-07-19

Large animals should have higher lifetime probabilities of cancer than small animals because each cell division carries an attendant risk of mutating towards a tumour lineage. However, this is not observed--a (Peto's) paradox that suggests large and/or long-lived species have evolved effective cancer suppression mechanisms. Using the Euler-Lotka population model, we demonstrate the evolutionary value of cancer suppression as determined by the 'cost' (decreased fecundity) of suppression verses the 'cost' of cancer (reduced survivorship). Body size per se will not select for sufficient cancer suppression to explain the paradox. Rather, cancer suppression should be most extreme when the probability of non-cancer death decreases with age (e.g. alligators), maturation is delayed, fecundity rates are low and fecundity increases with age. Thus, the value of cancer suppression is predicted to be lowest in the vole (short lifespan, high fecundity) and highest in the naked mole rat (long lived with late female sexual maturity). The life history of pre-industrial humans likely selected for quite low levels of cancer suppression. In modern humans that live much longer, this level results in unusually high lifetime cancer risks. The model predicts a lifetime risk of 49% compared with the current empirical value of 43%. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Predicting the combinatorial effects of water activity, pH and organic acids on Listeria growth in media and complex food matrices.

Science.gov (United States)

Nyhan, L; Begley, M; Mutel, A; Qu, Y; Johnson, N; Callanan, M

2018-09-01

The aim of this study was to develop a model to predict growth of Listeria in complex food matrices as a function of pH, water activity and undissociated acetic and propionic acid concentration i.e. common food hurdles. Experimental growth curves of Listeria in food products and broth media were collected from ComBase, the literature and industry sources from which a bespoke secondary gamma model was constructed. Model performance was evaluated by comparing predictions to measured growth rates in growth media (BHI broth) and two adjusted food matrices (zucchini purée and béarnaise sauce). In general, observed growth rates were higher in broth than in the food matrices which resulted in the model over-estimating growth in the adjusted food matrices. In addition, model outputs were more accurate for conditions without acids, indicating that the organic acid component of the model was a source of inaccuracy. In summary, a new predictive growth model for innovating or renovating food products that rely on multi-hurdle technology was created. This study is the first to report on modelling of propionic acid as an inhibitor of Listeria in combination with other hurdles. Our findings provide valuable insights into predictive model design and performance and highlight the importance of experimental validation of models in real food matrices rather than laboratory media alone. Copyright © 2018 Elsevier Ltd. All rights reserved.

Soluble Suppression of Tumorigenicity-2 Predicts Hospital Mortality in Burn Patients: An Observational Prospective Cohort Pilot Study.

Science.gov (United States)

Ruiz-Castilla, Mireia; Bosacoma, Pau; Dos Santos, Bruce; Baena, Jacinto; Guilabert, Patricia; Marin-Corral, Judith; Masclans, Joan R; Roca, Oriol; Barret, Juan P

2018-04-10

The IL33/ST2 pathway has been implicated in the pathogenesis of different inflammatory diseases. Our aim was to analyze whether plasma levels of biomarkers involved in the IL33/ST2 axis might help to predict mortality in burn patients. Single-center prospective observational cohort pilot study performed at the Burns Unit of the Plastic and Reconstructive Surgery Department of the Vall d'Hebron University Hospital (Barcelona). All patients aged ≥18 years old with second or third-degree burns requiring admission to the Burns Unit were considered for inclusion. Blood samples were taken to measure levels of interleukins (IL)6, IL8, IL33, and soluble suppression of tumorigenicity-2 (sST2) within 24 h of admission to the Burns Unit and at day 3. Results are expressed as medians and interquartile ranges or as frequencies and percentages. Sixty-nine patients (58 [84.1%] male, mean age 52 [35-63] years, total body surface area burned 21% [13%-30%], Abbreviated Burn Severity Index 6 [4-8]) were included. Thirteen (18.8%) finally died in the Burns Unit. Plasma levels of sST2 measured at day 3 after admission demonstrated the best prediction accuracy for survival (area under the ROC curve 0.85 [0.71-0.99]; P < 0.001). The best cutoff point for the AUROC index was estimated to be 2,561. In the Cox proportional hazards model, after adjusting for potential confounding, a plasma sST2 level ≥2,561 measured at day 3 was significantly associated with mortality (HR 6.94 [1.73-27.74]; P = 0.006). Plasma sST2 at day 3 predicts hospital mortality in burn patients.

Prediction of valid acidity in intact apples with Fourier transform near infrared spectroscopy*

OpenAIRE

Liu, Yan-de; Ying, Yi-bin; Fu, Xia-ping

2005-01-01

To develop nondestructive acidity prediction for intact Fuji apples, the potential of Fourier transform near infrared (FT-NIR) method with fiber optics in interactance mode was investigated. Interactance in the 800 nm to 2619 nm region was measured for intact apples, harvested from early to late maturity stages. Spectral data were analyzed by two multivariate calibration techniques including partial least squares (PLS) and principal component regression (PCR) methods. A total of 120 Fuji appl...

Tumor necrosis factor alpha is associated with insulin-mediated suppression of free fatty acids and net lipid oxidation in HIV-infected patients with lipodystrophy

DEFF Research Database (Denmark)

Haugaard, SB; Andersen, O; Pedersen, Steen Bønløkke

2006-01-01

Tumor necrosis factor alpha (TNF-alpha) stimulates lipolysis in man. We examined whether plasma TNF-alpha is associated with the degree by which insulin suppresses markers of lipolysis, for example, plasma free fatty acid (FFA) and net lipid oxidation (LIPOX) rate in HIV-infected patients...... with lipodystrophy (LIPO) and those without (controls). LIPOX was estimated by indirect calorimetry during fasting and steady state of a hyperinsulinemic euglycemic clamp in 36 (18 LIPO and 18 controls) normoglycemic HIV-infected men on highly active antiretroviral therapy. In LIPO, TNF-alpha correlated with clamp...... were significant in controls. In all patients, TNF-alpha correlated with clamp FFA (r = 0.61, P

THE PREDICTIVE VALUE OF SERUM URIC ACID FOR THE OCCURRENCE, SEVERITY AND OUTCOMES OF PRE-ECLAMPSIA AMONG PARTURIENTS AT NNEWI, NIGERIA.

Science.gov (United States)

Osakwe, Chukwudi Richmond; Ikpeze, Okechukwu C; Ezebialu, Ifeanyi Uzoma; Osakwe, Joy Oluchi; Mbadugha, Norah Nwadiogo

2015-01-01

To determine the predictive value of serum uric acid for preeclampsia, its severity and pregnancy outcome. This is a cohort study that was performed on normal pregnant women attending antenatal clinic at Nnamdi Azikiwe University Teaching Hospital Nnewi Nigeria. Serum uric acid was determined in 200 women attending antenatal clinic between the gestational ages of 14 and 26 weeks. The women were followed up at 2 weekly intervals until 36 weeks and weekly thereafter until delivery. Women who developed pre-eclampsia or eclampsia were identified. Pregnancy outcomes were determined as well as fetal and placental weights. The data was analised with SPSS version 16.0. The chi square was used for test of significance. The positive and negative predictive values were determined. A total of 200 normal pregnant women were recruited for the study. Nine of them were lost to follow up. Subsequently, 10.5% of the women developed preeclampsia. The positive and negative predictive values of serum uric acid for preeclampsia were 78.9% and 97.1%, respectively. Serum uric acid was found to be a useful predictor of the occurrence of preeclampsia and its severity.

The Role of Geochemical Modeling in Predicting Quality Evolution of Acid Mine Drainage

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Andrea Šlesárová

2004-12-01

Full Text Available In recent years the massive reduction of raw materials production brings a wide scale of problems. Among the most frequent exposes of mining activities belong besides old spoil heaps and sludge lagoons, also the drainage of acidic and highly mineralized mine waters known as “the Acid Mine Drainage” (thereinafter AMD from old mine workings. The acid mine drainage presents to the surrounding environment a massive problem. These waters are toxic to the plant and animal life, including fishes and aquatic insects. The primary control of the drainage pH and the metal content is the exposure of sulphide minerals to weathering, the availability of atmospheric oxygen, and the sensitivity of non-sulphide minerals to buffer acidity. A geochemical modeling software is increasingly used to solve evolution of the complex chemical systems such as the interaction of acid mine drainage with wall rocks, migration of AMD components. Beyond the better computer facilities it allows to study of thermodynamic properties substances and to enlarge thermodynamic databases. A model is a simplified version of reality based on its observation and experiments. A goal of the modeling process is the tendency to better understand processes taking place inside of the system, the attempt to assume the system’s behaviour in the future or to predict the effect of changed conditions in the system’s environment on the system itself.

Active Suppression of Rotating Stall Inception with Distributed Jet Actuation

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Huu Duc Vo

2007-01-01

Full Text Available An analytical and experimental investigation of the effectiveness of full-span distributed jet actuation for active suppression of long length-scale rotating stall inception is carried out. Detailed modeling and experimental verification highlight the important effects of mass addition, discrete injectors, and feedback dynamics, which may be overlooked in preliminary theoretical studies of active control with jet injection. A model of the compression system incorporating nonideal injection and feedback dynamics is verified with forced response measurements to predict the right trends in the movement of the critical pole associated with the stall precursor. Active control experiments with proportional feedback control show that the predicted stall precursors are suppressed to give a 5.5% range extension in compressor flow coefficient. In addition, results suggest that the proposed model could be used to design a more sophisticated controller to further improve performance while reducing actuator bandwidth requirements.

Suppressive role of OGT-mediated O-GlcNAcylation of BAP1 in retinoic acid signaling.

Science.gov (United States)

Moon, Seungtae; Lee, Yong-Kyu; Lee, Sang-Wang; Um, Soo-Jong

2017-10-07

BRCA1-associated protein 1 (BAP1) has been implicated in diverse biological functions, including tumor suppression. However, its regulation via glycosylation and its role in embryonic stem (ES) cells are poorly defined. BAP1 was recently reported to interact with O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT). Here, we confirmed the physical interaction and investigated its functional significance. The O-GlcNAcylation of BAP1, which requires OGT, was examined in vivo and in vitro, and was proven using alloxan, an OGT inhibitor. OGT promoted the BAP1-induced repression of retinoic acid (RA)-induced RA receptor (RAR) activation. The repressive activity of BAP1 was relieved by alloxan but exacerbated by PUGNAc, an O-GlcNAcase (OGA) inhibitor. Finally, we addressed the role of O-GlcNAcylation in the RA-induced differentiation of murine ES cells. Alkaline phosphatase staining revealed the cooperation of RA and alloxan for impairing the pluripotency of ES cells. This cooperation was also observed by measuring the size of embryonic bodies and the expression of Sox2, a pluripotency marker. Overall, our data suggest that OGT-mediated O-GlcNAcylation of BAP1 prefers the maintenance of pluripotency, whereas its inhibition facilitates RA-induced differentiation in ES cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Suppression of umami aftertaste by polysaccharides in soy sauce.

Science.gov (United States)

Imamura, Miho; Matsushima, Kenichiro

2013-08-01

Umami is one of 5 basic tastes that make foods savory and palatable. The umami aftertaste is a long-lasting taste sensation that is important for Japanese broth (dashi) utilized for various Japanese foods. Soy sauce is usually added when making dashi-based dishes; however, different soy sauces produce distinct effects on the umami aftertaste. In this study, we attempted to identify the substances that cause the suppression of the umami aftertaste in soy sauce by combining sensory analysis, size fractionation, chemical analysis, and enzymatic treatment. The suppressive substance was revealed to be polysaccharides with molecular weights between 44900 and 49700. The results of acid hydrolysis and enzymatic treatment suggested that the polysaccharides were cellulose. These results indicate that a type of water-soluble cellulose derived from soybean, wheat, or microorganisms has a suppressive effect on the umami aftertaste of soy sauce. Future studies should focus on developing a strategy that regulates the amount of these polysaccharides generated during soy sauce production, to maintain or enhance the umami aftertaste. © 2013 Institute of Food Technologists®

Citric Acid Metabolism in Resistant Hypertension: Underlying Mechanisms and Metabolic Prediction of Treatment Response.

Science.gov (United States)

Martin-Lorenzo, Marta; Martinez, Paula J; Baldan-Martin, Montserrat; Ruiz-Hurtado, Gema; Prado, Jose Carlos; Segura, Julian; de la Cuesta, Fernando; Barderas, Maria G; Vivanco, Fernando; Ruilope, Luis Miguel; Alvarez-Llamas, Gloria

2017-11-01

Resistant hypertension (RH) affects 9% to 12% of hypertensive adults. Prolonged exposure to suboptimal blood pressure control results in end-organ damage and cardiovascular risk. Spironolactone is the most effective drug for treatment, but not all patients respond and side effects are not negligible. Little is known on the mechanisms responsible for RH. We aimed to identify metabolic alterations in urine. In addition, a potential capacity of metabolites to predict response to spironolactone was investigated. Urine was collected from 29 patients with RH and from a group of 13 subjects with pseudo-RH. For patients, samples were collected before and after spironolactone administration and were classified in responders (n=19) and nonresponders (n=10). Nuclear magnetic resonance was applied to identify altered metabolites and pathways. Metabolites were confirmed by liquid chromatography-mass spectrometry. Citric acid cycle was the pathway most significantly altered ( P citric acid cycle and deregulation of reactive oxygen species homeostasis control continue its activation after hypertension was developed. A metabolic panel showing alteration before spironolactone treatment and predicting future response of patients is shown. These molecular indicators will contribute optimizing the rate of control of RH patients with spironolactone. © 2017 American Heart Association, Inc.

Hydroxysafflor yellow A suppress oleic acid-induced acute lung injury via protein kinase A

International Nuclear Information System (INIS)

Wang, Chaoyun; Huang, Qingxian; Wang, Chunhua; Zhu, Xiaoxi; Duan, Yunfeng; Yuan, Shuai; Bai, Xianyong

2013-01-01

Inflammation response and oxidative stress play important roles in acute lung injury (ALI). Activation of the cAMP/protein kinase A (PKA) signaling pathway may attenuate ALI by suppressing immune responses and inhibiting the generation of reactive oxygen species (ROS). Hydroxysafflor yellow A (HSYA) is a natural flavonoid compound that reduces oxidative stress and inflammatory cytokine-mediated damage. In this study, we examined whether HSYA could protect the lungs from oleic acid (OA)-induced injury, which was used to mimic ALI, and determined the role of the cAMP/PKA signaling pathway in this process. Arterial oxygen tension (PaO 2 ), carbon dioxide tension, pH, and the PaO 2 /fraction of inspired oxygen ratio in the blood were detected using a blood gas analyzer. We measured wet/dry lung weight ratio and evaluated tissue morphology. The protein and inflammatory cytokine levels in the bronchoalveolar lavage fluid and serum were determined using enzyme-linked immunoassay. The activities of superoxide dismutase, glutathione peroxidase, PKA, and nicotinamide adenine dinucleotide phosphate oxidase, and the concentrations of cAMP and malondialdehyde in the lung tissue were detected using assay kits. Bcl-2, Bax, caspase 3, and p22 phox levels in the lung tissue were analyzed using Western blotting. OA increased the inflammatory cytokine and ROS levels and caused lung dysfunction by decreasing cAMP synthesis, inhibiting PKA activity, stimulating caspase 3, and reducing the Bcl-2/Bax ratio. H-89 increased these effects. HSYA significantly increased the activities of antioxidant enzymes, inhibited the inflammatory response via cAMP/PKA pathway activation, and attenuated OA-induced lung injury. Our results show that the cAMP/PKA signaling pathway is required for the protective effect of HSYA against ALI. - Highlights: • Oleic acid (OA) cause acute lung injury (ALI) via inhibiting cAMP/PKA signal pathway. • Blocking protein kinase A (PKA) activation may enhance Cytokine

Retinoid acid-induced microRNA-27b-3p impairs C2C12 myoblast proliferation and differentiation by suppressing α-dystrobrevin

Energy Technology Data Exchange (ETDEWEB)

Li, Nan; Tang, Yi; Liu, Bo; Cong, Wei; Liu, Chao, E-mail: liuchao_19760711@yahoo.com; Xiao, Jing, E-mail: xiaoj@dmu.edu.cn

2017-01-15

We previously reported that excess retinoic acid (RA) resulted in hypoplastic and derangement of myofilaments in embryonic tongue by inhibiting myogenic proliferation and differentiation through CamKIID pathway. Our further studies revealed that the expression of a series of miRNAs was altered by RA administration in embryonic tongue as well as in C2C12 cells. Thus, if excess RA impairs myogenic proliferation and differentiation through miRNAs is taken into account. In present study, miR-27b-3p was found up-regulated in RA-treated C2C12 cells as in embryonic tongue, and predicted to target the 3′UTR of α-dystrobrevin (DTNA). Luciferase reporter assays confirmed the direct interaction between miR-27b-3p and the 3′UTR of DTNA. MiR-27b-3p mimics recapitulated the RA repression on DTNA expression, C2C12 proliferation and differentiation, while the miR-27b-3p inhibitor circumvented these defects resulting from excess RA. As expected, the effects of siDTNA on C2C12 were coincided with those by RA treatment or miR-27b-3p mimics. Therefore, these findings indicated that excess RA inhibited the myoblast proliferation and differentiation by up-regulating miR-27b-3p to target DTNA, which implied a new mechanism in myogenic hypoplasia. - Highlights: • A mechanism that RA results in tongue deformity by disrupting the myogenesis. • A non-muscle specific miR mediating the RA suppression on tongue myogenesis. • A target gene of non-muscle specific miR involved in RA induced tongue deformity.

Gallic acid suppresses cell viability, proliferation, invasion and angiogenesis in human glioma cells

OpenAIRE

Lu, Yong; Jiang, Feng; Jiang, Hao; Wu, Kalina; Zheng, Xuguang; Cai, Yizhong; Katakowski, Mark; Chopp, Michael; To, Shing-Shun Tony

2010-01-01

Gallic acid, an organic acid, also known as 3,4,5-trihydroxybenzoic acid, is cytotoxic against certain cancer cells, without harming normal cells. The objective of this study is to evaluate whether gallic acid can inhibit glioma cell viability, proliferation, invasion and reduce glioma cell mediated angiogenesis. Treatment of U87 and U251n glioma cells with gallic acid inhibited cell viability in a dose- and time-dependent manner. BrdU and tube formation assays indicated that gallic acid sign...

Suppressive composts: microbial ecology links between abiotic environments and healthy plants.

Science.gov (United States)

Hadar, Yitzhak; Papadopoulou, Kalliope K

2012-01-01

Suppressive compost provides an environment in which plant disease development is reduced, even in the presence of a pathogen and a susceptible host. Despite the numerous positive reports, its practical application is still limited. The main reason for this is the lack of reliable prediction and quality control tools for evaluation of the level and specificity of the suppression effect. Plant disease suppression is the direct result of the activity of consortia of antagonistic microorganisms that naturally recolonize the compost during the cooling phase of the process. Thus, it is imperative to increase the level of understanding of compost microbial ecology and population dynamics. This may lead to the development of an ecological theory for complex ecosystems as well as favor the establishment of hypothesis-driven studies.

Durability and service life prediction of GFRP bars embedded in concrete under acid environment

Energy Technology Data Exchange (ETDEWEB)

Zhou Jikai, E-mail: jkzhou@hotmail.com [College of Civil and Transportation Engineering, Hohai University, Nanjing, Jiangsu 210098 (China); Chen Xudong, E-mail: cxdong1985@hotmail.com [College of Civil and Transportation Engineering, Hohai University, Nanjing, Jiangsu 210098 (China); Chen Shixue, E-mail: 710567525@qq.com [College of Civil and Transportation Engineering, Hohai University, Nanjing, Jiangsu 210098 (China)

2011-10-15

Highlights: > Bond strength of GFRP bars decrease with an increase in pH of acid solutions. > Bond strength of steel bars decrease with an increase in pH of acid solutions. > Durability of GFRP bars could be predicted by modified Arrhenius relation. - Abstract: In recent years, glass fiber reinforcing polymers (GFRP) has emerged as an alternative to conventional steel reinforcing bars in concrete structures. The bond behavior of GFRP bars to concrete under acidic environment is important because of increasing acid rain in China nowadays. This paper presents an experimental investigation into comparison of the durability of the bond between GFRP and steel bars to concrete under acid environment. The specimens were subject to corrosion by immersion in acid solutions with different concentration. One hundred and twenty pullout specimens were used to study the effect of different environment on bond strength of GFRP and steel bars to concrete. Experimental results showed that, For GFRP bars, at the end of 75 days of conditioning duration, maximum bond strength loss of 11%, 22%, 17.2% and 14% were observed in tap water, pH = 2, pH = 3, and pH = 4 environment, respectively. For steel bars, at the end of 75 days of conditioning duration, maximum bond strength loss of 19.6% and 12.3% were observed in pH = 2 and pH = 3 environment, respectively. The influence of solution concentration on bond strength of GFRP bars was determined using Arrhenius equation and time shift method (TSF).

The Use of Wetting Agents/Fume Suppressants for Minimizing the Atmospheric Emissions from Hard Chromium Electroplating Baths

Science.gov (United States)

2004-03-01

PFOA), perfluorooctane sulphonic acid (PFOSA) and clofibric acid . Biochim Biophys Acta 1128: 65-72 Kannan K, Koistinen J, Beckmen K, Evans T...mg/dscm (6.6 x 10-6 gr/dscf) Decorative Chromium Plating Baths Using Chromic Acid All new and existing baths 0.01 mg/dscm (4.4 x 10-6 gr/dscf...surface of the baths, causing the production of chromic acid mist. “Surface active” fume suppressants (also called surfactants) are added directly

CSF 5-HIAA and DST non-suppression--orthogonal biologic risk factors for suicide in male mood disorder inpatients.

Science.gov (United States)

Jokinen, Jussi; Nordström, Anna-Lena; Nordström, Peter

2009-01-30

Two biomarkers of suicide risk; non-suppression in the dexamethasone suppression test (DST) and low 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) have been reported to be predictors of suicide in mood disorders. The interrelation of the two systems seems to be different in suicide attempters compared with depressed inpatients who have not made a suicide attempt, indicating that the two biomarkers may be seen as independent. This investigation examined the interrelation of low CSF 5-HIAA and DST non-suppression in suicide victims with mood disorder. Fifty-eight mood disorder inpatients not receiving any treatment with antidepressants underwent lumbar puncture and the DST. Plasma cortisol levels at 8:00 a.m., 4:00 p.m. and 11:00 p.m. were analysed in relation to CSF 5-HIAA. All patients were followed up for causes of death and suicides were verified with death certificates. During follow-up (mean 21 years), 11 (19%) patients had committed suicide. In male suicide victims (n=6), the serum cortisol level at 4:00 p.m. showed a significant positive correlation with CSF 5-HIAA. Low CSF 5-HIAA predicted all early suicides (within 1 year), whereas all males who committed suicide after 1 year were DST non-suppressors. In female suicide victims (n=5), the post-DST serum cortisol did not correlate with CSF 5-HIAA. Low CSF 5-HIAA and DST non-suppression are orthogonal biologic risk factors for suicide in male mood disorder inpatients. CSF 5-HIAA is associated with short-term suicide risk; dysregulation of the hypothalamic-pituitary-adrenal axis seems to be a long-term suicide predictor.

Measured and simulated performance of Compton-suppressed TIGRESS HPGe clover detectors

Science.gov (United States)

Schumaker, M. A.; Hackman, G.; Pearson, C. J.; Svensson, C. E.; Andreoiu, C.; Andreyev, A.; Austin, R. A. E.; Ball, G. C.; Bandyopadhyay, D.; Boston, A. J.; Chakrawarthy, R. S.; Churchman, R.; Drake, T. E.; Finlay, P.; Garrett, P. E.; Grinyer, G. F.; Hyland, B.; Jones, B.; Maharaj, R.; Morton, A. C.; Phillips, A. A.; Sarazin, F.; Scraggs, H. C.; Smith, M. B.; Valiente-Dobón, J. J.; Waddington, J. C.; Watters, L. M.

2007-01-01

Tests of the performance of a 32-fold segmented HPGe clover detector coupled to a 20-fold segmented Compton-suppression shield, which form a prototype element of the TRIUMF-ISAC Gamma-Ray Escape-Suppressed Spectrometer (TIGRESS), have been made. Peak-to-total ratios and relative efficiencies have been measured for a variety of γ-ray energies. These measurements were used to validate a GEANT4 simulation of the TIGRESS detectors, which was then used to create a simulation of the full 12-detector array. Predictions of the expected performance of TIGRESS are presented. These predictions indicate that TIGRESS will be capable, for single 1 MeV γ rays, of absolute detection efficiencies of 17% and 9.4%, and peak-to-total ratios of 54% and 61% for the "high-efficiency" and "optimized peak-to-total" configurations of the array, respectively.

Short communication: Prediction of milk coagulation and acidity traits in Mediterranean buffalo milk using Fourier-transform mid-infrared spectroscopy.

Science.gov (United States)

Manuelian, C L; Visentin, G; Boselli, C; Giangolini, G; Cassandro, M; De Marchi, M

2017-09-01

Milk coagulation and acidity traits are important factors to inform the cheesemaking process. Those traits have been deeply studied in bovine milk, whereas scarce information is available for buffalo milk. However, the dairy industry is interested in a method to determine milk coagulation and acidity features quickly and in a cost-effective manner, which could be provided by Fourier-transform mid-infrared (FT-MIR) spectroscopy. The aim of this study was to evaluate the potential of FT-MIR to predict coagulation and acidity traits of Mediterranean buffalo milk. A total of 654 records from 36 herds located in central Italy with information on milk yield, somatic cell score, milk chemical composition, milk acidity [pH, titratable acidity (TA)], and milk coagulation properties (rennet coagulation time, curd firming time, and curd firmness) were available for statistical analysis. Reference measures of milk acidity and coagulation properties were matched with milk spectral information, and FT-MIR prediction models were built using partial least squares regression. The data set was divided into a calibration set (75%) and a validation set (25%). The capacity of FT-MIR spectroscopy to correctly classify milk samples based on their renneting ability was evaluated by a canonical discriminant analysis. Average values for milk coagulation traits were 13.32 min, 3.24 min, and 39.27 mm for rennet coagulation time, curd firming time, and curd firmness, respectively. Milk acidity traits averaged 6.66 (pH) and 7.22 Soxhlet-Henkel degrees/100 mL (TA). All milk coagulation and acidity traits, except for pH, had high variability (17 to 46%). Prediction models of coagulation traits were moderately to scarcely accurate, whereas the coefficients of determination of external validation were 0.76 and 0.66 for pH and TA, respectively. Canonical discriminant analysis indicated that information on milk coagulating ability is present in the MIR spectra, and the model correctly classified as

Variation in plant defense suppresses herbivore performance

Science.gov (United States)

Pearse, Ian; Paul, Ryan; Ode, Paul J.

2018-01-01

Defensive variability of crops and natural systems can alter herbivore communities and reduce herbivory. However, it is still unknown how defense variability translates into herbivore suppression. Nonlinear averaging and constraints in physiological tracking (also more generally called time-dependent effects) are the two mechanisms by which defense variability might impact herbivores. We conducted a set of experiments manipulating the mean and variability of a plant defense, showing that defense variability does suppress herbivore performance and that it does so through physiological tracking effects that cannot be explained by nonlinear averaging. While nonlinear averaging predicted higher or the same herbivore performance on a variable defense than on an invariable defense, we show that variability actually decreased herbivore performance and population growth rate. Defense variability reduces herbivore performance in a way that is more than the average of its parts. This is consistent with constraints in physiological matching of detoxification systems for herbivores experiencing variable toxin levels in their diet and represents a more generalizable way of understanding the impacts of variability on herbivory. Increasing defense variability in croplands at a scale encountered by individual herbivores can suppress herbivory, even if that is not anticipated by nonlinear averaging.

Experimental Status Of $J/\\psi$ Suppression

CERN Document Server

Kluberg, L; Alessandro, B; Alexa, C; Arnaldi, R; Astruc, J; Atayan, M; Baglin, C; Baldit, A; Bedjidian, M; Bellaiche, F; Beolè, S; Boldea, V; Bordalo, P; Bussière, A; Capelli,L; Capony, V; Casagrande, L; Castor, J; Chambon, T; Chaurand, B; Chevrot, I; Cheynis, B; Chiavassa, E; Cicalò, C; Comets, M P; Constans, N; Constantinescu, S; Cruz, J; De Falco, A; De Marco, N; Dellacasa, G; Devaux, A; Dita, S; Drapier, O; Ducroux, L; Espagnon, B; Fargeix, J; Filippov, S N; Fleuret, F; Force, P; Gallio, M; Gavrilov, Y K; Gerschel, C; Giubellino, P; Golubeva, M B; Gonin, M; Grigorian, A A; Grossiord, J Y; Guber, F F; Guichard, A; Gulkanyan, H; Hakobyan, R; Haroutunian, R; Idzik, M; Jouan, D; Karavitcheva, T L; Kurepin, A B; Le Bornec, Y; Lourenrço, C; Macciotta, P; Mac Cormick, M; Marzari- Chiesa, A; Masera, M; Masoni, A; Mehrabyan, S; Monteno, M; Mourgues, S; Musso, A; Ohlsson-Malek, F; Petiau, P; Piccotti, A; Pizzi, J R; Prado da Silva, W L; Puddu, G; Quintans, C; Racca, C; Ramello, L; Ramos, S; Rato-Mendes, P; Riccati, L; Romana, A; Ropotar, I; Saturnini, P; Scomparin, E; Serci, S; Shahoyan, R; Silva, S; Sitta, M; Soave, C; Sonderegger, P; Tarrago, X; Topilskaya, N S; Usai, G L; Vercellin, E; Villatte, L; Willis, N

2001-01-01

The most recent results obtained by experiment NA50 show that the $J /\\psi$ cross-section per nucleon-nucleon collision in semi-peripheral Pb-Pb reactions is "normally" suppressed in the sense that it follows the trend already observed from p-p and up to the most central S-U reactions. A clear change of behaviour is observed for more central Pb-Pb collisions which could be due to the transition of normal nuclear matter to its predicted Quark-Gluon Plasma state

Accurate prediction of hot spot residues through physicochemical characteristics of amino acid sequences

KAUST Repository

Chen, Peng; Li, Jinyan; Limsoon, Wong; Kuwahara, Hiroyuki; Huang, Jianhua Z.; Gao, Xin

2013-01-01

Hot spot residues of proteins are fundamental interface residues that help proteins perform their functions. Detecting hot spots by experimental methods is costly and time-consuming. Sequential and structural information has been widely used in the computational prediction of hot spots. However, structural information is not always available. In this article, we investigated the problem of identifying hot spots using only physicochemical characteristics extracted from amino acid sequences. We first extracted 132 relatively independent physicochemical features from a set of the 544 properties in AAindex1, an amino acid index database. Each feature was utilized to train a classification model with a novel encoding schema for hot spot prediction by the IBk algorithm, an extension of the K-nearest neighbor algorithm. The combinations of the individual classifiers were explored and the classifiers that appeared frequently in the top performing combinations were selected. The hot spot predictor was built based on an ensemble of these classifiers and to work in a voting manner. Experimental results demonstrated that our method effectively exploited the feature space and allowed flexible weights of features for different queries. On the commonly used hot spot benchmark sets, our method significantly outperformed other machine learning algorithms and state-of-the-art hot spot predictors. The program is available at http://sfb.kaust.edu.sa/pages/software.aspx. © 2013 Wiley Periodicals, Inc.

