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Sample records for plasma n-terminal probnp

  1. Relationship of plasma level of NT- ProBNP with development of AF in CABG patients

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    Tanaray B

    2010-10-01

    Full Text Available "nBackground: Studies of the association between post operative AF and Plasma level of NT- Pro BNP have reported conflicting findings. The aim of the present study was evaluation of the association between post coronary bypass graft- Atrial Fibrillation (AF and Plasma level of NT- ProBNP as an independent risk factor of AF development in patients undergoing coronary artery bypass graft."n "nMethods: In a cohort study, 79 patients with sinus rhythm who admitted in Imam Khomeini Hospital in Tehran, Iran, during February 2009 and February 2010 for CABG are included the study and followed for developing post operative AF rhythm."n "nResults: Post operative AF was found in 17.7% of patients. The peak time from the operation to the first AF episode was in second post op day in ten patients (71.4%. The serum level of ProBNP in patients with AF was significantly higher (1624± 647 versus 221± 238 pg/ml, p< 0/0001. Increased age, Increased LA size and high plasma level of ProBNP were associated with increased risk for post op AF. After adjustment of risk factors, plasma level of ProBNP was the most important risk factor with odds ratio of 15.34 with CI 95% 1.77-132.95 and then LA diameter with odds ratio of 6.11 with CI 95% 0.99-37.42 was independently correlated with post op AF. Correlation between plasma level of ProBNP with age and LA size was seen too (LA size r = 0.0281, p= 0.012. Between age and ProBNP (r= 0.337, p= 0.002. The best cut off point for plasma ProBNP as a predictor of post op AF was 854 pg/ml."n "nConclusion: Increased level of preoperative ProBNP levels could be an independent predictor of post operative Atrial Fibrillation.

  2. Significance of changes of levels of plasma proBNP1-76 in patients with chronic pulmonary heart disease

    International Nuclear Information System (INIS)

    Li Guizhong; Xu Hua; Cao Jun; Jiang Wei; Pang Yongzheng; Tang Chaoshu

    2003-01-01

    Objective: To investigate the significance of the changes levels of plasma proBNP 1-76 in patients with COPD and chronic pulmonary heart disease. Methods: Plasma proBNP 1-76 levels were determined with radioimmunoassay in patients with CHPD (n=23), COPD (n=24) and 32 controls. Results: The concentrations of plasma proBNP 1-76 in patients with chronic obstructive pulmonary disease were significantly increased (vs controls, p 1-76 (r=0.541, p 1-76 , right inferior pulmonary artery diameter, right ventricle out flow tract diameter and right ventricle anterior wall thickness in patients with chronic pulmonary heart disease were increased significantly (vs COPD patients and controls, p 1-76 (r=0.477, p 1-76 is an early marker of right ventricular hypertrophy and right ventricular dysfunction, measurement of which is useful in the management of patients with chronic pulmonary heart disease in daily practice

  3. Combined measurement of copeptin, high-sensitivity troponin T, and N-terminal proBNP improves the identification of patients at risk of cardiovascular death

    DEFF Research Database (Denmark)

    Alehagen, Urban; Dahlström, Ulf; Carstensen, John

    2012-01-01

    and all mortality was registered. Cardiovascular mortality was evaluated using Kaplan–Meier plots and multivariate Cox proportional hazard regression analyses. Results: Copeptin, HS-TnT, and NT-proBNP measurements provided independent prognostic information in a multivariate setting over 5 years (hazard......Objectives: A multimarker strategy for the handling of patients with heart failure has been suggested in the literature. Therefore, the potential prognostic relevance of combined copeptin, high-sensitivity troponin T (HS-TnT), and N-terminal proBNP (NT-proBNP) measurement in plasma from elderly...... patients with symptoms of heart failure was evaluated. Methods: This study included 470 elderly patients (mean age 73 years) from a rural municipality with symptoms of heart failure. Clinical examination, echocardiography, and biomarker measurements were performed. All patients were followed for 13 years...

  4. Unraveling the Molecular Complexity of O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide Forms in Blood Plasma of Patients with Severe Heart Failure.

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    Halfinger, Bernhard; Hammerer-Lercher, Angelika; Amplatz, Benno; Sarg, Bettina; Kremser, Leopold; Lindner, Herbert H

    2017-01-01

    Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). Commercial NT-proBNP and BNP immunoassays cross-react to varying degrees with unprocessed proBNP, which is also found in the circulation. ProBNP processing and immunoassay response are related to O-linked glycosylation of NT-proBNP and proBNP. There is a clear and urgent need to identify the glycosylation sites in the endogenously circulating peptides requested by the community to gain further insights into the different naturally occurring forms. The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. We describe 9 distinct glycosylation sites on circulating (NT-) proBNP in HF patients. Differentially glycosylated variants were detected based on highly accurate mass determination and multistage mass spectrometry. Remarkably, for each of the identified proteolytic glycopeptides, a nonglycosylated form also was detectable. Our results directly demonstrate for the first time a rather complex distribution of the endogenously circulating glycoforms by mass spectrometric analysis in HF patients, and show 9 glycosites in human (NT-) proBNP. This information may also have an impact on commercial immunoassays applying antibodies specific for the central region of (NT-) proBNP, which detect mostly nonglycosylated forms. © 2016 American Association for Clinical Chemistry.

  5. [Expression of proBNP and NT-proBNP in Sudden Death of Coronary Heart Disease].

    Science.gov (United States)

    Zeng, Q; Sun, R F; Li, Z; Zhai, L Q; Liu, M Z; Guo, X J; Gao, C R

    2017-10-01

    To study the expression change of pro-brain natriuretic peptide (proBNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in sudden death of coronary atherosclerotic heart disease, and to explore its application in forensic diagnosis. Myocardial and blood samples were collected from normal control group, sudden death of coronary atherosclerotic heart disease group and single coronary stenosis group (20 cases in each group). The expression of proBNP in myocardial samples were detected by immunohistochemical staining and Western blotting, and that of BNP mRNA were detected by reverse transcription PCR (RT-PCR). The content of NT-proBNP in plasma were detected by ELISA. Immunohistochemical staining showed positive expression of proBNP in both sudden death of coronary atherosclerotic heart disease group and single coronary stenosis group. There was no positive expression in normal control group. For sudden death of coronary atherosclerotic heart disease group and single coronary stenosis group, the relative expression of proBNP protein and BNP mRNA in myocardial tissue and the NT-proBNP content in plasma were higher than that of normal control group ( P heart disease group was higher than that of single coronary stenosis group ( P heart disease and determine whether the sudden death due to coronary atherosclerotic heart disease. Copyright© by the Editorial Department of Journal of Forensic Medicine

  6. Direct comparison of mid-regional pro-atrial natriuretic peptide with N-terminal pro B-type natriuretic peptide in the diagnosis of patients with atrial fibrillation and dyspnoea.

    Science.gov (United States)

    Eckstein, Jens; Potocki, Mihael; Murray, Karsten; Breidthardt, Tobias; Ziller, Ronny; Mosimann, Tamina; Klima, Theresia; Hoeller, Rebeca; Moehring, Berit; Sou, Seoung Mann; Rubini Gimenez, Maria; Morgenthaler, Nils G; Mueller, Christian

    2012-10-01

    Due to different release mechanisms, mid-regional pro-atrial natriuretic peptide (MR proANP) may be superior to N-terminal pro-B-type natriuretic peptide (NT proBNP) in the diagnosis of acute heart failure (AHF) in patients with atrial fibrillation (AF). We compared MR proANP and NT proBNP for their diagnostic value in patients with AF and sinus rhythm (SR). Prospective cohort study. University hospital, emergency department. 632 consecutive patients presenting with acute dyspnoea. MR proANP and NT proBNP plasma levels were determined. The diagnosis of AHF was adjudicated by two independent cardiologists using all available data. Patients received long-term follow-up. AF was present in 151 patients (24%). MR proANP and NT proBNP levels were significantly higher in the AF group compared with the SR group (385 (258-598) versus 201 (89-375) pmol/l for MR proANP, pvalue for the diagnosis of AHF. The rhythm at presentation has to be taken into account because plasma levels of both peptides are significantly higher in patients with AF compared with SR.

  7. Impact of epitope specificity and precursor maturation in pro-B-type natriuretic peptide measurement

    DEFF Research Database (Denmark)

    Goetze, J.P.; Dahlstrom, U.; Alehagen, U.

    2008-01-01

    with different epitope specificities in a cohort of elderly patients presenting with symptoms associated with heart failure (n = 415). RESULTS: Comparison of N-terminal proBNP with proBNP 1-76 measurement in plasma revealed a high correlation on regression analysis (r(2) = 0.91, P ..., the proBNP 1-76 assay measured lower concentrations in the high range than the N-terminal proBNP assay. Correlations between assay measurements in a clinical setting were comparable for all the assays (r(2) approximately 0.57-0.83), and ROC analyses revealed area-under-the-curve values ranging between 0......BACKGROUND: Cardiac-derived natriuretic peptides are sensitive plasma markers of cardiac dysfunction. Recent reports have disclosed a more complex molecular heterogeneity of B-type natriuretic peptide precursor (proBNP)-derived peptides than previously suggested. In this study, we examined...

  8. Can venous ProBNP levels predict placenta accreta?

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    Ersoy, Ali Ozgur; Oztas, Efser; Ozler, Sibel; Ersoy, Ebru; Erkenekli, Kudret; Uygur, Dilek; Caglar, Ali Turhan; Danisman, Nuri

    2016-12-01

    Placenta previa (PP) is a potential life-threatening pregnancy complication. Pro-brain natriuretic peptide (ProBNP), creatine kinase (CK), cardiac form of CK (CK-MB) and Troponin I are circulatory biomarkers related to cardiac functions. We aimed to determine whether these biomarkers are related to PP and placenta accreta. In this case-control study, fifty-four pregnant women who attended our tertiary care center for perinatology with the diagnosis of PP totalis, and of them, 14 patients with placenta accreta were recruited as the study groups. Forty-six uncomplicated control patients who were matched for age, BMI were also included. Maternal venous ProBNP, CK, CK-MB and Troponin I levels were compared between the three groups. Obstetric history characteristics were comparable among groups, generally. CK and CK-MB levels were similar among three groups. Troponin I levels in the previa and accreta groups were significantly higher than the controls. ProBNP levels in the accreta group were significantly higher than other two groups. The multivariate regression model revealed that ProBNP could predict placental adhesion anomalies. Troponin I and ProBNP levels in PP cases were higher than controls and ProBNP could predict placenta accreta.

  9. N-terminal Pro-B-type natriuretic peptide: a measure of significant patent cuctus arteriosus

    LENUS (Irish Health Repository)

    OFarombi-Oghuvbu, IO

    2008-01-24

    Background: B type natriuretic peptide (BNP) is a marker for ventricular dysfunction secreted as a pre-prohormone, Pro-B-type natriuretic peptide (ProBNP), and cleaved into BNP and a biologically inactive fragment, N-terminal pro-B-type natriuretic peptide (NT-proBNP). Little is known about the clinical usefulness of NT-proBNP in preterm infants.\\r\

  10. The diagnostic value of plasma N-terminal connective tissue growth factor levels in children with heart failure.

    Science.gov (United States)

    Li, Gang; Song, Xueqing; Xia, Jiyi; Li, Jing; Jia, Peng; Chen, Pengyuan; Zhao, Jian; Liu, Bin

    2017-01-01

    The aim of this study was to assess the diagnostic value of plasma N-terminal connective tissue growth factor in children with heart failure. Methods and results Plasma N-terminal connective tissue growth factor was determined in 61 children, including 41 children with heart failure, 20 children without heart failure, and 30 healthy volunteers. The correlations between plasma N-terminal connective tissue growth factor levels and clinical parameters were investigated. Moreover, the diagnostic value of N-terminal connective tissue growth factor levels was evaluated. Compared with healthy volunteers and children without heart failure, plasma N-terminal connective tissue growth factor levels were significantly elevated in those with heart failure (p0.05), but it obviously improved the ability of diagnosing heart failure in children, as demonstrated by the integrated discrimination improvement (6.2%, p=0.013) and net re-classification improvement (13.2%, p=0.017) indices. Plasma N-terminal connective tissue growth factor is a promising diagnostic biomarker for heart failure in children.

  11. Troponin T, N-terminal pro natriuretic peptide and a patent ductus arteriosus scoring system predict death before discharge or neurodevelopmental outcome at 2 years in preterm infants.

    LENUS (Irish Health Repository)

    El-Khuffash, Afif F

    2011-03-01

    There is little consensus regarding the use of echocardiography in patent ductus arteriosus (PDA) treatment in preterm infants. The use of troponin T (cTnT) and N-terminal Pro-BNP (NTpBNP) in combination with echocardiography assessment may facilitate the development of a superior predictive model.

  12. Usefulness of N-terminal pro-brain natriuretic peptide as a biomarker of the presence of carcinoid heart disease.

    Science.gov (United States)

    Bhattacharyya, Sanjeev; Toumpanakis, Christos; Caplin, Martyn Evan; Davar, Joseph

    2008-10-01

    We sought to investigate whether N-terminal pro-brain natriuretic peptide (NT-pro-BNP) can be used as a biomarker for the detection of carcinoid heart disease (CHD); 200 patients with carcinoid syndrome were screened for CHD using transthoracic echocardiography. A carcinoid score was formulated to quantify severity of CHD. NT-pro-BNP was measured in all patients before echocardiography. Patients were categorised into New York Heart Association class. CHD was present in 39 patients (19.5%). NT-pro-BNP was significantly higher in those with CHD (median 1,149 pg/ml) than in those without CHD (median 101 pg/ml, p pro-BNP at a cut-off level of 260 pg/ml for detection of CHD were 0.92 and 0.91, respectively. NT-pro-BNP positively correlated both with carcinoid score (r = 0.81, p pro-BNP seems to be an excellent biomarker of CHD. A high negative predictive value may allow it to provide a screening test for CHD.

  13. N-terminal arginines modulate plasma-membrane localization of Kv7.1/KCNE1 channel complexes.

    Directory of Open Access Journals (Sweden)

    Zenawit Girmatsion

    Full Text Available BACKGROUND AND OBJECTIVE: The slow delayed rectifier current (I(Ks is important for cardiac action potential termination. The underlying channel is composed of Kv7.1 α-subunits and KCNE1 β-subunits. While most evidence suggests a role of KCNE1 transmembrane domain and C-terminus for the interaction, the N-terminal KCNE1 polymorphism 38G is associated with reduced I(Ks and atrial fibrillation (a human arrhythmia. Structure-function relationship of the KCNE1 N-terminus for I(Ks modulation is poorly understood and was subject of this study. METHODS: We studied N-terminal KCNE1 constructs disrupting structurally important positively charged amino-acids (arginines at positions 32, 33, 36 as well as KCNE1 constructs that modify position 38 including an N-terminal truncation mutation. Experimental procedures included molecular cloning, patch-clamp recording, protein biochemistry, real-time-PCR and confocal microscopy. RESULTS: All KCNE1 constructs physically interacted with Kv7.1. I(Ks resulting from co-expression of Kv7.1 with non-atrial fibrillation '38S' was greater than with any other construct. Ionic currents resulting from co-transfection of a KCNE1 mutant with arginine substitutions ('38G-3xA' were comparable to currents evoked from cells transfected with an N-terminally truncated KCNE1-construct ('Δ1-38'. Western-blots from plasma-membrane preparations and confocal images consistently showed a greater amount of Kv7.1 protein at the plasma-membrane in cells co-transfected with the non-atrial fibrillation KCNE1-38S than with any other construct. CONCLUSIONS: The results of our study indicate that N-terminal arginines in positions 32, 33, 36 of KCNE1 are important for reconstitution of I(Ks. Furthermore, our results hint towards a role of these N-terminal amino-acids in membrane representation of the delayed rectifier channel complex.

  14. Is proBNP a Reliable Marker for the Evaluation of Fluid Load in Patients Undergoing Continuous Renal Replacement Therapy?

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    Seher Erdogan

    2016-11-01

    Full Text Available Aim: Pro-B type natriuretic peptide (proBNP has been defined as a volume marker in hemodialysis patients. In the present study we aimed to evaluate the role of serum proBNP levels to indicate fluid load in patients undergoing continuous renal replacement therapy (CRRT due to overhydration. Material and Method: Patients who were admitted to a tertiary 7-bed pediatric intensive care unit and underwent CRRT due to overhydration were included in the study. Results: The study was conducted with 15 girls (53.6% and 13 boys (46.4%. The mean age was 61.46±56.13 months (range, 2-183 months; the mean CRRT administration time was 20.8±14.9 hours (range, 5-60 hours; and the mean percentage of fluid extracted from the body was 8.43 ± 4.51% (range, 2.5-20%. CRRT was administered to 12 patients because of fluid overload (42.9% and to 12 (57.1% because of fluid load accompanied by uremia.. There was a statistically significant difference between body weight, urea, and creatinine levels of patients before and after treatment (p= 0.001. The mean proBNP level was 23.306 ± 13.943 pg/mL immediately before CRRT and the mean proBNP after CRRT was 22.178 ± 15.473 pg/mL. There was no statistically significant difference between the initial and final proBNP levels (p= 0.756. With the exception of serum sodium levels, there was no correlation between the final proBNP levels and body weight, urea, and creatinine (p>0.05. Similarly, there was also no correlation between initial proBNP levels and fluid load (p= 0.602 or between the percentage of extracted fluid and final proBNP levels (p= 0.155. Discussion: There was no significant correlation between the fluid load and initial proBNP levels or with the extracted fluid percentage and final proBNP levels in patients undergoing CRRT because of fluid overload.In conclusion, no appropriate marker was determined to evaluate cumulative fluid load and the extracted liquid volume.

  15. Practical use of natriuretic peptide measurement

    DEFF Research Database (Denmark)

    Husby, Simon; Lind, Bent; Goetze, Jens P

    2012-01-01

    To elucidate the knowledge regarding B-type natriuretic peptide (BNP)/N-terminal proBNP (NT-proBNP) measurement among doctors using this biomarker.......To elucidate the knowledge regarding B-type natriuretic peptide (BNP)/N-terminal proBNP (NT-proBNP) measurement among doctors using this biomarker....

  16. Discordant expression of pro-B-type and pro-C-type natriuretic peptide in newborn infants of mothers with type 1 diabetes

    DEFF Research Database (Denmark)

    Nybo, Mads; Nielsen, Lars Bo; Nielsen, Søren Junge

    2007-01-01

    CNP-derived peptides in newborn infants. METHODS: Plasma concentrations of proCNP-derived peptides were measured in umbilical cord plasma and human placental tissue extracts using sequence-specific radioimmunoassays raised against N-terminal and C-terminal proCNP regions, respectively. RESULTS: The median pro...... in umbilical cord plasma compared to adult plasma (4.6 vs. 1.1), which parallels our earlier findings for proBNP and BNP peptides. CONCLUSIONS: There is a discordant expression of CNP and BNP peptides in newborn infants of mothers with diabetes. Moreover, fetal metabolism of proCNP and CNP appears to differ...

  17. Troponin T and NT ProBNP Levels in Gestational, Type 1 and Type 2 Diabetic Mothers and Macrosomic Infants.

    Science.gov (United States)

    Mert, Mustafa Kurthan; Satar, Mehmet; Özbarlas, Nazan; Yaman, Akgün; Özgünen, Fatma Tuncay; Asker, Hüseyin Selim; Çekinmez, Eren Kale; Tetiker, Tamer

    2016-01-01

    This study compares NT proBNP and troponin T levels in umbilical cord arterial blood and postnatal echocardiographic findings for infants of gestational and pregestational diabetic mothers and macrosomic infants. Twenty-seven infants of pregestational diabetic mothers, 61 infants of gestational diabetic mothers and 37 macrosomic infants of nondiabetic mothers were prospectively enrolled in this study along with a control group of 58 healthy infants of mothers without any pregestational or gestational disorders as the control group. All enrollees were born after 34 weeks of gestation. For this study, umbilical cord blood was drawn during delivery to determine NT proBNP and troponin T levels. Echocardiography was performed 24-72 h after the delivery. Umbilical cord troponin T and NT proBNP levels were found to be higher in the diabetic and macrosomic groups than in the control group (all of them p gestational infants of diabetic mothers groups (r = 0.564 and r = 0.560, respectively, p gestational diabetic mothers were divided into two groups according to HbA1c levels in the third trimester as good (6.1 %) metabolic control. In the good and suboptimal metabolic control diabetic groups, NT proBNP levels were also positively correlated with interventricular septum thickness (r = 0.536 and r = 0.576, respectively, p mothers and the control group, the myocardial performance index of macrosomic infants was lower than that of the control group (p = 0.017). Cardiac biomarkers (NT proBNP and troponin T) were elevated in infants of diabetic mothers and macrosomic infants. While there was a positive correlation between NT proBNP levels and cardiac structure in infants of pregestational and gestational diabetic mothers, there was no relationship between NT proBNP levels and cardiac function.

  18. Discriminating between cardiac and pulmonary dysfunction in the general population with dyspnea by plasma pro-B-type natriuretic peptide

    DEFF Research Database (Denmark)

    Mogelvang, R; Goetze, JP; Schnohr, P

    2007-01-01

    OBJECTIVES: This study was designed to determine whether measurement of plasma pro-B-type natriuretic peptide (proBNP) could be used in discriminating between cardiac and pulmonary dyspnea in the general population. BACKGROUND: Natriuretic peptides are useful markers in ruling out acute cardiac...... the expected concentration of plasma proBNP based on age and gender was established for dyspneic subjects: an actual plasma proBNP concentration below half of the expected value ruled out left ventricular systolic and diastolic dysfunction (sensitivity 100%, 95% CI 100% to 100%; specificity 15%, 95% CI 12...

  19. Cardiac function in offspring of women with diabetes using fetal ECG, umbilical cord blood pro-BNP, and neonatal interventricular septal thickness

    DEFF Research Database (Denmark)

    Halse, Karen; Lindegaard, Marie Louise Skakkebæk; Amer-Wahlin, Isis

    2013-01-01

    were included prospectively. Umbilical cord blood pro-BNP concentrations were measured immediately after delivery (n=68) and echocardiography was performed in the newborns (n=75). Fetal ECG in combination with cardiotocography, that is STAN technology was also performed during labor. Results......Objective: Increased pro-brain natriuretic peptide (BNP) concentrations in newborns of diabetic women are associated with fetal stress, and fetal ECG changes often occur in labor in diabetic women. These findings could reflect a degree of fetal cardiomyopathy. We aimed to explore possible relations......: The concentration of umbilical cord blood pro-BNP was associated positively with the neonatal cardiac interventricular septal thickness (P=0.025) and associated negatively with umbilical cord blood pH levels (P=0.036). Fetal ECG changes (STAN events) were recorded in 22 of 53 labors where STAN was used (42...

  20. Specificity of B-type natriuretic peptide assays

    DEFF Research Database (Denmark)

    Saenger, Amy K.; Rodriguez-Fraga, Olaia; Ler, Ranka

    2017-01-01

    BACKGROUND: B-type natriuretic peptides (BNPs) are used clinically to diagnose and monitor heart failure and are present in the circulation as multiple proBNP-derived fragments. We investigated the specificity of BNP immunoassays with glycosylated and nonglycosylated BNP, N-terminal proBNP (NT......-proBNP), and proBNP peptides to probe the cross-reactivity of each assay. METHODS: Nine B-type natriuretic peptides were studied, including synthetic and recombinant BNP (Shionogi, Scios, Mayo), human and synthetic glycosylated and nonglycosylated NT-proBNP (HyTest, Roche Diagnostics), and human glycosylated......-Rad, Goetze] were evaluated. Specificity was assessed by calculating the recovery between baseline and peptide-spiked human plasma pools at target concentrations of 100 ng/L BNP, 300 ng/L proBNP, or 450 ng/L NT-proBNP. All assays were performed in duplicate. RESULTS: BNP and NT-proBNP assays demonstrated...

  1. Plasma N-terminal pro B-type natriuretic peptide concentrations in dogs with pulmonic stenosis.

    Science.gov (United States)

    Kobayashi, Keiya; Hori, Yasutomo; Chimura, Syuuichi

    2014-06-01

    The detailed information between plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations and dogs with pulmonic stenosis (PS) is still unknown. The aim of the present study was to investigate the clinical utility of measuring plasma NT-proBNP concentrations in dogs with PS and to determine whether plasma NT-proBNP concentration could be used to assess disease severity. This retrospective study enrolled 30 client-owned, untreated dogs with PS (asymptomatic [n=23] and symptomatic [n=7]) and 11 healthy laboratory beagles. Results of physical examination, thoracic radiography and echocardiography were recorded. Plasma NT-proBNP concentrations were measured using commercial laboratories. Compared to the healthy control dogs, cardiothoracic ratio was significantly increased in dogs with both asymptomatic and symptomatic PS. Similarly, the ratio of the main pulmonary artery to aorta was significantly decreased in dogs with both asymptomatic and symptomatic PS. The pulmonic pressure gradient in the symptomatic PS dogs was significantly higher than that in the asymptomatic PS dogs. Plasma NT-proBNP concentration was significantly elevated in the symptomatic PS dogs compared to the healthy control dogs and the asymptomatic PS dogs. Furthermore, the Doppler-derived pulmonic pressure gradient was significantly correlated with the plasma NT-proBNP concentration (r=0.78, r(2)=0.61, P764 pmol/l to identify severe PS had a sensitivity of 76.2% and specificity of 81.8%. The plasma NT-proBNP concentration increased by spontaneous PS, i.e. right-sided pressure overload and can be used as an additional method to assess the severity of PS in dogs.

  2. Clinical implications of B-type natriuretic peptide and N-terminal pro--B-type natriuretic peptide in the care of the vascular surgery patient.

    Science.gov (United States)

    Wayne Causey, Marlin; Singh, Niten

    2014-12-01

    B-type natriuretic peptide (also known as brain natriuretic peptide or BNP) is a physiologic marker that is often used to assess a patient's global cardiovascular health. BNP is secreted from the ventricular cardiac myocytes in response to stretch that occurs due to increased intravascular volume. PreproBNP is cleaved into BNP and N-terminal proBNP (NT proBNP) to cause diuresis, natriuresis, and vasodilation, and can be measured with a blood laboratory assay test or point-of-care testing. BNP/NT proBNP has been most extensively studied in the diagnosis and management of heart failure, but within the past 5 years, interest has carried over to vascular surgery patients. Studies have demonstrated that elevated levels of BNP/NT-proBNP (typically >100 pg/mL/>300 pg/mL) are associated with major adverse cardiac events at 30 and 180 days. Additional analysis of BNP/NT-proBNP has demonstrated that patients can be classified as very low risk (400 pg/mL). BNP/NT-proBNP in the low- and very-low-risk groups suggests patients are unlikely to have a major adverse cardiac event. An elevated BNP/NT-proBNP, excluding those with reasons for abnormal values, suggests the need for additional risk stratification and medical risk factor optimization. A preoperative measure of BNP or NT-proBNP affords an easy and rapid opportunity to individually and objectively quantify perioperative cardiovascular risk. Recent studies have also identified other biomarkers, none superior to BNP or NT-proBNP, but that, when used concomitantly, aid in further stratifying perioperative risk and will likely be the focus of future investigations. Published by Elsevier Inc.

  3. Níveis séricos de NT pro-BNP: relação com função sistólica e diastólica nas miocardiopatias e pericardiopatias

    OpenAIRE

    Mady,Charles; Fernandes,Fábio; Arteaga,Edmundo; Ramires,Felix José Alvarez; Buck,Paula de Cássia; Salemi,Vera Maria Cury; Ianni,Barbara Maria; Nastari,Luciano; Dias,Ricardo Ribeiro

    2008-01-01

    FUNDAMENTO: O NT pro-BNP é marcador de disfunção sistólica e diastólica. OBJETIVO: Determinar os níveis de NT pro-BNP em pacientes com cardiopatia chagásica, hipertrófica, restritiva e afecções pericárdicas, e sua relação com medidas ecocardiográficas de disfunção sistólica e diastólica. MÉTODOS: Cento e quarenta e cinco pacientes foram divididos nos respectivos grupos: 1) cardiopatia chagásica (CCh) - 14 pacientes; 2) miocardiopatia hipertrófica (CMH) - 71 pacientes; 3) endomiocardiofibrose ...

  4. Antral content, secretion and peripheral metabolism of N-terminal progastrin fragments

    DEFF Research Database (Denmark)

    Goetze, Jens Peter; Hansen, Carsten Palnaes; Rehfeld, Jens F

    2006-01-01

    OBJECTIVES: In addition to the acid-stimulatory gastrins, progastrin also release N-terminal fragments. In order to examine the cellular content, secretion and peripheral metabolism of these fragments, we developed an immunoassay specific for the N-terminal sequence of human progastrin. RESULTS......-terminal progastrin fragments. The basal concentration of N-terminal fragments in normal human plasma was almost 30-fold higher than that of the amidated, acid-stimulatory gastrins (286 pmol/l versus 9.8 pmol/l, n=26, P...-35 in circulation was 30 min, and a pig model revealed the kidneys and the vasculature to the head as the primary sites of degradation. CONCLUSION: The cellular and circulatory concentration profiles of N-terminal progastrin fragments differ markedly from those of the acid-stimulatory gastrins. The high basal...

  5. Impact of hemoglobin on plasma pro-B-type natriuretic peptide concentrations in the general population

    DEFF Research Database (Denmark)

    Nybo, Mads; Benn, Marianne; Mogelvang, Rasmus

    2007-01-01

    , the impact of hemoglobin status on proBNP concentrations has not been established in the general population. METHODS: In the 4th examination in the Copenhagen City Heart Study, we performed a nested case-control study of 6238 individuals from a Danish general population. Of these, 3497 randomly selected...... participants also underwent an echocardiographic examination. The population was stratified into groups depending on health and hemoglobin status. Correlations between hemoglobin and proBNP concentrations were examined by simple and multiple regression analyses, adjusted for variables known to influence...... the proBNP plasma concentration. RESULTS: The mean proBNP concentration was increased 1.7-fold in the group with anemia vs the nonanemic group [mean (SD) 42 (45) pmol/L vs 25 (29) pmol/L, P hemoglobin on pro...

  6. The N-terminal region of the dopamine D2 receptor, a rhodopsin-like GPCR, regulates correct integration into the plasma membrane and endocytic routes

    Science.gov (United States)

    Cho, DI; Min, C; Jung, KS; Cheong, SY; Zheng, M; Cheong, SJ; Oak, MH; Cheong, JH; Lee, BK; Kim, KM

    2012-01-01

    BACKGROUND AND PURPOSE Functional roles of the N-terminal region of rhodopsin-like GPCR family remain unclear. Using dopamine D2 and D3 receptors as a model system, we probed the roles of the N-terminal region in the signalling, intracellular trafficking of receptor proteins, and explored the critical factors that determine the functionality of the N-terminal region. EXPERIMENTAL APPROACH The N-terminal region of the D2 receptor was gradually shortened or switched with that of the D3 receptor or a non-specific sequence (FLAG), or potential N-terminal glycosylation sites were mutated. Effects of these manipulations on surface expression, internalization, post-endocytic behaviours and signalling were determined. KEY RESULTS Shortening the N-terminal region of the D2 receptor enhanced receptor internalization and impaired surface expression and signalling; ligand binding, desensitization and down-regulation were not affected but their association with a particular microdomain, caveolae, was disrupted. Replacement of critical residues within the N-terminal region with the FLAG epitope failed to restore surface expression but partially restored the altered internalization and signalling. When the N-terminal regions were switched between D2 and D3 receptors, cell surface expression pattern of each receptor was switched. Mutations of potential N-terminal glycosylation sites inhibited surface expression but enhanced internalization of D2 receptors. CONCLUSIONS AND IMPLICATIONS Shortening of N-terminus or mutation of glycosylation sites located within the N-terminus enhanced receptor internalization but impaired the surface expression of D2 receptors. The N-terminal region of the D2 receptor, in a sequence-specific manner, controls the receptor's conformation and integration into the plasma membrane, which determine its subcellular localization, intracellular trafficking and signalling properties. PMID:22117524

  7. Discriminating between cardiac and pulmonary dysfunction in the general population with dyspnea by plasma pro-B-type natriuretic peptide

    DEFF Research Database (Denmark)

    Mogelvang, R; Goetze, JP; Schnohr, P

    2007-01-01

    OBJECTIVES: This study was designed to determine whether measurement of plasma pro-B-type natriuretic peptide (proBNP) could be used in discriminating between cardiac and pulmonary dyspnea in the general population. BACKGROUND: Natriuretic peptides are useful markers in ruling out acute cardiac d......% to 17%). CONCLUSIONS: In the general population with dyspnea, plasma proBNP concentrations are increased in left ventricular dilatation, hypertrophy, systolic dysfunction, or diastolic dysfunction, but are unaffected by pulmonary dysfunction.......OBJECTIVES: This study was designed to determine whether measurement of plasma pro-B-type natriuretic peptide (proBNP) could be used in discriminating between cardiac and pulmonary dyspnea in the general population. BACKGROUND: Natriuretic peptides are useful markers in ruling out acute cardiac...... dyspnea in the emergency department, but their diagnostic significance in evaluating chronic dyspnea in the general population is unknown. METHODS: Within the Copenhagen City Heart Study, a large, community-based population study, dyspnea was evaluated by spirometry, oxygen saturation, echocardiography...

  8. NEW POSSIBILITIES FOR EVALUATION OF SEVERITY AND PROGNOSIS IN PATIENTS WITH CHRONIC HEART FAILURE BASED ON N-TERMINAL PRO-BRAIN NATRIURETIC PEPTIDE PLASMA LEVEL

    Directory of Open Access Journals (Sweden)

    A. S. Galjavich

    2016-01-01

    Full Text Available Aim. To study an importance of plasma N-terminal pro-brain natriuretic peptide (N-proBNP in evaluation of severity and prognosis in patients with chronic heart failure (CHF of ischemic genesis.Material and methods. 77 patients (60 men and 17 women; 59,4±10,7 y.o. with CHF of ischemic genesis were included in the study. All patients had sinus rhythm and history of Q wave myocardial infarction. Standard examination was performed to all patients. Besides N-proBNP plasma level and patients yearly survival were evaluated.Results. N-proBNP plasma level had direct correlation with clinical indices (exercise tolerance, blood pressure, heart rate and echocardiographic heart sizes. N-proBNP plasma level had relationship with prognosis of CHF patients. Baseline N-proBNP level was more than 2 times higher in died patients in comparison with survived patients. The yearly survival rate of CHF patients was 51,3% if N-proBNP level had been more than 400 fmol/ml (>15% of normal value. The clinico-laboratory index (based on N-proBNP plasma level of severity and prognosis in CHF patients was developed.Conclusion. The clinico-laboratory index based on N-proBNP plasma level is easy to use and can improve medical practice.

  9. NEW POSSIBILITIES FOR EVALUATION OF SEVERITY AND PROGNOSIS IN PATIENTS WITH CHRONIC HEART FAILURE BASED ON N-TERMINAL PRO-BRAIN NATRIURETIC PEPTIDE PLASMA LEVEL

    Directory of Open Access Journals (Sweden)

    A. S. Galjavich

    2009-01-01

    Full Text Available Aim. To study an importance of plasma N-terminal pro-brain natriuretic peptide (N-proBNP in evaluation of severity and prognosis in patients with chronic heart failure (CHF of ischemic genesis.Material and methods. 77 patients (60 men and 17 women; 59,4±10,7 y.o. with CHF of ischemic genesis were included in the study. All patients had sinus rhythm and history of Q wave myocardial infarction. Standard examination was performed to all patients. Besides N-proBNP plasma level and patients yearly survival were evaluated.Results. N-proBNP plasma level had direct correlation with clinical indices (exercise tolerance, blood pressure, heart rate and echocardiographic heart sizes. N-proBNP plasma level had relationship with prognosis of CHF patients. Baseline N-proBNP level was more than 2 times higher in died patients in comparison with survived patients. The yearly survival rate of CHF patients was 51,3% if N-proBNP level had been more than 400 fmol/ml (>15% of normal value. The clinico-laboratory index (based on N-proBNP plasma level of severity and prognosis in CHF patients was developed.Conclusion. The clinico-laboratory index based on N-proBNP plasma level is easy to use and can improve medical practice.

  10. A novel calmodulin-regulated Ca2+-ATPase (ACA2) from Arabidopsis with an N-terminal autoinhibitory domain

    Science.gov (United States)

    Harper, J. F.; Hong, B.; Hwang, I.; Guo, H. Q.; Stoddard, R.; Huang, J. F.; Palmgren, M. G.; Sze, H.; Evans, M. L. (Principal Investigator)

    1998-01-01

    To study transporters involved in regulating intracellular Ca2+, we isolated a full-length cDNA encoding a Ca2+-ATPase from a model plant, Arabidopsis, and named it ACA2 (Arabidopsis Ca2+-ATPase, isoform 2). ACA2p is most similar to a "plasma membrane-type" Ca2+-ATPase, but is smaller (110 kDa), contains a unique N-terminal domain, and is missing a long C-terminal calmodulin-binding regulatory domain. In addition, ACA2p is localized to an endomembrane system and not the plasma membrane, as shown by aqueous-two phase fractionation of microsomal membranes. ACA2p was expressed in yeast as both a full-length protein (ACA2-1p) and an N-terminal truncation mutant (ACA2-2p; Delta residues 2-80). Only the truncation mutant restored the growth on Ca2+-depleted medium of a yeast mutant defective in both endogenous Ca2+ pumps, PMR1 and PMC1. Although basal Ca2+-ATPase activity of the full-length protein was low, it was stimulated 5-fold by calmodulin (50% activation around 30 nM). In contrast, the truncated pump was fully active and insensitive to calmodulin. A calmodulin-binding sequence was identified within the first 36 residues of the N-terminal domain, as shown by calmodulin gel overlays on fusion proteins. Thus, ACA2 encodes a novel calmodulin-regulated Ca2+-ATPase distinguished by a unique N-terminal regulatory domain and a non-plasma membrane localization.

  11. Plasmatic levels of N-terminal pro-atrial natriuretic peptide in preeclamptic patients and healthy normotensive pregnant women.