Accurate prediction of hot spot residues through physicochemical characteristics of amino acid sequences

KAUST Repository

Chen, Peng

2013-07-23

Hot spot residues of proteins are fundamental interface residues that help proteins perform their functions. Detecting hot spots by experimental methods is costly and time-consuming. Sequential and structural information has been widely used in the computational prediction of hot spots. However, structural information is not always available. In this article, we investigated the problem of identifying hot spots using only physicochemical characteristics extracted from amino acid sequences. We first extracted 132 relatively independent physicochemical features from a set of the 544 properties in AAindex1, an amino acid index database. Each feature was utilized to train a classification model with a novel encoding schema for hot spot prediction by the IBk algorithm, an extension of the K-nearest neighbor algorithm. The combinations of the individual classifiers were explored and the classifiers that appeared frequently in the top performing combinations were selected. The hot spot predictor was built based on an ensemble of these classifiers and to work in a voting manner. Experimental results demonstrated that our method effectively exploited the feature space and allowed flexible weights of features for different queries. On the commonly used hot spot benchmark sets, our method significantly outperformed other machine learning algorithms and state-of-the-art hot spot predictors. The program is available at http://sfb.kaust.edu.sa/pages/software.aspx. © 2013 Wiley Periodicals, Inc.

Accurate prediction of hot spot residues through physicochemical characteristics of amino acid sequences.

Science.gov (United States)

Chen, Peng; Li, Jinyan; Wong, Limsoon; Kuwahara, Hiroyuki; Huang, Jianhua Z; Gao, Xin

2013-08-01

Hot spot residues of proteins are fundamental interface residues that help proteins perform their functions. Detecting hot spots by experimental methods is costly and time-consuming. Sequential and structural information has been widely used in the computational prediction of hot spots. However, structural information is not always available. In this article, we investigated the problem of identifying hot spots using only physicochemical characteristics extracted from amino acid sequences. We first extracted 132 relatively independent physicochemical features from a set of the 544 properties in AAindex1, an amino acid index database. Each feature was utilized to train a classification model with a novel encoding schema for hot spot prediction by the IBk algorithm, an extension of the K-nearest neighbor algorithm. The combinations of the individual classifiers were explored and the classifiers that appeared frequently in the top performing combinations were selected. The hot spot predictor was built based on an ensemble of these classifiers and to work in a voting manner. Experimental results demonstrated that our method effectively exploited the feature space and allowed flexible weights of features for different queries. On the commonly used hot spot benchmark sets, our method significantly outperformed other machine learning algorithms and state-of-the-art hot spot predictors. The program is available at http://sfb.kaust.edu.sa/pages/software.aspx. Copyright © 2013 Wiley Periodicals, Inc.

Burst suppression probability algorithms: state-space methods for tracking EEG burst suppression

Science.gov (United States)

Chemali, Jessica; Ching, ShiNung; Purdon, Patrick L.; Solt, Ken; Brown, Emery N.

2013-10-01

Objective. Burst suppression is an electroencephalogram pattern in which bursts of electrical activity alternate with an isoelectric state. This pattern is commonly seen in states of severely reduced brain activity such as profound general anesthesia, anoxic brain injuries, hypothermia and certain developmental disorders. Devising accurate, reliable ways to quantify burst suppression is an important clinical and research problem. Although thresholding and segmentation algorithms readily identify burst suppression periods, analysis algorithms require long intervals of data to characterize burst suppression at a given time and provide no framework for statistical inference. Approach. We introduce the concept of the burst suppression probability (BSP) to define the brain's instantaneous propensity of being in the suppressed state. To conduct dynamic analyses of burst suppression we propose a state-space model in which the observation process is a binomial model and the state equation is a Gaussian random walk. We estimate the model using an approximate expectation maximization algorithm and illustrate its application in the analysis of rodent burst suppression recordings under general anesthesia and a patient during induction of controlled hypothermia. Main result. The BSP algorithms track burst suppression on a second-to-second time scale, and make possible formal statistical comparisons of burst suppression at different times. Significance. The state-space approach suggests a principled and informative way to analyze burst suppression that can be used to monitor, and eventually to control, the brain states of patients in the operating room and in the intensive care unit.

Suppression dampens unpleasant emotion faster than reappraisal: Neural dynamics in a Chinese sample.

Science.gov (United States)

Yuan, JiaJin; Long, QuanShan; Ding, NanXiang; Lou, YiXue; Liu, YingYing; Yang, JieMin

2015-05-01

The timing dynamics of regulating negative emotion with expressive suppression and cognitive reappraisal were investigated in a Chinese sample. Event-Related Potentials were recorded while subjects were required to view, suppress emotion expression to, or reappraise emotional pictures. The results showed a similar reduction in self-reported negative emotion during both strategies. Additionally, expressive suppression elicited larger amplitudes than reappraisal in central-frontal P3 component (340-480 ms). More importantly, the Late Positive Potential (LPP) amplitudes were decreased in each 200 ms of the 800-1600 ms time intervals during suppression vs. viewing conditions. In contrast, LPP amplitudes were similar for reappraisal and viewing conditions in all the time windows, except for the decreased amplitudes during reappraisal in the 1400-1600 ms. The LPP (but not P3) amplitudes were positively related to negative mood ratings, whereas the amplitudes of P3, rather than LPP, predict self-reported expressive suppression. These results suggest that expressive suppression decreases emotion responding more rapidly than reappraisal, at the cost of greater cognitive resource involvements in Chinese individuals.

Silverleaf whitefly induces salicylic acid defenses and suppresses effectual jasmonic acid defenses.

Science.gov (United States)

Zarate, Sonia I; Kempema, Louisa A; Walling, Linda L

2007-02-01

The basal defenses important in curtailing the development of the phloem-feeding silverleaf whitefly (Bemisia tabaci type B; SLWF) on Arabidopsis (Arabidopsis thaliana) were investigated. Sentinel defense gene RNAs were monitored in SLWF-infested and control plants. Salicylic acid (SA)-responsive gene transcripts accumulated locally (PR1, BGL2, PR5, SID2, EDS5, PAD4) and systemically (PR1, BGL2, PR5) during SLWF nymph feeding. In contrast, jasmonic acid (JA)- and ethylene-dependent RNAs (PDF1.2, VSP1, HEL, THI2.1, FAD3, ERS1, ERF1) were repressed or not modulated in SLWF-infested leaves. To test for a role of SA and JA pathways in basal defense, SLWF development on mutant and transgenic lines that constitutively activate or impair defense pathways was determined. By monitoring the percentage of SLWF nymphs in each instar, we show that mutants that activate SA defenses (cim10) or impair JA defenses (coi1) accelerated SLWF nymphal development. Reciprocally, mutants that activate JA defenses (cev1) or impair SA defenses (npr1, NahG) slowed SLWF nymphal development. Furthermore, when npr1 plants, which do not activate downstream SA defenses, were treated with methyl jasmonate, a dramatic delay in nymph development was observed. Collectively, these results showed that SLWF-repressed, JA-regulated defenses were associated with basal defense to the SLWF.

Analysis of nine food additives in red wine by ion-suppression reversed-phase high-performance liquid chromatography using trifluoroacetic acid and ammonium acetate as ion-suppressors.

Science.gov (United States)

Zhao, Yong-Gang; Chen, Xiao-Hong; Yao, Shan-Shan; Pan, Sheng-Dong; Li, Xiao-Ping; Jin, Mi-Cong

2012-01-01

A reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed for the simultaneous determination of nine food additives, i.e., acesulfame, saccharin, caffeine, aspartame, benzoic acid, sorbic acid, stevioside, dehydroacetic acid and neotame in red wine. The effects of ion-suppressors, i.e., trifluoroacetic acid (TFA) and ammonium acetate (AmAc) on retention behavior of nine food additives in RP-HPLC separation were discussed in detail. The relationships between retention factors of solutes and volume percent of ion-suppressors in the mobile-phase systems of acetonitrile-TFA aqueous solution and acetonitrile-TFA-AmAc aqueous solution were quantitatively established, respectively. The results showed that the ion suppressors had not only an ion suppression effect, but also an organic modification effect on the acidic analytes. The baseline separation of nine food additives was completed by a gradient elution with acetonitrile-TFA(0.01%, v/v)-AmAc(2.5 mmol L(-1)) aqueous solution as the mobile phase. The recoveries were between 80.2 - 99.5% for all analytes with RSDs in the range of 1.5 - 8.9%. The linearities were in the range of 0.2 - 100.0 mg L(-1) with determination coefficients (r(2)) higher than 0.9991 for all analytes. The limits of quantification (LOQs) were between 0.53 - 0.99 mg L(-1). The applicability of the proposed method to detect and quantify food additives has been demonstrated in the analysis of 30 real samples.

Trans-Fatty Acids Aggravate Obesity, Insulin Resistance and Hepatic Steatosis in C57BL/6 Mice, Possibly by Suppressing the IRS1 Dependent Pathway

Directory of Open Access Journals (Sweden)

Xiaona Zhao

2016-05-01

Full Text Available Trans-fatty acid consumption has been reported as a risk factor for metabolic disorders and targeted organ damages. Nonetheless, little is known about the roles and mechanisms of trans-fatty acids in obesity, insulin resistance (IR and hepatic steatosis. Adult C57BL/6 male mice were fed with four different diets for 20 weeks: normal diet (ND, high fat diet (HFD, low trans-fatty acids diet (LTD and high trans-fatty acid diet (HTD. The diet-induced metabolic disorders were assessed by evaluating body weight, glucose tolerance test, hepatic steatosis and plasma lipid profiles post 20-week diet. Histological (H&E, Oil-Red-O staining and western blot analysis were employed to assess liver steatosis and potential signaling pathways. After 20-weeks of diet, the body weights of the four groups were 29.61 ± 1.89 g (ND, 39.04 ± 4.27 g (HFD, 34.09 ± 2.62 g (LTD and 43.78 ± 4.27 g (HTD (p < 0.05, respectively. HFD intake significantly impaired glucose tolerance, which was impaired further in the mice consuming the HTD diet. The effect was further exacerbated by HTD diet. Moreover, the HTD group exhibited significantly more severe liver steatosis compared with HFD group possibly through regulating adipose triglyceride lipase. The group consuming the HTD also exhibited significantly reduced levels of IRS1, phosphor-PKC and phosphor-AKT. These results support our hypothesis that consumption of a diet high in trans-fatty acids induces higher rates of obesity, IR and hepatic steatosis in male C57BL/6 mice, possibly by suppressing the IRS1dependent pathway.

Limited sampling strategies drawn within 3 hours postdose poorly predict mycophenolic acid area-under-the-curve after enteric-coated mycophenolate sodium.

NARCIS (Netherlands)

Winter, B.C. de; Gelder, T. van; Mathôt, R.A.A.; Glander, P.; Tedesco-Silva, H.; Hilbrands, L.B.; Budde, K.; Hest, R.M. van

2009-01-01

Previous studies predicted that limited sampling strategies (LSS) for estimation of mycophenolic acid (MPA) area-under-the-curve (AUC(0-12)) after ingestion of enteric-coated mycophenolate sodium (EC-MPS) using a clinically feasible sampling scheme may have poor predictive performance. Failure of

Expressive Suppression of Emotions and Overeating in Individuals with Overweight and Obesity.

Science.gov (United States)

Görlach, Mirja Gianna; Kohlmann, Sebastian; Shedden-Mora, Meike; Rief, Winfried; Westermann, Stefan

2016-09-01

Emotions have a considerable impact on eating behaviour; however, research addressing emotion regulation in obesity is rare. The present study is the first to investigate the association between emotional suppression and overeating in individuals with overweight. In total, 314 participants including 190 individuals with obesity filled in a cross-sectional online survey, which assessed emotional suppression, eating behaviour and psychopathology. A hierarchical linear regression analysis was conducted to identify factors associated with overeating. Individuals with obesity reported more frequent overeating compared with individuals without obesity. The habitual use of emotional suppression was associated with more overeating; however, this link was moderated by increased body mass index (BMI). The results suggest that suppression of emotional expression contributes to overeating and is maladaptive especially in individuals with obesity. Further research should longitudinally investigate the predictive value of emotional suppression on overweight, as the training of emotion regulation could contribute to treating obesity. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

Prediction of flexible/rigid regions from protein sequences using k-spaced amino acid pairs

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Ruan Jishou

2007-04-01

Full Text Available Abstract Background Traditionally, it is believed that the native structure of a protein corresponds to a global minimum of its free energy. However, with the growing number of known tertiary (3D protein structures, researchers have discovered that some proteins can alter their structures in response to a change in their surroundings or with the help of other proteins or ligands. Such structural shifts play a crucial role with respect to the protein function. To this end, we propose a machine learning method for the prediction of the flexible/rigid regions of proteins (referred to as FlexRP; the method is based on a novel sequence representation and feature selection. Knowledge of the flexible/rigid regions may provide insights into the protein folding process and the 3D structure prediction. Results The flexible/rigid regions were defined based on a dataset, which includes protein sequences that have multiple experimental structures, and which was previously used to study the structural conservation of proteins. Sequences drawn from this dataset were represented based on feature sets that were proposed in prior research, such as PSI-BLAST profiles, composition vector and binary sequence encoding, and a newly proposed representation based on frequencies of k-spaced amino acid pairs. These representations were processed by feature selection to reduce the dimensionality. Several machine learning methods for the prediction of flexible/rigid regions and two recently proposed methods for the prediction of conformational changes and unstructured regions were compared with the proposed method. The FlexRP method, which applies Logistic Regression and collocation-based representation with 95 features, obtained 79.5% accuracy. The two runner-up methods, which apply the same sequence representation and Support Vector Machines (SVM and Naïve Bayes classifiers, obtained 79.2% and 78.4% accuracy, respectively. The remaining considered methods are

[EFFECT OF α-LIPOIC ACID IN INHIBITING OXIDATIVE STRESS AND PROMOTING DIABETIC WOUND HEALING BY SUPPRESSING EXPRESSION OF miR-29b IN MICE].

Science.gov (United States)

Wu, Jun; Tang, Huiqin; Liu, Qun; Gan, Dingyun; Zhou, Man

2016-08-08

To investigate the effect of α-lipoic acid on the oxidative stress of wound tissues and diabetic wound healing in mice with diabetic feet. Sixty male C57BL/6J mice weighting 200-300 g were randomly divided into model group (control group, n =15), α-lipoic acid-treated model group ( n =15), miR-29b mimic group ( n =15), and miR-29b mimic negative control group (NC group, n =15). All animals received intraperitoneal injection of streptozocin to establish the diabetic model. Then, a full thickness wound of 5 mm×2 mm in size was created at 4 weeks after modeling. All mice were administrated with high-sugar-fat-diet. At the same day after modeling, α-lipoic acid-treated model group was continuously given intravenous injection of 100 mg/(kg·d) α-lipoic acid for 14 days; miR-29b mimic group and NC group received the tail intravenous injection of lentiviral vector for miR-29b mimic and miR-29b mimic negative control (a total of 2×10 7 TU), respectively, with the treatment of α-lipoic acid. The wound healing was observed and wound area was measured at 7 and 14 days. The wound tissues were harvested to detect the levels of superoxide dismutase (SOD) and glutathione (GSH) using xanthine oxidase method and 5, 5-dithiobis-2-nitrobenzoic acid staining method at 14 days. At the same day, 7, and 14 days after modeling, the relative miR-29b expression in wound tissues from control and α-lipoic acid-treated model groups was detected by real-time fluorescence quantitative PCR. All mice survived to the experiment end. The wound healing was faster in α-lipoic acid-treated group than control group. At 7 and 14 days, the relative wound area and miR-29b expression level were significantly lower, while the contents of SOD and GSH were significantly higher in α-lipoic acid-treated group than control group ( P diabetic wound healing by suppressing expression of miR-29b in mice.

DAX1 suppresses FXR transactivity as a novel co-repressor

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Li, Jin; Lu, Yan; Liu, Ruya; Xiong, Xuelian; Zhang, Zhijian; Zhang, Xianfeng [Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025 (China); Ning, Guang, E-mail: guangning@gmail.com.cn [Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025 (China); The Key Laboratory of Endocrine Tumors and The Division of Endocrine and Metabolic Diseases, E-Institute of Shanghai Universities, Shanghai 200025 (China); Li, Xiaoying, E-mail: lixy@sibs.ac.cn [Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025 (China); The Key Laboratory of Endocrine Tumors and The Division of Endocrine and Metabolic Diseases, E-Institute of Shanghai Universities, Shanghai 200025 (China)

2011-09-09

Highlights: {yields} DAX1 is co-localized with FXR and interacts with FXR. {yields} DAX1 acts as a negative regulator of FXR. {yields} Three LXXLL motifs in the N-terminus of DAX1 were required. {yields} DAX1 suppresses FXR transactivation by competing with co-activators. -- Abstract: Bile acid receptor FXR (farnesoid X receptor) is a key regulator of hepatic bile acid, glucose and lipid homeostasis through regulation of numerous genes involved in the process of bile acid, triglyceride and glucose metabolism. DAX1 (dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on X chromosome, gene 1) is an atypical member of the nuclear receptor family due to lack of classical DNA-binding domains and acts primarily as a co-repressor of many nuclear receptors. Here, we demonstrated that DAX1 is co-localized with FXR in the nucleus and acted as a negative regulator of FXR through a physical interaction with FXR. Our study showed that over-expression of DAX1 down-regulated the expression of FXR target genes, whereas knockdown of DAX1 led to their up-regulation. Furthermore, three LXXLL motifs in the N-terminus of DAX1 were required for the full repression of FXR transactivation. In addition, our study characterized that DAX1 suppresses FXR transactivation via competing with co-activators such as SRC-1 and PGC-1{alpha}. In conclusion, DAX1 acts as a co-repressor to negatively modulate FXR transactivity.

DAX1 suppresses FXR transactivity as a novel co-repressor

International Nuclear Information System (INIS)

Li, Jin; Lu, Yan; Liu, Ruya; Xiong, Xuelian; Zhang, Zhijian; Zhang, Xianfeng; Ning, Guang; Li, Xiaoying

2011-01-01

Highlights: → DAX1 is co-localized with FXR and interacts with FXR. → DAX1 acts as a negative regulator of FXR. → Three LXXLL motifs in the N-terminus of DAX1 were required. → DAX1 suppresses FXR transactivation by competing with co-activators. -- Abstract: Bile acid receptor FXR (farnesoid X receptor) is a key regulator of hepatic bile acid, glucose and lipid homeostasis through regulation of numerous genes involved in the process of bile acid, triglyceride and glucose metabolism. DAX1 (dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on X chromosome, gene 1) is an atypical member of the nuclear receptor family due to lack of classical DNA-binding domains and acts primarily as a co-repressor of many nuclear receptors. Here, we demonstrated that DAX1 is co-localized with FXR in the nucleus and acted as a negative regulator of FXR through a physical interaction with FXR. Our study showed that over-expression of DAX1 down-regulated the expression of FXR target genes, whereas knockdown of DAX1 led to their up-regulation. Furthermore, three LXXLL motifs in the N-terminus of DAX1 were required for the full repression of FXR transactivation. In addition, our study characterized that DAX1 suppresses FXR transactivation via competing with co-activators such as SRC-1 and PGC-1α. In conclusion, DAX1 acts as a co-repressor to negatively modulate FXR transactivity.

Improved nucleic acid descriptors for siRNA efficacy prediction.

Science.gov (United States)

Sciabola, Simone; Cao, Qing; Orozco, Modesto; Faustino, Ignacio; Stanton, Robert V

2013-02-01

Although considerable progress has been made recently in understanding how gene silencing is mediated by the RNAi pathway, the rational design of effective sequences is still a challenging task. In this article, we demonstrate that including three-dimensional descriptors improved the discrimination between active and inactive small interfering RNAs (siRNAs) in a statistical model. Five descriptor types were used: (i) nucleotide position along the siRNA sequence, (ii) nucleotide composition in terms of presence/absence of specific combinations of di- and trinucleotides, (iii) nucleotide interactions by means of a modified auto- and cross-covariance function, (iv) nucleotide thermodynamic stability derived by the nearest neighbor model representation and (v) nucleic acid structure flexibility. The duplex flexibility descriptors are derived from extended molecular dynamics simulations, which are able to describe the sequence-dependent elastic properties of RNA duplexes, even for non-standard oligonucleotides. The matrix of descriptors was analysed using three statistical packages in R (partial least squares, random forest, and support vector machine), and the most predictive model was implemented in a modeling tool we have made publicly available through SourceForge. Our implementation of new RNA descriptors coupled with appropriate statistical algorithms resulted in improved model performance for the selection of siRNA candidates when compared with publicly available siRNA prediction tools and previously published test sets. Additional validation studies based on in-house RNA interference projects confirmed the robustness of the scoring procedure in prospective studies.

Multisized Inert Particle Loading for Solid Rocket Axial Combustion Instability Suppression

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David R. Greatrix

2012-01-01

Full Text Available In the present investigation, various factors and trends, related to the usage of two or more sets of inert particles comprised of the same material (nominally aluminum but at different diameters for the suppression of axial shock wave development, are numerically predicted for a composite-propellant cylindrical-grain solid rocket motor. The limit pressure wave magnitudes at a later reference time in a given pulsed firing simulation run are collected for a series of runs at different particle sizes and loading distributions and mapped onto corresponding attenuation trend charts. The inert particles’ presence in the central core flow is demonstrated to be an effective means of instability symptom suppression, in correlating with past experimental successes in the usage of particles. However, the predicted results of this study suggest that one needs to be careful when selecting more than one size of particle for a given motor application.

Simulation of Axial Combustion Instability Development and Suppression in Solid Rocket Motors

OpenAIRE

David R. Greatrix

2009-01-01

In the design of solid-propellant rocket motors, the ability to understand and predict the expected behaviour of a given motor under unsteady conditions is important. Research towards predicting, quantifying, and ultimately suppressing undesirable strong transient axial combustion instability symptoms necessitates a comprehensive numerical model for internal ballistic simulation under dynamic flow and combustion conditions. An updated numerical model incorporating recent developments in predi...

Nicotine-mediated suppression of the retinoic acid metabolizing enzyme CYP26A1 limits the oncogenic potential of breast cancer.

Science.gov (United States)

Osanai, Makoto; Lee, Gang-Hong

2011-06-01

Tobacco smoke influences cancer development in tissues that are not directly exposed, and epidemiological studies have indicated that smoking women might experience decreased risk of breast cancer as a result of antiestrogenic effects. However, it remains to be clarified whether nicotine, one of the major addictive and best-investigated constituents of tobacco smoke, has any effect on breast cancer. Our recent work demonstrated that the retinoic acid metabolizing enzyme CYP26A1 enhances oncogenic and cell survival properties of breast carcinoma cells, implying a role as an oncogene. Here, we present evidence that nicotine significantly suppresses constitutive expression of CYP26A1, and that cells treated with nicotine exhibit enhanced sensitivity to apoptosis. In addition, nicotine may inhibit anchorage independent growth, cellular invasiveness and motility. These data show that nicotine can limit CYP26A1-mediated oncogenic characteristics, and suggest mechanisms by which nicotine might inhibit breast cancer development. © 2011 Japanese Cancer Association.

Value of eight-amino-acid matches in predicting the allergenicity status of proteins: an empirical bioinformatic investigation

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ThirumalaiswamySekhar Arvind

2009-10-01

Full Text Available Abstract The use of biotechnological techniques to introduce novel proteins into food crops (transgenic or GM crops has motivated investigation into the properties of proteins that favor their potential to elicit allergic reactions. As part of the allergenicity assessment, bioinformatic approaches are used to compare the amino-acid sequence of candidate proteins with sequences in a database of known allergens to predict potential cross reactivity between novel food proteins and proteins to which people have become sensitized. Two criteria commonly used for these queries are searches over 80-amino-acid stretches for >35% identity, and searches for 8-amino-acid contiguous matches. We investigated the added value provided by the 8-amino-acid criterion over that provided by the >35%-identity-over-80-amino-acid criterion, by identifying allergens pairs that only met the former criterion, but not the latter criterion. We found that the allergen-sequence pairs only sharing 8-amino-acid identity, but not >35% identity over 80 amino acids, were unlikely to be cross reactive allergens. Thus, the common search for 8-amino-acid identity between novel proteins and known allergens appears to be of little additional value in assessing the potential allergenicity of novel proteins.

Effectors from Wheat Rust Fungi Suppress Multiple Plant Defense Responses.

Science.gov (United States)

Ramachandran, Sowmya R; Yin, Chuntao; Kud, Joanna; Tanaka, Kiwamu; Mahoney, Aaron K; Xiao, Fangming; Hulbert, Scot H

2017-01-01

Fungi that cause cereal rust diseases (genus Puccinia) are important pathogens of wheat globally. Upon infection, the fungus secretes a number of effector proteins. Although a large repository of putative effectors has been predicted using bioinformatic pipelines, the lack of available high-throughput effector screening systems has limited functional studies on these proteins. In this study, we mined the available transcriptomes of Puccinia graminis and P. striiformis to look for potential effectors that suppress host hypersensitive response (HR). Twenty small (wheat, confirming its activity in a homologous system. Overall, this study provides the first evidence for the presence of effectors in Puccinia species suppressing multiple plant defense responses.

Prediction of citrullination sites by incorporating k-spaced amino acid pairs into Chou's general pseudo amino acid composition.

Science.gov (United States)

Ju, Zhe; Wang, Shi-Yun

2018-04-22

As one of the most important and common protein post-translational modifications, citrullination plays a key role in regulating various biological processes and is associated with several human diseases. The accurate identification of citrullination sites is crucial for elucidating the underlying molecular mechanisms of citrullination and designing drugs for related human diseases. In this study, a novel bioinformatics tool named CKSAAP_CitrSite is developed for the prediction of citrullination sites. With the assistance of support vector machine algorithm, the highlight of CKSAAP_CitrSite is to adopt the composition of k-spaced amino acid pairs surrounding a query site as input. As illustrated by 10-fold cross-validation, CKSAAP_CitrSite achieves a satisfactory performance with a Sensitivity of 77.59%, a Specificity of 95.26%, an Accuracy of 89.37% and a Matthew's correlation coefficient of 0.7566, which is much better than those of the existing prediction method. Feature analysis shows that the N-terminal space containing pairs may play an important role in the prediction of citrullination sites, and the arginines close to N-terminus tend to be citrullinated. The conclusions derived from this study could offer useful information for elucidating the molecular mechanisms of citrullination and related experimental validations. A user-friendly web-server for CKSAAP_CitrSite is available at 123.206.31.171/CKSAAP_CitrSite/. Copyright © 2017. Published by Elsevier B.V.

Degree of thyrotropin suppression as a prognostic determinant in differentiated thyroid cancer.

Science.gov (United States)

Pujol, P; Daures, J P; Nsakala, N; Baldet, L; Bringer, J; Jaffiol, C

1996-12-01

We investigate whether the prognosis of patients with differentiated thyroid cancer is improved by maintaining a greater level of TSH suppression. One hundred and forty-one patients who underwent hormone therapy after thyroidectomy were followed up from 1970 to 1993 (mean, 95 months). Patients received levothyroxine (L-T4; mean dose, 2.6 micrograms/kg-day). TSH suppression was evaluated by TRH stimulation test until 1986 and thereafter by a second generation immunoradiometric assay. As TSH underwent fluctuation over time in most patients, we focused on subgroups of patients with relatively constant TSH levels during the follow-up. The relapse-free survival (RFS) was longer in the group with constantly suppressed TSH (all TSH values, or = 1 mU/L; n = 15; P 90% of undetectable TSH values; n = 19) had a trend toward a longer RFS than the remaining population (n = 102; P = 0.14). The patients with a lesser degree of TSH suppression (< 10% of undetectable TSH values; n = 27) had a shorter RFS than the remaining patients (n = 94; P < 0.01). In multivariate analysis that included TSH suppression, age, sex, histology, and tumor node metastasis stage, the degree of TSH suppression predicted RFS independently of other factors (P = 0.02). This study shows that a lesser degree of TSH suppression is associated with an increased incidence of relapse, supporting the hypothesis that a high level of TSH suppression is required for the endocrine management of thyroid cancer.

Suppressive and enhancing effects in early visual cortex during illusory shape perception: A comment on.

Science.gov (United States)

Moors, Pieter

2015-01-01

In a recent functional magnetic resonance imaging study, Kok and de Lange (2014) observed that BOLD activity for a Kanizsa illusory shape stimulus, in which pacmen-like inducers elicit an illusory shape percept, was either enhanced or suppressed relative to a nonillusory control configuration depending on whether the spatial profile of BOLD activity in early visual cortex was related to the illusory shape or the inducers, respectively. The authors argued that these findings fit well with the predictive coding framework, because top-down predictions related to the illusory shape are not met with bottom-up sensory input and hence the feedforward error signal is enhanced. Conversely, for the inducing elements, there is a match between top-down predictions and input, leading to a decrease in error. Rather than invoking predictive coding as the explanatory framework, the suppressive effect related to the inducers might be caused by neural adaptation to perceptually stable input due to the trial sequence used in the experiment.

Predictive factors of plasma HIV suppression during pregnancy: a prospective cohort study in Benin.

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Lise Denoeud-Ndam

Full Text Available To investigate the factors associated with HIV1 RNA plasma viral load (pVL below 40 copies/mL at the third trimester of pregnancy, as part of prevention of mother-to-child transmission (PMTCT in Benin.Sub study of the PACOME clinical trial of malaria prophylaxis in HIV-infected pregnant women, conducted before and after the implementation of the WHO 2009 revised guidelines for PMTCT.HIV-infected women were enrolled in the second trimester of pregnancy. Socio-economic characteristics, HIV history, clinical and biological characteristics were recorded. Malaria prevention and PMTCT involving antiretroviral therapy (ART for mothers and infants were provided. Logistic regression helped identifying factors associated with virologic suppression at the end of pregnancy.Overall 217 third trimester pVLs were available, and 71% showed undetectability. Virologic suppression was more frequent in women enrolled after the change in PMTCT recommendations, advising to start ART at 14 weeks instead of 28 weeks of pregnancy. In multivariate analysis, Fon ethnic group (the predominant ethnic group in the study area, regular job, first and second pregnancy, higher baseline pVL and impaired adherence to ART were negative factors whereas higher weight, higher antenatal care attendance and longer ART duration were favorable factors to achieve virologic suppression.This study provides more evidence that ART has to be initiated before the last trimester of pregnancy to achieve an undetectable pVL before delivery. In Benin, new recommendations supporting early initiation were well implemented and, together with a high antenatal care attendance, led to high rate of virologic control.

Predictive factors of plasma HIV suppression during pregnancy: a prospective cohort study in Benin.

Science.gov (United States)

Denoeud-Ndam, Lise; Fourcade, Camille; Ogouyemi-Hounto, Aurore; Azon-Kouanou, Angèle; d'Almeida, Marcelline; Azondékon, Alain; Alao, Marouf J; Dossou-Gbété, Véronique; Afangnihoun, Aldric; Girard, Pierre-Marie; Cot, Michel; Zannou, Djimon-Marcel

2013-01-01

To investigate the factors associated with HIV1 RNA plasma viral load (pVL) below 40 copies/mL at the third trimester of pregnancy, as part of prevention of mother-to-child transmission (PMTCT) in Benin. Sub study of the PACOME clinical trial of malaria prophylaxis in HIV-infected pregnant women, conducted before and after the implementation of the WHO 2009 revised guidelines for PMTCT. HIV-infected women were enrolled in the second trimester of pregnancy. Socio-economic characteristics, HIV history, clinical and biological characteristics were recorded. Malaria prevention and PMTCT involving antiretroviral therapy (ART) for mothers and infants were provided. Logistic regression helped identifying factors associated with virologic suppression at the end of pregnancy. Overall 217 third trimester pVLs were available, and 71% showed undetectability. Virologic suppression was more frequent in women enrolled after the change in PMTCT recommendations, advising to start ART at 14 weeks instead of 28 weeks of pregnancy. In multivariate analysis, Fon ethnic group (the predominant ethnic group in the study area), regular job, first and second pregnancy, higher baseline pVL and impaired adherence to ART were negative factors whereas higher weight, higher antenatal care attendance and longer ART duration were favorable factors to achieve virologic suppression. This study provides more evidence that ART has to be initiated before the last trimester of pregnancy to achieve an undetectable pVL before delivery. In Benin, new recommendations supporting early initiation were well implemented and, together with a high antenatal care attendance, led to high rate of virologic control.