    Science.gov (United States)

    Reyna-Villasmil, Eduardo; Mejia-Montilla, Jorly; Reyna-Villasmil, Nadia; Mayner-Tresol, Gabriel; Herrera-Moya, Pedro; Fernández-Ramírez, Andreina; Rondón-Tapía, Marta

    2018-05-11

    To compare plasma N-terminal pro-atrial natriuretic peptide concentrations in preeclamptic patients and healthy normotensive pregnant women. A cases-controls study was done with 180 patients at Hospital Central Dr. Urquinaona, Maracaibo, Venezuela, that included 90 preeclamptic patients (group A; cases) and 90 healthy normotensive pregnant women selected with the same age and body mass index similar to group A (group B; controls). Blood samples were collected one hour after admission and prior to administration of any medication in group A to determine plasma N-terminal pro-atrial natriuretic peptide and other laboratory parameters. Plasma N-terminal pro-atrial natriuretic peptide concentrations in group A (mean 1.01 [0.26] pg/mL) showed a significant difference when compared with patients in group B (mean 0.55 [0.07] pg/mL; P<.001]. There was no significant correlation with systolic and diastolic blood pressure values in preeclamptic patients (P=ns). A cut-off value of 0.66ng/mL had an area under the curve of 0.93, sensitivity of 87.8%, specificity of 83.3%, a positive predictive value of 84.0% and a negative predictive value of 87.2%, with a diagnostic accuracy of 85.6%. Preeclamptic patients have significantly higher concentrations of plasma N-terminal pro-atrial natriuretic peptide compared with healthy normotensive pregnant women, with high predictive values for diagnosis. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  12. The value of use of amino-terminal brain naturitic peptide as marker in cases of pleural effusion of different etiologies

    Directory of Open Access Journals (Sweden)

    Laila A. Banawan

    2013-10-01

    Conclusion: The results support the feasibility of using the pleural fluid amino terminal proBNP measurement in thoracentesis that would enhance discrimination among the different causes of pleural effusion especially for heart failure patients. Serum and pleural fluid levels of NT-pro BNP were closely correlated and measurement of NT-pro BNP in serum showed equally good diagnostic properties.

  13. Regulation of plant plasma membrane H+- and Ca2+-ATPases by terminal domains

    DEFF Research Database (Denmark)

    Bækgaard, Lone; Fuglsang, Anja Thoe; Palmgren, Michael Gjedde

    2005-01-01

    In the last few years, major progress has been made to elucidate the structure, function, and regulation of P-type plasma membrane H(+)-and Ca(2+)-ATPases. Even though a number of regulatory proteins have been identified, many pieces are still lacking in order to understand the complete regulatory...... mechanisms of these pumps. In plant plasma membrane H(+)- and Ca(2+)-ATPases, autoinhibitory domains are situated in the C- and N-terminal domains, respectively. A model for a common mechanism of autoinhibition is discussed....

  14. N-terminal pro-atrial natriuretic peptide measurement in plasma suggests covalent modification

    DEFF Research Database (Denmark)

    Hunter, Ingrid; Alehagen, Urban; Dahlström, Ulf

    2011-01-01

    different proANP assays on clinical outcome. METHODS: We examined 474 elderly patients with symptoms of heart failure presenting in a primary healthcare setting. Samples were analyzed with an automated immunoluminometric midregion proANP (MR-proANP) assay and a new processing-independent assay (PIA.......74 (95% CI, 0.66–0.81); P = 0.32]. The prognostic ability to report cardiovascular mortality during a 10-year follow-up revealed AUC values of 0.66 (95% CI, 0.60–0.71) for the proANP PIA and 0.69 (95% CI, 0.63–0.74) for the MR-proANP assay (P = 0.08, for comparing the 2 assays). CONCLUSIONS: Our data......BACKGROUND: The N-terminal fragment of cardiac-derived pro–B-type natriuretic peptide is a glycosylated polypeptide. It is unknown whether N-terminal pro–atrial natriuretic peptide (proANP) fragments are also covalently modified. We therefore evaluated the clinical performance of 2 distinctly...

  15. Ground Simulations of Near-Surface Plasma Field and Charging at the Lunar Terminator

    Science.gov (United States)

    Polansky, J.; Ding, N.; Wang, J.; Craven, P.; Schneider, T.; Vaughn, J.

    2012-12-01

    Charging in the lunar terminator region is the most complex and is still not well understood. In this region, the surface potential is sensitively influenced by both solar illumination and plasma flow. The combined effects from localized shadow generated by low sun elevation angles and localized wake generated by plasma flow over the rugged terrain can generate strongly differentially charged surfaces. Few models currently exist that can accurately resolve the combined effects of plasma flow and solar illumination over realistic lunar terminator topographies. This paper presents an experimental investigation of lunar surface charging at the terminator region in simulated plasma environments in a vacuum chamber. The solar wind plasma flow is simulated using an electron bombardment gridded Argon ion source. An electrostatic Langmuir probe, nude Faraday probes, a floating emissive probe, and retarding potential analyzer are used to quantify the plasma flow field. Surface potentials of both conducting and dielectric materials immersed in the plasma flow are measured with a Trek surface potential probe. The conducting material surface potential will simultaneously be measured with a high impedance voltmeter to calibrate the Trek probe. Measurement results will be presented for flat surfaces and objects-on-surface for various angles of attack of the plasma flow. The implications on the generation of localized plasma wake and surface charging at the lunar terminator will be discussed. (This research is supported by the NASA Lunar Advanced Science and Exploration Research program.)

  16. Cardiac natriuretic peptides in plasma increase after dietary induced weight loss in obesity.

    Science.gov (United States)

    Kistorp, Caroline; Bliddal, Henning; Goetze, Jens P; Christensen, Robin; Faber, Jens

    2014-01-01

    Cardiac natriuretic peptides are established biomarkers in heart disease, but are also affected by body mass index (BMI). The purpose of the present study was to examine the impact of weight loss and changes in body composition following dietary intervention on plasma concentrations of the prohormones to A- and B-type natriuretic peptides (proANP and proBNP) and adrenomedullin (proADM). A total of 52 healthy obese subjects, 47 women and 5 men (BMI 36.5 ± 5.6 kg/m(2)) were randomised to either an intensive weight reduction programme using a combination of very low calorie diet (810 kcal/day) and conventional hypo-energetic diet (1200 kcal/day) for 52 weeks, or to a control group that was offered diet-related counselling. N-terminal proBNP (NT-proBNP), mid-regional proANP (MR-proANP) and proADM (MR-proADM) and body composition using dual-energy x-ray absorptiometry (DEXA) scanning were determined at baseline and after 52 weeks. Comparisons between groups were analysed using t-tests. Changes from the baseline within the groups were analysed with paired tests. Changes in the variables, delta (∆), were calculated as 52 weeks minus the baseline. In the intervention group, BMI decreased by almost 20% (31.6 ± 6.2 vs. 37.1 ± 6.1 kg/m(2); P <0.001) with a loss of body fat of 23.5 ± 15.5% (P < 0.001). Plasma concentrations of NT-proBNP and MR-proANP increased (from 55 ± 31 to 97 ± 55 pg/ml; P < 0.001, and from 59 ± 21 to 74 ± 26 pmol/L; P < 0.001), whereas MR-proADM decreased (from 573 ± 153 to 534 ± 173 pmol/L; P <0.001). Changes (Δ) in MR-proANP correlated with Δfat mass (r = -0.359; P = 0.011) and Δglucose (r = -0.495; P <0.001), while increases in NT-proBNP were primarily associated with reduced plasma glucose (r = -0.462; P <0.001). A modest but significant weight loss of 6% (P < 0.001) was found in the control group with no changes in plasma concentrations of NT-proBNP or MR-proANP, and a minor change in MR-proADM. Plasma NT-proBNP and MR

  17. Dusty plasma in the region of the lunar terminator

    Energy Technology Data Exchange (ETDEWEB)

    Popel, S. I., E-mail: popel@iki.rssi.ru; Zelenyi, L. M. [Russian Academy of Sciences, Space Research Institute (Russian Federation); Atamaniuk, B. [Polish Academy of Sciences, Space Research Center (Poland)

    2016-05-15

    Dusty plasma in the region of the lunar terminator is considered. It is shown that, in this region, a structure resembling a plasma sheath forms near the lunar surface. This sheath creates a potential barrier, due to which electrons over the illuminated part of the Moon are confined by electrostatic forces. The width of the sheath-like structure is on the order of the ion Debye length. In this structure, significant (about several hundred V/m) electric fields arise, which lift charged micron-size dust grains to heights of several tens of centimeters. The suggested effect may be used to explain the glow observed by the Surveyor spacecraft over the lunar terminator.

  18. Formation and termination of High ion temperature mode in Heliotron/torsatron plasmas

    International Nuclear Information System (INIS)

    Ida, K.; Kondo, K.; Nagasaki, K.

    1997-01-01

    Physics of the formation and termination of High ion temperature mode (high T i mode) are studied by controlling density profiles and radial electric field. High ion temperature mode is observed for neutral beam heated plasmas in Heliotron/torsatron plasmas (Heliotron-E). This high T i mode plasma is characterized by a peaked ion temperature profile and is associated with a peaked electron density profile produced by neutral beam fueling with low wall recycling. This high T i mode is terminated by flattening the electron density caused by either gas puffing or second harmonic ECH (core density 'pump-out'). (author)

  19. N-terminal pro B-type natriuretic peptide predicts mortality in patients with left ventricular hypertrophy.

    Science.gov (United States)

    Garcia, Santiago; Akbar, Muhammad S; Ali, Syed S; Kamdar, Forum; Tsai, Michael Y; Duprez, Daniel A

    2010-09-03

    Left ventricular hypertrophy adversely affects outcomes in patients with hypertension. Whether N-terminal pro B-type natriuretic peptide (NT-proBNP) adds incremental prognostic information in patients with hypertension and left ventricular hypertrophy (LVH) is not well established. We aimed to study the prognostic value of NT-proBNP in hypertensive patients with LVH. Echocardiography was performed in 232 patients (mean age 61±15, 102 males, 130 females) for the diagnosis of left ventricular hypertrophy. Left ventricular mass was measured according to The American Society of Echocardiography guidelines. A blood sample was taken for NT-proBNP determination. NT-proBNP levels were analyzed in quartiles after log transformation. Long term survival was established by review of electronic medical records. Arterial hypertension was present in 130 patients (56%) and left ventricular hypertrophy was present in 105 patients (45%). In patients with left ventricular hypertrophy, NT-proBNP levels predicted long term survival (Chi-square=10, p=0.01). After adjusting by age, presence of coronary artery disease, ejection fraction, diabetes status, and hypertension; patients in highest NT pro-BNP quartile were twice as likely to die when compared to patients in the lowest NT-ptoBNP quartile (OR=2.2, 95% CI=1.0-4.6, p=0.03). NT-proBNP is an independent predictor of survival in patients with hypertension and increased left ventricular mass. Copyright © 2009 Elsevier B.V. All rights reserved.

  20. Plasma N-terminal pro-brain natriuretic peptide levels in patients with acute myocardial infarction, unstable angina pectoris and non-insulin-dependent diabetes

    International Nuclear Information System (INIS)

    Zhang Yonggang; Li Yuguang

    2004-01-01

    Objective: Determination of plasma N-terminal pro-brain natriuretic peptide [NT-proBNP (1-76)] levels is useful for the diagnosis of heart failure. Present study was to investigate the significance of changes of plasma NT-proBNP (1-76) levels in patients with acute myocardial infarction (AMI), unstable angina pectoris (UAP) and non-insulin-dependent diabetes (NIDD). Methods: Plasma NT-proBNP (1-76) levels were determined with RIA in 32 patients with AMI, 27 patients with UAP, 12 patients with NIDD and 20 controls. Moreover, 16 of the 32 AMI patients underwent percutaneous transluminal coronary angioplasty (PTCA) and plasma (1-76) levels were again determined 12hr before and 12hr after the procedure. Results: The plasma NT-proBNP (1-76) levels in controls were 360.8 ± 57.3 pg/ ml with no significant difference between the sexes. In patients with AMI, UAP and NIDD, NT-proBNP (1-76) levels were 554.1 ± 195.9 pg/ml, 525.7 ± 199.1 pg/ml and 552.6 ± 141.9 pg/ml respectively; all of them were significantly higher than those in controls (P 0.05). Conclusion: The plasma NT-proBNP (1-76) levels in patients with AMI, UAP and NIDD were increased significantly and the result suggested that NT-proBNP (1-76) might be a useful risk marker for these diseases. (authors)

  1. Pro B-type natriuretic peptide plasma value: a new criterion for the prediction of short- and long-term outcomes after transcatheter aortic valve implantation.

    Science.gov (United States)

    López-Otero, Diego; Trillo-Nouche, Ramiro; Gude, Francisco; Cid-Álvarez, Belen; Ocaranza-Sanchez, Raimundo; Alvarez, Melisa Santas; Lear, Pamela V; Gonzalez-Juanatey, José R

    2013-09-30

    To determine the prognostic value of pro B-type natriuretic peptide (pro-BNP) to predict mortality after transcatheter aortic valve implantation (TAVI). Logistic EuroSCORE (LES) overestimates observed mortality after TAVI. A new risk score specific to TAVI is needed to accurately assess mortality and outcome. Eighty-five patients were included. Indications for TAVI were nonoperable or surgically high-risk patients (LES>20%). Pro-BNP was measured 24h before the procedure. Cox proportional hazards model was used to evaluate clinical factors. The predictive accuracy of these Cox models was determined by using time-dependent receiver operating characteristic (ROC) curves. Pro-BNP levels (log-transformed) were significantly higher in non-survivors than in survivors at 30 days (3.36 ± 0.43 vs. 3.81 ± 0.43, p<0.004) and at the end of follow-up (3.34 ± 0.42 vs. 3.63 ± 0.48, p<0.011). Multivariate analysis revealed that only increased log pro-BNP levels were associated with higher mortality rate at short [hazard ratio (HR) (95% confidence intervals (CI)]=5.35 (1.74-16.5), p=0.003] and long-term follow-ups [HR=11 (CI: 1.51-81.3), p=0.018]. LES was not associated with increased mortality at either time point [HR=1.03 (CI: 0.95-1.10), p=0.483 and HR=1.03 (CI: 0.98-1.07), p=0.230, respectively]. At 30, 90, 180, and 365 days, the c-index was 0.72 for log pro-BNP and 0.63 for LES (p=0.044). Pre-procedure log transform of plasma pro-BNP levels are an independent and strong predictor of short- and long-term outcomes after TAVI and are more discriminatory than LES. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  2. Liquid jets for fast plasma termination in tokamaks

    International Nuclear Information System (INIS)

    Rosenbluth, M.N.; Putvinskij, S.V.; Parks, P.B.

    1997-01-01

    Recent simulations by Putvisnkij et al. (PSI Conference, 1996) have shown that introducing impurities into the plasma in order to mitigate adverse disruption effects in ITER may actually be deleterious because of a potentially unwelcome phenomenon: generation of multi-MeV runaway electrons by the collisional avalanche mechanism (Rosenbluth, M.N., et al., in Fusion Energy 1996 (Proc. 16th Int. Conf. Montreal, 1996) Vol. 2, IAEA, Vienna (in press) Paper FP-26). The injection of a liquid hydrogen jet to deliver a massive density increase is proposed as a means of avoiding runaways, while providing the same beneficial effects as impurities. A discussion of many jet related topics, such as ablation/penetration, jet breakup time and stability, is presented. Owing to an ablation pressure instability, it is predicted that the jet will quickly break up into a regular chain of droplets with dimensions of approximately the size of the jet radius. It is found that while deep penetration in the plasma can easily be achieved, bubble growth and disruptive boiling (flashing) during the propagation in the vacuum gap between the nozzle exit and the plasma are the main processes limiting the jet survival time. Calculations indicate that for ITER reference parameters, the jet can remain coherent in vacuum for a distance ∼ 1 m before disintegrating. On the basis of this present understanding, the prospect for the safe termination of ITER discharges by high density liquid jet injection appears promising. (author). 20 refs, 6 figs, 3 tabs

  3. N-terminal nesprin-2 variants regulate β-catenin signalling

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Qiuping; Minaisah, Rose-Marie; Ferraro, Elisa; Li, Chen; Porter, Lauren J.; Zhou, Can; Gao, Fang; Zhang, Junyi; Rajgor, Dipen; Autore, Flavia; Shanahan, Catherine M.; Warren, Derek T., E-mail: derek.warren@kcl.ac.uk

    2016-07-15

    The spatial compartmentalisation of biochemical signalling pathways is essential for cell function. Nesprins are a multi-isomeric family of proteins that have emerged as signalling scaffolds, herein, we investigate the localisation and function of novel nesprin-2 N-terminal variants. We show that these nesprin-2 variants display cell specific distribution and reside in both the cytoplasm and nucleus. Immunofluorescence microscopy revealed that nesprin-2 N-terminal variants colocalised with β-catenin at cell-cell junctions in U2OS cells. Calcium switch assays demonstrated that nesprin-2 and β-catenin are lost from cell-cell junctions in low calcium conditions whereas emerin localisation at the NE remained unaltered, furthermore, an N-terminal fragment of nesprin-2 was sufficient for cell-cell junction localisation and interacted with β-catenin. Disruption of these N-terminal nesprin-2 variants, using siRNA depletion resulted in loss of β-catenin from cell-cell junctions, nuclear accumulation of active β-catenin and augmented β-catenin transcriptional activity. Importantly, we show that U2OS cells lack nesprin-2 giant, suggesting that the N-terminal nesprin-2 variants regulate β-catenin signalling independently of the NE. Together, these data identify N-terminal nesprin-2 variants as novel regulators of β-catenin signalling that tether β-catenin to cell-cell contacts to inhibit β-catenin transcriptional activity. - Highlights: • N-terminal nesprin-2 variants display cell specific expression patterns. • N-terminal spectrin repeats of nesprin-2 interact with β-catenin. • N-terminal nesprin-2 variants scaffold β-catenin at cell-cell junctions.. • Nesprin-2 variants play multiple roles in β-catenin signalling.

  4. Towards the N-terminal acetylome

    DEFF Research Database (Denmark)

    Zhang, Xumin; Højrup, Peter

    2013-01-01

    Protein N-terminal acetylation (N(α)-acetylation) is observed widely from prokaryotes to eukaryotes. It gains increased importance in biological field, due to its multiple roles in many aspects of the protein life, such as assembly, stability, activity, and location. Today, mass spectrometry (MS...

  5. Measurements of plasma termination in ICRF heated long pulse discharges with fast framing cameras in the Large Helical Device

    International Nuclear Information System (INIS)

    Shoji, Mamoru; Kasahara, Hiroshi; Tanaka, Hirohiko

    2015-01-01

    The termination process of long pulse plasma discharges in the Large Helical Device (LHD) have been observed with fast framing cameras, which shows that the reason for the termination of the discharged has been changed with increased plasma heating power, improvements of plasma heating systems and change of the divertor configuration, etc. For long pulse discharges in FYs2010-2012, the main reason triggering the plasma termination was reduction of ICRF heating power with rise of iron ion emission due to electric breakdown in an ICRF antenna. In the experimental campaign in FY2013, the duration time of ICRF heated long pulse plasma discharges has been extended to about 48 minutes with a plasma heating power of ∼1.2 MW and a line-averaged electron density of ∼1.2 × 10"1"9 m"-"3. The termination of the discharges was triggered by release of large amounts of carbon dusts from closed divertor regions, indicating that the control of dust formation in the divertor regions is indispensable for extending the duration time of long pulse discharges. (author)

  6. Carbamylation of N-terminal proline.

    Science.gov (United States)

    Olajuyigbe, Folasade M; Demitri, Nicola; Ajele, Joshua O; Maurizio, Elisa; Randaccio, Lucio; Geremia, Silvano

    2010-09-09

    Protein carbamylation is of great concern both in vivo and in vitro. Here, we report the first structural characterization of a protein carbamylated at the N-terminal proline. The unexpected carbamylation of the α-amino group of the least reactive codified amino acid has been detected in high-resolution electron density maps of a new crystal form of the HIV-1 protease/saquinavir complex. The carbamyl group is found coplanar to the proline ring with a trans conformation. The reaction of N-terminal with cyanate ion derived from the chaotropic agent urea was confirmed by mass spectra analysis on protease single crystals. Implications of carbamylation process in vitro and in vivo are discussed.

  7. NetAcet: prediction of N-terminal acetylation sites

    DEFF Research Database (Denmark)

    Kiemer, Lars; Bendtsen, Jannick Dyrløv; Blom, Nikolaj

    2005-01-01

    Summary: We present here a neural network based method for prediction of N-terminal acetylation-by far the most abundant post-translational modification in eukaryotes. The method was developed on a yeast dataset for N-acetyltransferase A (NatA) acetylation, which is the type of N-acetylation for ......Summary: We present here a neural network based method for prediction of N-terminal acetylation-by far the most abundant post-translational modification in eukaryotes. The method was developed on a yeast dataset for N-acetyltransferase A (NatA) acetylation, which is the type of N...

  8. N-Terminal Pro-B-Type Natriuretic Peptide and Phonocardiography in Differentiating Innocent Cardiac Murmurs from Congenital Cardiac Anomalies in Asymptomatic Puppies

    NARCIS (Netherlands)

    Marinus, S M; Engelen, H.G.H.; Szatmári, V.

    2017-01-01

    Background: Differentiating innocent cardiac murmurs from murmurs caused by congenital cardiac anomalies can be challenging with auscultation alone in asymptomatic puppies. Hypothesis: Plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations and phonocardiograms recorded by an

  9. Interaction of N-terminal peptide analogues of the Na+,K+-ATPase with membranes.

    Science.gov (United States)

    Nguyen, Khoa; Garcia, Alvaro; Sani, Marc-Antoine; Diaz, Dil; Dubey, Vikas; Clayton, Daniel; Dal Poggetto, Giovanni; Cornelius, Flemming; Payne, Richard J; Separovic, Frances; Khandelia, Himanshu; Clarke, Ronald J

    2018-06-01

    The Na + ,K + -ATPase, which is present in the plasma membrane of all animal cells, plays a crucial role in maintaining the Na + and K + electrochemical potential gradients across the membrane. Recent studies have suggested that the N-terminus of the protein's catalytic α-subunit is involved in an electrostatic interaction with the surrounding membrane, which controls the protein's conformational equilibrium. However, because the N-terminus could not yet be resolved in any X-ray crystal structures, little information about this interaction is so far available. In measurements utilising poly-l-lysine as a model of the protein's lysine-rich N-terminus and using lipid vesicles of defined composition, here we have identified the most likely origin of the interaction as one between positively charged lysine residues of the N-terminus and negatively charged headgroups of phospholipids (notably phosphatidylserine) in the surrounding membrane. Furthermore, to isolate which segments of the N-terminus could be involved in membrane binding, we chemically synthesized N-terminal fragments of various lengths. Based on a combination of results from RH421 UV/visible absorbance measurements and solid-state 31 P and 2 H NMR using these N-terminal fragments as well as MD simulations it appears that the membrane interaction arises from lysine residues prior to the conserved LKKE motif of the N-terminus. The MD simulations indicate that the strength of the interaction varies significantly between different enzyme conformations. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. N-Terminal Domains in Two-Domain Proteins Are Biased to Be Shorter and Predicted to Fold Faster Than Their C-Terminal Counterparts

    Directory of Open Access Journals (Sweden)

    Etai Jacob

    2013-04-01

    Full Text Available Computational analysis of proteomes in all kingdoms of life reveals a strong tendency for N-terminal domains in two-domain proteins to have shorter sequences than their neighboring C-terminal domains. Given that folding rates are affected by chain length, we asked whether the tendency for N-terminal domains to be shorter than their neighboring C-terminal domains reflects selection for faster-folding N-terminal domains. Calculations of absolute contact order, another predictor of folding rate, provide additional evidence that N-terminal domains tend to fold faster than their neighboring C-terminal domains. A possible explanation for this bias, which is more pronounced in prokaryotes than in eukaryotes, is that faster folding of N-terminal domains reduces the risk for protein aggregation during folding by preventing formation of nonnative interdomain interactions. This explanation is supported by our finding that two-domain proteins with a shorter N-terminal domain are much more abundant than those with a shorter C-terminal domain.

  11. Heparan sulfate regulates fibrillin-1 N- and C-terminal interactions

    DEFF Research Database (Denmark)

    Cain, Stuart A; Baldwin, Andrew K; Mahalingam, Yashithra

    2008-01-01

    Fibrillin-1 N- and C-terminal heparin binding sites have been characterized. An unprocessed monomeric N-terminal fragment (PF1) induced a very high heparin binding response, indicating heparin-mediated multimerization. Using PF1 deletion and short fragments, a heparin binding site was localized w......-terminal interactions with heparin/heparan sulfate directly influence cell behavior, whereas C-terminal interactions with heparin/heparan sulfate regulate elastin deposition. These data highlight how heparin/heparan sulfate controls fibrillin-1 interactions....

  12. The C-terminal domain of TRPV4 is essential for plasma membrane localization.

    Science.gov (United States)

    Becker, Daniel; Müller, Margarethe; Leuner, Kristina; Jendrach, Marina

    2008-02-01

    Many members of the TRP superfamily oligomerize in the ER before trafficking to the plasma membrane. For membrane localization of the non-selective cation channel TRPV4 specific domains in the N-terminus are required, but the role of the C-terminus in the oligomerization and trafficking process has been not determined until now. Therefore, the localization of recombinant TRPV4 in two cell models was analyzed: HaCaT keratinocytes that express TRPV4 endogenously were compared to CHO cells that are devoid of endogenous TRPV4. When deletions were introduced in the C-terminal domain three states of TRPV4 localization were defined: a truncated TRPV4 protein of 855 amino acids was exported to the plasma membrane like the full-length channel (871 aa) and was also functional. Mutants with a length of 828 to 844 amino acids remained in the ER of CHO cells, but in HaCaT cells plasma membrane localization was partially rescued by oligomerization with endogenous TRPV4. This was confirmed by coexpression of recombinant full-length TRPV4 together with these deletion mutants, which resulted in an almost complete plasma membrane localization of both proteins and significant FRET in the plasma membrane and the ER. All deletions upstream of amino acid 828 resulted in total ER retention that could not rescued by coexpression with the full-length protein. However, these deletion mutants did not impair export of full-length TRPV4, implying that no oligomerization took place. These data indicate that the C-terminus of TRPV4 is required for oligomerization, which takes place in the ER and precedes plasma membrane trafficking.

  13. N-terminal pro-brain natriuretic peptide in relation to inflammation, myocardial necrosis, and the effect of an invasive strategy in unstable coronary artery disease.

    Science.gov (United States)

    Jernberg, Tomas; Lindahl, Bertil; Siegbahn, Agneta; Andren, Bertil; Frostfeldt, Gunnar; Lagerqvist, Bo; Stridsberg, Mats; Venge, Per; Wallentin, Lars

    2003-12-03

    We sought to examine whether measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP), in addition to cardiac troponin T (cTnT) and interleukin-6 (IL-6), improve the ability to identify high-risk patients who benefit from an early invasive strategy. Biochemical indicators of cardiac performance (e.g., NT-proBNP), inflammation (e.g., IL-6), and myocardial damage (e.g., cTnT) predict mortality in unstable coronary artery disease (UCAD) (i.e., unstable angina or non-ST-segment elevation myocardial infarction [MI]). In these patients, an early invasive treatment strategy improves the outcome. Levels of NT-proBNP, cTnT, and IL-6 were measured in 2,019 patients with UCAD randomized to an invasive or non-invasive strategy in the FRagmin and fast revascularization during InStability in Coronary artery disease (FRISC-II) trial. Patients were followed up for two years to determine death and MI. Patients in the third NT-proBNP tertile had a 4.1-fold (95% confidence interval [CI] 2.4 to 7.2) and 3.5-fold (95% CI 1.8 to 6.8) increased mortality in the non-invasive and invasive groups, respectively. An increased NT-proBNP level was independently associated with mortality. In patients with increased levels of both NT-proBNP and IL-6, an early invasive strategy reduced mortality by 7.3% (risk ratio 0.46, 95% CI 0.21 to 1.00). In patients with lower NT-proBNP or IL-6 levels, the mortality was not reduced. Only elevated cTnT was independently associated with future MI and a reduction of MI by means of an invasive strategy. N-terminal proBNP is independently associated with mortality. The combination of NT-proBNP and IL-6 seems to be a useful tool in the identification of patients with a definite survival benefit from an early invasive strategy. Only cTnT is independently associated with future MI and a reduction of MI by an invasive strategy.

  14. The N-terminal leucine-zipper motif in PTRF/cavin-1 is essential and sufficient for its caveolae-association

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Zhuang [State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Laboratory of System Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Zou, Xinle [State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Wang, Hongzhong; Lei, Jigang; Wu, Yuan [State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Laboratory of System Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Liao, Kan, E-mail: kliao@sibs.ac.cn [State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Laboratory of System Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China)

    2015-01-16

    Highlight: • The N-terminal leucine-zipper motif in PTRF/cavin-1 determines caveolar association. • Different cellular localization of PTRF/cavin-1 influences its serine 389 and 391 phosphorylation state. • PTRF/cavin-1 regulates cell motility via its caveolar association. - Abstract: PTRF/cavin-1 is a protein of two lives. Its reported functions in ribosomal RNA synthesis and in caveolae formation happen in two different cellular locations: nucleus vs. plasma membrane. Here, we identified that the N-terminal leucine-zipper motif in PTRF/cavin-1 was essential for the protein to be associated with caveolae in plasma membrane. It could counteract the effect of nuclear localization sequence in the molecule (AA 235–251). Deletion of this leucine-zipper motif from PTRF/cavin-1 caused the mutant to be exclusively localized in nuclei. The fusion of this leucine-zipper motif with histone 2A, which is a nuclear protein, could induce the fusion protein to be exported from nucleus. Cell migration was greatly inhibited in PTRF/cavin-1{sup −/−} mouse embryonic fibroblasts (MEFs). The inhibited cell motility could only be rescued by exogenous cavin-1 but not the leucine-zipper motif deleted cavin-1 mutant. Plasma membrane dynamics is an important factor in cell motility control. Our results suggested that the membrane dynamics in cell migration is affected by caveolae associated PTRF/cavin-1.

  15. The N-terminal leucine-zipper motif in PTRF/cavin-1 is essential and sufficient for its caveolae-association

    International Nuclear Information System (INIS)

    Wei, Zhuang; Zou, Xinle; Wang, Hongzhong; Lei, Jigang; Wu, Yuan; Liao, Kan

    2015-01-01

    Highlight: • The N-terminal leucine-zipper motif in PTRF/cavin-1 determines caveolar association. • Different cellular localization of PTRF/cavin-1 influences its serine 389 and 391 phosphorylation state. • PTRF/cavin-1 regulates cell motility via its caveolar association. - Abstract: PTRF/cavin-1 is a protein of two lives. Its reported functions in ribosomal RNA synthesis and in caveolae formation happen in two different cellular locations: nucleus vs. plasma membrane. Here, we identified that the N-terminal leucine-zipper motif in PTRF/cavin-1 was essential for the protein to be associated with caveolae in plasma membrane. It could counteract the effect of nuclear localization sequence in the molecule (AA 235–251). Deletion of this leucine-zipper motif from PTRF/cavin-1 caused the mutant to be exclusively localized in nuclei. The fusion of this leucine-zipper motif with histone 2A, which is a nuclear protein, could induce the fusion protein to be exported from nucleus. Cell migration was greatly inhibited in PTRF/cavin-1 −/− mouse embryonic fibroblasts (MEFs). The inhibited cell motility could only be rescued by exogenous cavin-1 but not the leucine-zipper motif deleted cavin-1 mutant. Plasma membrane dynamics is an important factor in cell motility control. Our results suggested that the membrane dynamics in cell migration is affected by caveolae associated PTRF/cavin-1

  16. A glycosylated form of the human cardiac hormone pro B-type natriuretic peptide is an intrinsically unstructured monomeric protein.

    Science.gov (United States)

    Crimmins, Dan L; Kao, Jeffrey L-F

    2008-07-01

    The N-terminal fragment of pro B-type natriuretic peptide (NT-proBNP) and proBNP are used as gold standard clinical markers of myocardial dysfunction such as cardiac hypertrophy and left ventricle heart failure. The actual circulating molecular forms of these peptides have been the subject of intense investigation particularly since these analytes are measured in clinical assays. Conflicting data has been reported and no firm consensus on the exact nature of the molecular species exists. Because these clinical assays are immunoassay-based, specific epitopes are detected. It is conceivable then that certain epitopes may be masked and therefore unavailable for antibody binding, thus the importance of determining the nature of the circulating molecular forms of these analytes. This situation is an unavoidable Achilles' heel of immunoassays in general. A recombinant O-linked glycosylated form of proBNP has been show to mimic some of the properties of extracted plasma from a heart failure patient. In particular the recombinant and native material co-migrated as diffuse Western-immunostained bands on SDS-PAGE and each band collapsed to an apparent homogeneous band following deglycosylation. Thus, glycosylated-proBNP may be one such circulating form. Here we provide extensive physiochemical characterization for this O-linked protein and compare these results to other described circulating species, non-glycosylated-proBNP and NT-proBNP. It will be shown that glycosylation has no influence on the secondary and quaternary structure of proBNP. In fact, at moderate concentration in benign physiological neutral pH buffer, all three likely circulating species are essentially devoid of major secondary structure, i.e., are intrinsically unstructured proteins (IUPs). Furthermore, all three proteins exist as monomers in solution. These results may have important implications in the design of NT-proBNP/BNP immunoassays.

  17. Limitations of N-Terminal Pro-B-Type Natriuretic Peptide in the Diagnosis of Heart Disease among Cancer Patients Who Present with Cardiac or Pulmonary Symptoms.

    Science.gov (United States)

    Wieshammer, Siegfried; Dreyhaupt, Jens; Müller, Dirk; Momm, Felix; Jakob, Andreas

    2016-01-01

    Recognizing heart disease is relevant to oncologists because cancer patients are at an increased risk of cardiac mortality due to shared risk factors and the adverse effects of cancer therapy. This study assessed the extent to which the measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) aids in the diagnosis of heart disease in addition to a history of coronary artery disease and the presence of atrial fibrillation (composite test). The NT- proBNP cutoff value was 100 pg/ml. A series of 583 consecutive cancer patients (68.4 ± 11.0 years) who were referred because of cardiac or pulmonary symptoms prospectively underwent a diagnostic work-up. Heart disease was diagnosed if at least one of the following conditions was present: (a) history of coronary artery disease, (b) atrial fibrillation, (c) impaired left ventricular systolic function, (d) significant valvular disease, (e) pulmonary hypertension, or (f) left ventricular hypertrophy. Except for (a), all 6 conditions were associated with NT-proBNP >100 pg/ml. The sensitivity/specificity values of the composite test were 0.92/0.50 for any heart disease. Several extracardiac covariates were associated with NT-proBNP >100 pg/ml, which contributed to the low test specificity. The low specificity of NT-proBNP limits its value for the diagnosis of heart disease in cancer patients. © 2016 The Author(s) Published by S. Karger AG, Basel.

  18. Association between resting heart rate and N-terminal pro-brain natriuretic peptide in a community-based population study in Beijing

    Directory of Open Access Journals (Sweden)

    Cao R

    2014-12-01

    Full Text Available Ruihua Cao, Yongyi Bai, Ruyi Xu, Ping Ye Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, People’s Republic of China Background: N-terminal pro-brain natriuretic peptide (NT-proBNP is associated with an increased risk of cardiac insufficiency, which possibly leads to heart failure. However, the relationship between resting heart rate and NT-proBNP is unclear.Objective: This study focuses on this relativity between resting heart rate and plasma NT-proBNP levels in a surveyed community-based population.Methods: We evaluated the relativity between resting heart rate and plasma levels of NT-proBNP in 1,567 participants (mean age 61.0 years, range 21–96 years from a community-based population in Beijing, People’s Republic of China.Results: In patients with high resting heart rate (≥75 beats/min, NT-proBNP was higher than in those having low resting heart rate (<75 beats/min. In multiple linear stepwise regression analysis, plasma NT-proBNP was associated with resting heart rate (partial correlation coefficient, 0.82; 95% confidence interval, 0.18–1.51; P=0.011. A subsequent subgroup analysis revealed that the association between resting heart rate and plasma NT-proBNP was strengthened in subjects over 60 years old (partial correlation coefficient 1.28; 95% confidence interval, 0.49–2.36; P=0.031; while the relativity between resting heart rate and plasma NT-proBNP was not emerged in the younger subgroup (<60 years old.Conclusions: Resting heart rate was associated with plasma NT-proBNP in the elderly, which indicated a relationship between resting heart rate and cardiac function damage. Keywords: resting heart rate, N-terminal pro-brain natriuretic peptide, epidemiology, cardiac function, relationship

  19. N-terminal pro brain natriuretic peptide as a cardiac biomarker in Japanese hemodialysis patients.

    Science.gov (United States)

    Shimizu, Minako; Doi, Shigehiro; Nakashima, Ayumu; Naito, Takayuki; Masaki, Takao

    2018-03-01

    This study examined the clinical significance of N-terminal pro brain natriuretic peptide level as a cardiac marker in Japanese hemodialysis patients. This was a multicenter cross-sectional study involving 1428 Japanese hemodialysis patients. Ultrasonic cardiography data at post-hemodialysis were obtained from 395 patients. We examined whether serum N-terminal pro brain natriuretic peptide levels were associated with cardiac parameters and assessed cut-off values and investigated factors associated with a reduced ratio of N-terminal pro brain natriuretic peptide levels pre- and post-hemodialysis. Multivariate logistic regression analysis showed that pre- and post-hemodialysis N-terminal pro brain natriuretic peptide levels were associated with left ventricular hypertrophy on electrocardiogram (odds ratio: 3.10; p N-terminal pro brain natriuretic peptide levels were also significantly associated with ejection fraction on urine chorionic gonadotrophin (ultrasonic cardiography; odds ratio: 35.83; p N-terminal pro brain natriuretic peptide reduction ratio during a hemodialysis session correlated with Kt/V, membrane area, membrane type, modality, body weight gain ratio, treatment time, and ultrafiltration rate with multiple linear regression ( R: 0.53; p N-terminal pro brain natriuretic peptide are associated with the presence of left ventricular hypertrophy in this population. The post-hemodialysis N-terminal pro brain natriuretic peptide level is a useful marker for systolic dysfunction.

  20. Procollagen III N-terminal Propeptide and Desmosine are Released by Matrix Destruction in Pulmonary Tuberculosis

    Science.gov (United States)

    Seddon, Jo; Kasprowicz, Victoria; Walker, Naomi F.; Yuen, Ho Ming; Sunpath, Henry; Tezera, Liku; Meintjes, Graeme; Wilkinson, Robert J.; Bishai, William R.; Friedland, Jon S.; Elkington, Paul T.