Expressive suppression and neural responsiveness to nonverbal affective cues.

Science.gov (United States)

Petrican, Raluca; Rosenbaum, R Shayna; Grady, Cheryl

2015-10-01

Optimal social functioning occasionally requires concealment of one's emotions in order to meet one's immediate goals and environmental demands. However, because emotions serve an important communicative function, their habitual suppression disrupts the flow of social exchanges and, thus, incurs significant interpersonal costs. Evidence is accruing that the disruption in social interactions, linked to habitual expressive suppression use, stems not only from intrapersonal, but also from interpersonal causes, since the suppressors' restricted affective displays reportedly inhibit their interlocutors' emotionally expressive behaviors. However, expressive suppression use is not known to lead to clinically significant social impairments. One explanation may be that over the lifespan, individuals who habitually suppress their emotions come to compensate for their interlocutors' restrained expressive behaviors by developing an increased sensitivity to nonverbal affective cues. To probe this issue, the present study used functional magnetic resonance imaging (fMRI) to scan healthy older women while they viewed silent videos of a male social target displaying nonverbal emotional behavior, together with a brief verbal description of the accompanying context, and then judged the target's affect. As predicted, perceivers who reported greater habitual use of expressive suppression showed increased neural processing of nonverbal affective cues. This effect appeared to be coordinated in a top-down manner via cognitive control. Greater neural processing of nonverbal cues among perceivers who habitually suppress their emotions was linked to increased ventral striatum activity, suggestive of increased reward value/personal relevance ascribed to emotionally expressive nonverbal behaviors. These findings thus provide neural evidence broadly consistent with the hypothesized link between habitual use of expressive suppression and compensatory development of increased responsiveness to

Prediction of Starch, Soluble Sugars and Amino Acids in Potatoes (Solanum tuberosum L.) Using Hyperspectral Imaging, Dielectric and LF-NMR Methodologies

DEFF Research Database (Denmark)

Kjær, Anders; Nielsen, Glenn; Stærke, Søren

2016-01-01

Handling and processing of potatoes is performed in increasingly large and more automated facilities, and the industry calls for more automated machinery for quality assessment and sorting by concentration of starch, soluble sugars, protein, amino acids etc. of the potato tubers. The present study...... cultivars were simultaneously sampled for analyses of content and scanned by the five different scanning methods. The resulting multivariate dataset was used to estimate the prediction ability of the individual scanning methods on starch-related parameters, selected simple sugars, selected amino acids......, conductivity of pressed cell sap and cell sizes. Results showed that most types of spectral analyses had relatively high potential for predicting the starch-related parameters and medium potential for predicting the concentration of the reducing sugars fructose and glucose. Most methods showed medium potential...

Effect of Gastric Acid Suppressant Prophylaxis on Incidence of Gastrointestinal Bleeding in Pediatric Intensive Care Unit

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Tahoora Abdollahi

2016-11-01

Full Text Available Background: Critically ill children admitted to pediatric intensive care unit (PICU are at increased risk of gastrointestinal bleeding due to stress related mucosal injury. Reducing gastric acid by acid suppressant medication is the accepted prophylaxis treatment, but there is not any definitive guideline for using prophylaxis in PICU patients. The present study aimed to assess the effect of Proton Pump Inhibitor (PPI and H2 Blocker (H2B prophylaxis on gastrointestinal bleeding in admitted patients of PICU, Mashhad- Iran.Materials and Methods: In this study, 100 patients admitted in PICU divided into two equal groups on the first day of admission. They received ranitidine or pantoprazole as prophylaxis of stress ulcer. Those patients who had history of gastrointestinal bleeding or coagulation disorder were excluded. 100 PICU patients who had not received prophylaxis during last 6 months retrospectively evaluated as control of the study. Data were collected as demographic characteristics, admission reason, definitive diagnosis, receiving corticosteroid and mechanical ventilation in each patient. Gastrointestinal bleeding (hematemesis, coffee ground aspirate, and melena and clinically significant gastrointestinal bleeding were daily monitored. Data analyzed through descriptive statistical tests, Chi-square, logistic regression, t-test and using SPSS-16 software.Results: Among 204 patients (control group=105 and case group=99, incidence of gastrointestinal bleeding (GB was 13.2% in which 6.9% of cases presented with clinically significant gastrointestinal bleeding (CSGB. Loss of consciousness and respiratory distress were the main reason of admission. There was no significant differences between the incidence of (GB and (CSGB in experimental and control groups (P>0.05 as well as ranitidine and pantoprazole prophylaxis (P>0.05. Significant risk factors of (GB were mechanical ventilation and loss of consciousness and corticosteroid therapy

[Study on predicting sugar content and valid acidity of apples by near infrared diffuse reflectance technique].

Science.gov (United States)

Liu, Yan-de; Ying, Yi-bin; Fu, Xia-ping

2005-11-01

The nondestructive method for quantifying sugar content (SC) and available acid (VA) of intact apples using diffuse near infrared reflectance and optical fiber sensing techniques were explored in the present research. The standard sample sets and prediction models were established by partial least squares analysis (PLS). A total of 120 Shandong Fuji apples were tested in the wave number of 12,500 - 4000 cm(-1) using Fourier transform near infrared spectroscopy. The results of the research indicated that the nondestructive quantification of SC and VA, gave a high correlation coefficient 0.970 and 0.906, a low root mean square error of prediction (RMSEP) 0.272 and 0.056 2, a low root mean square error of calibration (RMSEC) 0.261 and 0.0677, and a small difference between RMSEP and RMSEC 0.011 a nd 0.0115. It was suggested that the diffuse nearinfrared reflectance technique be feasible for nondestructive determination of apple sugar content in the wave number range of 10,341 - 5461 cm(-1) and for available acid in the wave number range of 10,341 - 3818 cm(-1).

Regulatory CD8{sup +} T cells induced by exposure to all-trans retinoic acid and TGF-{beta} suppress autoimmune diabetes

Energy Technology Data Exchange (ETDEWEB)

Kishi, Minoru [Department of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Yasuda, Hisafumi, E-mail: yasuda@med.kobe-u.ac.jp [Department of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Abe, Yasuhisa; Sasaki, Hirotomo; Shimizu, Mami; Arai, Takashi; Okumachi, Yasuyo; Moriyama, Hiroaki; Hara, Kenta; Yokono, Koichi; Nagata, Masao [Department of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan)

2010-03-26

Antigen-specific regulatory CD4{sup +} T cells have been described but there are few reports on regulatory CD8{sup +} T cells. We generated islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)-specific regulatory CD8{sup +} T cells from 8.3-NOD transgenic mice. CD8{sup +} T cells from 8.3-NOD splenocytes were cultured with IGRP, splenic dendritic cells (SpDCs), TGF-{beta}, and all-trans retinoic acid (ATRA) for 5 days. CD8{sup +} T cells cultured with either IGRP alone or IGRP and SpDCs in the absence of TGF-{beta} and ATRA had low Foxp3{sup +} expression (1.7 {+-} 0.9% and 3.2 {+-} 4.5%, respectively). In contrast, CD8{sup +} T cells induced by exposure to IGRP, SpDCs, TGF-{beta}, and ATRA showed the highest expression of Foxp3{sup +} in IGRP-reactive CD8{sup +} T cells (36.1 {+-} 10.6%), which was approximately 40-fold increase compared with that before induction culture. CD25 expression on CD8{sup +} T cells cultured with IGRP, SpDCs, TGF-{beta}, and ATRA was only 7.42%, whereas CD103 expression was greater than 90%. These CD8{sup +} T cells suppressed the proliferation of diabetogenic CD8{sup +} T cells from 8.3-NOD splenocytes in vitro and completely prevented diabetes onset in NOD-scid mice in cotransfer experiments with diabetogenic splenocytes from NOD mice in vivo. Here we show that exposure to ATRA and TGF-{beta} induces CD8{sup +}Foxp3{sup +} T cells ex vivo, which suppress diabetogenic T cells in vitro and in vivo.

Dependence of J/ψ suppression in heavy ion collisions on total transverse energy, nucleon numbers and J/ψ transverse momentum

International Nuclear Information System (INIS)

Ftacnik, J.; Lichard, P.

1989-01-01

We present a set of semiquantitative predictions for the behaviour of J/ψ suppression in heavy ion collisions as a function of the total transverse energy, nucleon numbers of colliding ions and the J/ψ transverse momentum. These predictions are based on the assumption that all of J/ψ suppression is due to J/ψ and χ disintegrations in collisions with hadrons in a dense hadronic gas formed in the heavy ion collisions. The hydrodynamic evolution of the hadron gas is taken into account. The onset of the quark-gluon plasma formation should manifest itself by clear qualitative deviations from J/ψ suppression calculated in this way, in particular as thresholds or kinks in the E T -dependence, or as a threshold for J/ψ suppression as a function of the atomic number of the target, expected at Cu or below. (orig.)

[Overexpression of four fatty acid synthase genes elevated the efficiency of long-chain polyunsaturated fatty acids biosynthesis in mammalian cells].

Science.gov (United States)

Zhu, Guiming; Saleh, Abdulmomen Ali Mohammed; Bahwal, Said Ahmed; Wang, Kunfu; Wang, Mingfu; Wang, Didi; Ge, Tangdong; Sun, Jie

2014-09-01

Three long-chain polyunsaturated fatty acids, docosahexaenoic acid (DHA, 22:6n-3), eicosapentaenoic acid (EPA, 20:5n-3) and arachidonic acid (ARA, 20:4n-6), are the most biologically active polyunsaturated fatty acids in the body. They are important in developing and maintaining the brain function, and in preventing and treating many diseases such as cardiovascular disease, inflammation and cancer. Although mammals can biosynthesize these long-chain polyunsaturated fatty acids, the efficiency is very low and dietary intake is needed to meet the requirement. In this study, a multiple-genes expression vector carrying mammalian A6/A5 fatty acid desaturases and multiple-genes expression vector carrying mammalian Δ6/Δ5 fatty acid desaturases and Δ6/Δ5 fatty acid elongases coding genes was used to transfect HEK293T cells, then the overexpression of the target genes was detected. GC-MS analysis shows that the biosynthesis efficiency and level of DHA, EPA and ARA were significantly increased in cells transfected with the multiple-genes expression vector. Particularly, DHA level in these cells was 2.5 times higher than in the control cells. This study indicates mammal possess a certain mechanism for suppression of high level of biosynthesis of long chain polyunsaturated fatty acids, and the overexpression of Δ6/Δ5 fatty acid desaturases and Δ6/Δ5 fatty acid elongases broke this suppression mechanism so that the level of DHA, EPA and ARA was significantly increased. This study also provides a basis for potential applications of this gene construct in transgenic animal to produce high level of these long-chain polyunsaturated fatty acid.

Suppression of 9-cis-epoxycarotenoid dioxygenase, which encodes a key enzyme in abscisic acid biosynthesis, alters fruit texture in transgenic tomato.

Science.gov (United States)

Sun, Liang; Sun, Yufei; Zhang, Mei; Wang, Ling; Ren, Jie; Cui, Mengmeng; Wang, Yanping; Ji, Kai; Li, Ping; Li, Qian; Chen, Pei; Dai, Shengjie; Duan, Chaorui; Wu, Yan; Leng, Ping

2012-01-01

Cell wall catabolism during fruit ripening is under complex control and is key for fruit quality and shelf life. To examine the role of abscisic acid (ABA) in tomato (Solanum lycopersicum) fruit ripening, we suppressed SlNCED1, which encodes 9-cis-epoxycarotenoid dioxygenase (NCED), a key enzyme in the biosynthesis of ABA. To suppress SlNCED1 specifically in tomato fruits, and thus avoid the pleiotropic phenotypes associated with ABA deficiency, we used an RNA interference construct driven by the fruit-specific E8 promoter. ABA accumulation and SlNCED1 transcript levels in the transgenic fruit were down-regulated to between 20% and 50% of the levels measured in the control fruit. This significant reduction in NCED activity led to a down-regulation in the transcription of genes encoding major cell wall catabolic enzymes, specifically polygalacturonase (SlPG), pectin methyl esterase (SlPME), β-galactosidase precursor mRNA (SlTBG), xyloglucan endotransglycosylase (SlXET), endo-1,4-β-cellulose (SlCels), and expansin (SlExp). This resulted in an increased accumulation of pectin during ripening. In turn, this led to a significant extension of the shelf life to 15 to 29 d compared with a shelf life of only 7 d for the control fruit and an enhancement of fruit firmness at the mature stage by 30% to 45%. In conclusion, ABA affects cell wall catabolism during tomato fruit ripening via down-regulation of the expression of major catabolic genes (SlPG, SlPME, SlTBG, SlXET, SlCels, and SlExp).

Pressure suppression pool thermal mixing

International Nuclear Information System (INIS)

Cook, D.H.

1984-01-01

A model is developed and verified to describe the thermal mixing that occurs in the pressure suppression pool (PSP) of a commercial BWR. The model is designed specifically for a Mark-I containment and is intended for use in severe accident sequence analyses. The model produces space and time dependent temperature results throughout the PSP and is useful for evaluating the bulk PSP thermal mixing, the condensation effectiveness of the PSP, and the long-term containment integrity. The model is designed to accommodate single or multiple discharging T-quenchers, a PSP circumferential circulation induced by the residual heat removal system discharge, and the thermal stratification of the pool that occurs immediately after the relief valves close. The PSP thermal mixing model is verified by comparing the model predicted temperatures to experimental temperatures that were measured in an operating BWR suppression pool. The model is then used to investigate several PSP thermal mixing problems that include the time to saturate at full relief valve flow, the temperature response to a typical stuck open relief valve scenario, and the effect of operator rotation of the relief valve discharge point

Comparative analysis of QSAR models for predicting pK(a) of organic oxygen acids and nitrogen bases from molecular structure.

Science.gov (United States)

Yu, Haiying; Kühne, Ralph; Ebert, Ralf-Uwe; Schüürmann, Gerrit

2010-11-22

For 1143 organic compounds comprising 580 oxygen acids and 563 nitrogen bases that cover more than 17 orders of experimental pK(a) (from -5.00 to 12.23), the pK(a) prediction performances of ACD, SPARC, and two calibrations of a semiempirical quantum chemical (QC) AM1 approach have been analyzed. The overall root-mean-square errors (rms) for the acids are 0.41, 0.58 (0.42 without ortho-substituted phenols with intramolecular H-bonding), and 0.55 and for the bases are 0.65, 0.70, 1.17, and 1.27 for ACD, SPARC, and both QC methods, respectively. Method-specific performances are discussed in detail for six acid subsets (phenols and aromatic and aliphatic carboxylic acids with different substitution patterns) and nine base subsets (anilines, primary, secondary and tertiary amines, meta/para-substituted and ortho-substituted pyridines, pyrimidines, imidazoles, and quinolines). The results demonstrate an overall better performance for acids than for bases but also a substantial variation across subsets. For the overall best-performing ACD, rms ranges from 0.12 to 1.11 and 0.40 to 1.21 pK(a) units for the acid and base subsets, respectively. With regard to the squared correlation coefficient r², the results are 0.86 to 0.96 (acids) and 0.79 to 0.95 (bases) for ACD, 0.77 to 0.95 (acids) and 0.85 to 0.97 (bases) for SPARC, and 0.64 to 0.87 (acids) and 0.43 to 0.83 (bases) for the QC methods, respectively. Attention is paid to structural and method-specific causes for observed pitfalls. The significant subset dependence of the prediction performances suggests a consensus modeling approach.

Further increased production of free fatty acids by overexpressing a predicted transketolase gene of the pentose phosphate pathway in Aspergillus oryzae faaA disruptant.

Science.gov (United States)

Tamano, Koichi; Miura, Ai

2016-09-01

Free fatty acids are useful as source materials for the production of biodiesel fuel and various chemicals such as pharmaceuticals and dietary supplements. Previously, we attained a 9.2-fold increase in free fatty acid productivity by disrupting a predicted acyl-CoA synthetase gene (faaA, AO090011000642) in Aspergillus oryzae. In this study, we achieved further increase in the productivity by overexpressing a predicted transketolase gene of the pentose phosphate pathway in the faaA disruptant. The A. oryzae genome is predicted to have three transketolase genes and overexpression of AO090023000345, one of the three genes, resulted in phenotypic change and further increase (corresponding to an increased production of 0.38 mmol/g dry cell weight) in free fatty acids at 1.4-fold compared to the faaA disruptant. Additionally, the biomass of hyphae increased at 1.2-fold by the overexpression. As a result, free fatty acid production yield per liter of liquid culture increased at 1.7-fold by the overexpression.

Acid-Gangue Interactions in Heap Leach Operations: A Review of the Role of Mineralogy for Predicting Ore Behaviour

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Deshenthree Chetty

2018-01-01

Full Text Available Heap leaching accounts for a fifth of global copper production, sourced primarily from porphyry ores, yet metal recoveries are often not optimal. Gangue, and its interaction with acid, plays an important role in such processes. Thus, a proper understanding of gangue minerals present in the ore, their textural relationships relative to particle size distribution, reactivity with acid under different conditions, and relationship to lithotypes and geological alteration in the orebody, is necessary to predict ore behaviour in the comminution, agglomeration, curing and heap leach unit operations. Mineralogical tools available for characterisation are routine X-ray diffraction, optical microscopy, automated scanning electron microscopy, and electron probe microanalysis, accompanied by more recent advancements in hyperspectral infrared imaging and X-ray computed tomography. Integrated use of these techniques allows mineral abundance, textural relationships and mineral chemistry to be addressed over the range of particle and agglomerate sizes. Additionally, diagnostic leach results can be better interpreted when calibrated against robust mineralogical data. The linkage of ore attributes, metallurgical behaviour and their distribution in the orebody forms an integral part of a geometallurgical approach to predicting, and addressing, changes during the heap leaching process. Further investigation should address the fundamentals of gangue reaction with strong acid, and concomitant structural breakdown during curing and agglomeration processes, and how this differs from gangue-acid reactivity under weaker acid conditions, combined with temperature and fluid flow effects of heap leaching. Pre-and post- characterisation is necessary to understand and quantify the effects of variables for gangue-acid reactivity in these various operations. The characterisation outcomes should lead to a refinement of the hierarchy of gangue mineral reactivity under different

Prediction of acid generation potential

International Nuclear Information System (INIS)

Nalbandyan, V.B.

1992-01-01

This paper discusses acid rock drainage (ARD), a term used to describe leachate, seepage, or drainage that has been affected by the natural oxidation of sulfide minerals contained in rock which is exposed to air and water. The principal ingredients for ARD formation are reactive sulfide minerals, oxygen, and water. The oxidation reactions responsible for the formation of ARD are often accelerated by biological activity. These reactions yield low pH (acidic) water that has the potential to mobilize heavy metals that may be contained in the geologic materials that are contacted. ARD can cause a detrimental impact on the quality of ground or surface water to which it discharges. ARD likely has been associated with mines since mining began. ARD is not necessarily confined to mining activities, but can occur naturally wherever sulfide-bearing rock is exposed to air and water. It is important to recognize that not all operations that expose sulfide-bearing rock will result in ARD

Suppressed Belief

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Komarine Romdenh-Romluc

2009-12-01

Full Text Available Moran’s revised conception of conscious belief requires us to reconceptualise suppressed belief. The work of Merleau-Ponty offers a way to do this. His account of motor-skills allows us to understand suppressed beliefs as pre-reflective ways of dealing with the world.

Consequences of stereotype suppression and internal suppression motivation : A self-regulation approach

NARCIS (Netherlands)

Gordijn, Ernestine H; Hindriks, Inge; Koomen, W; Dijksterhuis, Ap; van Knipppenberg, A.

The present research studied the effects of suppression of stereotypes on subsequent stereotyping. Moreover, the moderating influence of motivation to suppress stereotypes was examined. The first three experiments showed that suppression of stereotypes leads to the experience of engaging in

LC-MS/MS signal suppression effects in the analysis of pesticides in complex environmental matrices.

Science.gov (United States)

Choi, B K; Hercules, D M; Gusev, A I

2001-02-01

The application of LC separation and mobile phase additives in addressing LC-MS/MS matrix signal suppression effects for the analysis of pesticides in a complex environmental matrix was investigated. It was shown that signal suppression is most significant for analytes eluting early in the LC-MS analysis. Introduction of different buffers (e.g. ammonium formate, ammonium hydroxide, formic acid) into the LC mobile phase was effective in improving signal correlation between the matrix and standard samples. The signal improvement is dependent on buffer concentration as well as LC separation of the matrix components. The application of LC separation alone was not effective in addressing suppression effects when characterizing complex matrix samples. Overloading of the LC column by matrix components was found to significantly contribute to analyte-matrix co-elution and suppression of signal. This signal suppression effect can be efficiently compensated by 2D LC (LC-LC) separation techniques. The effectiveness of buffers and LC separation in improving signal correlation between standard and matrix samples is discussed.

Ion-exclusion chromatography with conductimetric detection of aliphatic carboxylic acids on a weakly acidic cation-exchange resin by elution with benzoic acid-beta-cyclodextrin.

Science.gov (United States)

Tanaka, Kazuhiko; Mori, Masanobu; Xu, Qun; Helaleh, Murad I H; Ikedo, Mikaru; Taoda, Hiroshi; Hu, Wenzhi; Hasebe, Kiyoshi; Fritz, James S; Haddad, Paul R

2003-05-16

In this study, an aqueous solution consisting of benzoic acid with low background conductivity and beta-cyclodextrin (beta-CD) of hydrophilic nature and the inclusion effect to benzoic acid were used as eluent for the ion-exclusion chromatographic separation of aliphatic carboxylic acids with different pKa values and hydrophobicity on a polymethacrylate-based weakly acidic cation-exchange resin in the H+ form. With increasing concentration of beta-cyclodextrin in the eluent, the retention times of the carboxylic acids decreased due to the increased hydrophilicity of the polymethacrylate-based cation-exchange resin surface from the adsorption of OH groups of beta-cyclodextrin. Moreover, the eluent background conductivity decreased with increasing concentration of beta-cyclodextrin in 1 mM benzoic acid, which could result in higher sensitivity for conductimetric detection. The ion-exclusion chromatographic separation of carboxylic acids with high resolution and sensitivity was accomplished successfully by elution with a 1 mM benzoic acid-10 mM cyclodextrin solution without chemical suppression.

Reflection/suppression coatings for 900 - 1200 A radiation

Science.gov (United States)

Edelstein, Jerry

1989-01-01

The design and performance of multiple-layer, selective-reflection, selective-suppression coatings for the 900 - 1200 A band are described. These coatings are designed to optimize both high reflectivity at a desirable wavelength and low reflectivity at an undesirable wavelength. The minimum structure for a selective coating consists of a thin metal or metal oxide layer (50 - 150 A thickness) over an aluminum substrate protected with a semi-transparent dielectric (100 - 1000 A thickness). Predicted coating performance is strongly effected by varying the layer combination and thickness. A graphical method of optimizing the coating layer structure is developed. Aluminum, silicon, their oxides, and gold have been investigated as coating layer materials. A very simple coating with a 1026 to 1216 A reflectivity ratio greater than 100 was fabricated. Such reflection/suppression coatings may be of great utility to spaceborne EUV spectrographs.

lncRNATargets: A platform for lncRNA target prediction based on nucleic acid thermodynamics.

Science.gov (United States)

Hu, Ruifeng; Sun, Xiaobo

2016-08-01

Many studies have supported that long noncoding RNAs (lncRNAs) perform various functions in various critical biological processes. Advanced experimental and computational technologies allow access to more information on lncRNAs. Determining the functions and action mechanisms of these RNAs on a large scale is urgently needed. We provided lncRNATargets, which is a web-based platform for lncRNA target prediction based on nucleic acid thermodynamics. The nearest-neighbor (NN) model was used to calculate binging-free energy. The main principle of NN model for nucleic acid assumes that identity and orientation of neighbor base pairs determine stability of a given base pair. lncRNATargets features the following options: setting of a specific temperature that allow use not only for human but also for other animals or plants; processing all lncRNAs in high throughput without RNA size limitation that is superior to any other existing tool; and web-based, user-friendly interface, and colored result displays that allow easy access for nonskilled computer operators and provide better understanding of results. This technique could provide accurate calculation on the binding-free energy of lncRNA-target dimers to predict if these structures are well targeted together. lncRNATargets provides high accuracy calculations, and this user-friendly program is available for free at http://www.herbbol.org:8001/lrt/ .

A Mycobacterium avium subsp. paratuberculosis predicted serine protease is associated with acid stress and intraphagosomal survival

Directory of Open Access Journals (Sweden)

Abirami Kugadas

2016-08-01

Full Text Available AbstractThe ability to maintain intra-cellular pH is crucial for bacteria and other microbes to survive in diverse environments, particularly those that undergo fluctuations in pH. Mechanisms of acid resistance remain poorly understood in mycobacteria. Although studies investigating acid stress in M. tuberculosis are gaining traction, few center on Mycobacterium avium subsp. paratuberculosis (MAP, the etiological agent of chronic enteritis in ruminants. We identified a MAP acid stress response network involved in macrophage infection. The central node of this network was MAP0403, a predicted serine protease that shared an 86% amino acid identity with MarP in M. tuberculosis. Previous studies confirmed MarP as a serine protease integral to maintaining intra-bacterial pH and survival in acid in vitro and in vivo. We show that MAP0403 is upregulated in infected macrophage and MAC-T cells and coincided with phagosome acidification. Treatment of mammalian cells with bafilomcyin A1, a potent inhibitor of phagosomal vATPases, diminished MAP0403 transcription. MAP0403 expression was also noted in acidic medium. A surrogate host, M. smegmatis mc2 155, was designed to express MAP0403 and when exposed to either macrophages or in vitro acid stress had increase bacterial cell viability, which corresponds to maintenance of intra-bacterial pH in acidic (pH = 5 conditions. These data suggest that MAP0403 may be the equivalent of MarP in MAP. Future studies confirming MAP0403 as a serine protease and exploring its structure and possible substrates are warranted.

Prediction of digestible and metabolizable energy content and standardized ileal amino Acid digestibility in wheat shorts and red dog for growing pigs.

Science.gov (United States)

Huang, Q; Piao, X S; Ren, P; Li, D F

2012-12-01

Two experiments were conducted to evaluate the effects of chemical composition of wheat shorts and red dog on energy and amino acid digestibility in growing pigs and to establish prediction models to estimate their digestible (DE) and metabolizable (ME) energy content and as well as their standardized ileal digestible (SID) amino acid content. For Exp. 1, sixteen diets were fed to thirty-two growing pigs according to a completely randomized design during three successive periods. The basal diet was based on corn and soybean meal while the other fifteen diets contained 28.8% wheat shorts (N = 7) or red dog (N = 8), added at the expense of corn and soybean meal. Over the three periods, each diet was fed to six pigs with each diet being fed to two pigs during each period. The apparent total tract digestibility (ATTD) of energy in wheat shorts and red dog averaged 75.1 and 87.9%. The DE values of wheat shorts and red dog averaged 13.8 MJ/kg (range 13.1 to 15.0 MJ/kg) and 15.1 MJ/kg (range 13.3 to 16.6 MJ/kg) of dry matter, respectively. For Exp. 2, twelve growing pigs were allotted to two 6×6 Latin Square Designs with six periods. Ten of the diets were formulated based on 60% wheat shorts or red dog and the remaining two diets were nitrogen-free diets based on cornstarch and sucrose. Chromic oxide (0.3%) was used as an indigestible marker in all diets. There were no differences (p>0.05) in SID values for the amino acids in wheat shorts and red dog except for lysine and methionine. Apparent ileal digestibility (AID) and SID values for lysine in different sources of wheat shorts or red dog, which averaged 78.1 and 87.8%, showed more variation than either methionine or tryptophan. A stepwise regression was performed to establish DE, ME and amino acid digestibility prediction models. Data indicated that fiber content and amino acid concentrations were good indicators to predict energy values and amino acid digestibility, respectively. The present study confirms the large

Predictive properties of plasma amino acid profile for cardiovascular disease in patients with type 2 diabetes.

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Shinji Kume

Full Text Available Prevention of cardiovascular disease (CVD is an important therapeutic object of diabetes care. This study assessed whether an index based on plasma free amino acid (PFAA profiles could predict the onset of CVD in diabetic patients. The baseline concentrations of 31 PFAAs were measured with high-performance liquid chromatography-electrospray ionization-mass spectrometry in 385 Japanese patients with type 2 diabetes registered in 2001 for our prospective observational follow-up study. During 10 years of follow-up, 63 patients developed cardiovascular composite endpoints (myocardial infarction, angina pectoris, worsening of heart failure and stroke. Using the PFAA profiles and clinical information, an index (CVD-AI consisting of six amino acids to predict the onset of any endpoints was retrospectively constructed. CVD-AI levels were significantly higher in patients who did than did not develop CVD. The area under the receiver-operator characteristic curve of CVD-AI (0.72 [95% confidence interval (CI: 0.64-0.79] showed equal or slightly better discriminatory capacity than urinary albumin excretion rate (0.69 [95% CI: 0.62-0.77] on predicting endpoints. A multivariate Cox proportional hazards regression analysis showed that the high level of CVD-AI was identified as an independent risk factor for CVD (adjusted hazard ratio: 2.86 [95% CI: 1.57-5.19]. This predictive effect of CVD-AI was observed even in patients with normoalbuminuria, as well as those with albuminuria. In conclusion, these results suggest that CVD-AI based on PFAA profiles is useful for identifying diabetic patients at risk for CVD regardless of the degree of albuminuria, or for improving the discriminative capability by combining it with albuminuria.

Predictive Properties of Plasma Amino Acid Profile for Cardiovascular Disease in Patients with Type 2 Diabetes

Science.gov (United States)

Kume, Shinji; Araki, Shin-ichi; Ono, Nobukazu; Shinhara, Atsuko; Muramatsu, Takahiko; Araki, Hisazumi; Isshiki, Keiji; Nakamura, Kazuki; Miyano, Hiroshi; Koya, Daisuke; Haneda, Masakazu; Ugi, Satoshi; Kawai, Hiromichi; Kashiwagi, Atsunori; Uzu, Takashi; Maegawa, Hiroshi

2014-01-01

Prevention of cardiovascular disease (CVD) is an important therapeutic object of diabetes care. This study assessed whether an index based on plasma free amino acid (PFAA) profiles could predict the onset of CVD in diabetic patients. The baseline concentrations of 31 PFAAs were measured with high-performance liquid chromatography-electrospray ionization-mass spectrometry in 385 Japanese patients with type 2 diabetes registered in 2001 for our prospective observational follow-up study. During 10 years of follow-up, 63 patients developed cardiovascular composite endpoints (myocardial infarction, angina pectoris, worsening of heart failure and stroke). Using the PFAA profiles and clinical information, an index (CVD-AI) consisting of six amino acids to predict the onset of any endpoints was retrospectively constructed. CVD-AI levels were significantly higher in patients who did than did not develop CVD. The area under the receiver-operator characteristic curve of CVD-AI (0.72 [95% confidence interval (CI): 0.64–0.79]) showed equal or slightly better discriminatory capacity than urinary albumin excretion rate (0.69 [95% CI: 0.62–0.77]) on predicting endpoints. A multivariate Cox proportional hazards regression analysis showed that the high level of CVD-AI was identified as an independent risk factor for CVD (adjusted hazard ratio: 2.86 [95% CI: 1.57–5.19]). This predictive effect of CVD-AI was observed even in patients with normoalbuminuria, as well as those with albuminuria. In conclusion, these results suggest that CVD-AI based on PFAA profiles is useful for identifying diabetic patients at risk for CVD regardless of the degree of albuminuria, or for improving the discriminative capability by combining it with albuminuria. PMID:24971671

Prediction and mastering of wine acidity and tartaric precipitations: the Mextar® software tool

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Audrey Devatine

2002-06-01

The article describes the theoretical background upon which MEXTAR® has been developed and details the computation procedures associated to the simulation of the operations described above. Iterative processes are used to determine the various parameters enounced above. They aim in particular at the verification of the electroneutrality of the sample. However, at first electroneutrality is rarely verified because the wine chemical analytical determination is never exhaustive. Therefore, we introduce the concept of «vinic acid» to compensate the negative ion deficit of usual wine chemical analytical determination. This «vinic acid» is describe as a diacid with a fixed second dissociation constant (pK2 = 5 and a first dissociation constant determined automatically by MEXTAR®. This enables MEXTAR® to simulate accurately experimental tartaric precipitations for several samples. Thanks to the predicting capacity of MEXTAR®, the correlation between the total polyphenol content (IPT in red wines and the difficulty to stabilise high IPT wine with respect to tartaric salts is confirmed. Finally, malolactic fermentations are also well simulated. A validation of MEXTAR® for the acid addition or removal has yet to be done when reliable experimental data are available.