    2013-01-01

    Background. Tuberculosis is transmitted by patients with pulmonary disease. Matrix metalloproteinases (MMPs) drive lung destruction in tuberculosis but the resulting matrix degradation products (MDPs) have not been studied. We investigate the hypothesis that MMP activity generates matrix turnover products as correlates of lung pathology. Methods. Induced sputum and plasma were collected prospectively from human immunodeficiency virus (HIV) positive and negative patients with pulmonary tuberculosis and controls. Concentrations of MDPs and MMPs were analyzed by ELISA and Luminex array in 2 patient cohorts. Results. Procollagen III N-terminal propeptide (PIIINP) was 3.8-fold higher in induced sputum of HIV-uninfected tuberculosis patients compared to controls and desmosine, released during elastin degradation, was 2.4-fold higher. PIIINP was elevated in plasma of tuberculosis patients. Plasma PIIINP correlated with induced sputum MMP-1 concentrations and radiological scores, demonstrating that circulating MDPs reflect lung destruction. In a second patient cohort of mixed HIV seroprevalence, plasma PIIINP concentration was increased 3.0-fold above controls (P tuberculosis patients (P = .001). Receiver operating characteristic analysis utilizing these 2 variables demonstrated an area under the curve of 0.832 (P pulmonary tuberculosis, MMP-driven immunopathology generates matrix degradation products. PMID:23922364

  1. The N-terminal domain of Slack determines the formation and trafficking of Slick/Slack heteromeric sodium-activated potassium channels.

    Science.gov (United States)

    Chen, Haijun; Kronengold, Jack; Yan, Yangyang; Gazula, Valeswara-Rao; Brown, Maile R; Ma, Liqun; Ferreira, Gonzalo; Yang, Youshan; Bhattacharjee, Arin; Sigworth, Fred J; Salkoff, Larry; Kaczmarek, Leonard K

    2009-04-29

    Potassium channels activated by intracellular Na(+) ions (K(Na)) play several distinct roles in regulating the firing patterns of neurons, and, at the single channel level, their properties are quite diverse. Two known genes, Slick and Slack, encode K(Na) channels. We have now found that Slick and Slack subunits coassemble to form heteromeric channels that differ from the homomers in their unitary conductance, kinetic behavior, subcellular localization, and response to activation of protein kinase C. Heteromer formation requires the N-terminal domain of Slack-B, one of the alternative splice variants of the Slack channel. This cytoplasmic N-terminal domain of Slack-B also facilitates the localization of heteromeric K(Na) channels to the plasma membrane. Immunocytochemical studies indicate that Slick and Slack-B subunits are coexpressed in many central neurons. Our findings provide a molecular explanation for some of the diversity in reported properties of neuronal K(Na) channels.

  2. N-terminal Proteomics Assisted Profiling of the Unexplored Translation Initiation Landscape in Arabidopsis thaliana.

    Science.gov (United States)

    Willems, Patrick; Ndah, Elvis; Jonckheere, Veronique; Stael, Simon; Sticker, Adriaan; Martens, Lennart; Van Breusegem, Frank; Gevaert, Kris; Van Damme, Petra

    2017-06-01

    Proteogenomics is an emerging research field yet lacking a uniform method of analysis. Proteogenomic studies in which N-terminal proteomics and ribosome profiling are combined, suggest that a high number of protein start sites are currently missing in genome annotations. We constructed a proteogenomic pipeline specific for the analysis of N-terminal proteomics data, with the aim of discovering novel translational start sites outside annotated protein coding regions. In summary, unidentified MS/MS spectra were matched to a specific N-terminal peptide library encompassing protein N termini encoded in the Arabidopsis thaliana genome. After a stringent false discovery rate filtering, 117 protein N termini compliant with N-terminal methionine excision specificity and indicative of translation initiation were found. These include N-terminal protein extensions and translation from transposable elements and pseudogenes. Gene prediction provided supporting protein-coding models for approximately half of the protein N termini. Besides the prediction of functional domains (partially) contained within the newly predicted ORFs, further supporting evidence of translation was found in the recently released Araport11 genome re-annotation of Arabidopsis and computational translations of sequences stored in public repositories. Most interestingly, complementary evidence by ribosome profiling was found for 23 protein N termini. Finally, by analyzing protein N-terminal peptides, an in silico analysis demonstrates the applicability of our N-terminal proteogenomics strategy in revealing protein-coding potential in species with well- and poorly-annotated genomes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Crystal Structures of GaN Nanodots by Nitrogen Plasma Treatment on Ga Metal Droplets

    Directory of Open Access Journals (Sweden)

    Yang-Zhe Su

    2018-06-01

    Full Text Available Gallium nitride (GaN is one of important functional materials for optoelectronics and electronics. GaN exists both in equilibrium wurtzite and metastable zinc-blende structural phases. The zinc-blende GaN has superior electronic and optical properties over wurtzite one. In this report, GaN nanodots can be fabricated by Ga metal droplets in ultra-high vacuum and then nitridation by nitrogen plasma. The size, shape, density, and crystal structure of GaN nanodots can be characterized by transmission electron microscopy. The growth parameters, such as pre-nitridation treatment on Si surface, substrate temperature, and plasma nitridation time, affect the crystal structure of GaN nanodots. Higher thermal energy could provide the driving force for the phase transformation of GaN nanodots from zinc-blende to wurtzite structures. Metastable zinc-blende GaN nanodots can be synthesized by the surface modification of Si (111 by nitrogen plasma, i.e., the pre-nitridation treatment is done at a lower growth temperature. This is because the pre-nitridation process can provide a nitrogen-terminal surface for the following Ga droplet formation and a nitrogen-rich condition for the formation of GaN nanodots during droplet epitaxy. The pre-nitridation of Si substrates, the formation of a thin SiNx layer, could inhibit the phase transformation of GaN nanodots from zinc-blende to wurtzite phases. The pre-nitridation treatment also affects the dot size, density, and surface roughness of samples.

  4. Cyclization of the N-Terminal X-Asn-Gly Motif during Sample Preparation for Bottom-Up Proteomics

    DEFF Research Database (Denmark)

    Zhang, Xumin; Højrup, Peter

    2010-01-01

    We, herein, report a novel -17 Da peptide modification corresponding to an N-terminal cyclization of peptides possessing the N-terminal motif of X-Asn-Gly. The cyclization occurs spontaneously during sample preparation for bottom-up proteomics studies. Distinct from the two well-known N-terminal ......We, herein, report a novel -17 Da peptide modification corresponding to an N-terminal cyclization of peptides possessing the N-terminal motif of X-Asn-Gly. The cyclization occurs spontaneously during sample preparation for bottom-up proteomics studies. Distinct from the two well-known N......-terminal cyclizations, cyclization of N-terminal glutamine and S-carbamoylmethylcysteine, it is dependent on pH instead of [NH(4)(+)]. The data set from our recent study on large-scale N(α)-modified peptides revealed a sequence requirement for the cyclization event similar to the well-known deamidation of Asn to iso...

  5. Improved Ohmic-contact to AlGaN/GaN using Ohmic region recesses by self-terminating thermal oxidation assisted wet etching technique

    Science.gov (United States)

    Liu, J.; Wang, J.; Wang, H.; Zhu, L.; Wu, W.

    2017-06-01

    Lower Ti/Al/Ni/Au Ohmic contact resistance on AlGaN/GaN with wider rapid thermal annealing (RTA) temperature window was achieved using recessed Ohmic contact structure based on self-terminating thermal oxidation assisted wet etching technique (STOAWET), in comparison with conventional Ohmic contacts. Even at lower temperature such as 650°C, recessed structure by STOAWET could still obtain Ohmic contact with contact resistance of 1.97Ω·mm, while conventional Ohmic structure mainly featured as Schottky contact. Actually, both Ohmic contact recess and mesa isolation processes could be accomplished by STOAWET in one process step and the process window of STOAWET is wide, simplifying AlGaN/GaN HEMT device process. Our experiment shows that the isolation leakage current by STOAWET is about one order of magnitude lower than that by inductivity coupled plasma (ICP) performed on the same wafer.

  6. Blocking an N-terminal acetylation–dependent protein interaction inhibits an E3 ligase

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Daniel C.; Hammill, Jared T.; Min, Jaeki; Rhee, David Y.; Connelly, Michele; Sviderskiy, Vladislav O.; Bhasin, Deepak; Chen, Yizhe; Ong, Su-Sien; Chai, Sergio C.; Goktug, Asli N.; Huang, Guochang; Monda, Julie K.; Low, Jonathan; Kim, Ho Shin; Paulo, Joao A.; Cannon, Joe R.; Shelat, Anang A.; Chen, Taosheng; Kelsall, Ian R.; Alpi, Arno F.; Pagala, Vishwajeeth; Wang, Xusheng; Peng, Junmin; Singh , Bhuvanesh; Harper, J. Wade; Schulman, Brenda A.; Guy, R. Kip (MSKCC); (Dundee); (SJCH); (Harvard-Med); (MXPL)

    2017-06-05

    N-terminal acetylation is an abundant modification influencing protein functions. Because ~80% of mammalian cytosolic proteins are N-terminally acetylated, this modification is potentially an untapped target for chemical control of their functions. Structural studies have revealed that, like lysine acetylation, N-terminal acetylation converts a positively charged amine into a hydrophobic handle that mediates protein interactions; hence, this modification may be a druggable target. We report the development of chemical probes targeting the N-terminal acetylation–dependent interaction between an E2 conjugating enzyme (UBE2M or UBC12) and DCN1 (DCUN1D1), a subunit of a multiprotein E3 ligase for the ubiquitin-like protein NEDD8. The inhibitors are highly selective with respect to other protein acetyl-amide–binding sites, inhibit NEDD8 ligation in vitro and in cells, and suppress anchorage-independent growth of a cell line with DCN1 amplification. Overall, our data demonstrate that N-terminal acetyl-dependent protein interactions are druggable targets and provide insights into targeting multiprotein E2–E3 ligases.

  7. Echocardiographic parameters and brain natriuretic peptide in patients after surgical repair of tetralogy of Fallot.

    Science.gov (United States)

    Tatani, Solange B; Carvalho, Antonio Carlos C; Andriolo, Adagmar; Rabelo, Rogério; Campos, Orlando; Moises, Valdir A

    2010-04-01

    Although the residual lesions after surgical correction of tetralogy of Fallot (TOF) can be evaluated by Doppler echocardiography (DE), the relation of DE parameters with the proBNP level, a potential biomarker of right ventricle overload, is not well known. The objective of this study was to evaluate the DE parameters and their relation to proBNP levels. proBNP plasma level and Doppler echocardiography parameters were obtained on the same day in 49 patients later after repair of TOF (mean age of 14.7 years, 51% female, mean PO time of 9.5 years). The DE parameters studied were the dimensions of the right atrium (RA) and ventricle (RV), RV diastolic and systolic function, and residual pulmonary lesions. The relation between them and proBNP levels were analyzed and the cutoff values of DE parameters for elevated proBNP determined. proBNP was elevated in 53% and correlated with RV diastolic diameter (r = 0.41; P = 0.003), RA longitudinal (r = 0.52; P = 0.0001) and transversal (r = 0.47; P = 0.001) diameters, pressure half time of pulmonary regurgitation (PR) velocity (PHT) (r =-0.42; P = 0.005), and the PR index (r =-0.60; P < 0.001). By multivariate analysis, the PR index (r =-597; P = 0,001; CI: -913.2 to -280.8) and RA longitudinal (r = 7.74; P < 0,001; CI 4.18 to 11.31) were independent predictors of elevated proBNP. PHT lower than 64 msec (0.76) and PRi lower than 0.65 (0.81) had the best accuracy for elevated proBNP. proBNP may be increased in patients after surgical repair of TOF, correlated with the size of right cardiac chambers and the severity of PR.

  8. The 14-3-3 protein interacts directly with the C-terminal region of the plant plasma membrane H(+)-ATPase

    DEFF Research Database (Denmark)

    Jahn, T.; Fuglsang, A.T.; Olsson, A.

    1997-01-01

    Accumulating evidence suggests that 14-3-3 proteins are involved in the regulation of plant plasma membrane H(+)-ATPase activity. However, it is not known whether the 14-3-3 protein interacts directly or indirectly with the H(+)-ATPase. In this study, detergent-solubilized plasma membrane H...... plasma membrane H(+)-ATPase. We propose that the 14-3-3 protein is a natural ligand of the plasma membrane H(+)-ATPase, regulating proton pumping by displacing the C-terminal autoinhibitory domain of the H(+)-ATPase....

  9. Electronic structures of the F-terminated AlN nanoribbons

    Indian Academy of Sciences (India)

    Using the first-principles calculations, electronic properties for the F-terminated AlN nanoribbons with both zigzag and armchair edges are studied. The results show that both the zigzag and armchair AlN nanoribbons are semiconducting and nonmagnetic, and the indirect band gap of the zigzag AlN nanoribbons and the ...

  10. N-terminal modifications of cellular proteins: The enzymes involved, their substrate specificities and biological effects

    Science.gov (United States)

    Varland, Sylvia; Osberg, Camilla; Arnesen, Thomas

    2015-01-01

    The vast majority of eukaryotic proteins are N-terminally modified by one or more processing enzymes. Enzymes acting on the very first amino acid of a polypeptide include different peptidases, transferases, and ligases. Methionine aminopeptidases excise the initiator methionine leaving the nascent polypeptide with a newly exposed amino acid that may be further modified. N-terminal acetyl-, methyl-, myristoyl-, and palmitoyltransferases may attach an acetyl, methyl, myristoyl, or palmitoyl group, respectively, to the α-amino group of the target protein N-terminus. With the action of ubiquitin ligases, one or several ubiquitin molecules are transferred, and hence, constitute the N-terminal modification. Modifications at protein N-termini represent an important contribution to proteomic diversity and complexity, and are essential for protein regulation and cellular signaling. Consequently, dysregulation of the N-terminal modifying enzymes is implicated in human diseases. We here review the different protein N-terminal modifications occurring co- or post-translationally with emphasis on the responsible enzymes and their substrate specificities. PMID:25914051

  11. Plasma bubbles near the dawn terminator in the topside ionosphere

    International Nuclear Information System (INIS)

    Burke, W.J.

    1979-01-01

    The physical properties of plasma bubbles in the topside ionosphere near the dawn terminator are investigated. It is assumed that the bubbles result from either a Rayleigh-Taylor or an E X B instability on the bottom side of the F-layer. While the E-region is in darkness, the top and bottomsides of the ionospheres are electrically decoupled and the motion of the bubbles can be described by non-linear, two-dimensional theory. After sunrise, electric fields within the bubbles discharge through the conducting lower ionosphere. The upward drift of the bubbles is effectively halted. To achieve a dayside state of diffusive equilibrium the bubbles slowly begin to collapse from the bottom. (author)

  12. Practical use of natriuretic peptide measurement: questionnaire results from general practitioners and cardiologists.

    Science.gov (United States)

    Husby, Simon; Lind, Bent; Goetze, Jens P

    2012-02-01

    To elucidate the knowledge regarding B-type natriuretic peptide (BNP)/N-terminal proBNP (NT-proBNP) measurement among doctors using this biomarker. We performed a questionnaire-based study on the use of BNP/NT-proBNP measurement among doctors; 21 general practitioners and 23 randomly chosen doctors at cardiology departments were interviewed. 12 general practitioners (57%) answered 'yes', eight (38%) answered 'no' and one (5%) was 'undecided' for use of BNP/NT-proBNP measurement to exclude a diagnosis of heart failure. Among cardiologists, 11 (48%) answered 'yes', ten (43%) answered 'no' and two (9%) were 'undecided' (no difference between groups, p = 0.56). The majority of doctors were familiar with BNP/NT-proBNP being affected by age but were unaware of the impact of gender and obesity. We propose that BNP/NT-proBNP measurement results should be supplied with age- and gender-related cut-off values, along with a notion of the negative predictive value and other parameters affecting the concentration in plasma.

  13. Cardiac natriuretic peptides in plasma increase after dietary induced weight loss in obesity

    DEFF Research Database (Denmark)

    Kistorp, Caroline Michaela Nervil; Bliddal, Henning; Gøtze, Jens P.

    2014-01-01

    BACKGROUND: Cardiac natriuretic peptides are established biomarkers in heart disease, but are also affected by body mass index (BMI). The purpose of the present study was to examine the impact of weight loss and changes in body composition following dietary intervention on plasma concentrations...... of the prohormones to A- and B-type natriuretic peptides (proANP and proBNP) and adrenomedullin (proADM). RESULTS: A total of 52 healthy obese subjects, 47 women and 5 men (BMI 36.5 ± 5.6 kg/m(2)) were randomised to either an intensive weight reduction programme using a combination of very low calorie diet (810 kcal...

  14. A Convenient Approach to Synthesizing Peptide C-Terminal N-Alkyl Amides

    Science.gov (United States)

    Fang, Wei-Jie; Yakovleva, Tatyana; Aldrich, Jane V.

    2014-01-01

    Peptide C-terminal N-alkyl amides have gained more attention over the past decade due to their biological properties, including improved pharmacokinetic and pharmacodynamic profiles. However, the synthesis of this type of peptide on solid phase by current available methods can be challenging. Here we report a convenient method to synthesize peptide C-terminal N-alkyl amides using the well-known Fukuyama N-alkylation reaction on a standard resin commonly used for the synthesis of peptide C-terminal primary amides, the PAL-PEG-PS (Peptide Amide Linker-polyethylene glycol-polystyrene) resin. The alkylation and oNBS deprotection were conducted under basic conditions and were therefore compatible with this acid labile resin. The alkylation reaction was very efficient on this resin with a number of different alkyl iodides or bromides, and the synthesis of model enkephalin N-alkyl amide analogs using this method gave consistently high yields and purities, demonstrating the applicability of this methodology. The synthesis of N-alkyl amides was more difficult on a Rink amide resin, especially the coupling of the first amino acid to the N-alkyl amine, resulting in lower yields for loading the first amino acid onto the resin. This method can be widely applied in the synthesis of peptide N-alkyl amides. PMID:22252422

  15. Localization of the N-terminal domain of cauliflower mosaic virus coat protein precursor

    International Nuclear Information System (INIS)

    Champagne, Julie; Benhamou, Nicole; Leclerc, Denis

    2004-01-01

    Cauliflower mosaic virus (CaMV) open reading frame (ORF) IV encodes a coat protein precursor (pre-CP) harboring an N-terminal extension that is cleaved off by the CaMV-encoded protease. In transfected cells, pre-CP is present in the cytoplasm, while the processed form (p44) of CP is targeted to the nucleus, suggesting that the N-terminal extension might be involved in keeping the pre-CP in the cytoplasm for viral assembly. This study reports for the first time the intracellular localization of the N-terminal extension during CaMV infection in Brassica rapa. Immunogold-labeling electron microscopy using polyclonal antibodies directed to the N-terminal extension of the pre-CP revealed that this region is closely associated with viral particles present in small aggregates, which we called small bodies, adjacent to the main inclusion bodies typical of CaMV infection. Based on these results, we propose a model for viral assembly of CaMV

  16. C-Jun N-terminal kinase signalling pathway in response to cisplatin.

    Science.gov (United States)

    Yan, Dong; An, GuangYu; Kuo, Macus Tien

    2016-11-01

    Cisplatin (cis diamminedichloroplatinum II, cDDP) is one of the most effective cancer chemotherapeutic agents and is used in the treatment of many types of human malignancies. However, inherent tumour resistance is a major barrier to effective cisplatin therapy. So far, the mechanism of cDDP resistance has not been well defined. In general, cisplatin is considered to be a cytotoxic drug, for damaging DNA and inhibiting DNA synthesis, resulting in apoptosis via the mitochondrial death pathway or plasma membrane disruption. cDDP-induced DNA damage triggers signalling pathways that will eventually decide between cell life and death. As a member of the mitogen-activated protein kinases family, c-Jun N-terminal kinase (JNK) is a signalling pathway in response to extracellular stimuli, especially drug treatment, to modify the activity of numerous proteins locating in the mitochondria or the nucleus. Recent studies suggest that JNK signalling pathway plays a major role in deciding the fate of the cell and inducing resistance to cDDP-induced apoptosis in human tumours. c-Jun N-terminal kinase regulates several important cellular functions including cell proliferation, differentiation, survival and apoptosis while activating and inhibiting substrates for phosphorylation transcription factors (c-Jun, ATF2: Activating transcription factor 2, p53 and so on), which subsequently induce pro-apoptosis and pro-survival factors expression. Therefore, it is suggested that JNK signal pathway is a double-edged sword in cDDP treatment, simultaneously being a significant pro-apoptosis factor but also being associated with increased resistance to cisplatin-based chemotherapy. This review focuses on current knowledge concerning the role of JNK in cell response to cDDP, as well as their role in cisplatin resistance. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  17. The N-terminal domain determines the affinity and specificity of H1 binding to chromatin

    International Nuclear Information System (INIS)

    Öberg, Christine; Belikov, Sergey

    2012-01-01

    Highlights: ► wt Human histone H1.4 and hH1.4 devoid of N-terminal domain, ΔN-hH1.4, were compared. ► Both histones bind to chromatin, however, ΔN-hH1.4 displays lower binding affinity. ► Interaction of ΔN-hH1.4 with chromatin includes a significant unspecific component. ► N-terminal domain is a determinant of specificity of histone H1 binding to chromatin. -- Abstract: Linker histone H1, one of the most abundant nuclear proteins in multicellular eukaryotes, is a key component of the chromatin structure mainly due to its role in the formation and maintenance of the 30 nm chromatin fiber. It has a three-domain structure; a central globular domain flanked by a short N-terminal domain and a long, highly basic C-terminal domain. Previous studies have shown that the binding abilities of H1 are at large determined by the properties of the C-terminal domain; much less attention has been paid to role of the N-terminal domain. We have previously shown that H1 can be reconstituted via cytoplasmic mRNA injection in Xenopus oocytes, cells that lack somatic H1. The heterologously expressed H1 proteins are incorporated into in vivo assembled chromatin at specific sites and the binding event is monitored as an increase in nucleosomal repeat length (NRL). Using this setup we have here compared the binding properties of wt-H1.4 and hH1.4 devoid of its N-terminal domain (ΔN-hH1.4). The ΔN-hH1.4 displays a drastically lower affinity for chromatin binding as compared to the wild type hH1.4. Our data also indicates that ΔN-hH1.4 is more prone to unspecific chromatin binding than the wild type. We conclude that the N-terminal domain of H1 is an important determinant of affinity and specificity of H1-chromatin interactions.