Charmonia suppression in nucleus-nucleus interactions at CERN SPS

CERN Document Server

Arnaldi, R; Alexa, C; Arnaldi, R; Atayan, M; Baglin, C; Baldit, A; Bedjidian, M; Beolè, S; Boldea, V; Bordalo, P; Borenstein, S R; Borges, G; Bussière, A; Capelli, L; Castanier, C; Castor, J I; Chaurand, B; Cheynis, B; Chiavassa, E; Cicalò, C; Claudino, T; Comets, M P; Constantinescu, S; Cortese, P; Cruz, J; De Falco, A; De Marco, N; Dellacasa, G; Devaux, A; Dita, S; Drapier, O; Espagnon, B; Fargeix, J; Force, P; Gallio, M; Gavrilov, Yu K; Gerschel, C; Giubellino, P; Golubeva, M B; Gonin, M; Grigorian, A A; Grigorian, S; Grossiord, J Y; Guber, F F; Guichard, A; Gulkanian, H R; Hakobyan, R S; Haroutunian, R; Idzik, M; Jouan, D; Karavitcheva, T L; Kluberg, L; Kurepin, A B; Le Bornec, Y; Lourenço, C; Macciotta, P; MacCormack, M; Marzari-Chiesa, A; Masera, M; Masoni, A; Monteno, M; Musso, A; Petiau, P; Piccotti, A; Pizzi, J R; Prado da Silva, W L; Prino, F; Puddu, G; Quintans, C; Ramello, L; Ramos, S; Rato-Mendes, P; Riccati, L; Romana, A; Scalas, E; Saturnini, P; Scomparin, E; Serci, S; Shahoyan, R; Sigaudo, F; Sitta, M; Sonderegger, P; Tarrago, X; Topilskaya, N S; Usai, G L; Vercellin, E; Villatte, L; Willis, N; Wu, T

2004-01-01

The NA50 experiment at CERN SPS has studied charmonium production in Pb-Pb collisions at 158 GeV/c per nucleon. According to the theoretical predictions the observation of the suppression of the J/ psi production yield is expected to be an unambiguous probe for a phase transition from ordinary nuclear matter towards a state in which quarks and gluons are deconfined. (10 refs).

In Vivo Predictive Dissolution: Comparing the Effect of Bicarbonate and Phosphate Buffer on the Dissolution of Weak Acids and Weak Bases.

Science.gov (United States)

Krieg, Brian J; Taghavi, Seyed Mohammad; Amidon, Gordon L; Amidon, Gregory E

2015-09-01

Bicarbonate is the main buffer in the small intestine and it is well known that buffer properties such as pKa can affect the dissolution rate of ionizable drugs. However, bicarbonate buffer is complicated to work with experimentally. Finding a suitable substitute for bicarbonate buffer may provide a way to perform more physiologically relevant dissolution tests. The dissolution of weak acid and weak base drugs was conducted in bicarbonate and phosphate buffer using rotating disk dissolution methodology. Experimental results were compared with the predicted results using the film model approach of (Mooney K, Mintun M, Himmelstein K, Stella V. 1981. J Pharm Sci 70(1):22-32) based on equilibrium assumptions as well as a model accounting for the slow hydration reaction, CO2 + H2 O → H2 CO3 . Assuming carbonic acid is irreversible in the dehydration direction: CO2 + H2 O ← H2 CO3 , the transport analysis can accurately predict rotating disk dissolution of weak acid and weak base drugs in bicarbonate buffer. The predictions show that matching the dissolution of weak acid and weak base drugs in phosphate and bicarbonate buffer is possible. The phosphate buffer concentration necessary to match physiologically relevant bicarbonate buffer [e.g., 10.5 mM (HCO3 (-) ), pH = 6.5] is typically in the range of 1-25 mM and is very dependent upon drug solubility and pKa . © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Deconstructing continuous flash suppression.

Science.gov (United States)

Yang, Eunice; Blake, Randolph

2012-03-08

In this paper, we asked to what extent the depth of interocular suppression engendered by continuous flash suppression (CFS) varies depending on spatiotemporal properties of the suppressed stimulus and CFS suppressor. An answer to this question could have implications for interpreting the results in which CFS influences the processing of different categories of stimuli to different extents. In a series of experiments, we measured the selectivity and depth of suppression (i.e., elevation in contrast detection thresholds) as a function of the visual features of the stimulus being suppressed and the stimulus evoking suppression, namely, the popular "Mondrian" CFS stimulus (N. Tsuchiya & C. Koch, 2005). First, we found that CFS differentially suppresses the spatial components of the suppressed stimulus: Observers' sensitivity for stimuli of relatively low spatial frequency or cardinally oriented features was more strongly impaired in comparison to high spatial frequency or obliquely oriented stimuli. Second, we discovered that this feature-selective bias primarily arises from the spatiotemporal structure of the CFS stimulus, particularly within information residing in the low spatial frequency range and within the smooth rather than abrupt luminance changes over time. These results imply that this CFS stimulus operates by selectively attenuating certain classes of low-level signals while leaving others to be potentially encoded during suppression. These findings underscore the importance of considering the contribution of low-level features in stimulus-driven effects that are reported under CFS.

Dexamethasone suppression test

Science.gov (United States)

DST; ACTH suppression test; Cortisol suppression test ... During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medicine. Afterward, your blood is drawn ...

Tranexamic acid for acute intracerebral hemorrhage growth predicted by spot sign trial: Rationale and design.

Science.gov (United States)

Liu, Liping; Wang, Yilong; Meng, Xia; Li, Na; Tan, Ying; Nie, Ximing; Liu, Dacheng; Zhao, Xingquan

2017-04-01

Rationale Acute intracerebral hemorrhage inflicts a high-economic and -health burden. Computed tomography angiography spot sign is a predictor of hematoma expansion, is associated with poor clinical outcome and is an important stratifying variable for patients treated with haemostatic therapy. Aims We aim to compare the effect of treatment with tranexamic acid to placebo for the prevention of hemorrhage growth in patients with high-risk acute intracerebral hemorrhage with a positive spot sign. Design The tranexamic acid for acute intracerebral hemorrhage growth predicted by spot sign (TRAIGE) is a prospective, multicenter, placebo-controlled, double-blind, investigator-led, randomized clinical trial that will include an estimated 240 participants. Patients with intracerebral hemorrhage demonstrating symptom onset within 8 h and with the spot sign as a biomarker for ongoing hemorrhage, and no contraindications for antifibrinolytic therapy, will be enrolled to receive either tranexamic acid or placebo. The primary outcome measure is the presence of hemorrhage growth defined as an increase in intracerebral hemorrhage volume >33% or >6 ml from baseline to 24 ± 2 h. The secondary outcomes include safety and clinical outcomes. Conclusion The TRAIGE trial evaluates the efficacy of haemostatic therapy with tranexamic acid in the prevention of hemorrhage growth among high-risk patients with acute intracerebral hemorrhage.

Deconstructing continuous flash suppression

OpenAIRE

Yang, Eunice; Blake, Randolph

2012-01-01

In this paper, we asked to what extent the depth of interocular suppression engendered by continuous flash suppression (CFS) varies depending on spatiotemporal properties of the suppressed stimulus and CFS suppressor. An answer to this question could have implications for interpreting the results in which CFS influences the processing of different categories of stimuli to different extents. In a series of experiments, we measured the selectivity and depth of suppression (i.e., elevation in co...

Improving protein fold recognition and structural class prediction accuracies using physicochemical properties of amino acids.

Science.gov (United States)

Raicar, Gaurav; Saini, Harsh; Dehzangi, Abdollah; Lal, Sunil; Sharma, Alok

2016-08-07

Predicting the three-dimensional (3-D) structure of a protein is an important task in the field of bioinformatics and biological sciences. However, directly predicting the 3-D structure from the primary structure is hard to achieve. Therefore, predicting the fold or structural class of a protein sequence is generally used as an intermediate step in determining the protein's 3-D structure. For protein fold recognition (PFR) and structural class prediction (SCP), two steps are required - feature extraction step and classification step. Feature extraction techniques generally utilize syntactical-based information, evolutionary-based information and physicochemical-based information to extract features. In this study, we explore the importance of utilizing the physicochemical properties of amino acids for improving PFR and SCP accuracies. For this, we propose a Forward Consecutive Search (FCS) scheme which aims to strategically select physicochemical attributes that will supplement the existing feature extraction techniques for PFR and SCP. An exhaustive search is conducted on all the existing 544 physicochemical attributes using the proposed FCS scheme and a subset of physicochemical attributes is identified. Features extracted from these selected attributes are then combined with existing syntactical-based and evolutionary-based features, to show an improvement in the recognition and prediction performance on benchmark datasets. Copyright © 2016 Elsevier Ltd. All rights reserved.

Styrene maleic acid-encapsulated RL71 micelles suppress tumor growth in a murine xenograft model of triple negative breast cancer

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Martey O

2017-10-01

Full Text Available Orleans Martey,1 Mhairi Nimick,1 Sebastien Taurin,1 Vignesh Sundararajan,1 Khaled Greish,2 Rhonda J Rosengren1 1Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand; 2Department of Molecular Medicine, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain Abstract: Patients with triple negative breast cancer have a poor prognosis due in part to the lack of targeted therapies. In the search for novel drugs, our laboratory has developed a second-generation curcumin derivative, 3,5-bis(3,4,5-trimethoxybenzylidene-1-methylpiperidine-4-one (RL71, that exhibits potent in vitro cytotoxicity. To improve the clinical potential of this drug, we have encapsulated it in styrene maleic acid (SMA micelles. SMA-RL71 showed improved biodistribution, and drug accumulation in the tumor increased 16-fold compared to control. SMA-RL71 (10 mg/kg, intravenously, two times a week for 2 weeks also significantly suppressed tumor growth compared to control in a xenograft model of triple negative breast cancer. Free RL71 was unable to alter tumor growth. Tumors from SMA-RL71-treated mice showed a decrease in angiogenesis and an increase in apoptosis. The drug treatment also modulated various cell signaling proteins including the epidermal growth factor receptor, with the mechanisms for tumor suppression consistent with previous work with RL71 in vitro. The nanoformulation was also nontoxic as shown by normal levels of plasma markers for liver and kidney injury following weekly administration of SMA-RL71 (10 mg/kg for 90 days. Thus, we report clinical potential following encapsulation of a novel curcumin derivative, RL71, in SMA micelles. Keywords: curcumin derivatives, nanomedicine, EGFR, biodistribution

pKa prediction for acidic phosphorus-containing compounds using multiple linear regression with computational descriptors.

Science.gov (United States)

Yu, Donghai; Du, Ruobing; Xiao, Ji-Chang

2016-07-05

Ninety-six acidic phosphorus-containing molecules with pKa 1.88 to 6.26 were collected and divided into training and test sets by random sampling. Structural parameters were obtained by density functional theory calculation of the molecules. The relationship between the experimental pKa values and structural parameters was obtained by multiple linear regression fitting for the training set, and tested with the test set; the R(2) values were 0.974 and 0.966 for the training and test sets, respectively. This regression equation, which quantitatively describes the influence of structural parameters on pKa , and can be used to predict pKa values of similar structures, is significant for the design of new acidic phosphorus-containing extractants. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The Technology of Suppressing Harmonics with Complex Neural Network is Applied to Microgrid

Science.gov (United States)

Zhang, Jing; Li, Zhan-Ying; Wang, Yan-ping; Li, Yang; Zong, Ke-yong

2018-03-01

According to the traits of harmonics in microgrid, a new CANN controller which combines BP and RBF neural network is proposed to control APF to detect and suppress harmonics. This controller has the function of current prediction. By simulation in Matlab / Simulink, this design can shorten the delay time nearly 0.02s (a power supply current cycle) in comparison with the traditional controller based on ip-iq method. The new controller also has higher compensation accuracy and better dynamic tracking traits, it can greatly suppress the harmonics and improve the power quality.

Acid-suppressive drugs and risk of kidney disease: A systematic review and meta-analysis.

Science.gov (United States)

Qiu, Tingting; Zhou, Junwen; Zhang, Chao

2018-04-12

More concerns had been raised about the risk of kidney disease (KD) associated with acid-suppressive drugs (ASDs). But whether they could directly increase such risk remained unclear. Meta-analysis was conducted to comprehensively investigate this relationship. PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and three Chinese databases were searched until April 2017 for observational studies investigating the associations between ASDs and KD. Pooled log (odds ratios, ORs) or log (hazard ratios, HRs) with standard errors for KD risk were calculated using the generic inverse variance method and random-effect model. Ten studies involving 128,020 KD patients were included. Proton pump inhibitor (PPI) therapy was associated with higher risks of acute interstitial nephritis (AIN) (OR, 2.78; 95% confidence interval (CI), 1.25-6.17), acute kidney injury (AKI) (HR, 1.85; 95% CI, 1.33-2.59), chronic kidney disease (CKD) (HR, 1.47; 95% CI, 1.03-2.09), and end-stage renal disease (ESRD) (HR, 1.61; 95% CI, 1.26-2.04) than non-PPI therapy. Additionally, PPI significantly increased the risks of AKI (HR, 1.32; 95% CI, 1.16-1.51), CKD (HR, 1.28; 95% CI, 1.24-1.33) and ESRD (HR, 1.96; 95% CI, 1.21-3.17) compared to histamine 2 receptor antagonist (H 2 RA). Relationship between H 2 RA therapy and AKI (OR, 0.98; 95% CI, 0.90-1.07) or CKD (OR, 1.00; 95% CI, 0.89-1.11) was not found. PPI therapy significantly increased the risks of AIN, AKI, CKD and ESRD. Similar risks were not identified for H 2 RA therapy. More clinical trials are needed to confirm our findings. This article is protected by copyright. All rights reserved.

Screening for suppression in young children: the Polaroid Suppression test

NARCIS (Netherlands)

Pott, J.W.R.; Oosterveen, DK; Van Hof-van Duin, J

1998-01-01

Background: Assessment of monocular visual impairment during screening of young children is often hampered by lack of cooperation. Because strabismus, amblyopia, or anisometropia may lead to monocular suppression during binocular viewing conditions, a test was developed to screen far suppression in

Albugo-imposed changes to tryptophan-derived antimicrobial metabolite biosynthesis may contribute to suppression of non-host resistance to Phytophthora infestans in Arabidopsis thaliana

DEFF Research Database (Denmark)

Prince, David C.; Rallapalli, Ghanasyam; Xu, Deyang

2017-01-01

-derived antimicrobial compounds enables P. infestans colonization of Arabidopsis, although to a lesser extent than Albugo-infected tissue. A. laibachii also suppresses a subset of genes regulated by salicylic acid; however, salicylic acid plays only a minor role in non-host resistance to P. infestans. CONCLUSIONS......: Albugo sp. alter tryptophan-derived metabolites and suppress elements of the responses to salicylic acid in Arabidopsis. Albugo sp. imposed alterations in tryptophan-derived metabolites may play a role in Arabidopsis non-host resistance to P. infestans. Understanding the basis of non-host resistance...

Atorvastatin induces bile acid-synthetic enzyme Cyp7a1 by suppressing FXR signaling in both liver and intestine in mice[S

Science.gov (United States)

Fu, Zidong Donna; Cui, Julia Yue; Klaassen, Curtis D.

2014-01-01

Statins are effective cholesterol-lowering drugs to treat CVDs. Bile acids (BAs), the end products of cholesterol metabolism in the liver, are important nutrient and energy regulators. The present study aims to investigate how statins affect BA homeostasis in the enterohepatic circulation. Male C57BL/6 mice were treated with atorvastatin (100 mg/kg/day po) for 1 week, followed by BA profiling by ultra-performance LC-MS/MS. Atorvastatin decreased BA pool size, mainly due to less BA in the intestine. Surprisingly, atorvastatin did not alter total BAs in the serum or liver. Atorvastatin increased the ratio of 12α-OH/non12α-OH BAs. Atorvastatin increased the mRNAs of the BA-synthetic enzymes cholesterol 7α-hydroxylase (Cyp7a1) (over 10-fold) and cytochrome P450 27a1, the BA uptake transporters Na+/taurocholate cotransporting polypeptide and organic anion transporting polypeptide 1b2, and the efflux transporter multidrug resistance-associated protein 2 in the liver. Noticeably, atorvastatin suppressed the expression of BA nuclear receptor farnesoid X receptor (FXR) target genes, namely small heterodimer partner (liver) and fibroblast growth factor 15 (ileum). Furthermore, atorvastatin increased the mRNAs of the organic cation uptake transporter 1 and cholesterol efflux transporters Abcg5 and Abcg8 in the liver. The increased expression of BA-synthetic enzymes and BA transporters appear to be a compensatory response to maintain BA homeostasis after atorvastatin treatment. The Cyp7a1 induction by atorvastatin appears to be due to suppressed FXR signaling in both the liver and intestine. PMID:25278499

Non-linear direct effects of acid rain on leaf photosynthetic rate of terrestrial plants

NARCIS (Netherlands)

Dong, Dan; Du, Enzai; Sun, Zhengzhong; Zeng, Xuetong; Vries, de Wim

2017-01-01

Anthropogenic emissions of acid precursors have enhanced global occurrence of acid rain, especially in East Asia. Acid rain directly suppresses leaf function by eroding surface waxes and cuticle and leaching base cations from mesophyll cells, while the simultaneous foliar uptake of nitrates in

3-Aminoquinoline/p-coumaric acid as a MALDI matrix for glycopeptides, carbohydrates, and phosphopeptides.

Science.gov (United States)

Fukuyama, Yuko; Funakoshi, Natsumi; Takeyama, Kohei; Hioki, Yusaku; Nishikaze, Takashi; Kaneshiro, Kaoru; Kawabata, Shin-Ichirou; Iwamoto, Shinichi; Tanaka, Koichi

2014-02-18

Glycosylation and phosphorylation are important post-translational modifications in biological processes and biomarker research. The difficulty in analyzing these modifications is mainly their low abundance and dissociation of labile regions such as sialic acids or phosphate groups. One solution in matrix-assisted laser desorption/ionization (MALDI) mass spectrometry is to improve matrices for glycopeptides, carbohydrates, and phosphopeptides by increasing the sensitivity and suppressing dissociation of the labile regions. Recently, a liquid matrix 3-aminoquinoline (3-AQ)/α-cyano-4-hydroxycinnamic acid (CHCA) (3-AQ/CHCA), introduced by Kolli et al. in 1996, has been reported to increase sensitivity for carbohydrates or phosphopeptides, but it has not been systematically evaluated for glycopeptides. In addition, 3-AQ/CHCA enhances the dissociation of labile regions. In contrast, a liquid matrix 1,1,3,3-tetramethylguanidium (TMG, G) salt of p-coumaric acid (CA) (G3CA) was reported to suppress dissociation of sulfate groups or sialic acids of carbohydrates. Here we introduce a liquid matrix 3-AQ/CA for glycopeptides, carbohydrates, and phosphopeptides. All of the analytes were detected as [M + H](+) or [M - H](-) with higher or comparable sensitivity using 3-AQ/CA compared with 3-AQ/CHCA or 2,5-dihydroxybenzoic acid (2,5-DHB). The sensitivity was increased 1- to 1000-fold using 3-AQ/CA. The dissociation of labile regions such as sialic acids or phosphate groups and the fragmentation of neutral carbohydrates were suppressed more using 3-AQ/CA than using 3-AQ/CHCA or 2,5-DHB. 3-AQ/CA was thus determined to be an effective MALDI matrix for high sensitivity and the suppression of dissociation of labile regions in glycosylation and phosphorylation analyses.

When suppressing one stereotype leads to rebound of another: on the procedural nature of stereotype rebound.

Science.gov (United States)

Geeraert, Nicolas

2013-09-01

A known consequence of stereotype suppression is post-suppressional rebound (PSR), an ironic activation of the suppressed stereotype. This is typically explained as an unintended by-product from a dual-process model of mental control. Relying on this model, stereotype rebound is believed to be conceptual. Alternative accounts predict PSR to be featural or procedural. According to the latter account, stereotype rebound would not be limited to the suppressed social category, but could occur for a target from any social category. The occurrence of procedural stereotype rebound was examined across five experiments. Suppression of one particular stereotype consistently led to rebound for social targets belonging to the same or a different stereotype in an essay-writing task (Experiments 1-3) and led to facilitation in recognition of stereotype-consistent words (Experiment 4). Finally, stereotype suppression was shown to impact on assessments of stereotype use but not on heuristic thinking (Experiment 5).

Gamma-Aminobutyric Acid Concentration is Reduced in Visual Cortex in Schizophrenia and Correlates with Orientation-Specific Surround Suppression

Science.gov (United States)

Yoon, Jong H.; Maddock, Richard J.; Rokem, Ariel; Silver, Michael A.; Minzenberg, Michael J.; Ragland, J. Daniel; Carter, Cameron S.

2010-01-01

The neural mechanisms underlying cognitive deficits in schizophrenia remain largely unknown. The gamma-aminobutyric acid (GABA) hypothesis proposes that reduced neuronal GABA concentration and neurotransmission results in cognitive impairments in schizophrenia. However, few in vivo studies have directly examined this hypothesis. We employed magnetic resonance spectroscopy (MRS) at high field to measure visual cortical GABA levels in 13 subjects with schizophrenia and 13 demographically matched healthy control subjects. We found that the schizophrenia group had an approximately 10% reduction in GABA concentration. We further tested the GABA hypothesis by examining the relationship between visual cortical GABA levels and orientation-specific surround suppression (OSSS), a behavioral measure of visual inhibition thought to be dependent on GABAergic synaptic transmission. Previous work has shown that subjects with schizophrenia exhibit reduced OSSS of contrast discrimination (Yoon et al., 2009). For subjects with both MRS and OSSS data (n=16), we found a highly significant positive correlation (r=0.76) between these variables. GABA concentration was not correlated with overall contrast discrimination performance for stimuli without a surround (r=-0.10). These results suggest that a neocortical GABA deficit in subjects with schizophrenia leads to impaired cortical inhibition and that GABAergic synaptic transmission in visual cortex plays a critical role in OSSS. PMID:20220012

Periodic variation in bile acids controls circadian changes in uric acid via regulation of xanthine oxidase by the orphan nuclear receptor PPARα.

Science.gov (United States)

Kanemitsu, Takumi; Tsurudome, Yuya; Kusunose, Naoki; Oda, Masayuki; Matsunaga, Naoya; Koyanagi, Satoru; Ohdo, Shigehiro

2017-12-29

Xanthine oxidase (XOD), also known as xanthine dehydrogenase, is a rate-limiting enzyme in purine nucleotide degradation, which produces uric acid. Uric acid concentrations in the blood and liver exhibit circadian oscillations in both humans and rodents; however, the underlying mechanisms remain unclear. Here, we demonstrate that XOD expression and enzymatic activity exhibit circadian oscillations in the mouse liver. We found that the orphan nuclear receptor peroxisome proliferator-activated receptor-α (PPARα) transcriptionally activated the mouse XOD gene and that bile acids suppressed XOD transactivation. The synthesis of bile acids is known to be under the control of the circadian clock, and we observed that the time-dependent accumulation of bile acids in hepatic cells interfered with the recruitment of the co-transcriptional activator p300 to PPARα, thereby repressing XOD expression. This time-dependent suppression of PPARα-mediated transactivation by bile acids caused an oscillation in the hepatic expression of XOD, which, in turn, led to circadian alterations in uric acid production. Finally, we also demonstrated that the anti-hyperuricemic effect of the XOD inhibitor febuxostat was enhanced by administering it at the time of day before hepatic XOD activity increased. These results suggest an underlying mechanism for the circadian alterations in uric acid production and also underscore the importance of selecting an appropriate time of day for administering XOD inhibitors. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Mfold web server for nucleic acid folding and hybridization prediction.

Science.gov (United States)

Zuker, Michael

2003-07-01

The abbreviated name, 'mfold web server', describes a number of closely related software applications available on the World Wide Web (WWW) for the prediction of the secondary structure of single stranded nucleic acids. The objective of this web server is to provide easy access to RNA and DNA folding and hybridization software to the scientific community at large. By making use of universally available web GUIs (Graphical User Interfaces), the server circumvents the problem of portability of this software. Detailed output, in the form of structure plots with or without reliability information, single strand frequency plots and 'energy dot plots', are available for the folding of single sequences. A variety of 'bulk' servers give less information, but in a shorter time and for up to hundreds of sequences at once. The portal for the mfold web server is http://www.bioinfo.rpi.edu/applications/mfold. This URL will be referred to as 'MFOLDROOT'.

Differential and Synergistic Functionality of Acylsugars in Suppressing Oviposition by Insect Herbivores.

Directory of Open Access Journals (Sweden)

Brian M Leckie

Full Text Available Acylsugars are secondary metabolites exuded from type IV glandular trichomes that provide broad-spectrum insect suppression for Solanum pennellii Correll, a wild relative of cultivated tomato. Acylsugars produced by different S. pennellii accessions vary by sugar moieties (glucose or sucrose and fatty acid side chains (lengths and branching patterns. Our objective was to determine which acylsugar compositions more effectively suppressed oviposition of the whitefly Bemisia tabaci (Gennadius (Middle East--Asia Minor 1 Group, tobacco thrips, Frankliniella fusca (Hinds, and western flower thrips, Frankliniella occidentalis (Pergande. We extracted and characterized acylsugars from four S. pennellii accessions with different compositions, as well as from an acylsugar-producing tomato breeding line. We also fractionated the acylsugars of one S. pennellii accession to examine the effects of its components. Effects of acylsugars on oviposition were evaluated by administering a range of doses to oviposition sites of adult whiteflies and thrips in non-choice and choice bioassays, respectively. The acylsugars from S. pennellii accessions and the tomato breeding line demonstrated differential functionality in their ability to alter the distribution of whitefly oviposition and suppress oviposition on acylsugar treated substrates. Tobacco thrips were sensitive to all compositions while western flower thrips and whiteflies were more sensitive to acylsugars from a subset of S. pennellii accessions. It follows that acylsugars could thus mediate plant-enemy interactions in such a way as to affect evolution of host specialization, resistance specificity, and potentially host differentiation or local adaptation. The acylsugars from S. pennellii LA1376 were separated by polarity into two fractions that differed sharply for their sugar moieties and fatty acid side chains. These fractions had different efficacies, with neither having activity approaching that of the

The role of acid suppressants in upper gastrointestinal ulcer bleeding

NARCIS (Netherlands)

van Leerdam, M. E.; Rauws, E. A.

2001-01-01

Re-bleeding and mortality remain significant in peptic ulcer haemorrhage despite the widespread use of endoscopic therapy. The acidic gastric environment interferes with coagulation. In vitro studies show that an intragastric pH of above 6 results in normal blood coagulation and platelet function.

Measuring ability to enhance and suppress emotional expression: The Flexible Regulation of Emotional Expression (FREE) Scale.

Science.gov (United States)

Burton, Charles L; Bonanno, George A

2016-08-01

Flexibility in self-regulatory behaviors has proved to be an important quality for adjusting to stressful life events and requires individuals to have a diverse repertoire of emotion regulation abilities. However, the most commonly used emotion regulation questionnaires assess frequency of behavior rather than ability, with little evidence linking these measures to observable capacity to enact a behavior. The aim of the current investigation was to develop and validate a Flexible Regulation of Emotional Expression (FREE) Scale that measures a person's ability to enhance and suppress displayed emotion across an array of hypothetical contexts. In Studies 1 and 2, a series of confirmatory factor analyses revealed that the FREE Scale consists of 4 first-order factors divided by regulation and emotional valence type that can contribute to 2 higher order factors: expressive enhancement ability and suppression ability. In Study 1, we also compared the FREE Scale to other commonly used emotion regulation measures, which revealed that suppression ability is conceptually distinct from suppression frequency. In Study 3, we compared the FREE Scale with a composite of traditional frequency-based indices of expressive regulation to predict performance in a previously validated emotional modulation paradigm. Participants' enhancement and suppression ability scores on the FREE Scale predicted their corresponding performance on the laboratory task, even when controlling for baseline expressiveness. These studies suggest that the FREE Scale is a valid and flexible measure of expressive regulation ability. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

HBC-Evo: predicting human breast cancer by exploiting amino acid sequence-based feature spaces and evolutionary ensemble system.

Science.gov (United States)

Majid, Abdul; Ali, Safdar

2015-01-01

We developed genetic programming (GP)-based evolutionary ensemble system for the early diagnosis, prognosis and prediction of human breast cancer. This system has effectively exploited the diversity in feature and decision spaces. First, individual learners are trained in different feature spaces using physicochemical properties of protein amino acids. Their predictions are then stacked to develop the best solution during GP evolution process. Finally, results for HBC-Evo system are obtained with optimal threshold, which is computed using particle swarm optimization. Our novel approach has demonstrated promising results compared to state of the art approaches.

Emotion suppression moderates the quadratic association between RSA and executive function.

Science.gov (United States)

Spangler, Derek P; Bell, Martha Ann; Deater-Deckard, Kirby

2015-09-01

There is uncertainty about whether respiratory sinus arrhythmia (RSA), a cardiac marker of adaptive emotion regulation, is involved in relatively low or high executive function performance. In the present study, we investigated (a) whether RSA during rest and tasks predict both relatively low and high executive function within a larger quadratic association among the two variables, and (b) the extent to which this quadratic trend was moderated by individual differences in emotion regulation. To achieve these aims, a sample of ethnically and socioeconomically diverse women self-reported reappraisal and emotion suppression. They next experienced a 2-min resting period during which electrocardiogram (ECG) was continually assessed. In the next phase, the women completed an array of executive function and nonexecutive cognitive tasks while ECG was measured throughout. As anticipated, resting RSA showed a quadratic association with executive function that was strongest for high suppression. These results suggest that relatively high resting RSA may predict poor executive function ability when emotion regulation consumes executive control resources needed for ongoing cognitive performance. © 2015 Society for Psychophysiological Research.

Structured triacylglycerol containing behenic and oleic acids suppresses triacylglycerol absorption and prevents obesity in rats

Directory of Open Access Journals (Sweden)

Takamatsu Kiyoharu

2010-07-01

Full Text Available Abstract Background Dietary 1(3-behenoyl-2,3(1-dioleoyl-rac-glycerol (BOO has been reported to inhibit pancreatic lipase activity in vitro and suppress postprandial hypertriacylglycerolemia in humans. In the present study, the anti-obesity activities of BOO and its inhibitory effects on lymphatic triacylglycerol (TAG absorption were investigated in rats. Methods In Experiment 1, rats were fed either BOO or soybean oil (SO diet for 6 weeks. In the BOO diet, 20% of SO was replaced with an experimental oil rich in BOO. In Experiments 2 and 3, rats cannulated in the thoracic duct were administered an emulsions containing trioleoylglycerol (OOO or an oil mixture (OOO:BOO, 9:1. Tri[1-14C]oleoylglycerol (14C-OOO was added to the emulsions administered in Experiment 3. Results No observable differences were detected in food intake or body weight gain between the BOO and SO groups in Experiment 1. Plasma and liver TAG concentrations and visceral fat weights were significantly lower in the BOO group than in the SO group. The apparent absorption rate of fat was significantly lower in the BOO group than in the SO group. In Experiment 2, the lymphatic recovery of oleic and behenic acids was significantly lower at 5 and 6 h after BOO administration than after OOO administration. In Experiment 3, the lymphatic recovery of 14C-OOO was significantly lower at 5 and 6 h after BOO administration than after OOO administration. Conclusions These results suggest that BOO prevents deposition of visceral fat and hepatic TAG by lowering and delaying intestinal absorption of TAG.