  18. Elevation of serum N-terminal pro-brain natriuretic peptide after exercise is an index of myocardial damage or a cytoprotective reflection?

    Science.gov (United States)

    Faviou, E; Zachari, A; Nounopoulos, C; Agrafiotis, E; Vourli, G; Dionyssiou-Asteriou, A

    2008-03-01

    Recent investigations have suggested the occurrence of transient cardiac dysfunction and reversible myocardial injury in healthy individuals after heavy exercise. Our purpose was to examine if the release of N-terminal pro-brain natriuretic peptide (NT-proBNP) after intense exercise in obviously healthy participants may have cytoprotective and growth-regulating effects or may result from myocardial dysfunction/damage with changes in cTnT as a marker for myocardial cell necrosis during exercise. In 43 highly-trained male athletes hypertrophy. A normal plasma concentration of NT-proBNP in consecutive routine check-up, before and after exercise, could minimize the possibility of cardiac dysfunction, whereas persistent elevated plasma concentrations warrant further cardiological evaluation.

  19. The first N-terminal unprotected (Gly-Aib)n peptide: H-Gly-Aib-Gly-Aib-OtBu.

    Science.gov (United States)

    Gessmann, Renate; Brückner, Hans; Petratos, Kyriacos

    2015-12-01

    Glycine (Gly) is incorporated in roughly half of all known peptaibiotic (nonribosomally biosynthesized antibiotic peptides of fungal origin) sequences and is the residue with the greatest conformational flexibility. The conformational space of Aib (α-aminoisobutyric acid) is severely restricted by the second methyl group attached to the Cα atom. Most of the crystal structures containing Aib are N-terminal protected. Deprotection of the N- or C-terminus of peptides may alter the hydrogen-bonding scheme and/or the structure and may facilitate crystallization. The structure reported here for glycyl-α-aminoisobutyrylglycyl-α-aminoisobutyric acid tert-butyl ester, C16H30N4O5, describes the first N-terminal-unprotected (Gly-Aib)n peptide. The achiral peptide could form an intramolecular hydrogen bond between the C=O group of Gly1 and the N-H group of Aib4. This hydrogen bond is found in all tetrapeptides and N-terminal-protected tripeptides containing Aib, apart from one exception. In the present work, this hydrogen bond is not observed (N...O = 5.88 Å). Instead, every molecule is hydrogen bonded to six other symmetry-related molecules with a total of eight hydrogen bonds per molecule. The backbone conformation starts in the right-handed helical region (and the left-handed helical region for the inverted molecule) and reverses the screw sense in the last two residues.

  20. The influence of the N-terminal region of antimicrobial peptide pleurocidin on fungal apoptosis.

    Science.gov (United States)

    Choi, Hyemin; Lee, Dong Gun

    2013-10-28

    In our previous study, the 25-mer antimicrobial peptide pleurocidin (Ple) had been thought to induce apoptosis in Candida albicans. This study demonstrated that reactive oxygen species (ROS) production was a major cause of Ple-induced apoptosis. Four truncated analogs were synthesized to understand the functional roles in the N- and C-terminal regions of Ple on the apoptosis. Ple, Ple (4-25), Ple (1-22), and Ple (1-19) produced ROS, including hydroxyl radicals, on the order of [Ple > Ple (1-22) > Ple (4-25) > Ple (1-19)], whereas Ple (7-25) did not induce any ROS production. The results suggested that the N-terminal deletion affected the ROS-inducing activities much more than that of the C-terminal deletion, and net hydrophobicity [Ple > Ple (1-22) > Ple (4-25) > Ple (1-19) > Ple (7-25)] was related to ROS generation rather than other primary factors like net charge. Hence, we focused on the N-terminal-truncated peptides, Ple (4-25) and Ple (7-25), and examined other apoptotic features, including mitochondrial membrane depolarization, caspase activation, phosphatidylserine externalization, and DNA and nuclear fragmentation. The results also confirmed the disappearance of apoptotic activity of Ple (7-25) by the truncation of the N-terminal region (1-6) and the specific activity patterns between Ple and analogs. In conclusion, the N-terminal region of Ple played an important role in apoptosis.

  1. Influence of atrial fibrillation on plasma von willebrand factor, soluble E-selectin, and N-terminal pro B-type natriuretic peptide levels in systolic heart failure.

    Science.gov (United States)

    Freestone, Bethan; Gustafsson, Finn; Chong, Aun Yeong; Corell, Pernille; Kistorp, Caroline; Hildebrandt, Per; Lip, Gregory Y H

    2008-05-01

    Endothelial dysfunction is present in patients with heart failure (HF) due to left ventricular systolic dysfunction, as well as in patients with atrial fibrillation (AF) who have normal cardiac function. It is unknown whether AF influences the degree of endothelial dysfunction in patients with systolic HF. We measured levels of plasma von Willebrand factor (vWF) and E-selectin (as indexes of endothelial damage/dysfunction and endothelial activation, respectively; both enzyme-linked immunosorbent assay) in patients with AF and HF (AF-HF), who were compared to patients with sinus rhythm and HF (SR-HF), as well as in age-matched, healthy, control subjects. We also assessed the relationship of vWF and E-selectin to plasma N-terminal pro B-type natriuretic peptide (NTpro-BNP), a marker for HF severity and prognosis. One hundred ninety patients (73% men; mean age, 69.0 +/- 10.1 years [+/- SD]) with systolic HF were studied, who were compared to 117 healthy control subjects: 52 subjects (27%) were in AF, while 138 subjects (73%) were in sinus rhythm. AF-HF patients were older than SR-HF patients (p = 0.046), but left ventricular ejection fraction and New York Heart Association class were similar. There were significant differences in NT-proBNP (p NT-proBNP (p NT-proBNP levels (Spearman r = 0.139; p = 0.017). There is evidence of greater endothelial damage/dysfunction in AF-HF patients when compared to SR-HF patients. The clinical significance of this is unclear but may have prognostic value.

  2. Improvements in DC Current-Ioltage (I-V) Characteristics of n-GaN Schottky Diode using Metal Overlap Edge Termination

    International Nuclear Information System (INIS)

    Munir, T.; Aziz, A. A.; Abdullah, M. J.; Ain, M. F.

    2010-01-01

    Practical design of GaN Schottky diodes incorporating a field plate necessitates an understanding of how the addition of such plate affects the diode performance. In this paper, we investigated the effects on DC current-voltage (I-V) characteristics of n-GaN schottky diode by incorporating metal overlap edge termination. The thickness of the oxide film varies from 0.001 to 1 micron. Two-dimensional Atlas/Blaze simulations revealed that severe electric field crowding across the metal semiconductor contact will cause reliability concern and limit device breakdown voltage. DC current-voltage (I-V) measurements indicate that the forward currents are higher for thinner oxide film schottky diodes with metal overlap edge termination than those of unterminated schottky diodes. The forward current increased due to formation of an accumulation layer underneath the oxide layer. Extending the field plate to beyond periphery regions of schottky contact does not result in any significant increase in forward current. The new techniques of ramp oxide metal overlap edge termination have been implemented to increase the forward current of n-GaN schottky diode. In reverse bias, breakdown voltage increased with edge termination oxide up to a certain limit of oxide thickness.

  3. Regulation of presynaptic Ca2+, synaptic plasticity and contextual fear conditioning by a N-terminal β-amyloid fragment.

    Science.gov (United States)

    Lawrence, James L M; Tong, Mei; Alfulaij, Naghum; Sherrin, Tessi; Contarino, Mark; White, Michael M; Bellinger, Frederick P; Todorovic, Cedomir; Nichols, Robert A

    2014-10-22

    Soluble β-amyloid has been shown to regulate presynaptic Ca(2+) and synaptic plasticity. In particular, picomolar β-amyloid was found to have an agonist-like action on presynaptic nicotinic receptors and to augment long-term potentiation (LTP) in a manner dependent upon nicotinic receptors. Here, we report that a functional N-terminal domain exists within β-amyloid for its agonist-like activity. This sequence corresponds to a N-terminal fragment generated by the combined action of α- and β-secretases, and resident carboxypeptidase. The N-terminal β-amyloid fragment is present in the brains and CSF of healthy adults as well as in Alzheimer's patients. Unlike full-length β-amyloid, the N-terminal β-amyloid fragment is monomeric and nontoxic. In Ca(2+) imaging studies using a model reconstituted rodent neuroblastoma cell line and isolated mouse nerve terminals, the N-terminal β-amyloid fragment proved to be highly potent and more effective than full-length β-amyloid in its agonist-like action on nicotinic receptors. In addition, the N-terminal β-amyloid fragment augmented theta burst-induced post-tetanic potentiation and LTP in mouse hippocampal slices. The N-terminal fragment also rescued LTP inhibited by elevated levels of full-length β-amyloid. Contextual fear conditioning was also strongly augmented following bilateral injection of N-terminal β-amyloid fragment into the dorsal hippocampi of intact mice. The fragment-induced augmentation of fear conditioning was attenuated by coadministration of nicotinic antagonist. The activity of the N-terminal β-amyloid fragment appears to reside largely in a sequence surrounding a putative metal binding site, YEVHHQ. These findings suggest that the N-terminal β-amyloid fragment may serve as a potent and effective endogenous neuromodulator. Copyright © 2014 the authors 0270-6474/14/3414210-09$15.00/0.

  4. N-terminally truncated POM121C inhibits HIV-1 replication.

    Directory of Open Access Journals (Sweden)

    Hideki Saito

    Full Text Available Recent studies have identified host cell factors that regulate early stages of HIV-1 infection including viral cDNA synthesis and orientation of the HIV-1 capsid (CA core toward the nuclear envelope, but it remains unclear how viral DNA is imported through the nuclear pore and guided to the host chromosomal DNA. Here, we demonstrate that N-terminally truncated POM121C, a component of the nuclear pore complex, blocks HIV-1 infection. This truncated protein is predominantly localized in the cytoplasm, does not bind to CA, does not affect viral cDNA synthesis, reduces the formation of 2-LTR and diminished the amount of integrated proviral DNA. Studies with an HIV-1-murine leukemia virus (MLV chimeric virus carrying the MLV-derived Gag revealed that Gag is a determinant of this inhibition. Intriguingly, mutational studies have revealed that the blockade by N-terminally-truncated POM121C is closely linked to its binding to importin-β/karyopherin subunit beta 1 (KPNB1. These results indicate that N-terminally-truncated POM121C inhibits HIV-1 infection after completion of reverse transcription and before integration, and suggest an important role for KPNB1 in HIV-1 replication.

  5. Phactr3/scapinin, a member of protein phosphatase 1 and actin regulator (phactr family, interacts with the plasma membrane via basic and hydrophobic residues in the N-terminus.

    Directory of Open Access Journals (Sweden)

    Akihiro Itoh

    Full Text Available Proteins that belong to the protein phosphatase 1 and actin regulator (phactr family are involved in cell motility and morphogenesis. However, the mechanisms that regulate the actin cytoskeleton are poorly understood. We have previously shown that phactr3, also known as scapinin, localizes to the plasma membrane, including lamellipodia and membrane ruffles. In the present study, experiments using deletion and point mutants showed that the basic and hydrophobic residues in the N-terminus play crucial roles in the localization to the plasma membrane. A BH analysis (http://helixweb.nih.gov/bhsearch is a program developed to identify membrane-binding domains that comprise basic and hydrophobic residues in membrane proteins. We applied this program to phactr3. The results of the BH plot analysis agreed with the experimentally determined region that is responsible for the localization of phactr3 to the plasma membrane. In vitro experiments showed that the N-terminal itself binds to liposomes and acidic phospholipids. In addition, we showed that the interaction with the plasma membrane via the N-terminal membrane-binding sequence is required for phactr3-induced morphological changes in Cos7 cells. The membrane-binding sequence in the N-terminus is highly conserved in all members of the phactr family. Our findings may provide a molecular basis for understanding the mechanisms that allow phactr proteins to regulate cell morphogenesis.

  6. The amino-terminal 200 amino acids of the plasma membrane Na+,K+-ATPase alpha subunit confer ouabain sensitivity on the sarcoplasmic reticulum Ca(2+)-ATPase.

    OpenAIRE

    Ishii, T; Takeyasu, K

    1993-01-01

    Cardiac glycosides such as G-strophanthin (ouabain) bind to and inhibit the plasma membrane Na+,K(+)-ATPase but not the sarcoplasmic reticulum (SR) Ca(2+)-ATPase, whereas thapsigargin specifically blocks the SR Ca(2+)-ATPase. The chimera [n/c]CC, in which the amino-terminal amino acids Met1 to Asp162 of the SR Ca(2+)-ATPase (SERCA1) were replaced with the corresponding portion of the Na+,K(+)-ATPase alpha 1 subunit (Met1 to Asp200), retained thapsigargin- and Ca(2+)-sensitive ATPase activity,...

  7. Plasma diagnostics and device properties of AlGaN/GaN HEMT passivated with SiN deposited by plasma-enhanced chemical vapour deposition

    Energy Technology Data Exchange (ETDEWEB)

    Romero, M F; Sanz, M M; Munoz, E [ISOM-Universidad Politecnica de Madrid (UPM). ETSIT, Madrid (Spain); Tanarro, I [Instituto de Estructura de la Materia, CSIC, Madrid (Spain); Jimenez, A, E-mail: itanarro@iem.cfmac.csic.e [Departamento Electronica, Escuela Politecnica Superior, Universidad de Alcala, Alcala de Henares, Madrid (Spain)

    2010-12-15

    In this work, silicon nitride thin films have been deposited by plasma enhanced chemical vapour deposition on both silicon samples and AlGaN/GaN high electron mobility transistors (HEMT) grown on sapphire substrates. Commercial parallel-plate RF plasma equipment has been used. During depositions, the dissociation rates of SiH{sub 4} and NH{sub 3} precursors and the formation of H{sub 2} and N{sub 2} have been analysed by mass spectrometry as a function of the NH{sub 3}/SiH{sub 4} flow ratio and the RF power applied to the plasma reactor. Afterwards, the properties of the films and the HEMT electrical characteristics have been studied. Plasma composition has been correlated with the SiN deposition rate, refractive index, H content and the final electric characteristics of the passivated transistors.

  8. Inductively Coupled Plasma-Induced Etch Damage of GaN p-n Junctions

    International Nuclear Information System (INIS)

    SHUL, RANDY J.; ZHANG, LEI; BACA, ALBERT G.; WILLISON, CHRISTI LEE; HAN, JUNG; PEARTON, S.J.; REN, F.

    1999-01-01

    Plasma-induced etch damage can degrade the electrical and optical performance of III-V nitride electronic and photonic devices. We have investigated the etch-induced damage of an Inductively Coupled Plasma (ICP) etch system on the electrical performance of mesa-isolated GaN pn-junction diodes. GaN p-i-n mesa diodes were formed by Cl 2 /BCl 3 /Ar ICP etching under different plasma conditions. The reverse leakage current in the mesa diodes showed a strong relationship to chamber pressure, ion energy, and plasma flux. Plasma induced damage was minimized at moderate flux conditions (≤ 500 W), pressures ≥2 mTorr, and at ion energies below approximately -275 V

  9. The extracellular protein factor Epf from Streptococcus pyogenes is a cell surface adhesin that binds to cells through an N-terminal domain containing a carbohydrate-binding module.

    Science.gov (United States)

    Linke, Christian; Siemens, Nikolai; Oehmcke, Sonja; Radjainia, Mazdak; Law, Ruby H P; Whisstock, James C; Baker, Edward N; Kreikemeyer, Bernd

    2012-11-02

    Streptococcus pyogenes is an exclusively human pathogen. Streptococcal attachment to and entry into epithelial cells is a prerequisite for a successful infection of the human host and requires adhesins. Here, we demonstrate that the multidomain protein Epf from S. pyogenes serotype M49 is a streptococcal adhesin. An epf-deficient mutant showed significantly decreased adhesion to and internalization into human keratinocytes. Cell adhesion is mediated by the N-terminal domain of Epf (EpfN) and increased by the human plasma protein plasminogen. The crystal structure of EpfN, solved at 1.6 Å resolution, shows that it consists of two subdomains: a carbohydrate-binding module and a fibronectin type III domain. Both fold types commonly participate in ligand receptor and protein-protein interactions. EpfN is followed by 18 repeats of a domain classified as DUF1542 (domain of unknown function 1542) and a C-terminal cell wall sorting signal. The DUF1542 repeats are not involved in adhesion, but biophysical studies show they are predominantly α-helical and form a fiber-like stalk of tandem DUF1542 domains. Epf thus conforms with the widespread family of adhesins known as MSCRAMMs (microbial surface components recognizing adhesive matrix molecules), in which a cell wall-attached stalk enables long range interactions via its adhesive N-terminal domain.