The use of orthologous sequences to predict the impact of amino acid substitutions on protein function.

Directory of Open Access Journals (Sweden)

Nicholas J Marini

2010-05-01

Full Text Available Computational predictions of the functional impact of genetic variation play a critical role in human genetics research. For nonsynonymous coding variants, most prediction algorithms make use of patterns of amino acid substitutions observed among homologous proteins at a given site. In particular, substitutions observed in orthologous proteins from other species are often assumed to be tolerated in the human protein as well. We examined this assumption by evaluating a panel of nonsynonymous mutants of a prototypical human enzyme, methylenetetrahydrofolate reductase (MTHFR, in a yeast cell-based functional assay. As expected, substitutions in human MTHFR at sites that are well-conserved across distant orthologs result in an impaired enzyme, while substitutions present in recently diverged sequences (including a 9-site mutant that "resurrects" the human-macaque ancestor result in a functional enzyme. We also interrogated 30 sites with varying degrees of conservation by creating substitutions in the human enzyme that are accepted in at least one ortholog of MTHFR. Quite surprisingly, most of these substitutions were deleterious to the human enzyme. The results suggest that selective constraints vary between phylogenetic lineages such that inclusion of distant orthologs to infer selective pressures on the human enzyme may be misleading. We propose that homologous proteins are best used to reconstruct ancestral sequences and infer amino acid conservation among only direct lineal ancestors of a particular protein. We show that such an "ancestral site preservation" measure outperforms other prediction methods, not only in our selected set for MTHFR, but also in an exhaustive set of E. coli LacI mutants.

SUPPRESSION OF DIELECTRONIC RECOMBINATION DUE TO FINITE DENSITY EFFECTS

International Nuclear Information System (INIS)

Nikolić, D.; Gorczyca, T. W.; Korista, K. T.; Ferland, G. J.; Badnell, N. R.

2013-01-01

We have developed a general model for determining density-dependent effective dielectronic recombination (DR) rate coefficients in order to explore finite-density effects on the ionization balance of plasmas. Our model consists of multiplying by a suppression factor those highly-accurate total zero-density DR rate coefficients which have been produced from state-of-the-art theoretical calculations and which have been benchmarked by experiment. The suppression factor is based upon earlier detailed collision-radiative calculations which were made for a wide range of ions at various densities and temperatures, but used a simplified treatment of DR. A general suppression formula is then developed as a function of isoelectronic sequence, charge, density, and temperature. These density-dependent effective DR rate coefficients are then used in the plasma simulation code Cloudy to compute ionization balance curves for both collisionally ionized and photoionized plasmas at very low (n e = 1 cm –3 ) and finite (n e = 10 10 cm –3 ) densities. We find that the denser case is significantly more ionized due to suppression of DR, warranting further studies of density effects on DR by detailed collisional-radiative calculations which utilize state-of-the-art partial DR rate coefficients. This is expected to impact the predictions of the ionization balance in denser cosmic gases such as those found in nova and supernova shells, accretion disks, and the broad emission line regions in active galactic nuclei.

Mothers' responses to children's negative emotions and child emotion regulation: the moderating role of vagal suppression.

Science.gov (United States)

Perry, Nicole B; Calkins, Susan D; Nelson, Jackie A; Leerkes, Esther M; Marcovitch, Stuart

2012-07-01

The current study examined the moderating effect of children's cardiac vagal suppression on the association between maternal socialization of negative emotions (supportive and nonsupportive responses) and children's emotion regulation behaviors. One hundred and ninety-seven 4-year-olds and their mothers participated. Mothers reported on their reactions to children's negative emotions and children's regulatory behaviors. Observed distraction, an adaptive self-regulatory strategy, and vagal suppression were assessed during a laboratory task designed to elicit frustration. Results indicated that children's vagal suppression moderated the association between mothers' nonsupportive emotion socialization and children's emotion regulation behaviors such that nonsupportive reactions to negative emotions predicted lower observed distraction and lower reported emotion regulation behaviors when children displayed lower levels of vagal suppression. No interaction was found between supportive maternal emotion socialization and vagal suppression for children's emotion regulation behaviors. Results suggest physiological regulation may serve as a buffer against nonsupportive emotion socialization. Copyright © 2011 Wiley Periodicals, Inc.

Analysis of Tospovirus NSs Proteins in Suppression of Systemic Silencing.

Science.gov (United States)

Hedil, Marcio; Sterken, Mark G; de Ronde, Dryas; Lohuis, Dick; Kormelink, Richard

2015-01-01

RNA silencing is a sequence-specific gene regulation mechanism that in plants also acts antiviral. In order to counteract antiviral RNA silencing, viruses have evolved RNA silencing suppressors (RSS). In the case of tospoviruses, the non-structural NSs protein has been identified as the RSS. Although the tomato spotted wilt virus (TSWV) tospovirus NSs protein has been shown to exhibit affinity to long and small dsRNA molecules, its ability to suppress the non-cell autonomous part of RNA silencing has only been studied to a limited extent. Here, the NSs proteins of TSWV, groundnut ringspot virus (GRSV) and tomato yellow ring virus (TYRV), representatives for three distinct tospovirus species, have been studied on their ability and strength to suppress local and systemic silencing. A system has been developed to quantify suppression of GFP silencing in Nicotiana benthamiana 16C lines, to allow a comparison of relative RNA silencing suppressor strength. It is shown that NSs of all three tospoviruses are suppressors of local and systemic silencing. Unexpectedly, suppression of systemic RNA silencing by NSsTYRV was just as strong as those by NSsTSWV and NSsGRSV, even though NSsTYRV was expressed in lower amounts. Using the system established, a set of selected NSsTSWV gene constructs mutated in predicted RNA binding domains, as well as NSs from TSWV isolates 160 and 171 (resistance breakers of the Tsw resistance gene), were analyzed for their ability to suppress systemic GFP silencing. The results indicate another mode of RNA silencing suppression by NSs that acts further downstream the biogenesis of siRNAs and their sequestration. The findings are discussed in light of the affinity of NSs for small and long dsRNA, and recent mutant screen of NSsTSWV to map domains required for RSS activity and triggering of Tsw-governed resistance.

Glechoma hederacea Suppresses RANKL-mediated Osteoclastogenesis.

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Hwang, J K; Erkhembaatar, M; Gu, D R; Lee, S H; Lee, C H; Shin, D M; Lee, Y R; Kim, M S

2014-07-01

Glechoma hederacea (GH), commonly known as ground-ivy or gill-over-the-ground, has been extensively used in folk remedies for relieving symptoms of inflammatory disorders. However, the molecular mechanisms underlying the therapeutic action of GH are poorly understood. Here, we demonstrate that GH constituents inhibit osteoclastogenesis by abrogating receptor activator of nuclear κ-B ligand (RANKL)-induced free cytosolic Ca(2+) ([Ca(2+)]i) oscillations. To evaluate the effect of GH on osteoclastogenesis, we assessed the formation of multi-nucleated cells (MNCs), enzymatic activity of tartrate-resistant acidic phosphatase (TRAP), expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), and [Ca(2+)]i alterations in response to treatment with GH ethanol extract (GHE) in primarily cultured bone marrow-derived macrophages (BMMs). Treatment of RANKL-stimulated or non-stimulated BMMs with GHE markedly suppressed MNC formation, TRAP activity, and NFATc1 expression in a dose-dependent manner. Additionally, GHE treatment induced a large transient elevation in [Ca(2+)]i while suppressing RANKL-induced [Ca(2+)]i oscillations, which are essential for NFATc1 activation. GHE-evoked increase in [Ca(2+)]i was dependent on extracellular Ca(2+) and was inhibited by 1,4-dihydropyridine (DHP), inhibitor of voltage-gated Ca(2+) channels (VGCCs), but was independent of store-operated Ca(2+) channels. Notably, after transient [Ca(2+)] elevation, treatment with GHE desensitized the VGCCs, resulting in an abrogation of RANKL-induced [Ca(2+)]i oscillations and MNC formation. These findings demonstrate that treatment of BMMs with GHE suppresses RANKL-mediated osteoclastogenesis by activating and then desensitizing DHP-sensitive VGCCs, suggesting potential applications of GH in the treatment of bone disorders, such as periodontitis, osteoporosis, and rheumatoid arthritis. © International & American Associations for Dental Research.

Oral delivery of Acid Alpha Glucosidase epitopes expressed in plant chloroplasts suppresses antibody formation in treatment of Pompe mice.

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Su, Jin; Sherman, Alexandra; Doerfler, Phillip A; Byrne, Barry J; Herzog, Roland W; Daniell, Henry

2015-10-01

Deficiency of acid alpha glucosidase (GAA) causes Pompe disease in which the patients systemically accumulate lysosomal glycogen in muscles and nervous systems, often resulting in infant mortality. Although enzyme replacement therapy (ERT) is effective in treating patients with Pompe disease, formation of antibodies against rhGAA complicates treatment. In this report, we investigated induction of tolerance by oral administration of GAA expressed in chloroplasts. Because full-length GAA could not be expressed, N-terminal 410-amino acids of GAA (as determined by T-cell epitope mapping) were fused with the transmucosal carrier CTB. Tobacco transplastomic lines expressing CTB-GAA were generated through site-specific integration of transgenes into the chloroplast genome. Homoplasmic lines were confirmed by Southern blot analysis. Despite low-level expression of CTB-GAA in chloroplasts, yellow or albino phenotype of transplastomic lines was observed due to binding of GAA to a chloroplast protein that has homology to mannose-6 phosphate receptor. Oral administration of the plant-made CTB-GAA fusion protein even at 330-fold lower dose (1.5 μg) significantly suppressed immunoglobulin formation against GAA in Pompe mice injected with 500 μg rhGAA per dose, with several-fold lower titre of GAA-specific IgG1 and IgG2a. Lyophilization increased CTB-GAA concentration by 30-fold (up to 190 μg per g of freeze-dried leaf material), facilitating long-term storage at room temperature and higher dosage in future investigations. This study provides the first evidence that oral delivery of plant cells is effective in reducing antibody responses in ERT for lysosomal storage disorders facilitating further advances in clinical investigations using plant cell culture system or in vitro propagation. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Lipid profiling demonstrates that suppressing Arabidopsis phospholipase Dδ retards ABA-promoted leaf senescence by attenuating lipid degradation.

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Yanxia Jia

Full Text Available Senescence is the last phase of the plant life cycle and has an important role in plant development. Degradation of membrane lipids is an essential process during leaf senescence. Several studies have reported fundamental changes in membrane lipids and phospholipase D (PLD activity as leaves senesce. Suppression of phospholipase Dα1 (PLDα1 retards abscisic acid (ABA-promoted senescence. However, given the absence of studies that have profiled changes in the compositions of membrane lipid molecules during leaf senescence, there is no direct evidence that PLD affects lipid composition during the process. Here, we show that application of n-butanol, an inhibitor of PLD, and N-Acylethanolamine (NAE 12∶0, a specific inhibitor of PLDα1, retarded ABA-promoted senescence to different extents. Furthermore, phospholipase Dδ (PLDδ was induced in leaves treated with ABA, and suppression of PLDδ retarded ABA-promoted senescence in Arabidopsis. Lipid profiling revealed that detachment-induced senescence had different effects on plastidic and extraplastidic lipids. The accelerated degradation of plastidic lipids during ABA-induced senescence in wild-type plants was attenuated in PLDδ-knockout (PLDδ-KO plants. Dramatic increases in phosphatidic acid (PA and decreases in phosphatidylcholine (PC during ABA-induced senescence were also suppressed in PLDδ-KO plants. Our results suggest that PLDδ-mediated hydrolysis of PC to PA plays a positive role in ABA-promoted senescence. The attenuation of PA formation resulting from suppression of PLDδ blocks the degradation of membrane lipids, which retards ABA-promoted senescence.

Assessing the Role of ETHYLENE RESPONSE FACTOR Transcriptional Repressors in Salicylic Acid-Mediated Suppression of Jasmonic Acid-Responsive Genes

NARCIS (Netherlands)

Caarls, Lotte; van der Does, Adriana; Hickman, Richard; Jansen, Wouter; van Verk, Marcel; Proietti, Silvia; Lorenzo, Oscar; Solano, Roberto; Pieterse, Corné M J; Van Wees, Saskia C M

2017-01-01

Salicylic acid (SA) and jasmonic acid (JA) cross-communicate in the plant immune signaling network to finely regulate induced defenses. In Arabidopsis, SA antagonizes many JA-responsive genes, partly by targeting the ETHYLENE RESPONSE FACTOR (ERF)-type transcriptional activator ORA59. Members of the

College Chemistry Students' Mental Models of Acids and Acid Strength

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McClary, LaKeisha; Talanquer, Vicente

2011-01-01

The central goal of this study was to characterize the mental models of acids and acid strength expressed by advanced college chemistry students when engaged in prediction, explanation, and justification tasks that asked them to rank chemical compounds based on their relative acid strength. For that purpose we completed a qualitative research…

Aging and repeated thought suppression success.

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Ann E Lambert

Full Text Available Intrusive thoughts and attempts to suppress them are common, but while suppression may be effective in the short-term, it can increase thought recurrence in the long-term. Because intentional suppression involves controlled processing, and many aspects of controlled processing decline with age, age differences in thought suppression outcomes may emerge, especially over repeated thought suppression attempts as cognitive resources are expended. Using multilevel modeling, we examined age differences in reactions to thought suppression attempts across four thought suppression sequences in 40 older and 42 younger adults. As expected, age differences were more prevalent during suppression than during free monitoring periods, with younger adults indicating longer, more frequent thought recurrences and greater suppression difficulty. Further, younger adults' thought suppression outcomes changed over time, while trajectories for older adults' were relatively stable. Results are discussed in terms of older adults' reduced thought recurrence, which was potentially afforded by age-related changes in reactive control and distractibility.

Improved prediction of residue flexibility by embedding optimized amino acid grouping into RSA-based linear models.

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Zhang, Hua; Kurgan, Lukasz

2014-12-01

Knowledge of protein flexibility is vital for deciphering the corresponding functional mechanisms. This knowledge would help, for instance, in improving computational drug design and refinement in homology-based modeling. We propose a new predictor of the residue flexibility, which is expressed by B-factors, from protein chains that use local (in the chain) predicted (or native) relative solvent accessibility (RSA) and custom-derived amino acid (AA) alphabets. Our predictor is implemented as a two-stage linear regression model that uses RSA-based space in a local sequence window in the first stage and a reduced AA pair-based space in the second stage as the inputs. This method is easy to comprehend explicit linear form in both stages. Particle swarm optimization was used to find an optimal reduced AA alphabet to simplify the input space and improve the prediction performance. The average correlation coefficients between the native and predicted B-factors measured on a large benchmark dataset are improved from 0.65 to 0.67 when using the native RSA values and from 0.55 to 0.57 when using the predicted RSA values. Blind tests that were performed on two independent datasets show consistent improvements in the average correlation coefficients by a modest value of 0.02 for both native and predicted RSA-based predictions.

Structural, magnetic and microwave absorption behavior of Co-Zr substituted strontium hexaferrites prepared using tartaric acid fuel for electromagnetic interference suppression

Energy Technology Data Exchange (ETDEWEB)

Kaur, Prabhjyot, E-mail: prabhjyot.2525@gmail.com [Department of Chemistry, Centre for Advanced Studies-I, Guru Nanak Dev University, Amritsar 143005 (India); Chawla, S.K., E-mail: sschawla118@gmail.com [Department of Chemistry, Centre for Advanced Studies-I, Guru Nanak Dev University, Amritsar 143005 (India); Narang, Sukhleen Bindra, E-mail: sukhleen2@yahoo.com [Department of Electronics Technology, Guru Nanak Dev University, Amritsar 143005 (India); Pubby, Kunal, E-mail: kunalpubby02@gmail.com [Department of Electronics Technology, Guru Nanak Dev University, Amritsar 143005 (India)

2017-01-15

Strontium hexaferrites, doped with varying Co-Zr content (x) have been synthesized by sol-gel auto-combustion route using tartaric acid as fuel at 800 °C. X-ray diffraction and Fourier transform Infra-red have been carried out to confirm the phase formation, particle size (average 21.9–36.8 nm) and the bond formation respectively. Magnetic properties are scrutinized using vibrating sample magnetometer. Techniques like scanning electron microscopy, transmission electron microscopy and energy dispersive scattering have been employed to explore the surface morphology, particle size and composition of the nano-powders. Electromagnetic characterization of the prepared ferrites has been done using Vector Network Anlyzer in 12.4–18 GHz frequency range. The effect of calcination temperature (500–1000 °C) on the structure, morphology and magnetic properties has also been studied for x=0.2 and 800 °C has been found to be the most suitable temperature with the best magnetic properties. Increase in doping has resulted in resonance peaks in dielectric and magnetic loss spectra, leading to microwave absorption peaks. Ferrites with x=0.2, 0.8 and 1.0 have appropriate reflection loss less than −10 dB and bandwidth in Ku-band, hence can be used as effective absorbers in suppression of electromagnetic interference (EMI). The governance of impedance matching in deciding the absorption properties has been proved by using input impedance calculations. - Highlights: • Co-Zr doped strontium hexaferrite nanopowders have been prepared by sol-gel route. • 800 °C was most suitable temperaturewith best structural and magnetic properties. • Samples have M-type hexagonal structure with an average particle size of 36.47 nm. • Samples x=0.2, 0.8 and 1.0 are suitable for suppression of EM waves in Ku-band. • The origin of absorption peaks: impedance matching and losses has been explained.

Predicting recovery from acid rain using the micro-spatial heterogeneity of soil columns downhill the infiltration zone of beech stemflow: introduction of a hypothesis.

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Berger, Torsten W; Muras, Alexander

Release of stored sulfur may delay the recovery of soil pH from Acid Rain. It is hypothesized that analyzing the micro-spatial heterogeneity of soil columns downhill of a beech stem enables predictions of soil recovery as a function of historic acid loads and time. We demonstrated in a very simplified approach, how these two different factors may be untangled from each other using synthetic data. Thereafter, we evaluated the stated hypothesis based upon chemical soil data with increasing distance from the stem of beech trees. It is predicted that the top soil will recover from acid deposition, as already recorded in the infiltration zone of stemflow near the base of the stem. However, in the between trees areas and especially in deeper soil horizons recovery may be highly delayed.

4,5-Di-O-Caffeoylquinic Acid from Ligularia fischeri Suppresses Inflammatory Responses Through TRPV1 Activation.

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Kim, Yiseul; Kim, Jung Tae; Park, Joonwoo; Son, Hee Jin; Kim, Eun-Young; Lee, Young Joo; Rhyu, Mee-Ra

2017-10-01

Ligularia fischeri (Ledeb.) Turcz., a perennial plant native to northeastern Asia, has long been used as folk remedies for the alleviation of inflammatory symptoms. We investigated whether the extract of L. fischeri (LFEx) and caffeoylquinic acid (CQA) derivatives, the pharmacologically active ingredients identified from L. fischeri, regulate inflammation via a transient receptor potential vanilloid 1 (TRPV1)-mediated pathway. Changes in intracellular Ca 2+ levels to the LFEx and trans-5-O-CQA, 3,4-di-O-CQA, 3,5-di-O-CQA, and 4,5-di-O-CQA were monitored in TRPV1-expressing human embryonic kidney cell HEK 293T. LFEx and 4,5-di-O-CQA (EC 50  = 69.34 ± 1.12 μM) activated TRPV1, and these activations were significantly inhibited by ruthenium red, a general blocker of TRP channels, and capsazepine, a specific antagonist of TRPV1. 4,5-Di-O-CQA has been determined having antiinflammatory effect under hypoxic conditions by detecting the expression of cyclooxygenase-2 (COX-2), a representative inflammatory marker, and cellular migration in human pulmonary epithelial A549 cells. 4,5-Di-O-CQA suppressed COX-2 expression and cell migration, and this inhibition was countered by co-treatment with capsazepine. This study provides evidence that L. fischeri is selective to inflammatory responses via a TRPV1-mediated pathway, and 4,5-di-O-CQA might play a key role to create these effects. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Incorporating Pitzer equations in a new thermodynamic model for the prediction of acid gases solubility in aqueous alkanolamine solutions

NARCIS (Netherlands)

Alhseinat, E.; Mota Martinez, M.; Peters, C.J.; Banat, F.

2014-01-01

In gas sweetening, acid gases such as CO2 and/or H2S are usually removed by "chemical" absorption through aqueous amine solutions such as N-Methyldiethanolamine (MDEA) solution. Reliable prediction of equilibrium properties (vapor–liquid equilibrium and species distribution) is needed for a rigorous

Using multiple linear regression and physicochemical changes of amino acid mutations to predict antigenic variants of influenza A/H3N2 viruses.

Science.gov (United States)

Cui, Haibo; Wei, Xiaomei; Huang, Yu; Hu, Bin; Fang, Yaping; Wang, Jia

2014-01-01

Among human influenza viruses, strain A/H3N2 accounts for over a quarter of a million deaths annually. Antigenic variants of these viruses often render current vaccinations ineffective and lead to repeated infections. In this study, a computational model was developed to predict antigenic variants of the A/H3N2 strain. First, 18 critical antigenic amino acids in the hemagglutinin (HA) protein were recognized using a scoring method combining phi (ϕ) coefficient and information entropy. Next, a prediction model was developed by integrating multiple linear regression method with eight types of physicochemical changes in critical amino acid positions. When compared to other three known models, our prediction model achieved the best performance not only on the training dataset but also on the commonly-used testing dataset composed of 31878 antigenic relationships of the H3N2 influenza virus.

Low urine pH and acid excretion do not predict bone fractures or the loss of bone mineral density: a prospective cohort study

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Lyon Andrew W

2010-05-01

Full Text Available Abstract Background The acid-ash hypothesis, the alkaline diet, and related products are marketed to the general public. Websites, lay literature, and direct mail marketing encourage people to measure their urine pH to assess their health status and their risk of osteoporosis. The objectives of this study were to determine whether 1 low urine pH, or 2 acid excretion in urine [sulfate + chloride + 1.8x phosphate + organic acids] minus [sodium + potassium + 2x calcium + 2x magnesium mEq] in fasting morning urine predict: a fragility fractures; and b five-year change of bone mineral density (BMD in adults. Methods Design: Cohort study: the prospective population-based Canadian Multicentre Osteoporosis Study. Multiple logistic regression was used to examine associations between acid excretion (urine pH and urine acid excretion in fasting morning with the incidence of fractures (6804 person years. Multiple linear regression was used to examine associations between acid excretion with changes in BMD over 5-years at three sites: lumbar spine, femoral neck, and total hip (n = 651. Potential confounders controlled included: age, gender, family history of osteoporosis, physical activity, smoking, calcium intake, vitamin D status, estrogen status, medications, renal function, urine creatinine, body mass index, and change of body mass index. Results There were no associations between either urine pH or acid excretion and either the incidence of fractures or change of BMD after adjustment for confounders. Conclusion Urine pH and urine acid excretion do not predict osteoporosis risk.

Amino acid sequence motifs essential for P0-mediated suppression of RNA silencing in an isolate of potato leafroll virus from Inner Mongolia.

Science.gov (United States)

Zhuo, Tao; Li, Yuan-Yuan; Xiang, Hai-Ying; Wu, Zhan-Yu; Wang, Xian-Bin; Wang, Ying; Zhang, Yong-Liang; Li, Da-Wei; Yu, Jia-Lin; Han, Cheng-Gui

2014-06-01

Polerovirus P0 suppressors of host gene silencing contain a consensus F-box-like motif with Leu/Pro (L/P) requirements for suppressor activity. The Inner Mongolian Potato leafroll virus (PLRV) P0 protein (P0(PL-IM)) has an unusual F-box-like motif that contains a Trp/Gly (W/G) sequence and an additional GW/WG-like motif (G139/W140/G141) that is lacking in other P0 proteins. We used Agrobacterium infiltration-mediated RNA silencing assays to establish that P0(PL-IM) has a strong suppressor activity. Mutagenesis experiments demonstrated that the P0(PL-IM) F-box-like motif encompasses amino acids 76-LPRHLHYECLEWGLLCG THP-95, and that the suppressor activity is abolished by L76A, W87A, or G88A substitution. The suppressor activity is also weakened substantially by mutations within the G139/W140/G141 region and is eliminated by a mutation (F220R) in a C-terminal conserved sequence of P0(PL-IM). As has been observed with other P0 proteins, P0(PL-IM) suppression is correlated with reduced accumulation of the host AGO1-silencing complex protein. However, P0(PL-IM) fails to bind SKP1, which functions in a proteasome pathway that may be involved in AGO1 degradation. These results suggest that P0(PL-IM) may suppress RNA silencing by using an alternative pathway to target AGO1 for degradation. Our results help improve our understanding of the molecular mechanisms involved in PLRV infection.

Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, suppresses vasculogenic mimicry and proliferation of highly aggressive pancreatic cancer PaTu8988 cells

International Nuclear Information System (INIS)

Xu, Xing-dong; Yang, Lan; Zheng, Li-yun; Pan, Yan-yan; Cao, Zhi-fei; Zhang, Zhi-qing; Zhou, Quan-sheng; Yang, Bo; Cao, Cong

2014-01-01

Pancreatic cancer is one of the most aggressive human malignancies with a extremely low 5-year survival rate. Hence, the search for more effective anti-pancreatic cancer agents is urgent. PaTu8988 pancreatic cancer cells were treated with different concentrations of suberoylanilide hydroxamic acid (SAHA), cell survival, proliferation, migration and vasculogenic mimicry (VM) were analyzed. Associated signaling changes were also analyzed by RT-PCR and Western blots. Here, we reported that SAHA, a histone deacetylase inhibitor (HDACi), exerted significant inhibitory efficiency against pancreatic cancer cell survival, proliferation, migration and VM. SAHA dose-dependently inhibited PaTu8988 pancreatic cancer cell growth with the IC-50 of 3.4 ± 0. 7 μM. Meanwhile, SAHA suppressed PaTu8988 cell cycle progression through inducing G2/M arrest, which was associated with cyclin-dependent kinase 1 (CDK-1)/cyclin-B1 degradation and p21/p27 upregulation. Further, SAHA induced both apoptotic and non-apoptotic death of PaTu8988 cells. Significantly, SAHA suppressed PaTu8988 cell in vitro migration and cell-dominant tube formation or VM, which was accompanied by semaphorin-4D (Sema-4D) and integrin-β5 down-regulation. Our evidences showed that Akt activation might be important for Sema-4D expression in PaTu8988 cells, and SAHA-induced Sema-4D down-regulation might be associated with Akt inhibition. This study is among the first to report the VM formation in cultured human pancreatic cancer cells. And we provided strong evidence to suggest that SAHA executes significant anti-VM efficiency in the progressive pancreatic cancer cells. Thus, SAHA could be further investigated as a promising anti-pancreatic cancer agent

Young adults' internet addiction: Prediction by the interaction of parental marital conflict and respiratory sinus arrhythmia.

Science.gov (United States)

Zhang, Hui; Spinrad, Tracy L; Eisenberg, Nancy; Luo, Yun; Wang, Zhenhong

2017-10-01

The aim of the current study was to address the potential moderating roles of respiratory sinus arrhythmia (RSA; baseline and suppression) and participant sex in the relation between parents' marital conflict and young adults' internet addiction. Participants included 105 (65 men) Chinese young adults who reported on their internet addiction and their parents' marital conflict. Marital conflict interacted with RSA suppression to predict internet addiction. Specifically, high RSA suppression was associated with low internet addiction, regardless of parental marital conflict; however, for participants with low RSA suppression, a positive relation between marital conflict and internet addiction was found. Internet addiction also was predicted by a significant three-way interaction among baseline RSA, marital conflict, and participant sex. Specifically, for men, marital conflict positively predicted internet addiction under conditions of low (but not high) baseline RSA. For women, marital conflict positively predicted internet addiction under conditions of high (but not low) baseline RSA. Findings highlight the importance of simultaneous consideration of physiological factors, in conjunction with family factors, in the prediction of young adults' internet addiction. Copyright © 2017 Elsevier B.V. All rights reserved.

The predictive value of mean serum uric acid levels for developing prediabetes.

Science.gov (United States)

Zhang, Qing; Bao, Xue; Meng, Ge; Liu, Li; Wu, Hongmei; Du, Huanmin; Shi, Hongbin; Xia, Yang; Guo, Xiaoyan; Liu, Xing; Li, Chunlei; Su, Qian; Gu, Yeqing; Fang, Liyun; Yu, Fei; Yang, Huijun; Yu, Bin; Sun, Shaomei; Wang, Xing; Zhou, Ming; Jia, Qiyu; Zhao, Honglin; Huang, Guowei; Song, Kun; Niu, Kaijun

2016-08-01

We aimed to assess the predictive value of mean serum uric acid (SUA) levels for incident prediabetes. Normoglycemic adults (n=39,353) were followed for a median of 3.0years. Prediabetes is defined as impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or impaired HbA1c (IA1c), based on the American Diabetes Association criteria. Serum SUA levels were measured annually. Four diagnostic strategies were used to detect prediabetes in four separate analyses (Analysis 1: IFG. Analysis 2: IFG+IGT. Analysis 3: IFG+IA1c. Analysis 4: IFG+IGT+IA1c). Cox proportional hazards regression models were used to assess the relationship between SUA quintiles and prediabetes. C-statistic was additionally used in the final analysis to assess the accuracy of predictions based upon baseline SUA and mean SUA, respectively. After adjustment for potential confounders, the hazard ratios (95% confidence interval) of prediabetes for the highest versus lowest quintile of mean SUA were 1.22 (1.10, 1.36) in analysis 1; 1.59 (1.23, 2.05) in analysis 2; 1.62 (1.34, 1.95) in analysis 3 and 1.67 (1.31, 2.13) in analysis 4. In contrast, for baseline SUA, significance was only reached in analyses 3 and 4. Moreover, compared with baseline SUA, mean SUA value was associated with a significant increase in the C-statistic (Pprediabetes risk, and showed better predictive ability for prediabetes than baseline SUA. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Ursolic acid improves domoic acid-induced cognitive deficits in mice

International Nuclear Information System (INIS)

Wu, Dong-mei; Lu, Jun; Zhang, Yan-qiu; Zheng, Yuan-lin; Hu, Bin; Cheng, Wei; Zhang, Zi-feng; Li, Meng-qiu

2013-01-01

Our previous findings suggest that mitochondrial dysfunction is the mechanism underlying cognitive deficits induced by domoic acid (DA). Ursolic acid (UA), a natural triterpenoid compound, possesses many important biological functions. Evidence shows that UA can activate PI3K/Akt signaling and suppress Forkhead box protein O1 (FoxO1) activity. FoxO1 is an important regulator of mitochondrial function. Here we investigate whether FoxO1 is involved in the oxidative stress-induced mitochondrial dysfunction in DA-treated mice and whether UA inhibits DA-induced mitochondrial dysfunction and cognitive deficits through regulating the PI3K/Akt and FoxO1 signaling pathways. Our results showed that FoxO1 knockdown reversed the mitochondrial abnormalities and cognitive deficits induced by DA in mice through decreasing HO-1 expression. Mechanistically, FoxO1 activation was associated with oxidative stress-induced JNK activation and decrease of Akt phosphorylation. Moreover, UA attenuated the mitochondrial dysfunction and cognitive deficits through promoting Akt phosphorylation and FoxO1 nuclear exclusion in the hippocampus of DA-treated mice. LY294002, an inhibitor of PI3K/Akt signaling, significantly decreased Akt phosphorylation in the hippocampus of DA/UA mice, which weakened UA actions. These results suggest that UA could be recommended as a possible candidate for the prevention and therapy of cognitive deficits in excitotoxic brain disorders. - Highlights: • Ursolic acid (UA) is a naturally triterpenoid compound. • UA attenuated the mitochondrial dysfunction and cognitive deficits. • Mechanistically, UA activates PI3K/Akt signaling and suppresses FoxO1 activity. • UA could be recommended as a possible candidate for anti-excitotoxic brain disorders

Ursolic acid improves domoic acid-induced cognitive deficits in mice

Energy Technology Data Exchange (ETDEWEB)

Wu, Dong-mei [School of Environment and Spatial Informatics, China University of Mining and Technology, Xuzhou 221008, Jiangsu Province (China); Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province (China); Lu, Jun, E-mail: lu-jun75@163.com [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province (China); Zhang, Yan-qiu [School of Environment and Spatial Informatics, China University of Mining and Technology, Xuzhou 221008, Jiangsu Province (China); Zheng, Yuan-lin, E-mail: ylzheng@xznu.edu.cn [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province (China); Hu, Bin [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province (China); Cheng, Wei [School of Environment and Spatial Informatics, China University of Mining and Technology, Xuzhou 221008, Jiangsu Province (China); Zhang, Zi-feng; Li, Meng-qiu [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province (China)

2013-09-01

Our previous findings suggest that mitochondrial dysfunction is the mechanism underlying cognitive deficits induced by domoic acid (DA). Ursolic acid (UA), a natural triterpenoid compound, possesses many important biological functions. Evidence shows that UA can activate PI3K/Akt signaling and suppress Forkhead box protein O1 (FoxO1) activity. FoxO1 is an important regulator of mitochondrial function. Here we investigate whether FoxO1 is involved in the oxidative stress-induced mitochondrial dysfunction in DA-treated mice and whether UA inhibits DA-induced mitochondrial dysfunction and cognitive deficits through regulating the PI3K/Akt and FoxO1 signaling pathways. Our results showed that FoxO1 knockdown reversed the mitochondrial abnormalities and cognitive deficits induced by DA in mice through decreasing HO-1 expression. Mechanistically, FoxO1 activation was associated with oxidative stress-induced JNK activation and decrease of Akt phosphorylation. Moreover, UA attenuated the mitochondrial dysfunction and cognitive deficits through promoting Akt phosphorylation and FoxO1 nuclear exclusion in the hippocampus of DA-treated mice. LY294002, an inhibitor of PI3K/Akt signaling, significantly decreased Akt phosphorylation in the hippocampus of DA/UA mice, which weakened UA actions. These results suggest that UA could be recommended as a possible candidate for the prevention and therapy of cognitive deficits in excitotoxic brain disorders. - Highlights: • Ursolic acid (UA) is a naturally triterpenoid compound. • UA attenuated the mitochondrial dysfunction and cognitive deficits. • Mechanistically, UA activates PI3K/Akt signaling and suppresses FoxO1 activity. • UA could be recommended as a possible candidate for anti-excitotoxic brain disorders.

Physical-chemical model for cellular uptake of fatty acids: prediction of intracellular pool sizes

International Nuclear Information System (INIS)

Cooper, R.; Noy, N.; Zakim, D.

1987-01-01

If the uptake of fatty acids by liver is a physical, not a biological, process, then the size and location of the intrahepatic pool of fatty acids can be predicted from uptake rates and thermodynamic data. The purpose of the experiments in this paper was to test the accuracy of this idea. Rat livers were perfused with [ 3 H] palmitate bound to [ 14 C] albumin, and the total amounts of palmitate removed from the perfusate were measured at 3-s intervals. The intrahepatic pools of palmitate calculated from these data were 13.8 and 23.0 nmol/g of liver at ratios of palmitate/albumin (mol/mol) (afferent side) of 2/1 and 4/1, respectively, in the steady state. The intrahepatic pools of palmitate calculated from the distributions of palmitate between membranes, H 2 O, albumin, and fatty acid binding protein and the measured first-order rate constants for acyl-CoA ligases in mitochondria and microsomes were 12.1 and 34.6 nmol/g for perfusate ratios of palmitate/albumin of 2/1 and 4/1, in the steady state. Intrahepatic pools of palmitate measured after establishment of a steady-state rate of uptake were 15.0 and 31.8 nmol/g for these ratios of palmitate/albumin of 2/1 and 4/1

Deer Bone Oil Extract Suppresses Lipopolysaccharide-Induced Inflammatory Responses in RAW264.7 Cells.

Science.gov (United States)

Choi, Hyeon-Son; Im, Suji; Park, Yooheon; Hong, Ki-Bae; Suh, Hyung Joo

2016-01-01

The aim of this study was to investigate the effect of deer bone oil extract (DBOE) on lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 cells. DBOE was fractionated by liquid-liquid extraction to obtain two fractions: methanol fraction (DBO-M) and hexane fraction (DBO-H). TLC showed that DBO-M had relatively more hydrophilic lipid complexes, including unsaturated fatty acids, than DBOE and DBO-H. The relative compositions of tetradecenoyl carnitine, α-linoleic acid, and palmitoleic acid increased in the DBO-M fraction by 61, 38, and 32%, respectively, compared with DBOE. The concentration of sugar moieties was 3-fold higher in the DBO-M fraction than DBOE and DBO-H. DBO-M significantly decreased LPS-induced nitric oxide (NO) production in RAW264.7 cells in a dose-dependent manner. This DBO-M-mediated decrease in NO production was due to downregulation of mRNA and protein levels of inducible nitric oxide synthase (iNOS). In addition, mRNA expression of pro-inflammatory mediators, such as cyclooxygenase (COX-2), interleukin (IL)-1β, and IL-12β, was suppressed by DBO-M. Our data showed that DBO-M, which has relatively higher sugar content than DBOE and DBO-H, could play an important role in suppressing inflammatory responses by controlling pro-inflammatory cytokines and mediators.

Iron-chelating agents never suppress Fenton reaction but participate in quenching spin-trapped radicals

International Nuclear Information System (INIS)

Li Linxiang; Abe, Yoshihiro; Kanagawa, Kiyotada; Shoji, Tomoko; Mashino, Tadahiko; Mochizuki, Masataka; Tanaka, Miho; Miyata, Naoki

2007-01-01

Hydroxyl radical formation by Fenton reaction in the presence of an iron-chelating agent such as EDTA was traced by two different assay methods; an electron spin resonance (ESR) spin-trapping method with 5,5-dimethyl-1-pyrroline N-oxide (DMPO), and high Performance liquid chromatography (HPLC)-fluorescence detection with terephthalic acid (TPA), a fluorescent probe for hydroxyl radicals. From the ESR spin-trapping measurement, it was observed that EDTA seemed to suppress hydroxyl radical formation with the increase of its concentration. On the other hand, hydroxyl radical formation by Fenton reaction was not affected by EDTA monitored by HPLC assay. Similar inconsistent effects of other iron-chelating agents such as nitrylotriacetic acid (NTA), diethylenetriamine penta acetic acid (DTPA), oxalate and citrate were also observed. On the addition of EDTA solution to the reaction mixture 10 min after the Fenton reaction started, when hydroxyl radical formation should have almost ceased but the ESR signal of DMPO-OH radicals could be detected, it was observed that the DMPO-OH· signal disappeared rapidly. With the simultaneous addition of Fe(II) solution and EDTA after the Fenton reaction ceased, the DMPO-OH· signal disappeared more rapidly. The results indicated that these chelating agents should enhance the quenching of [DMPO-OH]· radicals by Fe(II), but they did not suppress Fenton reaction by forming chelates with iron ions

Can-Evo-Ens: Classifier stacking based evolutionary ensemble system for prediction of human breast cancer using amino acid sequences.

Science.gov (United States)

Ali, Safdar; Majid, Abdul

2015-04-01

The diagnostic of human breast cancer is an intricate process and specific indicators may produce negative results. In order to avoid misleading results, accurate and reliable diagnostic system for breast cancer is indispensable. Recently, several interesting machine-learning (ML) approaches are proposed for prediction of breast cancer. To this end, we developed a novel classifier stacking based evolutionary ensemble system "Can-Evo-Ens" for predicting amino acid sequences associated with breast cancer. In this paper, first, we selected four diverse-type of ML algorithms of Naïve Bayes, K-Nearest Neighbor, Support Vector Machines, and Random Forest as base-level classifiers. These classifiers are trained individually in different feature spaces using physicochemical properties of amino acids. In order to exploit the decision spaces, the preliminary predictions of base-level classifiers are stacked. Genetic programming (GP) is then employed to develop a meta-classifier that optimal combine the predictions of the base classifiers. The most suitable threshold value of the best-evolved predictor is computed using Particle Swarm Optimization technique. Our experiments have demonstrated the robustness of Can-Evo-Ens system for independent validation dataset. The proposed system has achieved the highest value of Area Under Curve (AUC) of ROC Curve of 99.95% for cancer prediction. The comparative results revealed that proposed approach is better than individual ML approaches and conventional ensemble approaches of AdaBoostM1, Bagging, GentleBoost, and Random Subspace. It is expected that the proposed novel system would have a major impact on the fields of Biomedical, Genomics, Proteomics, Bioinformatics, and Drug Development. Copyright © 2015 Elsevier Inc. All rights reserved.

HpARI Protein Secreted by a Helminth Parasite Suppresses Interleukin-33.

Science.gov (United States)

Osbourn, Megan; Soares, Dinesh C; Vacca, Francesco; Cohen, E Suzanne; Scott, Ian C; Gregory, William F; Smyth, Danielle J; Toivakka, Matilda; Kemter, Andrea M; le Bihan, Thierry; Wear, Martin; Hoving, Dennis; Filbey, Kara J; Hewitson, James P; Henderson, Holly; Gonzàlez-Cìscar, Andrea; Errington, Claire; Vermeren, Sonja; Astier, Anne L; Wallace, William A; Schwarze, Jürgen; Ivens, Alasdair C; Maizels, Rick M; McSorley, Henry J

2017-10-17

Infection by helminth parasites is associated with amelioration of allergic reactivity, but mechanistic insights into this association are lacking. Products secreted by the mouse parasite Heligmosomoides polygyrus suppress type 2 (allergic) immune responses through interference in the interleukin-33 (IL-33) pathway. Here, we identified H. polygyrus Alarmin Release Inhibitor (HpARI), an IL-33-suppressive 26-kDa protein, containing three predicted complement control protein (CCP) modules. In vivo, recombinant HpARI abrogated IL-33, group 2 innate lymphoid cell (ILC2) and eosinophilic responses to Alternaria allergen administration, and diminished eosinophilic responses to Nippostrongylus brasiliensis, increasing parasite burden. HpARI bound directly to both mouse and human IL-33 (in the cytokine's activated state) and also to nuclear DNA via its N-terminal CCP module pair (CCP1/2), tethering active IL-33 within necrotic cells, preventing its release, and forestalling initiation of type 2 allergic responses. Thus, HpARI employs a novel molecular strategy to suppress type 2 immunity in both infection and allergy. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

HIV-1 nef suppression by virally encoded microRNA

Directory of Open Access Journals (Sweden)

Brisibe Ebiamadon

2004-12-01

Full Text Available Abstract Background MicroRNAs (miRNAs are 21~25-nucleotides (nt long and interact with mRNAs to trigger either translational repression or RNA cleavage through RNA interference (RNAi, depending on the degree of complementarity with the target mRNAs. Our recent study has shown that HIV-1 nef dsRNA from AIDS patients who are long-term non-progressors (LTNPs inhibited the transcription of HIV-1. Results Here, we show the possibility that nef-derived miRNAs are produced in HIV-1 persistently infected cells. Furthermore, nef short hairpin RNA (shRNA that corresponded to a predicted nef miRNA (~25 nt, miR-N367 can block HIV-1 Nef expression in vitro and the suppression by shRNA/miR-N367 would be related with low viremia in an LTNP (15-2-2. In the 15-2-2 model mice, the weight loss, which may be rendered by nef was also inhibited by shRNA/miR-N367 corresponding to suppression of nef expression in vivo. Conclusions These data suggest that nef/U3 miRNAs produced in HIV-1-infected cells may suppress both Nef function and HIV-1 virulence through the RNAi pathway.

Mixing-controlled uncertainty in long-term predictions of acid rock drainage from heterogeneous waste-rock piles

Science.gov (United States)

Pedretti, D.; Beckie, R. D.; Mayer, K. U.

2015-12-01

The chemistry of drainage from waste-rock piles at mine sites is difficult to predict because of a number of uncertainties including heterogeneous reactive mineral content, distribution of minerals, weathering rates and physical flow properties. In this presentation, we examine the effects of mixing on drainage chemistry over timescales of 100s of years. We use a 1-D streamtube conceptualization of flow in waste rocks and multicomponent reactive transport modeling. We simplify the reactive system to consist of acid-producing sulfide minerals and acid-neutralizing carbonate minerals and secondary sulfate and iron oxide minerals. We create multiple realizations of waste-rock piles with distinct distributions of reactive minerals along each flow path and examine the uncertainty of drainage geochemistry through time. The limited mixing of streamtubes that is characteristic of the vertical unsaturated flow in many waste-rock piles, allows individual flowpaths to sustain acid or neutral conditions to the base of the pile, where the streamtubes mix. Consequently, mixing and the acidity/alkalinity balance of the streamtube waters, and not the overall acid- and base-producing mineral contents, control the instantaneous discharge chemistry. Our results show that the limited mixing implied by preferential flow and the heterogeneous distribution of mineral contents lead to large uncertainty in drainage chemistry over short and medium time scales. However, over longer timescales when one of either the acid-producing or neutralizing primary phases is depleted, the drainage chemistry becomes less controlled by mixing and in turn less uncertain. A correct understanding of the temporal variability of uncertainty is key to make informed long-term decisions in mining settings regarding the management of waste material.

PON-Sol: prediction of effects of amino acid substitutions on protein solubility.

Science.gov (United States)

Yang, Yang; Niroula, Abhishek; Shen, Bairong; Vihinen, Mauno

2016-07-01

Solubility is one of the fundamental protein properties. It is of great interest because of its relevance to protein expression. Reduced solubility and protein aggregation are also associated with many diseases. We collected from literature the largest experimentally verified solubility affecting amino acid substitution (AAS) dataset and used it to train a predictor called PON-Sol. The predictor can distinguish both solubility decreasing and increasing variants from those not affecting solubility. PON-Sol has normalized correct prediction ratio of 0.491 on cross-validation and 0.432 for independent test set. The performance of the method was compared both to solubility and aggregation predictors and found to be superior. PON-Sol can be used for the prediction of effects of disease-related substitutions, effects on heterologous recombinant protein expression and enhanced crystallizability. One application is to investigate effects of all possible AASs in a protein to aid protein engineering. PON-Sol is freely available at http://structure.bmc.lu.se/PON-Sol The training and test data are available at http://structure.bmc.lu.se/VariBench/ponsol.php mauno.vihinen@med.lu.se Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Diagnostic performance of calcification-suppressed coronary CT angiography using rapid kilovolt-switching dual-energy CT.

Science.gov (United States)

Yunaga, Hiroto; Ohta, Yasutoshi; Kaetsu, Yasuhiro; Kitao, Shinichiro; Watanabe, Tomomi; Furuse, Yoshiyuki; Yamamoto, Kazuhiro; Ogawa, Toshihide

2017-07-01

Multi-detector-row computed tomography angiography (MDCTA) plays an important role in the assessment of patients with suspected coronary artery disease. However, MDCTA tends to overestimate stenosis in calcified coronary artery lesions. The aim of our study was to evaluate the diagnostic performance of calcification-suppressed material density (MD) images produced by using a single-detector single-source dual-energy computed tomography (ssDECT). We enrolled 67 patients with suspected or known coronary artery disease who underwent ssDECT with rapid kilovolt-switching (80 and 140 kVp). Coronary artery stenosis was evaluated on the basis of MD images and virtual monochromatic (VM) images. The diagnostic performance of the two methods for detecting coronary artery disease was compared with that of invasive coronary angiography as a reference standard. We evaluated 239 calcified segments. In all the segments, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for detecting significant stenosis were respectively 88%, 88%, 75%, 95% and 88% for the MD images, 91%, 71%, 56%, 95% and 77% for the VM images. PPV was significantly higher on the MD images than on the VM images (P < 0.0001). Calcification-suppressed MD images improved PPV and diagnostic performance for calcified coronary artery lesions. • Computed tomography angiography tends to overestimate stenosis in calcified coronary artery. • Dual-energy CT enables us to suppress calcification of coronary artery lesions. • Calcification-suppressed material density imaging reduces false-positive diagnosis of calcified lesion.

Factor structure and clinical correlates of the Food Thought Suppression Inventory within treatment seeking obese women with binge eating disorder

Science.gov (United States)

Barnes, Rachel D.; Sawaoka, Takuya; White, Marney A.; Masheb, Robin M.; Grilo, Carlos M.

2013-01-01

Prior research on the relations among eating behaviors and thought suppression is limited to a measure of general thought suppression, the White Bear Suppression Inventory. To address this limitation, researchers recently validated the Food Thought Suppression Inventory (FTSI). Analyses using this measure suggest that food thought suppression is distinct from and is more predictive of eating disorder psychopathology than is general thought suppression. The FTSI, however, has not yet been validated in clinical samples. The purpose of the current study is to examine the factor structure and clinical correlates of the FTSI within treatment seeking obese women with binge eating disorder (BED; N = 128). Analyses revealed a valid and reliable one-factor measure of food thought suppression that was related to higher levels of eating and general psychopathology. The findings provide evidence for the use of the FTSI with obese women with BED. Future research should examine the psychometric properties of the FTSI within larger and more diverse samples. PMID:23265399

Factor structure and clinical correlates of the Food Thought Suppression Inventory within treatment seeking obese women with binge eating disorder.

Science.gov (United States)

Barnes, Rachel D; Sawaoka, Takuya; White, Marney A; Masheb, Robin M; Grilo, Carlos M

2013-01-01

Prior research on the relations among eating behaviors and thought suppression is limited to a measure of general thought suppression, the White Bear Suppression Inventory. To address this limitation, researchers recently validated the Food Thought Suppression Inventory (FTSI). Analyses using this measure suggest that food thought suppression is distinct from and is more predictive of eating disorder psychopathology than is general thought suppression. The FTSI, however, has not yet been validated in clinical samples. The purpose of the current study is to examine the factor structure and clinical correlates of the FTSI within treatment seeking obese women with binge eating disorder (BED; N=128). Analyses revealed a valid and reliable one-factor measure of food thought suppression that was related to higher levels of eating and general psychopathology. The findings provide evidence for the use of the FTSI with obese women with BED. Future research should examine the psychometric properties of the FTSI within larger and more diverse samples. Copyright © 2012. Published by Elsevier Ltd.

Defense Response and Suppression of Phytophthora Blight Disease of Pepper by Water Extract from Spent Mushroom Substrate of Lentinula edodes

Directory of Open Access Journals (Sweden)

Dae-Sun Kang

2017-06-01

Full Text Available The spent mushroom substrate (SMS of Lentinula edodes that was derived from sawdust bag cultivation was used as materials for controlling Phytophthora blight disease of pepper. Water extract from SMS (WESMS of L. edodes inhibited mycelial growth of Phytophthora capsici, suppressed Phytophthora blight disease of pepper seedlings by 65% and promoted growth of the plant over 30%. In high performance liquid chromatography (HPLC analysis, oxalic acid was detected as the main organic acid compound in WESMS and inhibited the fungal mycelium at a minimum concentration of 200 mg/l. In quantitative real-time PCR, the transcriptional expression of CaBPR1 (PR protein 1, CaBGLU (β-1,3-glucanase, CaPR-4 (PR protein 4, and CaPR-10 (PR protein 10 were significantly enhanced on WESMS and DL-β-aminobutyric acid (BABA treated pepper leaves. In addition, the salicylic acid content was also increased 4 to 6 folds in the WESMS and BABA treated pepper leaves compared to water treated leaf sample. These findings suggest that WESMS of L. edodes suppress Phytophthora blight disease of pepper through multiple effects including antifungal activity, plant growth promotion, and defense gene induction.

Suppression of elongation and growth of tomato seedlings by auxin biosynthesis inhibitors and modeling of the growth and environmental response.

Science.gov (United States)

Higashide, Tadahisa; Narukawa, Megumi; Shimada, Yukihisa; Soeno, Kazuo

2014-04-02

To develop a growth inhibitor, the effects of auxin inhibitors were investigated. Application of 30 μM L-α-aminooxy-β-phenylpropionic acid (AOPP) or (S)-methyl 2-((1,3-dioxoisoindolin-2-yl)oxy)-3-phenylpropanoate (KOK1101), decreased the endogenous IAA levels in tomato seedlings at 8 days after sowing. Then, 10-1200 μM AOPP or KOK1101 were sprayed on the leaves and stem of 2-3 leaf stage tomato plants grown under a range of environmental conditions. We predicted plant growth and environmental response using a model based on the observed suppression of leaf enlargement. Spraying AOPP or KOK1101 decreased stem length and leaf area. Concentration-dependent inhibitions and dose response curves were observed. Although the effects of the inhibitors on dry weight varied according to the environmental conditions, the net assimilation rate was not influenced by the inhibitors. Accordingly, the observed decrease in dry weight caused by the inhibitors may result from decreased leaf area. Validation of the model based on observed data independent of the dataset showed good correlations between the observed and predicted values of dry weight and leaf area index.

Distracted by the Unthought - Suppression and Reappraisal of Mind Wandering under Stereotype Threat.

Science.gov (United States)

Schuster, Carolin; Martiny, Sarah E; Schmader, Toni

2015-01-01

Previous research has found that subtle reminders of negative stereotypes about one's group can lead individuals to underperform on stereotype-relevant tests (e.g., women in math, ethnic minorities on intelligence tests). This so called stereotype threat effect can contribute to systematic group differences in performance that can obscure the true abilities of certain social groups and thereby sustain social inequalities. In the present study, we examined processes underlying stereotype threat effects on women's math performance, specifically focusing on the role of suppression of mind wandering (i.e., task-irrelevant thinking) in stereotype threat (ST) and no threat (NT) situations. Based on a process model of stereotype threat effects on performance, we hypothesized that women under stereotype threat spontaneously suppress mind wandering, and that this suppression impairs performance. An alternative regulation strategy that prevents suppression (i.e., reappraising task-irrelevant thoughts as normal) was predicted to prevent stereotype threat effects on performance. We manipulated stereotype threat (ST vs. NT) and cognitive regulation strategy (suppression, reappraisal, or no strategy) and measured women's performance on a math and a concentration task (N = 113). We expected three groups to perform relatively more poorly: Those in ST with either no strategy or suppression and those in NT with a suppression strategy. We tested the performance of these groups against the remaining three groups hypothesized to perform relatively better: those in NT with no strategy or reappraisal and those in ST with reappraisal. The results showed the expected pattern for participants' math performance, but not for concentration achievement. This pattern suggests that ineffective self-regulation by suppressing mind wandering can at least partly explain stereotype threat effects on performance, whereas a reappraisal strategy can prevent this impairment. We discuss implications for

On the Relationship Between Musicianship and Contralateral Suppression of Transient-Evoked Otoacoustic Emissions.

Science.gov (United States)

Stuart, Andrew; Daughtrey, Emma R

2016-04-01

The medial olivocochlear (MOC) efferent reflex that modulates outer hair cell function has been shown to be more robust in musicians versus nonmusicians as evidenced in greater contralateral suppression of transient-evoked otoacoustic emissions (TEOAEs). All previous research comparing musical ability and MOC efferent strength has defined musicianship dichotomously (i.e., high-level music students or professional classical musicians versus nonmusicians). The objective of the study was to further explore contralateral suppression of TEOAEs among adults with a full spectrum of musicianship ranging from no history of musicianship to professional musicians. Musicianship was defined by both self-report and with an objective test to quantify individual differences in perceptual music skills. A single-factor between-subjects and correlational research designs were employed. Forty-five normal-hearing young adults participated. Participants completed a questionnaire concerning their music experience and completed the Brief Profile of Music Perception Skills (PROMS) to quantify perceptual musical skills across multiple musical domains (i.e., accent, melody, tempo, and tuning). TEOAEs were evaluated with 60 dB peak equivalent sound pressure level click stimuli with and without a contralateral 65 dB sound pressure level white noise suppressor. TEOAE suppression was expressed in two ways, absolute TEOAE suppression in dB and a normalized index of TEOAE suppression (i.e., percentage of suppression). Participants who considered themselves musicians scored significantly higher on all subscales and total Brief PROMS score (p 0.05). There were no statistically significant correlations or linear predictive relationships between subscale or total Brief PROMS scores with absolute and percentage of TEOAE suppression (p > 0.05). The findings do not support the notion of a graded enhancement of MOC efferent suppression among adults with varied degrees of musicianship from nonmusicians to

Photodegradation kinetics, transformation, and toxicity prediction of ketoprofen, carprofen, and diclofenac acid in aqueous solutions.

Science.gov (United States)

Li, Jian; Ma, Li-Yun; Li, Lu-Shuang; Xu, Li

2017-12-01

Photodegradation of 3 commonly used nonsteroidal anti-inflammatory drugs, ketoprofen, carprofen, and diclofenac acid, was conducted under ultraviolet (UV) irradiation. The kinetic results showed that the 3 pharmaceuticals obeyed the first-order reaction with decreasing rate constants of 1.54 × 10 -4 , 5.91 × 10 -5 , and 7.78 × 10 -6  s -1 for carprofen, ketoprofen, and diclofenac acid, respectively. Moreover, the main transformation products were identified by ion-pair liquid-liquid extraction combined with injection port derivatization-gas chromatography-mass spectrometry and high-performance liquid chromatography-quadrupole-time of flight mass spectrometric analysis. There were 8, 3, and 6 transformation products identified for ketoprofen, carprofen, and diclofenac acid, respectively. Decarboxylation, dechlorination, oxidation, demethylation, esterification, and cyclization were proposed to be associated with the transformation of the 3 pharmaceuticals. Toxicity prediction of the transformation products was conducted on the EPI Suite software based on ECOSAR model, and the results indicate that some of the transformation products were more toxic than the parent compounds. The present study provides the foundation to understand the transformation behavior of the studied pharmaceuticals under UV irradiation. Environ Toxicol Chem 2017;36:3232-3239. © 2017 SETAC. © 2017 SETAC.

Pressure suppressing device

International Nuclear Information System (INIS)

Naito, Makoto.

1980-01-01

Purpose: To prevent the pressure in the reactor container from excessively increasing even when vapor leaks from the dry well to a space of the suppression chamber, without passing though the suppression pool at the time of loss of coolant accident. Constitution: When vapor of a high temperature and a high pressure at the time of loss of coolant accident flows from the dry well to the suppression chamber without passing through suppression pool water, vapor dose not condense with pool water, and therefore the pressure within the chamber abnormally increases. For this reason, this abnormal pressure is detected by a pressure detector thereby to start the operations of a blower and a pump. By starting the blower, the pressure in the dry well becomes lower than the pressure in the chamber, and vapor entirely passes through the pool water and entirely condenses with the pool water. By starting the pump, the pool water is sprayed over the space of the chamber, and vapor in the space is condensed. (Yoshino, Y.)

The role of suppression in amblyopia.

Science.gov (United States)

Li, Jingrong; Thompson, Benjamin; Lam, Carly S Y; Deng, Daming; Chan, Lily Y L; Maehara, Goro; Woo, George C; Yu, Minbin; Hess, Robert F

2011-06-13

This study had three main goals: to assess the degree of suppression in patients with strabismic, anisometropic, and mixed amblyopia; to establish the relationship between suppression and the degree of amblyopia; and to compare the degree of suppression across the clinical subgroups within the sample. Using both standard measures of suppression (Bagolini lenses and neutral density [ND] filters, Worth 4-Dot test) and a new approach involving the measurement of dichoptic motion thresholds under conditions of variable interocular contrast, the degree of suppression in 43 amblyopic patients with strabismus, anisometropia, or a combination of both was quantified. There was good agreement between the quantitative measures of suppression made with the new dichoptic motion threshold technique and measurements made with standard clinical techniques (Bagolini lenses and ND filters, Worth 4-Dot test). The degree of suppression was found to correlate directly with the degree of amblyopia within our clinical sample, whereby stronger suppression was associated with a greater difference in interocular acuity and poorer stereoacuity. Suppression was not related to the type or angle of strabismus when this was present or the previous treatment history. These results suggest that suppression may have a primary role in the amblyopia syndrome and therefore have implications for the treatment of amblyopia.

Suppression of Alfven Modes on the National Spherical Torus Experiment Upgrade with Outboard Beam Injection [Suppression of Alfven Modes on the NSTX-U with Outboard Beam Injection

International Nuclear Information System (INIS)

Fredrickson, E. D.; Belova, E. V.; Battaglia, D. J.

2017-01-01

In this paper we present data from experiments on the National Spherical Torus Experiment Upgrade, where it is shown for the first time that small amounts of high pitch-angle beam ions can strongly suppress the counterpropagating global Alfven eigenmodes (GAE). GAE have been implicated in the redistribution of fast ions and modification of the electron power balance in previous experiments on NSTX. The ability to predict the stability of Alfven modes, and developing methods to control them, is important for fusion reactors like the International Tokamak Experimental Reactor, which are heated by a large population of nonthermal, super-Alfvenic ions consisting of fusion generated alpha's and beam ions injected for current profile control. We present a qualitative interpretation of these observations using an analytic model of the Doppler-shifted ion-cyclotron resonance drive responsible for GAE instability which has an important dependence on k(perpendicular to rho L). A quantitative analysis of this data with the HYM stability code predicts both the frequencies and instability of the GAE prior to, and suppression of the GAE after the injection of high pitch-angle beam ions.

Auditory prediction during speaking and listening.

Science.gov (United States)

Sato, Marc; Shiller, Douglas M

2018-02-02

In the present EEG study, the role of auditory prediction in speech was explored through the comparison of auditory cortical responses during active speaking and passive listening to the same acoustic speech signals. Two manipulations of sensory prediction accuracy were used during the speaking task: (1) a real-time change in vowel F1 feedback (reducing prediction accuracy relative to unaltered feedback) and (2) presenting a stable auditory target rather than a visual cue to speak (enhancing auditory prediction accuracy during baseline productions, and potentially enhancing the perturbing effect of altered feedback). While subjects compensated for the F1 manipulation, no difference between the auditory-cue and visual-cue conditions were found. Under visually-cued conditions, reduced N1/P2 amplitude was observed during speaking vs. listening, reflecting a motor-to-sensory prediction. In addition, a significant correlation was observed between the magnitude of behavioral compensatory F1 response and the magnitude of this speaking induced suppression (SIS) for P2 during the altered auditory feedback phase, where a stronger compensatory decrease in F1 was associated with a stronger the SIS effect. Finally, under the auditory-cued condition, an auditory repetition-suppression effect was observed in N1/P2 amplitude during the listening task but not active speaking, suggesting that auditory predictive processes during speaking and passive listening are functionally distinct. Copyright © 2018 Elsevier Inc. All rights reserved.

Factors that influence therapeutic outcomes in symptomatic gastroesophageal reflux disease.