  10. Stability of AlGaN/GaN heterostructures after hydrogen plasma treatment

    Energy Technology Data Exchange (ETDEWEB)

    Babchenko, O., E-mail: oleg.babchenko@savba.sk [Institute of Electrical Engineering SAV, Dúbravská cesta 9, 841 04 Bratislava (Slovakia); Dzuba, J.; Lalinský, T. [Institute of Electrical Engineering SAV, Dúbravská cesta 9, 841 04 Bratislava (Slovakia); Vojs, M. [Institute of Electronics and Photonics STU, Ilkovičova 3, 812 19 Bratislava (Slovakia); Vincze, A. [International Laser Centre, Ilkovičova 3, 841 04 Bratislava (Slovakia); Ižák, T. [Institute of Physics AS CR, v.v.i., Cukrovarnicka 10, 162 53 Prague (Czech Republic); Vanko, G. [Institute of Electrical Engineering SAV, Dúbravská cesta 9, 841 04 Bratislava (Slovakia)

    2017-02-15

    Highlights: • AlGaN/GaNheterostructures with electric contacts were treated by hydrogen plasma. • No surface degradation after treatment was detected by SEM. • Hydrogen plasma caused increasing of sheet resistance up to 3.5 times after 60 min. • Incorporation of hydrogen in AlGaN sub-surface region was observed by SIMS. • Electrical measurements indicate hydrogen induced Schottky barrier lowering. - Abstract: We report on the investigation of low temperature (300 °C) hydrogen plasma treatment influence on the AlGaN/GaN heterostructures. This issue was raised in the frame of study on processes related to hybrid integration of diamond with GaN-based devices. At the same time, the capabilities of thin SiN{sub x} covering were investigated. The samples were exposed to low pressure hydrogen plasma ignited in the linear plasma system at low temperature. We analyze the surface morphology of samples by scanning electron microscopy while microstructural changes down to AlGaN/GaN interface were studied using secondary ion mass spectrometry. The sheet resistance, monitored using circular transmission line measurements, increases more than 3.5 times after 60 min treatment. The basic transport properties of the fabricated circular high electron mobility transistors after H{sub 2} plasma treatment were analyzed. The sheet resistance increasing was attributed to the decrease of effective mobility. Whilst, the observed Schottky barrier lowering indicates necessity of gate contact protection.

  11. Distinctive functions of Syk N-terminal and C-terminal SH2 domains in the signaling cascade elicited by oxidative stress in B cells.

    Science.gov (United States)

    Ding, J; Takano, T; Hermann, P; Gao, S; Han, W; Noda, C; Yanagi, S; Yamamura, H

    2000-05-01

    Syk plays a crucial role in the transduction of oxidative stress signaling. In this paper, we investigated the roles of Src homology 2 (SH2) domains of Syk in oxidative stress signaling, using Syk-negative DT40 cells expressing the N- or C-terminal SH2 domain mutant [mSH2(N) or mSH2(C)] of Syk. Tyrosine phosphorylation of Syk in cells expressing mSH2(N) Syk after H(2)O(2) treatment was higher than that in cells expressing wild-type Syk or mSH2(C) Syk. The tyrosine phosphorylation of wild-type Syk and mSH2(C) Syk, but not that of mSH2(N), was sensitive to PP2, a specific inhibitor of Src-family protein-tyrosine kinase. In oxidative stress, the C-terminal SH2 domain of Syk was demonstrated to be required for induction of tyrosine phosphorylation of cellular proteins, phospholipase C (PLC)-gamma2 phosphorylation, inositol 1,4, 5-triphosphate (IP(3)) generation, Ca(2)(+) release from intracellular stores, and c-Jun N-terminal kinase activation. In contrast, in mSH2(N) Syk-expressing cells, tyrosine phosphorylation of intracellular proteins including PLC-gamma2 was markedly induced in oxidative stress. The enhanced phosphorylation of mSH2(N) Syk and PLC-gamma2, however, did not link to Ca(2)(+) mobilization from intracellular pools and IP(3) generation. Thus, the N- and C-terminal SH2 domains of Syk possess distinctive functions in oxidative stress signaling.

  12. Atrial natriuretic peptides in plasma

    DEFF Research Database (Denmark)

    Goetze, Jens Peter; Hansen, Lasse H; Terzic, Dijana

    2014-01-01

    Measurement of cardiac natriuretic peptides in plasma has gained a diagnostic role in the assessment of heart failure. Plasma measurement is though hampered by the marked instability of the hormones, which has led to the development of analyses that target N-terminal fragments from the prohormone....... These fragments are stable in plasma and represent surrogate markers of the actual natriuretic hormone. Post-translational processing of the precursors, however, is revealing itself to be a complex event with new information still being reported on proteolysis, covalent modifications, and amino acid...

  13. Atrial natriuretic peptides in plasma

    DEFF Research Database (Denmark)

    Goetze, Jens P; Holst Hansen, Lasse; Terzic, Dijana

    2015-01-01

    Measurement of cardiac natriuretic peptides in plasma has gained a diagnostic role in the assessment of heart failure. Plasma measurement is though hampered by the marked instability of the hormones, which has led to the development of analyses that target N-terminal fragments from the prohormone....... These fragments are stable in plasma and represent surrogate markers of the actual natriuretic hormone. Post-translational processing of the precursors, however, is revealing itself to be a complex event with new information still being reported on proteolysis, covalent modifications, and amino acid...

  14. Site directed spin labeling studies of Escherichia coli dihydroorotate dehydrogenase N-terminal extension

    Energy Technology Data Exchange (ETDEWEB)

    Couto, Sheila G. [Instituto de Fisica de Sao Carlos, Universidade de Sao Paulo, Av. Trabalhador Sao-carlense 400, C.P. 369, 13560-970, Sao Carlos, SP (Brazil); Grupo de Biofisica e Fisica Aplicada a Medicina, Instituto de Fisica, Universidade Federal de Goias, Campus Samambaia, C.P. 131, 74001-970, Goiania, GO (Brazil); Cristina Nonato, M. [Laboratorio de Cristalografia de Proteinas, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Av. do Cafe S/N, 14040-903, Ribeirao Preto, SP (Brazil); Costa-Filho, Antonio J., E-mail: ajcosta@ffclrp.usp.br [Instituto de Fisica de Sao Carlos, Universidade de Sao Paulo, Av. Trabalhador Sao-carlense 400, C.P. 369, 13560-970, Sao Carlos, SP (Brazil); Departamento de Fisica, Faculdade de Filosofia, Ciencias e Letras de Ribeirao Preto, Av. Bandeirantes 3900, 14040-901, Ribeirao Preto, SP (Brazil)

    2011-10-28

    Highlights: Black-Right-Pointing-Pointer EcDHODH is a membrane-associated enzyme and a promising target for drug design. Black-Right-Pointing-Pointer Enzyme's N-terminal extension is responsible for membrane association. Black-Right-Pointing-Pointer N-terminal works as a molecular lid regulating access to the protein interior. -- Abstract: Dihydroorotate dehydrogenases (DHODHs) are enzymes that catalyze the fourth step of the de novo synthesis of pyrimidine nucleotides. In this reaction, DHODH converts dihydroorotate to orotate, using a flavine mononucleotide as a cofactor. Since the synthesis of nucleotides has different pathways in mammals as compared to parasites, DHODH has gained much attention as a promising target for drug design. Escherichia coli DHODH (EcDHODH) is a family 2 DHODH that interacts with cell membranes in order to promote catalysis. The membrane association is supposedly made via an extension found in the enzyme's N-terminal. In the present work, we used site directed spin labeling (SDSL) to specifically place a magnetic probe at positions 2, 5, 19, and 21 within the N-terminal and thus monitor, by using Electron Spin Resonance (ESR), dynamics and structural changes in this region in the presence of a membrane model system. Overall, our ESR spectra show that the N-terminal indeed binds to membranes and that it experiences a somewhat high flexibility that could be related to the role of this region as a molecular lid controlling the entrance of the enzyme's active site and thus allowing the enzyme to give access to quinones that are dispersed in the membrane and that are necessary for the catalysis.

  15. New OprM structure highlighting the nature of the N-terminal anchor

    Directory of Open Access Journals (Sweden)

    Laura eMONLEZUN

    2015-07-01

    Full Text Available Among the different mechanisms used by bacteria to resist antibiotics, active efflux plays a major role. In gram-negative bacteria, active efflux is carried out by tripartite efflux pumps that form a macromolecular assembly spanning both membranes of the cellular wall. At the outer membrane level, a well-conserved Outer Membrane Factor (OMF protein acts as an exit duct, but its sequence varies greatly among different species. The OMFs share a similar tri-dimensional structure that includes a beta-barrel pore domain that stabilizes the channel within the membrane. In addition, OMFs are often subjected to different N-terminal post-translational modifications, such as an acylation with a lipid. The role of additional N-terminal anchors is all the more intriguing since it is not always required among the OMFs family. Understanding this optional post-translational modification could open new research lines in the field of antibiotics resistance. In E. coli, it has been shown that CusC is modified with a tri-acylated lipid, whereas TolC does not show any. In the case of OprM from Pseudomonas aeruginosa, the N-terminal modification remains a matter of debate, therefore, we used several approaches to investigate this issue. As definitive evidence, we present a new X ray structure at 3.8Å resolution that was solved in a new space group, making it possible to model the N-terminal residue as a palmitylated cysteine.

  16. Identifying and quantifying proteolytic events and the natural N terminome by terminal amine isotopic labeling of substrates.

    Science.gov (United States)

    Kleifeld, Oded; Doucet, Alain; Prudova, Anna; auf dem Keller, Ulrich; Gioia, Magda; Kizhakkedathu, Jayachandran N; Overall, Christopher M

    2011-09-22

    Analysis of the sequence and nature of protein N termini has many applications. Defining the termini of proteins for proteome annotation in the Human Proteome Project is of increasing importance. Terminomics analysis of protease cleavage sites in degradomics for substrate discovery is a key new application. Here we describe the step-by-step procedures for performing terminal amine isotopic labeling of substrates (TAILS), a 2- to 3-d (depending on method of labeling) high-throughput method to identify and distinguish protease-generated neo-N termini from mature protein N termini with all natural modifications with high confidence. TAILS uses negative selection to enrich for all N-terminal peptides and uses primary amine labeling-based quantification as the discriminating factor. Labeling is versatile and suited to many applications, including biochemical and cell culture analyses in vitro; in vivo analyses using tissue samples from animal and human sources can also be readily performed. At the protein level, N-terminal and lysine amines are blocked by dimethylation (formaldehyde/sodium cyanoborohydride) and isotopically labeled by incorporating heavy and light dimethylation reagents or stable isotope labeling with amino acids in cell culture labels. Alternatively, easy multiplex sample analysis can be achieved using amine blocking and labeling with isobaric tags for relative and absolute quantification, also known as iTRAQ. After tryptic digestion, N-terminal peptide separation is achieved using a high-molecular-weight dendritic polyglycerol aldehyde polymer that binds internal tryptic and C-terminal peptides that now have N-terminal alpha amines. The unbound naturally blocked (acetylation, cyclization, methylation and so on) or labeled mature N-terminal and neo-N-terminal peptides are recovered by ultrafiltration and analyzed by tandem mass spectrometry (MS/MS). Hierarchical substrate winnowing discriminates substrates from the background proteolysis products and

  17. High-Density Plasma-Induced Etch Damage of GaN

    International Nuclear Information System (INIS)

    Baca, A.G.; Han, J.; Lester, L.F.; Pearton, S.J.; Ren, F.; Shul, R.J.; Willison, C.G.; Zhang, L.; Zolper, J.C.

    1999-01-01

    Anisotropic, smooth etching of the group-III nitrides has been reported at relatively high rates in high-density plasma etch systems. However, such etch results are often obtained under high de-bias and/or high plasma flux conditions where plasma induced damage can be significant. Despite the fact that the group-III nitrides have higher bonding energies than more conventional III-V compounds, plasma-induced etch damage is still a concern. Attempts to minimize such damage by reducing the ion energy or increasing the chemical activity in the plasma often result in a loss of etch rate or anisotropy which significantly limits critical dimensions and reduces the utility of the process for device applications requiring vertical etch profiles. It is therefore necessary to develop plasma etch processes which couple anisotropy for critical dimension and sidewall profile control and high etch rates with low-damage for optimum device performance. In this study we report changes in sheet resistance and contact resistance for n- and p-type GaN samples exposed to an Ar inductively coupled plasma (ICP). In general, plasma-induced damage was more sensitive to ion bombardment energies as compared to plasma flux. In addition, p-GaN was typically more sensitive to plasma-induced damage as compared to n-GaN

  18. Improved performance of AlGaN/GaN HEMT by N2O plasma pre-treatment

    International Nuclear Information System (INIS)

    Mi Min-Han; Zhang Kai; Zhao Sheng-Lei; Wang Chong; Zhang Jin-Cheng; Ma Xiao-Hua; Hao Yue

    2015-01-01

    The influence of an N 2 O plasma pre-treatment technique on characteristics of AlGaN/GaN high electron mobility transistor (HEMT) prepared by using a plasma-enhanced chemical vapor deposition (PECVD) system is presented. After the plasma treatment, the peak transconductance (g m ) increases from 209 mS/mm to 293 mS/mm. Moreover, it is observed that the reverse gate leakage current is lowered by one order of magnitude and the drain current dispersion is improved in the plasma-treated device. From the analysis of frequency-dependent conductance, it can be seen that the trap state density (D T ) and time constant (τ T ) of the N 2 O-treated device are smaller than those of a non-treated device. The results indicate that the N 2 O plasma pre-pretreatment before the gate metal deposition could be a promising approach to enhancing the performance of the device. (paper)

  19. Tipo de arcada y plano terminal molar de la dentición temporal y su correlación con las clases de maloclusión de la dentición permanente

    Directory of Open Access Journals (Sweden)

    Ana Pascual Serna

    2015-12-01

    Full Text Available El objetivo fue establecer la correlación del tipo de arcada y plano terminal molar de la dentición temporal con las clases de maloclusión de Angle en niños de 5 años de edad que acuden al Hospital Nacional “Daniel Alcides Carrión”de Cerro de Pasco, 2010 - 2011. La investigación se desarrolló bajo un diseño descriptivo longitudinal prospectivo. La muestra estuvo conformada por 40 niños escogidos por muestreo no probabilístico. Se realizó inicialmente la evaluación clínica del tipo de arcada y plano terminal molar de la dentición temporal y posteriormente al erupcionar las primeras molares permanentes se verificó la correlación con las clases de maloclusión de Angle, el tratamiento estadístico de la hipótesis fue con la Chi Cuadrada. Entre los resultados podemos mencionar que existe diferencia estadística significativa para asumir que el tipo de plano terminal molar y tipo de arcada de la dentición temporal se correlaciona con las clases de maloclusión de Angle, teniendo en consideración que la X2c=12,724>X2t = 9,488(4gl-95 %, rechazándose la Ho. En conclusión, el tipo de plano terminal molar recto y el tipo de arcada abierta de la dentición temporal se relaciona con mayor frecuencia con la normoclusión y la Clase I de maloclusión. Mientras que el tipo de plano terminal molar escalón mesial y el tipo de arcada cerrada de la dentición temporal se relaciona con la Clase III de maloclusión.

  20. Synthesis of N-graphene using microwave plasma-based methods

    Science.gov (United States)

    Dias, Ana; Tatarova, Elena; Henriques, Julio; Dias, Francisco; Felizardo, Edgar; Abrashev, Miroslav; Bundaleski, Nenad; Cvelbar, Uros

    2016-09-01

    In this work a microwave atmospheric plasma driven by surface waves is used to produce free-standing graphene sheets (FSG). Carbonaceous precursors are injected into a microwave plasma environment, where decomposition processes take place. The transport of plasma generated gas-phase carbon atoms and molecules into colder zones of plasma reactor results in carbon nuclei formation. The main part of the solid carbon is gradually carried from the ``hot'' plasma zone into the outlet plasma stream where carbon nanostructures assemble and grow. Subsequently, the graphene sheets have been N-doped using a N2-Ar large-scale remote plasma treatment, which consists on placing the FSG on a substrate in a remote zone of the N2-Ar plasma. The samples were treated with different compositions of N2-Ar gas mixtures, while maintaining 1 mbar pressure in the chamber and a power applied of 600 W. The N-doped graphene sheets were characterized by scanning and by high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy and Raman spectroscopy. Plasma characterization was also performed by optical emission spectroscopy. Work partially funded by Portuguese FCT - Fundacao para a Ciencia e a Tecnologia, under grant SFRH/BD/52413/2013 (PD-F APPLAuSE).

  1. Acetylation within the N- and C-Terminal Domains of Src Regulates Distinct Roles of STAT3-Mediated Tumorigenesis.

    Science.gov (United States)

    Huang, Chao; Zhang, Zhe; Chen, Lihan; Lee, Hank W; Ayrapetov, Marina K; Zhao, Ting C; Hao, Yimei; Gao, Jinsong; Yang, Chunzhang; Mehta, Gautam U; Zhuang, Zhengping; Zhang, Xiaoren; Hu, Guohong; Chin, Y Eugene

    2018-06-01

    Posttranslational modifications of mammalian c-Src N-terminal and C-terminal domains regulate distinct functions. Myristoylation of G 2 controls its cell membrane association and phosphorylation of Y419/Y527 controls its activation or inactivation, respectively. We provide evidence that Src-cell membrane association-dissociation and catalytic activation-inactivation are both regulated by acetylation. In EGF-treated cells, CREB binding protein (CBP) acetylates an N-terminal lysine cluster (K5, K7, and K9) of c-Src to promote dissociation from the cell membrane. CBP also acetylates the C-terminal K401, K423, and K427 of c-Src to activate intrinsic kinase activity for STAT3 recruitment and activation. N-terminal domain phosphorylation (Y14, Y45, and Y68) of STAT3 by c-Src activates transcriptionally active dimers of STAT3. Moreover, acetyl-Src translocates into nuclei, where it forms the Src-STAT3 enhanceosome for gene regulation and cancer cell proliferation. Thus, c-Src acetylation in the N-terminal and C-terminal domains play distinct roles in Src activity and regulation. Significance: CBP-mediated acetylation of lysine clusters in both the N-terminal and C-terminal regions of c-Src provides additional levels of control over STAT3 transcriptional activity. Cancer Res; 78(11); 2825-38. ©2018 AACR . ©2018 American Association for Cancer Research.

  2. Structural plasticity of the N-terminal capping helix of the TPR domain of kinesin light chain.

    Directory of Open Access Journals (Sweden)

    The Quyen Nguyen

    Full Text Available Kinesin1 plays a major role in neuronal transport by recruiting many different cargos through its kinesin light chain (KLC. Various structurally unrelated cargos interact with the conserved tetratricopeptide repeat (TPR domain of KLC. The N-terminal capping helix of the TPR domain exhibits an atypical sequence and structural features that may contribute to the versatility of the TPR domain to bind different cargos. We determined crystal structures of the TPR domain of both KLC1 and KLC2 encompassing the N-terminal capping helix and show that this helix exhibits two distinct and defined orientations relative to the rest of the TPR domain. Such a difference in orientation gives rise, at the N-terminal part of the groove, to the formation of one hydrophobic pocket, as well as to electrostatic variations at the groove surface. We present a comprehensive structural analysis of available KLC1/2-TPR domain structures that highlights that ligand binding into the groove can be specific of one or the other N-terminal capping helix orientations. Further, structural analysis reveals that the N-terminal capping helix is always involved in crystal packing contacts, especially in a TPR1:TPR1' contact which highlights its propensity to be a protein-protein interaction site. Together, these results underline that the structural plasticity of the N-terminal capping helix might represent a structural determinant for TPR domain structural versatility in cargo binding.