LENUS (Irish Health Repository)

Quigley, Eamonn M M

2012-02-03

The term "symptomatic gastroesophageal reflux disease" (GERD) refers to those patients who present with the typical GERD symptoms of heartburn and regurgitation, yet do not have endoscopic evidence of esophagitis. The primary goals of managing symptomatic GERD are to control symptoms and improve quality of life. A clinical assessment of the GERD patient can identify important clinical features, such as atypical and extraesophageal symptoms for which acid-suppressive agents tend to be less effective. Performing an endoscopy can further identify the patient as having nonerosive reflux disease, erosive esophagitis, or Barrett\\'s esophagus-diagnoses which can help determine treatment but may not prove predictive of therapeutic response. Determining acid exposure through pH testing can predict therapeutic response, with those revealing an abnormal acid exposure time being more responsive to acid-suppressive therapy. However, the performance of an endoscopy and pH testing on each patient is clearly not practical. Whereas the natural history of symptomatic GERD is still largely undefined, acid-suppressive therapy appears to be the best approach available for both the short-term and long-term management of this disease.

Effect of Interferon, Polyacrylic Acid, and Polymethacrylic Acid on Tail Lesions in Mice Infected with Vaccinia Virus

Science.gov (United States)

De Clercq, E.; De Somer, P.

1968-01-01

Intravenous inoculation of mice with vaccinia virus produced characteristic lesions of the tail surface which were suppressed by intraperitoneal administration of interferon and polyacrylic acid (PAA). Polymethacrylic acid (PMAA) stimulated the formation of vaccinia virus lesions. For full activity, both interferon and PAA must be given prior to infection. PAA was still significantly effective at small dose levels (3 mg/kg) and achieved protection for at least 4 weeks. Protection increased with increasing molecular weight of the polymer. The mode of action of PAA is discussed. PMID:5676405

Effect of essential fatty acids on glucose-induced cytotoxicity to retinal vascular endothelial cells

Directory of Open Access Journals (Sweden)

Shen Junhui

2012-07-01

Full Text Available Abstract Background Diabetic retinopathy is a major complication of dysregulated hyperglycemia. Retinal vascular endothelial cell dysfunction is an early event in the pathogenesis of diabetic retinopathy. Studies showed that hyperglycemia-induced excess proliferation of retinal vascular endothelial cells can be abrogated by docosahexaenoic acid (DHA, 22:6 ω-3 and eicosapentaenoic acid (EPA, 20:5 ω-3. The influence of dietary omega-3 PUFA on brain zinc metabolism has been previously implied. Zn2+ is essential for the activity of Δ6 desaturase as a co-factor that, in turn, converts essential fatty acids to their respective long chain metabolites. Whether essential fatty acids (EFAs α-linolenic acid and linoleic acid have similar beneficial effect remains poorly understood. Methods RF/6A cells were treated with different concentrations of high glucose, α-linolenic acid and linoleic acid and Zn2+. The alterations in mitochondrial succinate dehydrogenase enzyme activity, cell membrane fluidity, reactive oxygen species generation, SOD enzyme and vascular endothelial growth factor (VEGF secretion were evaluated. Results Studies showed that hyperglycemia-induced excess proliferation of retinal vascular endothelial cells can be abrogated by both linoleic acid (LA and α-linolenic acid (ALA, while the saturated fatty acid, palmitic acid was ineffective. A dose–response study with ALA showed that the activity of the mitochondrial succinate dehydrogenase enzyme was suppressed at all concentrations of glucose tested to a significant degree. High glucose enhanced fluorescence polarization and microviscocity reverted to normal by treatment with Zn2+ and ALA. ALA was more potent that Zn2+. Increased level of high glucose caused slightly increased ROS generation that correlated with corresponding decrease in SOD activity. ALA suppressed ROS generation to a significant degree in a dose dependent fashion and raised SOD activity significantly. ALA suppressed

Suppression of soft nuclear bremsstrahlung in proton-nucleus collisions

International Nuclear Information System (INIS)

Goethem, M.J. van; Bacelar, J.C.S.; Hoefman, M.; Huisman, H.; Kalantar-Nayestanaki, N.; Loehner, H.; Messchendorp, J.G.; Ostendorf, R.W.; Schadmand, S.; Siemssen, R.H.; Turrisi, R.; Volkerts, M.; Wilschut, H.W.; Aphecetche, L.; Delagrange, H.; D'Enterria, D.; Martinez, G.; Schutz, Y.; Diaz, J.; Holzmann, R.

2002-01-01

Photon energy spectra up to the kinematic limit have been measured in 190 MeV proton reactions with light and heavy nuclei to investigate the influence of the multiple-scattering process on the photon production. Relative to the predictions of models based on a quasifree production mechanism, a strong suppression of bremsstrahlung is observed in the low-energy region of the photon spectrum. We attribute this effect to the interference of photon amplitudes due to multiple scattering of nucleons in the nuclear medium

Anti-Inflammatory and Antinociceptive Activities of Anthraquinone-2-Carboxylic Acid.

Science.gov (United States)

Park, Jae Gwang; Kim, Seung Cheol; Kim, Yun Hwan; Yang, Woo Seok; Kim, Yong; Hong, Sungyoul; Kim, Kyung-Hee; Yoo, Byong Chul; Kim, Shi Hyung; Kim, Jong-Hoon; Cho, Jae Youl

2016-01-01

Anthraquinone compounds are one of the abundant polyphenols found in fruits, vegetables, and herbs. However, the in vivo anti-inflammatory activity and molecular mechanisms of anthraquinones have not been fully elucidated. We investigated the activity of anthraquinones using acute inflammatory and nociceptive experimental conditions. Anthraquinone-2-carboxylic acid (9,10-dihydro-9,10-dioxo-2-anthracenecarboxylic acid, AQCA), one of the major anthraquinones identified from Brazilian taheebo, ameliorated various inflammatory and algesic symptoms in EtOH/HCl- and acetylsalicylic acid- (ASA-) induced gastritis, arachidonic acid-induced edema, and acetic acid-induced abdominal writhing without displaying toxic profiles in body and organ weight, gastric irritation, or serum parameters. In addition, AQCA suppressed the expression of inflammatory genes such as cyclooxygenase- (COX-) 2 in stomach tissues and lipopolysaccharide- (LPS-) treated RAW264.7 cells. According to reporter gene assay and immunoblotting analyses, AQCA inhibited activation of the nuclear factor- (NF-) κB and activator protein- (AP-) 1 pathways by suppression of upstream signaling involving interleukin-1 receptor-associated kinase 4 (IRAK1), p38, Src, and spleen tyrosine kinase (Syk). Our data strongly suggest that anthraquinones such as AQCA act as potent anti-inflammatory and antinociceptive components in vivo, thus contributing to the immune regulatory role of fruits and herbs.

The tyrosine kinase inhibitor imatinib mesylate suppresses uric acid crystal-induced acute gouty arthritis in mice.

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Laurent L Reber

Full Text Available Gouty arthritis is caused by the deposition of monosodium urate (MSU crystals in joints. Despite many treatment options for gout, there is a substantial need for alternative treatments for patients unresponsive to current therapies. Tyrosine kinase inhibitors have demonstrated therapeutic benefit in experimental models of antibody-dependent arthritis and in rheumatoid arthritis in humans, but to date, the potential effects of such inhibitors on gouty arthritis has not been evaluated. Here we demonstrate that treatment with the tyrosine kinase inhibitor imatinib mesylate (imatinib can suppress inflammation induced by injection of MSU crystals into subcutaneous air pouches or into the ankle joint of wild type mice. Moreover, imatinib treatment also largely abolished the lower levels of inflammation which developed in IL-1R1-/- or KitW-sh/W-sh mice, indicating that this drug can inhibit IL-1-independent pathways, as well as mast cell-independent pathways, contributing to pathology in this model. Imatinib treatment not only prevented ankle swelling and synovial inflammation when administered before MSU crystals but also diminished these features when administrated after the injection of MSU crystals, a therapeutic protocol more closely mimicking the clinical situation in which treatment occurs after the development of an acute gout flare. Finally, we also assessed the efficiency of local intra-articular injections of imatinib-loaded poly(lactic-co-glycolic acid (PLGA nanoparticles in this model of acute gout. Treatment with low doses of this long-acting imatinib:PLGA formulation was able to reduce ankle swelling in a therapeutic protocol. Altogether, these results raise the possibility that tyrosine kinase inhibitors might have utility in the treatment of acute gout in humans.

Silymarin Suppresses Cellular Inflammation By Inducing Reparative Stress Signaling

Energy Technology Data Exchange (ETDEWEB)

Lovelace, Erica S.; Wagoner, Jessica; MacDonald, James; Bammler, Theo; Bruckner, Jacob; Brownell, Jessica; Beyer, Richard; Zink, Erika M.; Kim, Young-Mo; Kyle, Jennifer E.; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Metz, Thomas O.; Farin, Federico; Oberlies, Nicholas H.; Polyak, Steve

2015-08-28

Silymarin (SM), a natural product, is touted as a liver protectant and preventer of both chronic inflammation and diseases. To define how SM elicits these effects at a systems level, we performed transcriptional profiling, metabolomics, and signaling studies in human liver and T cell lines. Multiple pathways associated with cellular stress and metabolism were modulated by SM treatment within 0.5 to four hours: activation of Activating Transcription Factor 4 (ATF-4) and adenosine monophosphate protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) signaling, the latter being associated with induction of DNA-damage-inducible transcript 4 (DDIT4). Metabolomics analyses revealed suppression of glycolytic, TCA cycle, and amino acid metabolism by SM treatment. Antiinflammatory effects arose with prolonged (i.e. 24 hours) SM exposure, with suppression of multiple proinflammatory mRNAs and nuclear factor kappa B (NF-κB) and forkhead box O (FOXO) signaling. Studies with murine knock out cells revealed that SM inhibition of both mTOR and NF-κB was partially AMPK dependent, while SM inhibition of the mTOR pathway in part required DDIT4. Thus, SM activates stress and repair responses that culminate in an anti-inflammatory phenotype. Other natural products induced similar stress responses, which correlated with their ability to suppress inflammation. Therefore, natural products like SM may be useful as tools to define how metabolic, stress, and repair pathways regulate cellular inflammation.

Accuracy of near infrared spectroscopy for prediction of chemical composition, salt content and free amino acids in dry-cured ham.

Science.gov (United States)

Prevolnik, Maja; Škrlep, Martin; Janeš, Lucija; Velikonja-Bolta, Spela; Škorjanc, Dejan; Čandek-Potokar, Marjeta

2011-06-01

The capability of near infrared (NIR) spectroscopy was examined for the purposes of quality control of the traditional Slovenian dry-cured ham "Kraški pršut." Predictive models were developed for moisture, salt, protein, non-protein nitrogen, intramuscular fat and free amino acids in biceps femoris muscle (n = 135). The models' quality was assessed using statistical parameters: coefficient of determination (R(2)) and standard error (se) of cross-validation (CV) and external validation (EV). Residual predictive deviation (RPD) was also assessed. Best results were obtained for salt content and salt percentage in moisture/dry matter (R(CV)(2)>0.90, RPD>3.0), it was satisfactory for moisture, non-protein nitrogen, intramuscular fat and total free amino acids (R(CV)(2) = 0.75-0.90, RPD = 2.0-3.0), while not so for protein content and proteolysis index (R(CV)(2) = 0.65-0.75, RPD<2.0). Calibrations for individual free amino acids yielded R(CV)(2) from 0.40 to 0.90 and RPD from 1.3 to 2.9. Additional external validation of models on independent samples yielded comparable results. Based on the results, NIR spectroscopy can replace chemical methods in quality control of dry-cured ham. Copyright © 2011 Elsevier Ltd. All rights reserved.

Suppression of 9-cis-Epoxycarotenoid Dioxygenase, Which Encodes a Key Enzyme in Abscisic Acid Biosynthesis, Alters Fruit Texture in Transgenic Tomato1[W][OA

Science.gov (United States)

Sun, Liang; Sun, Yufei; Zhang, Mei; Wang, Ling; Ren, Jie; Cui, Mengmeng; Wang, Yanping; Ji, Kai; Li, Ping; Li, Qian; Chen, Pei; Dai, Shengjie; Duan, Chaorui; Wu, Yan; Leng, Ping

2012-01-01

Cell wall catabolism during fruit ripening is under complex control and is key for fruit quality and shelf life. To examine the role of abscisic acid (ABA) in tomato (Solanum lycopersicum) fruit ripening, we suppressed SlNCED1, which encodes 9-cis-epoxycarotenoid dioxygenase (NCED), a key enzyme in the biosynthesis of ABA. To suppress SlNCED1 specifically in tomato fruits, and thus avoid the pleiotropic phenotypes associated with ABA deficiency, we used an RNA interference construct driven by the fruit-specific E8 promoter. ABA accumulation and SlNCED1 transcript levels in the transgenic fruit were down-regulated to between 20% and 50% of the levels measured in the control fruit. This significant reduction in NCED activity led to a down-regulation in the transcription of genes encoding major cell wall catabolic enzymes, specifically polygalacturonase (SlPG), pectin methyl esterase (SlPME), β-galactosidase precursor mRNA (SlTBG), xyloglucan endotransglycosylase (SlXET), endo-1,4-β-cellulose (SlCels), and expansin (SlExp). This resulted in an increased accumulation of pectin during ripening. In turn, this led to a significant extension of the shelf life to 15 to 29 d compared with a shelf life of only 7 d for the control fruit and an enhancement of fruit firmness at the mature stage by 30% to 45%. In conclusion, ABA affects cell wall catabolism during tomato fruit ripening via down-regulation of the expression of major catabolic genes (SlPG, SlPME, SlTBG, SlXET, SlCels, and SlExp). PMID:22108525

Matrix metalloproteinase (MMP-9 in cancer-associated fibroblasts (CAFs is suppressed by omega-3 polyunsaturated fatty acids in vitro and in vivo.

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Ayumi Taguchi

Full Text Available Cancer associated fibroblasts (CAFs are responsible for tumor growth, angiogenesis, invasion, and metastasis. Matrix metalloproteinase (MMP-9 secreted from cancer stroma populated by CAFs is a prerequisite for cancer angiogenesis and metastasis. Omega-3 polyunsaturated fatty acids (omega-3 PUFA have been reported to have anti-tumor effects on diverse types of malignancies. Fat-1 mice, which can convert omega-6 to omega-3 PUFA independent of diet, are useful to investigate the functions of endogenous omega-3 PUFA. To examine the effect of omega-3 PUFA on tumorigenesis, TC-1 cells, a murine epithelial cell line immortalized by human papillomavirus (HPV oncogenes, were injected subcutaneously into fat-1 or wild type mice. Tumor growth and angiogenesis of the TC-1 tumor were significantly suppressed in fat-1 compared to wild type mice. cDNA microarray of the tumors derived from fat-1 and wild type mice revealed that MMP-9 is downregulated in fat-1 mice. Immunohistochemical study demonstrated immunoreactivity for MMP-9 in the tumor stromal fibroblasts was diffusely positive in wild type whereas focal in fat-1 mice. MMP-9 was expressed in primary cultured fibroblasts isolated from fat-1 and wild type mice but was not expressed in TC-1 cells. Co-culture of fibroblasts with TC-1 cells enhanced the expression and the proteinase activity of MMP-9, although the protease activity of MMP-9 in fat-1-derived fibroblasts was lower than that in wild type fibroblasts. Our data suggests that omega-3 PUFAs suppress MMP-9 induction and tumor angiogenesis. These findings may provide insight into mechanisms by which omega-3 PUFAs exert anti-tumor effects by modulating tumor microenvironment.

Epigenetic suppression of neprilysin regulates breast cancer invasion.

Science.gov (United States)

Stephen, H M; Khoury, R J; Majmudar, P R; Blaylock, T; Hawkins, K; Salama, M S; Scott, M D; Cosminsky, B; Utreja, N K; Britt, J; Conway, R E

2016-03-07

In women, invasive breast cancer is the second most common cancer and the second cause of cancer-related death. Therefore, identifying novel regulators of breast cancer invasion could lead to additional biomarkers and therapeutic targets. Neprilysin, a cell-surface enzyme that cleaves and inactivates a number of substrates including endothelin-1 (ET1), has been implicated in breast cancer, but whether neprilysin promotes or inhibits breast cancer cell progression and metastasis is unclear. Here, we asked whether neprilysin expression predicts and functionally regulates breast cancer cell invasion. RT-PCR and flow cytometry analysis of MDA-MB-231 and MCF-7 breast cancer cell lines revealed decreased neprilysin expression compared with normal epithelial cells. Expression was also suppressed in invasive ductal carcinoma (IDC) compared with normal tissue. In addition, in vtro invasion assays demonstrated that neprilysin overexpression decreased breast cancer cell invasion, whereas neprilysin suppression augmented invasion. Furthermore, inhibiting neprilysin in MCF-7 breast cancer cells increased ET1 levels significantly, whereas overexpressing neprilysin decreased extracellular-signal related kinase (ERK) activation, indicating that neprilysin negatively regulates ET1-induced activation of mitogen-activated protein kinase (MAPK) signaling. To determine whether neprilysin was epigenetically suppressed in breast cancer, we performed bisulfite conversion analysis of breast cancer cells and clinical tumor samples. We found that the neprilysin promoter was hypermethylated in breast cancer; chemical reversal of methylation in MDA-MB-231 cells reactivated neprilysin expression and inhibited cancer cell invasion. Analysis of cancer databases revealed that neprilysin methylation significantly associates with survival in stage I IDC and estrogen receptor-negative breast cancer subtypes. These results demonstrate that neprilysin negatively regulates the ET axis in breast cancer

The 1970 Clean Air Act and termination of rainfall suppression in a U.S. urban area

Science.gov (United States)

Diem, Jeremy E.

2013-08-01

The purpose of this paper is to determine the impact of reduced atmospheric particulate resulting from the Clean Air Act of 1970 on changes in summer rainfall in the Atlanta, Georgia USA region. In order to determine if rainfall at nine candidate stations in the metropolitan area was influenced by changes in particulate concentrations within the 1948-2009 period, predicted rainfall characteristics were derived from rainfall frequencies at nine reference stations located more than 80 km from downtown Atlanta. Both parametric and non-parametric tests were used to test for significant differences between observed values and predicted values within 34 overlapping 30-year periods. For the country as a whole, emissions of PM10 (i.e. particulates with a diameter less than or equal to 10 μm) decreased by approximately 40% from 1970 to 1975. The reduction in emissions caused a rapid rebound in summer rainfall in the Atlanta region. There was suppression of rainfall over and downwind of the Atlanta urbanized area during 30-yr periods that comprise all or portions of the decades of the 1950s, 1960s, and 1970s. This suppression occurred even while urban-related factors that promote rainfall enhancement were present. During the 1948-1977 suppression period, there was a decrease in rainfall of at least 40 mm at affected locales, which is substantial given that the mean seasonal rainfall was approximately 300 mm. The rainfall suppression involved a decrease of heavy-rainfall days. Atlanta is most likely not a unique case; therefore, particulate-induced rainfall suppression might have occurred over and downwind of other U.S. urban areas prior to the late 1970s.

Bile acids modulate glucocorticoid metabolism and the hypothalamic-pituitary-adrenal axis in obstructive jaundice

DEFF Research Database (Denmark)

McNeilly, Alison D; Macfarlane, David P; O'Flaherty, Emmett

2010-01-01

Suppression of the hypothalamic-pituitary-adrenal axis occurs in cirrhosis and cholestasis and is associated with increased concentrations of bile acids. We investigated whether this was mediated through bile acids acting to impair steroid clearance by inhibiting glucocorticoid metabolism by 5bet...

Suppression and enhancement of non-native molecules within biological systems

Energy Technology Data Exchange (ETDEWEB)

Jones, E.A. [Surface Analysis Research Centre, CEAS, School of Chemical Engineering and Analytical Science, University of Manchester, Manchester M60 1QD (United Kingdom)]. E-mail: e.jones@postgrad.manchester.ac.uk; Lockyer, N.P. [Surface Analysis Research Centre, CEAS, School of Chemical Engineering and Analytical Science, University of Manchester, Manchester M60 1QD (United Kingdom); Vickerman, J.C. [Surface Analysis Research Centre, CEAS, School of Chemical Engineering and Analytical Science, University of Manchester, Manchester M60 1QD (United Kingdom)

2006-07-30

With the aim of evaluating the potential of SIMS to provide molecular information from small molecules within biological systems, here we investigate the effect of different biological compounds as they act as matrices. The results highlight the fact that the chemical environment of a molecule can have a significant effect on its limit of detection. This has implications for the imaging of drugs and xenobiotics in tissue sections and other biological matrices. A 1:1 mixture of the organic acid 2,4,6-trihydroxyacetophenone and the dipeptide valine-valine demonstrates that almost complete suppression of the [M + H]{sup +} ion of one compound can be caused by the presence of a compound of higher proton affinity. The significance of this is highlighted when two similar drug molecules, atropine (a neutral molecule) and ipratropium bromide (a quaternary nitrogen containing salt) are mixed with brain homogenate. The atropine [M + H]{sup +} ion shows significant suppression whilst the [M - Br]{sup +} of ipratopium bromide is detected at an intensity that can be rationalised by its decreased surface concentration. By investigating the effect of two abundant tissue lipids, cholesterol and dipalmitoylphosphatidyl choline (DPPC), on the atropine [M + H]{sup +} signal detected in mixtures with these lipids we see that the DPPC has a strong suppressing effect, which may be attributed to gas phase proton transfer.

Thyroid suppression test with dextrothyroxine

International Nuclear Information System (INIS)

Rosenthal, D.; Fridman, J.; Ribeiro, H.B.

1978-01-01

The classic thyroid suppression test with triiodothyronine (l-T 3 ) has been shown to be efficient as an auxiliary method in the diagnosis of thyroid diseases, but should not be performed on elderly patients or on those with heart disease or a tendency to tachycardia. Since these subjects seem able to support a short period of dextro-thyronine (d-T 4 ) feeding, we compared the effect of d-T 4 and l-T 3 on the 24 hours thyroid uptake in euthyroid and hyperthyroid subjects. After basal radio-iodine uptake determination, 99 patients without hyperthyroidism and 27 with Graves' disease were randomly divided in 2 groups; one received 100μg of l-T 3 per day and the other 4 mg of d-T 4 per day, both groups being treated for a period of 10 days. At the end of this suppression period the 24 hours radio-iodine uptake was measured again and the percentual suppression index (S.I.) calculated. Since the comparison of the two groups showed no difference between the suppressive effect of l-T 3 and d-T 4 in euthyroid subjects, while dextro-thyronine, as levo-triiodothyronine, did not suppress the 24 hours uptake of hyperthyroid patients, l-T 3 or d-T 4 can be used interchangeably to test thyroid suppressibility. In the euthyroid subjects the normal range for the post-suppression uptake was 0-17.1% and for the suppression index 54,7.100% [pt

Suppression of cytochrome P450 reductase (POR) expression in hepatoma cells replicates the hepatic lipidosis observed in hepatic POR-null mice.

Science.gov (United States)

Porter, Todd D; Banerjee, Subhashis; Stolarczyk, Elzbieta I; Zou, Ling

2011-06-01

Cytochrome P450 reductase (POR) is a microsomal electron transport protein essential to cytochrome P450-mediated drug metabolism and sterol and bile acid synthesis. The conditional deletion of hepatic POR gene expression in mice results in a marked decrease in plasma cholesterol levels counterbalanced by the accumulation of triglycerides in lipid droplets in hepatocytes. To evaluate the role of cholesterol and bile acid synthesis in this hepatic lipidosis, as well as the possible role of lipid transport from peripheral tissues, we developed a stable, small interfering RNA (siRNA)-mediated cell culture model for the suppression of POR. POR mRNA and protein expression were decreased by greater than 50% in McArdle-RH7777 rat hepatoma cells 10 days after transfection with a POR-siRNA expression plasmid, and POR expression was nearly completely extinguished by day 20. Immunofluorescent analysis revealed a marked accumulation of lipid droplets in cells by day 15, accompanied by a nearly 2-fold increase in cellular triglyceride content, replicating the lipidosis seen in hepatic POR-null mouse liver. In contrast, suppression of CYP51A1 (lanosterol demethylase) did not result in lipid accumulation, indicating that loss of cholesterol synthesis is not the basis for this lipidosis. Indeed, addition of cholesterol to the medium appeared to augment the lipidosis in POR-suppressed cells, whereas removal of lipids from the medium reversed the lipidosis. Oxysterols did not accumulate in POR-suppressed cells, discounting a role for liver X receptor in stimulating triglyceride synthesis, but addition of chenodeoxycholate significantly repressed lipid accumulation, suggesting that the absence of bile acids and loss of farnesoid X receptor stimulation lead to excessive triglyceride synthesis.

Predicting the pKa and stability of organic acids and bases at an oil-water interface.

Science.gov (United States)

Andersson, M P; Olsson, M H M; Stipp, S L S

2014-06-10

We have used density functional theory and the implicit solvent model, COSMO-RS, to investigate how the acidity constant, pKa, of organic acids and bases adsorbed at the organic compound-aqueous solution interface changes, compared to its value in the aqueous phase. The pKa determine the surface charge density of the molecules that accumulate at the fluid-fluid interface. We have estimated the pKa by comparing the stability of the protonated and unprotonated forms of a series of molecules in the bulk aqueous solution and at an interface where parts of each molecule reside in the hydrophobic phase and the rest remains in the hydrophilic phase. We found that the pKa for acids is shifted by ∼1 pH unit to higher values compared to the bulk water pKa, whereas they are shifted to lower values by a similar amount for bases. Because this pKa shift is similar in magnitude for each of the molecules studied, we propose that the pKa for molecules at a water-organic compound interface can easily be predicted by adding a small shift to the aqueous pKa. This shift is general and correlates with the functional group. We also found that the relative composition of molecules at the fluid-fluid interface is not the same as in the bulk. For example, species such as carboxylic acids are enriched at the interface, where they can dominate surface properties, even when they are a modest component in the bulk fluid. For high surface concentrations of carboxylic acid groups at an interface, such as a self-assembled monolayer, we have demonstrated that the pKa depends on the degree of deprotonation through direct hydrogen bonding between protonated and deprotonated acidic headgroups.

Theoretical prediction of pKa in methanol: testing SM8 and SMD models for carboxylic acids, phenols, and amines.

Science.gov (United States)

Miguel, Elizabeth L M; Silva, Poliana L; Pliego, Josefredo R

2014-05-29

Methanol is a widely used solvent for chemical reactions and has solvation properties similar to those of water. However, the performance of continuum solvation models in this solvent has not been tested yet. In this report, we have investigated the performance of the SM8 and SMD models for pKa prediction of 26 carboxylic acids, 24 phenols, and 23 amines in methanol. The gas phase contribution was included at the X3LYP/TZVPP+diff//X3LYP/DZV+P(d) level. Using the proton exchange reaction with acetic acid, phenol, and ammonia as reference species leads to RMS error in the range of 1.4 to 3.6 pKa units. This finding suggests that the performance of the continuum models for methanol is similar to that found for aqueous solvent. Application of simple empirical correction through a linear equation leads to accurate pKa prediction, with uncertainty less than 0.8 units with the SM8 method. Testing with the less expensive PBE1PBE/6-311+G** method results in a slight improvement in the results.

Burst-suppression pattern in the electroencephalogram of newborns and infants. Its clinical expression

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Cervantes Blanco Jorge Mauricio

2014-07-01

Full Text Available Burst-suppression pattern in the electroencephalogram (EEG is associated with severe brain damage and has a bad prognosis in 85% of the cases. Objectives. To identify the prevalence of the EEG burst-suppression pattern (BSP in fullterm newborns and infants, determine its etiol- ogy, clinical features and course. Methods. A retrospective study was conducted. Between January 2008 and December 2012, 4,891 EEGs were reviewed. The EEGs of newborns and infants (< 3 months of age with BSP were selected. Results. 11 cases identified with burst suppression pattern. The overall prevalence of which was 3.5%; 8.1% among the newborns and 1.2% among infants. Seizures were the main reason for doing an EEG in the newborn period in 7 patients and after day 28 in three. The clinical manifestations were abnormal level of consciousness (n=8, hypotonia (n=2, and spasticity (n=6. The main causes were hypoxic ischemic injury, stroke and kernicterus. There were two cases of early infantile epileptic encephalopathy. Two patients died before the third month of age; 8 survived an average of 13 months. All had epilepsy, neurologic retardation and disability. Two patients had persistent EEG burst-suppression pattern; 1 and 3 months after the neonatal period respectively; 7 had focal spikes and an asymmetric pattern. Conclusions. Electroencephalographic burst-suppression pat- tern predicts a severe neurologic injury in fullterm newborns and infants.

Diphlorethohydroxycarmalol from Ishige okamurae Suppresses Osteoclast Differentiation by Downregulating the NF-κB Signaling Pathway

Directory of Open Access Journals (Sweden)

Hye Jung Ihn

2017-12-01

Full Text Available Marine algae possess a variety of beneficial effects on human health. In this study, we investigated whether diphlorethohydroxycarmalol (DPHC, isolated from Ishige okamurae, a brown alga, suppresses receptor activator of nuclear factor-κB ligand (RANKL-induced osteoclast differentiation. DPHC significantly suppressed RANKL-induced osteoclast differentiation and macrophage-colony stimulating factor (M-CSF expression in a dose-dependent manner. In addition, it significantly inhibited actin ring formation, the expression of osteoclast marker genes, such as tartrate-resistant acid phosphatase (TRAP, nuclear factor of activated T-cells cytoplasmic 1 (Nfatc1, cathepsin K (Ctsk, and dendritic cell-specific transmembrane protein (Dcstamp, and osteoclast-induced bone resorption. Analysis of the RANKL-mediated signaling pathway showed that the phosphorylation of both IκB and p65 was specifically inhibited by DPHC. These results suggest that DPHC substantially suppresses osteoclastogenesis by downregulating the RANK-NF-κB signaling pathway. Thus, it holds significant potential for the treatment of skeletal diseases associated with an enhanced osteoclast activity.

1-methylmalate from camu-camu (Myrciaria dubia) suppressed D-galactosamine-induced liver injury in rats.

Science.gov (United States)

Akachi, Toshiyuki; Shiina, Yasuyuki; Kawaguchi, Takumi; Kawagishi, Hirokazu; Morita, Tatsuya; Sugiyama, Kimio

2010-01-01

To evaluate the protective effects of fruit juices against D-galactosamine (GalN)-induced liver injury, lyophilized fruit juices (total 12 kinds) were fed to rats for 7 d, and then we evoked liver injury by injecting GalN. The juice of camu-camu (Myrciaria dubia) significantly suppressed GalN-induced liver injury when the magnitude of liver injury was assessed by plasma alanine aminotransferase and aspartate aminotransferase activities, although some other juices (acerola, dragon fruit, shekwasha, and star fruit) also tended to have suppressive effects. An active compound was isolated from camu-camu juice by solvent fractionation and silica gel column chromatography. The structure was determined to be 1-methylmalate. On the other hand, malate, 1,4-dimethylmalate, citrate, and tartrate had no significant effect on GalN-induced liver injury. It is suggested that 1-methylmalate might be a rather specific compound among organic acids and their derivatives in fruit juices in suppressing GalN-induced liver injury.

Suppression of PCD-related genes affects salt tolerance in Arabidopsis.

Science.gov (United States)

Bahieldin, Ahmed; Alqarni, Dhafer A M; Atef, Ahmed; Gadalla, Nour O; Al-matary, Mohammed; Edris, Sherif; Al-Kordy, Magdy A; Makki, Rania M; Al-Doss, Abdullah A; Sabir, Jamal S M; Mutwakil, Mohammed H Z; El-Domyati, Fotouh M

2016-01-01

This work aims at examining a natural exciting phenomenon suggesting that suppression of genes inducing programmed cell death (PCD) might confer tolerance against abiotic stresses in plants. PCD-related genes were induced in tobacco under oxalic acid (OA) treatment (20 mM), and plant cells were characterized to confirm the incidence of PCD. The results indicated that PCD was triggered 24 h after the exposure to OA. Then, RNAs were extracted from tobacco cells 0, 2, 6, 12 and 24 h after treatment for deep sequencing. RNA-Seq analyses were done with a special emphasis to clusters whose PCD-related genes were upregulated after 2 h of OA exposure. Accordingly, 23 tobacco PCD-related genes were knocked down via virus-induced gene silencing (VIGS), whereas our results indicated the influence of five of them on inducing or suppressing PCD. Knockout T-DNA insertion mutants of these five genes in Arabidopsis were tested under salt stress (0, 100, 150, and 200 mM NaCl), and the results indicated that a mutant of an antiapoptotic gene, namely Bax Inhibitor-1 (BI-1), whose VIGS induced PCD in tobacco, was salt sensitive, while a mutant of an apoptotic gene, namely mildew resistance locus O (Mlo), whose VIGS suppressed PCD, was salt tolerant as compared to the WT (Col) control. These data support our hypothesis that retarding PCD-inducing genes can result in higher levels of salt tolerance, while retarding PCD-suppressing genes can result in lower levels of salt tolerance in plants. Copyright © 2016 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Carrier-microencapsulation using Si-catechol complex for suppressing pyrite floatability

Energy Technology Data Exchange (ETDEWEB)

Jha, R.K.T.; Satur, J.; Hiroyoshi, N.; Ito, M.; Tsunekawa, M. [Hokkaido University, Hokkaido (Japan). Graduate School of Engineering

2008-11-15

Pyrite (FeS{sub 2}) is a common sulfide mineral associated with valuable metal minerals and coal, and it is rejected as a gangue mineral using physical separation techniques such as froth flotation and discharged into tailing pond. In the flotation, pyrite is frequently entrapped in the froth due to its hydrophobic nature. Formation of acid mine drainage due to the air-oxidation of pyrite in the tailing pond is also a serious problem. The authors have proposed carrier-microencapsulation (CME) as a method for suppressing both the floatability and oxidation of pyrite. In this method, pyrite is coated with a thin layer of metal oxide or hydroxide using catechol solution as a carrier combined with metal ions. The layer converts the pyrite surface from hydrophobic to hydrophilic and acts as a protective coating against oxidation. The present study demonstrates the effect of CME using Si-catechol complex to suppress the pyrite floatability: The bubble pick-up experiments showed that attachment of pyrite particles to air bubble is suppressed by the CME treatment at pH 4-10, Si-catechol complex concentration over 0.5 mol m{sup -3} and treatment time within 2 min. The Hallimond tube flotation experiments showed that the pyrite floatability is suppressed by the CME treatment even in the presence of typical flotation collectors such as kerosene and xanthate. SEM-EDX analysis confirmed that Si present on the pyrite surface treated by Si-catechol complex, implying that SiO{sub 2} or SiOH{sub 4} layer formed by the CME treatment convert the pyrite surface hydrophobic to hydrophilic.

Proton density-weighted MR imaging of the knee: fat suppression versus without fat suppression

Energy Technology Data Exchange (ETDEWEB)

Lee, So-Yeon; Kim, Sun Ki [Catholic University of Korea, Department of Radiology, Seoul St. Mary' s Hospital, Seoul (Korea, Republic of); Jee, Won-Hee [Catholic University of Korea, Department of Radiology, Seoul St. Mary' s Hospital, Seoul (Korea, Republic of); Catholic University of Korea, Diagnostic Radiology, Seoul St. Mary' s Hospital, School of Medicine, Seoul (Korea, Republic of); Kim, Jung-Man [Catholic University of Korea, Department of Orthopedic Surgery, Seoul St. Mary' s Hospital, Seoul (Korea, Republic of)

2011-02-15

To prospectively evaluate the diagnostic accuracy of proton density-weighted imaging with and without fat suppression for detecting meniscal tears. The study involved 48 patients who underwent arthroscopy less than 3 months after proton density-weighted imaging with and without fat suppression. Sagittal images were independently reviewed by two radiologists for the presence of meniscal tears. Medial and lateral menisci were separately analyzed in terms of anterior horn, body, and posterior horn. Interobserver agreement was assessed using {kappa} coefficients. The McNemar test was used to determine any differences between the two methods in terms of sensitivity and specificity. Arthroscopy findings were used as the diagnostic reference standard. Arthroscopy revealed 71 tears involving 85 meniscal segments: 34 medial meniscal segments and 51 lateral meniscal segments. The sensitivity, specificity, and accuracy of each radiologist were 95% (81/85), 92% (186/203), and 93% (267/288), and 93% (79/85), 93% (189/203), and 93% (268/288) when using fat-suppressed proton density-weighted imaging, and 91% (77/85), 93% (189/203), and 92% (266/288), and 91% (77/85), 93% (188/203), and 92% (265/288) when using proton density-weighted imaging without fat suppression, respectively. Interobserver agreement for meniscal tears was very high with proton-weighted imaging with ({kappa} = 0.87) or without ({kappa} = 0.86) fat suppression. There were no significant differences for detection of medial meniscal tears when using proton density-weighted imaging with or without fat suppression for both readers (p > 0.05). Fat-suppressed proton density-weighted imaging can replace proton density-weighted imaging without fat suppression for the detection of meniscal tears. (orig.)

Proton density-weighted MR imaging of the knee: fat suppression versus without fat suppression

International Nuclear Information System (INIS)

Lee, So-Yeon; Kim, Sun Ki; Jee, Won-Hee; Kim, Jung-Man

2011-01-01

To prospectively evaluate the diagnostic accuracy of proton density-weighted imaging with and without fat suppression for detecting meniscal tears. The study involved 48 patients who underwent arthroscopy less than 3 months after proton density-weighted imaging with and without fat suppression. Sagittal images were independently reviewed by two radiologists for the presence of meniscal tears. Medial and lateral menisci were separately analyzed in terms of anterior horn, body, and posterior horn. Interobserver agreement was assessed using κ coefficients. The McNemar test was used to determine any differences between the two methods in terms of sensitivity and specificity. Arthroscopy findings were used as the diagnostic reference standard. Arthroscopy revealed 71 tears involving 85 meniscal segments: 34 medial meniscal segments and 51 lateral meniscal segments. The sensitivity, specificity, and accuracy of each radiologist were 95% (81/85), 92% (186/203), and 93% (267/288), and 93% (79/85), 93% (189/203), and 93% (268/288) when using fat-suppressed proton density-weighted imaging, and 91% (77/85), 93% (189/203), and 92% (266/288), and 91% (77/85), 93% (188/203), and 92% (265/288) when using proton density-weighted imaging without fat suppression, respectively. Interobserver agreement for meniscal tears was very high with proton-weighted imaging with (κ = 0.87) or without (κ = 0.86) fat suppression. There were no significant differences for detection of medial meniscal tears when using proton density-weighted imaging with or without fat suppression for both readers (p > 0.05). Fat-suppressed proton density-weighted imaging can replace proton density-weighted imaging without fat suppression for the detection of meniscal tears. (orig.)

Development of an ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry method for the simultaneous determination of salicylic acid, jasmonic acid, and abscisic acid in rose leaves.

Science.gov (United States)

Bosco, Renato; Daeseleire, Els; Van Pamel, Els; Scariot, Valentina; Leus, Leen

2014-07-09

This paper describes a method to detect and quantitate the endogenous plant hormones (±)-2-cis-4-trans-abscisic acid, (-)-jasmonic acid, and salicylic acid by means of ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) in hybrid rose leaf matrices. Deuterium-labeled [(2)H6] (+)-2-cis-4-trans-abscisic acid, [(2)H6] (±)-jasmonic acid, and [(2)H4]-salicylic acid were used as internal standards. Rose samples (10 mg) were extracted with methanol/water/acetic acid (10:89:1) and subsequently purified on an Oasis MCX 1 cm(3) Vac SPE cartridge. Performance characteristics were validated according to Commission Decision 2002/657/EC. Recovery, repeatability, and within-laboratory reproducibility were acceptable for all phytohormones tested at three different concentrations. The decision limit and detection capability for (±)-2-cis-4-trans-abscisic acid, (-)-jasmonic acid, and salicylic acid were 0.0075 and 0.015 μg/g, 0.00015 and 0.00030 μg/g, and 0.0089 and 0.018 μg/g, respectively. Matrix effects (signal suppression or enhancement) appeared to be high for all substances considered, implying the need for quantitation based on matrix-matched calibration curves.

Sunlight suppressing rejection of 280- to 320-nm UV-radiation-induced skin tumors in mice

International Nuclear Information System (INIS)

Morison, W.L.; Kelley, S.P.

1985-01-01

Repeated exposure of female C3H/HeNCR- mice to sunlight prevented the normal immunologic rejection of a UV-induced tumor. This systemic immunologic alteration was transferred to syngeneic lethally X-irradiated animals with lymphoid cells from mice exposed to sunlight. The lymphoid cells also were able to suppress the capacity of lymphoid cells from normal animals to reject a UV-induced tumor. The 295- to 320-nm wave band appeared to be responsible for this immunosuppressive effect of sunlight because suppression was prevented by filtration of the radiation through Mylar and by application of a sunscreen containing para-aminobenzoic acid. These observations may have importance in understanding the pathogenesis of sunlight-induced skin cancer in humans

Pentastatin-1, a collagen IV derived 20-mer peptide, suppresses tumor growth in a small cell lung cancer xenograft model.

Science.gov (United States)

Koskimaki, Jacob E; Karagiannis, Emmanouil D; Tang, Benjamin C; Hammers, Hans; Watkins, D Neil; Pili, Roberto; Popel, Aleksander S

2010-02-01

Angiogenesis is the formation of neovasculature from a pre-existing vascular network. Progression of solid tumors including lung cancer is angiogenesis-dependent. We previously introduced a bioinformatics-based methodology to identify endogenous anti-angiogenic peptide sequences, and validated these predictions in vitro in human umbilical vein endothelial cell (HUVEC) proliferation and migration assays. One family of peptides with high activity is derived from the alpha-fibrils of type IV collagen. Based on the results from the in vitro screening, we have evaluated the ability of a 20 amino acid peptide derived from the alpha5 fibril of type IV collagen, pentastatin-1, to suppress vessel growth in an angioreactor-based directed in vivo angiogenesis assay (DIVAA). In addition, pentastatin-1 suppressed tumor growth with intraperitoneal peptide administration in a small cell lung cancer (SCLC) xenograft model in nude mice using the NCI-H82 human cancer cell line. Pentastatin-1 decreased the invasion of vessels into angioreactors in vivo in a dose dependent manner. The peptide also decreased the rate of tumor growth and microvascular density in vivo in a small cell lung cancer xenograft model. The peptide treatment significantly decreased the invasion of microvessels in angioreactors and the rate of tumor growth in the xenograft model, indicating potential treatment for angiogenesis-dependent disease, and for translational development as a therapeutic agent for lung cancer.

Pentastatin-1, a collagen IV derived 20-mer peptide, suppresses tumor growth in a small cell lung cancer xenograft model

International Nuclear Information System (INIS)

Koskimaki, Jacob E; Karagiannis, Emmanouil D; Tang, Benjamin C; Hammers, Hans; Watkins, D Neil; Pili, Roberto; Popel, Aleksander S

2010-01-01

Angiogenesis is the formation of neovasculature from a pre-existing vascular network. Progression of solid tumors including lung cancer is angiogenesis-dependent. We previously introduced a bioinformatics-based methodology to identify endogenous anti-angiogenic peptide sequences, and validated these predictions in vitro in human umbilical vein endothelial cell (HUVEC) proliferation and migration assays. One family of peptides with high activity is derived from the α-fibrils of type IV collagen. Based on the results from the in vitro screening, we have evaluated the ability of a 20 amino acid peptide derived from the α5 fibril of type IV collagen, pentastatin-1, to suppress vessel growth in an angioreactor-based directed in vivo angiogenesis assay (DIVAA). In addition, pentastatin-1 suppressed tumor growth with intraperitoneal peptide administration in a small cell lung cancer (SCLC) xenograft model in nude mice using the NCI-H82 human cancer cell line. Pentastatin-1 decreased the invasion of vessels into angioreactors in vivo in a dose dependent manner. The peptide also decreased the rate of tumor growth and microvascular density in vivo in a small cell lung cancer xenograft model. The peptide treatment significantly decreased the invasion of microvessels in angioreactors and the rate of tumor growth in the xenograft model, indicating potential treatment for angiogenesis-dependent disease, and for translational development as a therapeutic agent for lung cancer

Amino Acids Attenuate Insulin Action on Gluconeogenesis and Promote Fatty Acid Biosynthesis via mTORC1 Signaling Pathway in trout Hepatocytes

Directory of Open Access Journals (Sweden)

Weiwei Dai

2015-06-01

Full Text Available Background/Aims: Carnivores exhibit poor utilization of dietary carbohydrates and glucose intolerant phenotypes, yet it remains unclear what are the causal factors and underlying mechanisms. We aimed to evaluate excessive amino acids (AAs-induced effects on insulin signaling, fatty acid biosynthesis and glucose metabolism in rainbow trout and determine the potential involvement of mTORC1 and p38 MAPK pathway. Methods: We stimulated trout primary hepatocytes with different AA levels and employed acute administration of rapamycin to inhibit mTORC1 activation. Results: Increased AA levels enhanced the phosphorylation of ribosomal protein S6 kinase (S6K1, S6, and insulin receptor substrate 1 (IRS-1 on Ser302 but suppressed Akt and p38 phosphorylation; up-regulated the expression of genes related to gluconeogenesis and fatty acid biosynthesis. mTORC1 inhibition not only inhibited the phosphorylation of mTORC1 downstream targets, but also blunted IRS-1 Ser302 phosphorylation and restored excessive AAs-suppressed Akt phosphorylation. Rapamycin also inhibited fatty acid biosynthetic and gluconeogenic gene expression. Conclusion: High levels of AAs up-regulate hepatic fatty acid biosynthetic gene expression through an mTORC1-dependent manner, while attenuate insulin-mediated repression of gluconeogenesis through elevating IRS-1 Ser302 phosphorylation, which in turn impairs Akt activation and thereby weakening insulin action. We propose that p38 MAPK probably also involves in these AAs-induced metabolic changes.

Singly Cabibbo-suppressed hadronic decays of Λc+

Science.gov (United States)

Cheng, Hai-Yang; Kang, Xian-Wei; Xu, Fanrong

2018-04-01

We study singly Cabibbo-suppressed two-body hadronic decays of the charmed baryon Λc+, namely, Λc+→Λ K+,p π0,p η ,n π+,Σ0K+,Σ+K0 . We use the measured rate of Λc+→p ϕ to fix the effective Wilson coefficient a2 for naive color-suppressed modes and the effective number of color Nceff. We rely on the current-algebra approach to evaluate W -exchange and nonfactorizable internal W -emission amplitudes, that is, the commutator terms for the S wave and the pole terms for the P wave. Our prediction for Λc+→p η is in excellent agreement with the BESIII measurement. The p η (p π0) mode has a large (small) rate because of a large constructive (destructive) interference between the factorizable and nonfactorizable amplitudes for both S and P waves. Some of the SU(3) relations such as M (Λc+→n π+)=√{2 }M (Λc+→p π0) derived under the assumption of sextet dominance are not valid for decays with factorizable terms. Our calculation indicates that the branching fraction of Λc+→n π+ is about 3.5 times larger than that of Λc+→p π0 . Decay asymmetries are found to be negative for all singly Cabibbo-suppressed modes and range from -0.56 to -0.96 .

Suppressive effects of 3-bromopyruvate on the proliferation and the motility of hepatocellular carcinoma cells.

Science.gov (United States)

Tomizawa, Minoru; Shinozaki, Fuminobu; Motoyoshi, Yasufumi; Sugiyama, Takao; Yamamoto, Shigenori; Ishige, Naoki

2016-01-01

The compound 3-bromopyruvate (3BP) is an analogue of pyruvate, which is the final product of glycolysis that enters the citric acid cycle. The present study aimed to investigate the suppressive effects of 3BP on the proliferation and motility of hepatocellular carcinoma (HCC) cells. HLF and PLC/PRF/5 cells were cultured with 3BP and subjected to an MTS assay. Apoptosis was analyzed by hematoxylin and eosin staining. Cell motility was analyzed using a scratch assay. Real-time quantitative polymerase chain reaction (PCR) was performed to determine the expression levels of cyclin D1 and matrix metalloproteinase (MMP)9. Proliferation of both cell lines was significantly suppressed by 3BP at 100 µM (P<0.05). The expression level of cyclin D1 was decreased after 3BP treatment at 100 µM in both cell lines (P<0.05). Pyknotic nuclei were observed in the cells cultured with 3BP at 100 µM. These results revealed that 3BP suppressed cell proliferation, decreased the expression of cyclin D1, and induced apoptosis in HCC cells. 3BP significantly suppressed motility in both cell lines (P<0.05). The expression level of MMP9 was significantly decreased (P<0.05). 3BP suppressed the proliferation and motility of HCC cells by decreasing the expression of cyclin D1 and MMP9.

Suppression of Plant Defenses by Herbivorous Mites Is Not Associated with Adaptation to Host Plants

Directory of Open Access Journals (Sweden)

Jéssica T. Paulo

2018-06-01

Full Text Available Some herbivores suppress plant defenses, which may be viewed as a result of the coevolutionary arms race between plants and herbivores. However, this ability is usually studied in a one-herbivore-one-plant system, which hampers comparative studies that could corroborate this hypothesis. Here, we extend this paradigm and ask whether the herbivorous spider-mite Tetranychus evansi, which suppresses the jasmonic-acid pathway in tomato plants, is also able to suppress defenses in other host plants at different phylogenetic distances from tomatoes. We test this using different plants from the Solanales order, namely tomato, jimsonweed, tobacco, and morning glory (three Solanaceae and one Convolvulaceae, and bean plants (Fabales. First, we compare the performance of T. evansi to that of the other two most-commonly found species of the same genus, T. urticae and T. ludeni, on several plants. We found that the performance of T. evansi is higher than that of the other species only on tomato plants. We then showed, by measuring trypsin inhibitor activity and life history traits of conspecific mites on either clean or pre-infested plants, that T. evansi can suppress plant defenses on all plants except tobacco. This study suggests that the suppression of plant defenses may occur on host plants other than those to which herbivores are adapted.

Stability of the spreading in small-world network with predictive controller

International Nuclear Information System (INIS)

Bao, Z.J.; Jiang, Q.Y.; Yan, W.J.; Cao, Y.J.

2010-01-01

In this Letter, we apply the predictive control strategy to suppress the propagation of diseases or viruses in small-world network. The stability of small-world spreading model with predictive controller is investigated. The sufficient and necessary stability condition is given, which is closely related to the controller parameters and small-world rewiring probability p. Our simulations discover a phenomenon that, with the fixed predictive controller parameters, the spreading dynamics become more and more stable when p decreases from a larger value to a smaller one, and the suitable controller parameters can effectively suppress the spreading behaviors even when p varies within the whole spectrum, and the unsuitable controller parameters can lead to oscillation when p lies within a certain range.

Abscisic acid ameliorates atherosclerosis by suppressing macrophage and CD4+ T cell recruitment into the aortic wall.

Science.gov (United States)

Guri, Amir J; Misyak, Sarah A; Hontecillas, Raquel; Hasty, Alyssa; Liu, Dongmin; Si, Hongwei; Bassaganya-Riera, Josep

2010-12-01

Abscisic acid (ABA) is a natural phytohormone which improves insulin sensitivity and reduces adipose tissue inflammation when supplemented into diets of obese mice. The objective of this study was to investigate the mechanisms by which ABA prevents or ameliorates atherosclerosis. apolipoprotein E-deficient (ApoE(-/-)) mice were fed high-fat diets with or without ABA for 84 days. Systolic blood pressure was assessed on Days 0, 28, 56 and 72. Gene expression, immune cell infiltration and histological lesions were evaluated in the aortic root wall. Human aortic endothelial cells were used to examine the effect of ABA on 3',5'-cyclic adenosine monophosphate (cAMP) and nitric oxide (NO) production in vitro. We report that ABA-treated mice had significantly improved systolic blood pressure and decreased accumulation of F4/80(+)CD11b(+) macrophages and CD4(+) T cells in aortic root walls. At the molecular level, ABA significantly enhanced aortic endothelial nitric oxide synthase (eNOS) and tended to suppress aortic vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) expression and plasma MCP-1 concentrations. ABA also caused a dose-dependent increase in intracellular concentrations of cAMP and NO and up-regulated eNOS mRNA expression in human aortic endothelial cells. This is the first report showing that ABA prevents or ameliorates atherosclerosis-induced hypertension, immune cell recruitment into the aortic root wall and up-regulates aortic eNOS expression in ApoE(-/-) mice. Copyright © 2010 Elsevier Inc. All rights reserved.

Suppression and Two-Particle Correlations of Heavy Mesons in Heavy-Ion Collisions

Energy Technology Data Exchange (ETDEWEB)

Cao, Shanshan [Nuclear Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Qin, Guang-You [Institute of Particle Physics and Key Laboratory of Quark and Lepton Physics (MOE), Central China Normal University, Wuhan, 430079 (China); Bass, Steffen A. [Department of Physics, Duke University, Durham, NC 27708 (United States)

2016-12-15

We study the medium modification of heavy quarks produced in heavy-ion collisions. The evolution of heavy quarks inside the QGP is described using a modified Langevin framework that simultaneously incorporates their collisional and radiative energy loss. Within this framework, we provide good descriptions of the heavy meson suppression and predictions for the two-particle correlation functions of heavy meson pairs.

Nanoencapsulation of Mycolic acids as a deliverable to macrophages

CSIR Research Space (South Africa)

Benadie, Y

2008-06-01

Full Text Available , with peculiar physical and biological properties. For example, in a mouse model of asthma it was shown that mycolic acids can suppress inhaled allergen triggered inflammation, demonstrating their potential as immunotherapeutic agents. Due to the extremely...

Experimental results of active control on a large structure to suppress vibration

Science.gov (United States)

Dunn, H. J.

1991-01-01

Three design methods, Linear Quadratic Gaussian with Loop Transfer Recovery (LQG/LTR), H-infinity, and mu-synthesis, are used to obtain compensators for suppressing the vibrations of a 10-bay vertical truss structure, a component typical of what may be used to build a large space structure. For the design process the plant dynamic characteristics of the structure were determined experimentally using an identification method. The resulting compensators were implemented on a digital computer and tested for their ability to suppress the first bending mode response of the 10-bay vertical truss. Time histories of the measured motion are presented, and modal damping obtained during the experiments are compared with analytical predictions. The advantages and disadvantages of using the various design methods are discussed.

Gallic acid reduces cell viability, proliferation, invasion and angiogenesis in human cervical cancer cells

OpenAIRE

ZHAO, BING; HU, MENGCAI

2013-01-01

Gallic acid is a trihydroxybenzoic acid, also known as 3,4,5-trihydroxybenzoic acid, which is present in plants worldwide, including Chinese medicinal herbs. Gallic acid has been shown to have cytotoxic effects in certain cancer cells, without damaging normal cells. The objective of the present study was to determine whether gallic acid is able to inhibit human cervical cancer cell viability, proliferation and invasion and suppress cervical cancer cell-mediated angiogenesis. Treatment of HeLa...

Validation of a model for predicting smear-positive active pulmonary tuberculosis in patients with initial acid-fast bacilli smear-negative sputum

Energy Technology Data Exchange (ETDEWEB)

Yeh, Jun-Jun [Department of Chest Medicine, Section of Thoracic Imaging, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City (China); Chia Nan University of Pharmacy and Science, Tainan (China); Meiho University, Pingtung (China); Pingtung Christian Hospital, Pingtung (China); Heng Chun Christian Hospital, Pingtung (China)

2018-01-15

The objective of this study was to develop a predictive model for final smear-positive (SP) active pulmonary tuberculosis (aPTB) in patients with initial negative acid fast bacilli (AFB) sputum smears (iSN-SP-aPTB) based on high-resolution computed tomography (HRCT). Eighty (126, 21) patients of iSN-SP-aPTB and 402 (459, 876) patients of non-initial positive acid fast bacilli (non-iSP) pulmonary disease without iSN-SP-aPTB were included in a derivation (validation, prospective) cohort. HRCT characteristics were analysed, and multivariable regression and receiver operating characteristic (ROC) curve analysis was performed to develop a score predictive of iSN-SP-aPTB. The derivation cohort showed clusters of nodules/mass of the right upper lobe or left upper lobe were independent predictors of iSN-SP-aPTB, while bronchiectasis in the right middle lobe or left lingual lobe were negatively associated with iSN-SP-aPTB. A predictive score for iSN-SP-aPTB based on these findings was tested in the validation and prospective cohorts. With an ideal cut-off score = 1, the sensitivity, specificity, positive predictive value, and negative predictive value of the prediction model were 87.5% (90%, 90.5%), 99% (97.1%, 98.4%), 94.6% (81.3%, 57.5%), and 97.6% (97%, 99.8%) in the derivation (validation, prospective) cohorts, respectively. The model may help identify iSN-SP-aPTB among patients with non-iSP pulmonary diseases. circle Smear-positive active pulmonary tuberculosis that is initial smear-negative (iSN-SP-aPTB) is infectious. (orig.)

Suppressive and Enhancing Effects in Early Visual Cortex during Illusory Shape Perception: A Comment on Kok and de Lange (2014

Directory of Open Access Journals (Sweden)

Pieter Moors

2015-02-01

Full Text Available In a recent functional magnetic resonance imaging study, Kok and de Lange (2014 observed that BOLD activity for a Kanizsa illusory shape stimulus, in which pacmen-like inducers elicit an illusory shape percept, was either enhanced or suppressed relative to a nonillusory control configuration depending on whether the spatial profile of BOLD activity in early visual cortex was related to the illusory shape or the inducers, respectively. The authors argued that these findings fit well with the predictive coding framework, because top-down predictions related to the illusory shape are not met with bottom-up sensory input and hence the feedforward error signal is enhanced. Conversely, for the inducing elements, there is a match between top-down predictions and input, leading to a decrease in error. Rather than invoking predictive coding as the explanatory framework, the suppressive effect related to the inducers might be caused by neural adaptation to perceptually stable input due to the trial sequence used in the experiment.

Fundamental studies of aluminum corrosion in acidic and basic environments: Theoretical predictions and experimental observations

International Nuclear Information System (INIS)

Lashgari, Mohsen; Malek, Ali M.

2010-01-01

Using quantum electrochemical approaches based on density functional theory and cluster/polarized continuum model, we investigated the corrosion behavior of aluminum in HCl and NaOH media containing phenol inhibitor. In this regard, we determined the geometry and electronic structure of the species at metal/solution interface. The investigations revealed that the interaction energies of hydroxide corrosive agents with aluminum surface should be more negative than those of chloride ones. The inhibitor adsorption in acid is more likely to have a physical nature while it appears as though to be chemical in basic media. To verify these predictions, using Tafel plots, we studied the phenomena from experimental viewpoint. The studies confirmed that the rate of corrosion in alkaline solution is substantially greater than in HCl media. Moreover, phenol is a potential-molecule having mixed-type inhibition mechanism. The relationship between inhibitory action and molecular parameters was discussed and the activity in alkaline media was also theoretically anticipated. This prediction was in accord with experiment.

When passion makes the heart grow colder: the role of passion in alternative goal suppression.

Science.gov (United States)

Bélanger, Jocelyn J; Lafrenière, Marc-André K; Vallerand, Robert J; Kruglanski, Arie W

2013-01-01

Quality of goal engagement and alternative goal suppression were investigated in this research. Integrating the dualistic model of passion (Vallerand et al., 2003) with goal-systems theory (Kruglanski et al., 2002), we hypothesized that obsessive passion--associated with recurrent goal-conflicts--would predict greater alternative goal suppression (i.e., goal-shielding) than would harmonious passion--characterized by effective synthesis of the passionate activity with other life domains. Results from 5 laboratory studies supported these hypotheses. In Study 1, participants' dispositional measures of harmonious and obsessive passion were correlated with an implicit measure of goal-shielding. Obsessive (but not harmonious) passion predicted the suppression of alternative goals and the progressive inhibition of unfamiliar goals. In Study 2, we extended these findings by demonstrating the interrelation between quality of goal engagement and goal-commitment such that goal-shielding effects were enhanced, but only for goals in conflict with other life domains (vs. well-integrated goals). In Study 3, the causal influence of passion on goal-shielding was supported via an experimental manipulation of passion. In Study 4, we replicated and extended Studies 1 and 3 by experimentally demonstrating that obsessive (but not harmonious) passion is a mindset conducive to the development of inhibitory links with alternative goals. Study 5 explored the psychological costs associated with repeated unconscious goal suppression by examining its effects on the depletion of self-regulatory resources. Collectively, the present results suggest that the qualitative distinction between obsessive and harmonious passion has implications for the goal-shielding effect and for subsequent self-regulatory behavior.

Predicting soil acidification trends at Plynlimon using the SAFE model

Directory of Open Access Journals (Sweden)

B. Reynolds

1997-01-01

Full Text Available The SAFE model has been applied to an acid grassland site, located on base-poor stagnopodzol soils derived from Lower Palaeozoic greywackes. The model predicts that acidification of the soil has occurred in response to increased acid deposition following the industrial revolution. Limited recovery is predicted following the decline in sulphur deposition during the mid to late 1970s. Reducing excess sulphur and NOx deposition in 1998 to 40% and 70% of 1980 levels results in further recovery but soil chemical conditions (base saturation, soil water pH and ANC do not return to values predicted in pre-industrial times. The SAFE model predicts that critical loads (expressed in terms of the (Ca+Mg+K:Alcrit ratio for six vegetation species found in acid grassland communities are not exceeded despite the increase in deposited acidity following the industrial revolution. The relative growth response of selected vegetation species characteristic of acid grassland swards has been predicted using a damage function linking growth to soil solution base cation to aluminium ratio. The results show that very small growth reductions can be expected for 'acid tolerant' plants growing in acid upland soils. For more sensitive species such as Holcus lanatus, SAFE predicts that growth would have been reduced by about 20% between 1951 and 1983, when acid inputs were greatest. Recovery to c. 90% of normal growth (under laboratory conditions is predicted as acidic inputs decline.

On power flow suppression in straight elastic pipes by use of equally spaced eccentric inertial attachments

DEFF Research Database (Denmark)

Sorokin, Sergey; Holst-Jensen, Ole

2012-01-01

The paper addresses the power flow suppression in an elastic beam of the tubular cross section (a pipe) at relatively low excitation frequencies by deploying a small number of equally spaced inertial attachments. The methodology of boundary integral equations is used to obtain an exact solution...... of the problem in vibrations of this structure. The power flow analysis in a pipe with and without equally spaced eccentric inertial attachments is performed and the effect of suppression of the energy transmission is demonstrated theoretically. These results are put in the context of predictions from...

On the solubility of nicotinic acid and isonicotinic acid in water and organic solvents

International Nuclear Information System (INIS)

Abraham, Michael H.; Acree, William E.

2013-01-01

Highlights: ► Solubilities of nicotinic acid and isonicotinic acids in organicsolvents have been determined. ► Solubilities are used to calculate Abraham descriptors for the two acids. ► These descriptors then yield water-solvent and gas-solvent partitions into numerous solvents. ► The solubility of the neutral acids in water is obtained. ► The method is straightforward and can be applied to any set of compound solubilities. -- Abstract: We have determined the solubility of nicotinic acid in four solvents and the solubility of isonicotinic acid in another four solvents. These results, together with literature data on the solubility of nicotinic acid in five other organic solvents and isonicotinic acid in four other organic solvents, have been analyzed through two linear Gibbs energy relationships in order to extract compound properties, or descriptors, that encode various solute–solvent interactions. The descriptors for nicotinic acid and isonicotinic acid can then be used in known equations for partition of solutes between water and organic solvents to predict partition coefficients and then further solubility in a host of organic solvents, as well as to predict a number of other physicochemical properties

Interocular suppression

Science.gov (United States)

Tuna, Ana Rita; Almeida Neves Carrega, Filipa; Nunes, Amélia Fernandes