  3. Differential isotope dansylation labeling combined with liquid chromatography mass spectrometry for quantification of intact and N-terminal truncated proteins

    International Nuclear Information System (INIS)

    Tang, Yanan; Li, Liang

    2013-01-01

    Graphical abstract: -- Highlights: •LC–MS was developed for quantifying protein mixtures containing both intact and N-terminal truncated proteins. • 12 C 2 -Dansylation of the N-terminal amino acid of proteins was done first, followed by microwave-assisted acid hydrolysis. •The released 12 C 2 -dansyl labeled N-terminal amino acid was quantified using 13 C 2 -dansyl labeled amino acid standards. •The method provided accurate and precise results for quantifying intact and N-terminal truncated proteins within 8 h. -- Abstract: The N-terminal amino acids of proteins are important structure units for maintaining the biological function, localization, and interaction networks of proteins. Under different biological conditions, one or several N-terminal amino acids could be cleaved from an intact protein due to processes, such as proteolysis, resulting in the change of protein properties. Thus, the ability to quantify the N-terminal truncated forms of proteins is of great importance, particularly in the area of development and production of protein-based drugs where the relative quantity of the intact protein and its truncated form needs to be monitored. In this work, we describe a rapid method for absolute quantification of protein mixtures containing intact and N-terminal truncated proteins. This method is based on dansylation labeling of the N-terminal amino acids of proteins, followed by microwave-assisted acid hydrolysis of the proteins into amino acids. It is shown that dansyl labeled amino acids are stable in acidic conditions and can be quantified by liquid chromatography mass spectrometry (LC–MS) with the use of isotope analog standards

  4. Diagnostic Usefulness of N-terminal Pro-brain Natriuretic Peptide ...

    African Journals Online (AJOL)

    BACKGROUND: N-terminal pro-brain natriuretic peptide (NTproBNP) is useful in the diagnosis and management of adult patients with heart failure. OBJECTIVE: The objective of the study was to determine the usefulness of NT-proBNP in diagnosing congestive heart failure (CHF) in children and its correlation with left ...

  5. Human TRPA1 is intrinsically cold- and chemosensitive with and without its N-terminal ankyrin repeat domain.

    Science.gov (United States)

    Moparthi, Lavanya; Survery, Sabeen; Kreir, Mohamed; Simonsen, Charlotte; Kjellbom, Per; Högestätt, Edward D; Johanson, Urban; Zygmunt, Peter M

    2014-11-25

    We have purified and reconstituted human transient receptor potential (TRP) subtype A1 (hTRPA1) into lipid bilayers and recorded single-channel currents to understand its inherent thermo- and chemosensory properties as well as the role of the ankyrin repeat domain (ARD) of the N terminus in channel behavior. We report that hTRPA1 with and without its N-terminal ARD (Δ1-688 hTRPA1) is intrinsically cold-sensitive, and thus, cold-sensing properties of hTRPA1 reside outside the N-terminal ARD. We show activation of hTRPA1 by the thiol oxidant 2-((biotinoyl)amino)ethyl methanethiosulfonate (MTSEA-biotin) and that electrophilic compounds activate hTRPA1 in the presence and absence of the N-terminal ARD. The nonelectrophilic compounds menthol and the cannabinoid Δ(9)-tetrahydrocannabiorcol (C16) directly activate hTRPA1 at different sites independent of the N-terminal ARD. The TRPA1 antagonist HC030031 inhibited cold and chemical activation of hTRPA1 and Δ1-688 hTRPA1, supporting a direct interaction with hTRPA1 outside the N-terminal ARD. These findings show that hTRPA1 is an intrinsically cold- and chemosensitive ion channel. Thus, second messengers, including Ca(2+), or accessory proteins are not needed for hTRPA1 responses to cold or chemical activators. We suggest that conformational changes outside the N-terminal ARD by cold, electrophiles, and nonelectrophiles are important in hTRPA1 channel gating and that targeting chemical interaction sites outside the N-terminal ARD provides possibilities to fine tune TRPA1-based drug therapies (e.g., for treatment of pain associated with cold hypersensitivity and cardiovascular disease).

  6. KV4.3 N-terminal deletion mutant Δ2–39

    Science.gov (United States)

    Hovind, Laura J; Skerritt, Matthew R

    2011-01-01

    Gating transitions in the KV4.3 N-terminal deletion mutant Δ2–39 were characterized in the absence and presence of KChIP2b. We particularly focused on gating characteristics of macroscopic (open state) versus closed state inactivation (CSI) and recovery. In the absence of KChIP2b Δ2–39 did not significantly alter the steady-state activation “a4” relationship or general CSI characteristics, but it did slow the kinetics of deactivation, macroscopic inactivation and macroscopic recovery. Recovery kinetics (for both WT KV4.3 and Δ2–39) were complicated and displayed sigmoidicity, a process which was enhanced by Δ2–39. Deletion of the proximal N-terminal domain therefore appeared to specifically slow mechanisms involved in regulating gating transitions occurring after the channel open state(s) had been reached. In the presence of KChIP2b Δ2–39 recovery kinetics (from both macroscopic and CSI) were accelerated, with an apparent reduction in initial sigmoidicity. Hyperpolarizing shifts in both “a4” and isochronal inactivation “i” were also produced. KChIP2b-mediated remodeling of KV4.3 gating transitions was therefore not obligatorily dependent upon an intact N-terminus. To account for these effects we propose that KChIP2 regulatory domains exist in KV4.3 α subunit regions outside of the proximal N-terminal. In addition to regulating macroscopic inactivation, we also propose that the KV4.3 N-terminus may act as a novel regulator of deactivation-recovery coupling. PMID:21057209

  7. c-jun-N-Terminal Kinase (JNK) for the Treatment of Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    2015-03-01

    1 AWARD NUMBER: W81XWH-12-1-0431 TITLE: “c-jun-N-Terminal Kinase (JNK) for the Treatment of Amyotrophic Lateral Sclerosis ” PRINCIPAL...TITLE AND SUBTITLE “c-jun-N-Terminal Kinase (JNK) for the Treatment of Amyotrophic Lateral Scelerosis” 5a. CONTRACT NUMBER 5b. GRANT NUMBER... Lateral   Sclerosis ”   Final  Report:  Project  Period  Sept  2012-­‐Dec  2014     Personnel  List:     Feng,  Yangbo

  8. The Extracellular Protein Factor Epf from Streptococcus pyogenes Is a Cell Surface Adhesin That Binds to Cells through an N-terminal Domain Containing a Carbohydrate-binding Module*

    Science.gov (United States)

    Linke, Christian; Siemens, Nikolai; Oehmcke, Sonja; Radjainia, Mazdak; Law, Ruby H. P.; Whisstock, James C.; Baker, Edward N.; Kreikemeyer, Bernd

    2012-01-01

    Streptococcus pyogenes is an exclusively human pathogen. Streptococcal attachment to and entry into epithelial cells is a prerequisite for a successful infection of the human host and requires adhesins. Here, we demonstrate that the multidomain protein Epf from S. pyogenes serotype M49 is a streptococcal adhesin. An epf-deficient mutant showed significantly decreased adhesion to and internalization into human keratinocytes. Cell adhesion is mediated by the N-terminal domain of Epf (EpfN) and increased by the human plasma protein plasminogen. The crystal structure of EpfN, solved at 1.6 Å resolution, shows that it consists of two subdomains: a carbohydrate-binding module and a fibronectin type III domain. Both fold types commonly participate in ligand receptor and protein-protein interactions. EpfN is followed by 18 repeats of a domain classified as DUF1542 (domain of unknown function 1542) and a C-terminal cell wall sorting signal. The DUF1542 repeats are not involved in adhesion, but biophysical studies show they are predominantly α-helical and form a fiber-like stalk of tandem DUF1542 domains. Epf thus conforms with the widespread family of adhesins known as MSCRAMMs (microbial surface components recognizing adhesive matrix molecules), in which a cell wall-attached stalk enables long range interactions via its adhesive N-terminal domain. PMID:22977243

  9. Sex-Specific Associations Between Self-reported Sleep Duration, Cardiovascular Disease, Hypertension, and Mortality in an Elderly Population.

    Science.gov (United States)

    Broström, Anders; Wahlin, Ake; Alehagen, Urban; Ulander, Martin; Johansson, Peter

    2017-01-05

    Both short and long sleep durations have been associated to increased mortality. Knowledge about sex-specific differences among elderly regarding associations between sleep duration, cardiovascular health, and mortality is sparse. The aims of this study are to examine the association between self-reported sleep duration and mortality and to investigate whether this association is sex specific and/or moderated by cardiovascular morbidity, and also to explore potential mediators of sleep duration effects on mortality. A population-based, observational, cross-sectional design with 6-year follow-up with mortality as primary outcome was conducted. Self-rated sleep duration, clinical examinations, echocardiography, and blood samples (N-terminal fragment of proBNP) were collected. A total of 675 persons (50% women; mean age, 78 years) were divided into short sleepers (≤6 hours; n = 231), normal sleepers (7-8 hours; n = 338), and long sleepers (≥9 hours; n = 61). Data were subjected to principal component analyses. Cardiovascular disease (CVD) and hypertension factors were extracted and used as moderators and as mediators in the regression analyses. During follow-up, 55 short sleepers (24%), 68 normal sleepers (20%), and 21 long sleepers (34%) died. Mediator analyses showed that long sleep was associated with mortality in men (hazard ratio [HR], 1.8; P = .049), independently of CVD and hypertension. In men with short sleep, CVD acted as a moderator of the association with mortality (HR, 4.1; P = .025). However, when using N-terminal fragment of proBNP, this effect became nonsignificant (HR, 3.1; P = .06). In woman, a trend to moderation involving the hypertension factor and short sleep was found (HR, 4.6; P = .09). Short and long sleep duration may be seen as risk markers, particularly among older men with cardiovascular morbidity.

  10. Differential isotope dansylation labeling combined with liquid chromatography mass spectrometry for quantification of intact and N-terminal truncated proteins

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Yanan; Li, Liang, E-mail: Liang.Li@ualberta.ca

    2013-08-20

    Graphical abstract: -- Highlights: •LC–MS was developed for quantifying protein mixtures containing both intact and N-terminal truncated proteins. •{sup 12}C{sub 2}-Dansylation of the N-terminal amino acid of proteins was done first, followed by microwave-assisted acid hydrolysis. •The released {sup 12}C{sub 2}-dansyl labeled N-terminal amino acid was quantified using {sup 13}C{sub 2}-dansyl labeled amino acid standards. •The method provided accurate and precise results for quantifying intact and N-terminal truncated proteins within 8 h. -- Abstract: The N-terminal amino acids of proteins are important structure units for maintaining the biological function, localization, and interaction networks of proteins. Under different biological conditions, one or several N-terminal amino acids could be cleaved from an intact protein due to processes, such as proteolysis, resulting in the change of protein properties. Thus, the ability to quantify the N-terminal truncated forms of proteins is of great importance, particularly in the area of development and production of protein-based drugs where the relative quantity of the intact protein and its truncated form needs to be monitored. In this work, we describe a rapid method for absolute quantification of protein mixtures containing intact and N-terminal truncated proteins. This method is based on dansylation labeling of the N-terminal amino acids of proteins, followed by microwave-assisted acid hydrolysis of the proteins into amino acids. It is shown that dansyl labeled amino acids are stable in acidic conditions and can be quantified by liquid chromatography mass spectrometry (LC–MS) with the use of isotope analog standards.

  11. Controlling chaos based on a novel intelligent integral terminal sliding mode control in a rod-type plasma torch

    International Nuclear Information System (INIS)

    Khari, Safa; Rahmani, Zahra; Rezaie, Behrooz

    2016-01-01

    An integral terminal sliding mode controller is proposed in order to control chaos in a rod-type plasma torch system. In this method, a new sliding surface is defined based on a combination of the conventional sliding surface in terminal sliding mode control and a nonlinear function of the integral of the system states. It is assumed that the dynamics of a chaotic system are unknown and also the system is exposed to disturbance and unstructured uncertainty. To achieve a chattering-free and high-speed response for such an unknown system, an adaptive neuro-fuzzy inference system is utilized in the next step to approximate the unknown part of the nonlinear dynamics. Then, the proposed integral terminal sliding mode controller stabilizes the approximated system based on Lyapunov’s stability theory. In addition, a Bee algorithm is used to select the coefficients of integral terminal sliding mode controller to improve the performance of the proposed method. Simulation results demonstrate the improvement in the response speed, chattering rejection, transient response, and robustness against uncertainties. (paper)

  12. Identification of chronic heart failure patients with a high 12-month mortality risk using biomarkers including plasma C-terminal pro-endothelin-1.

    Directory of Open Access Journals (Sweden)

    Ewa A Jankowska

    Full Text Available OBJECTIVES: We hypothesised that assessment of plasma C-terminal pro-endothelin-1 (CT-proET-1, a stable endothelin-1 precursor fragment, is of prognostic value in patients with chronic heart failure (CHF, beyond other prognosticators, including N-terminal pro-B-type natriuretic peptide (NT-proBNP. METHODS: We examined 491 patients with systolic CHF (age: 63±11 years, 91% men, New York Heart Association [NYHA] class [I/II/III/IV]: 9%/45%/38%/8%, 69% ischemic etiology. Plasma CT-proET-1 was detected using a chemiluminescence immunoassay. RESULTS: Increasing CT-proET-1 was a predictor of increased cardiovascular mortality at 12-months of follow-up (standardized hazard ratio 1.42, 95% confidence interval [CI] 1.04-1.95, p = 0.03 after adjusting for NT-proBNP, left ventricular ejection fraction (LVEF, age, creatinine, NYHA class. In receiver operating characteristic curve analysis, areas under curve for 12-month follow-up were similar for CT-proET-1 and NT-proBNP (p = 0.40. Both NT-proBNP and CT-proET-1 added prognostic value to a base model that included LVEF, age, creatinine, and NYHA class. Adding CT-proET-1 to the base model had stronger prognostic power (p<0.01 than adding NT-proBNP (p<0.01. Adding CT-proET-1 to NT-proBNP in this model yielded further prognostic information (p = 0.02. CONCLUSIONS: Plasma CT-proET-1 constitutes a novel predictor of increased 12-month cardiovascular mortality in patients with CHF. High CT-proET-1 together with high NT-proBNP enable to identify patients with CHF and particularly unfavourable outcomes.

  13. Highly enantioselective catalytic cross-dehydrogenative coupling of N-carbamoyl tetrahydroisoquinolines and terminal alkynes.

    Science.gov (United States)

    Sun, Shutao; Li, Chengkun; Floreancig, Paul E; Lou, Hongxiang; Liu, Lei

    2015-04-03

    The first catalytic asymmetric cross-dehydrogenative coupling of cyclic carbamates and terminal alkynes has been established. The reaction features high enantiocontrol and excellent functional group tolerance and displays a wide range of structurally and electronically diverse carbamates as well as terminal alkynes. N-Acyl hemiaminals were identified as the reactive intermediates through preliminary control experiments. Employing readily removable carbamates as substrates rather than traditionally adopted N-aryl amines allows applications in complex molecule synthesis and therefore advances the C-H functionalization strategy to a synthetically useful level.

  14. An N-Terminal ER Export Signal Facilitates the Plasma Membrane Targeting of HCN1 Channels in Photoreceptors.

    Science.gov (United States)

    Pan, Yuan; Laird, Joseph G; Yamaguchi, David M; Baker, Sheila A

    2015-06-01

    Hyperpolarization-activated cyclic nucleotide-gated 1 (HCN1) channels are widely expressed in the retina. In photoreceptors, the hyperpolarization-activated current (Ih) carried by HCN1 is important for shaping the light response. It has been shown in multiple systems that trafficking HCN1 channels to specific compartments is key to their function. The localization of HCN1 in photoreceptors is concentrated in the plasma membrane of the inner segment (IS). The mechanisms controlling this localization are not understood. We previously identified a di-arginine endoplasmic reticulum (ER) retention motif that negatively regulates the surface targeting of HCN1. In this study, we sought to identify a forward trafficking signal that could counter the function of the ER retention signal. We studied trafficking of HCN1 and several mutants by imaging their subcellular localization in transgenic X. laevis photoreceptors. Velocity sedimentation was used to assay the assembly state of HCN1 channels. We found the HCN1 N-terminus can redirect a membrane reporter from outer segments (OS) to the plasma membrane of the IS. The sequence necessary for this behavior was mapped to a 20 amino acid region containing a leucine-based ER export motif. The ER export signal is necessary for forward trafficking but not channel oligomerization. Moreover, this ER export signal alone counteracted the di-arginine ER retention signal. We identified an ER export signal in HCN1 that functions with the ER retention signal to maintain equilibrium of HCN1 between the endomembrane system and the plasma membrane.

  15. Discovery and development of the N-terminal procollagen type II (NPII) biomarker: a tool for measuring collagen type II synthesis.

    Science.gov (United States)

    Nemirovskiy, O V; Sunyer, T; Aggarwal, P; Abrams, M; Hellio Le Graverand, M P; Mathews, W R

    2008-12-01

    Progression of joint damage in osteoarthritis (OA) is likely to result from an imbalance between cartilage degradation and synthesis processes. Markers reflecting these two components appear to be promising in predicting the rate of OA progression. Both N- and C-terminal propeptides of type II collagen reflect the rates of collagen type II synthesis. The ability to quantify the procollagen peptides in biological fluids would enable a better understanding of OA disease pathology and provide means for assessing the proof of mechanism of anabolic disease modifying OA drugs (DMOADs). A polyclonal antibody that recognizes the sequence GPKGQKGEPGDIKDI in the propeptide region of rat, dog, and human type II collagen was raised in chicken and peptide-affinity purified. The immunoaffinity liquid chromatography mass spectrometry (LC-MS/MS) was used to extensively characterize N-terminal procollagen type II (NPII) peptides found in biological fluids. The novel competition enzyme-linked immunosorbent assay (ELISA) assay was developed to quantitatively measure the NPII peptides. Several peptides ranging from 17 to 41 amino acids with various modifications including hydroxylations on proline and lysine residues, oxidation of lysines to allysines, and attachments of glucose and galactose moieties to hydroxylysines were identified in a simple system such as ex vivo cultures of human articular cartilage (HAC) explants as well as in more complex biological fluids such as human urine and plasma. A competitive ELISA assay has been developed and applied to urine, plasma, and synovial fluid matrices in human, rat and dog samples. A novel NPII assay has been developed and applied to OA and normal human subjects to understand the changes in collagen type II synthesis related to the pathology of OA.

  16. Structure of the human histone chaperone FACT Spt16 N-terminal domain

    Energy Technology Data Exchange (ETDEWEB)

    Marcianò, G.; Huang, D. T., E-mail: d.huang@beatson.gla.ac.uk [Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, Scotland (United Kingdom)

    2016-01-22

    The Spt16–SSRP1 heterodimer is a histone chaperone that plays an important role in regulating chromatin assembly. Here, a crystal structure of the N-terminal domain of human Spt16 is presented and it is shown that this domain may contribute to histone binding. The histone chaperone FACT plays an important role in facilitating nucleosome assembly and disassembly during transcription. FACT is a heterodimeric complex consisting of Spt16 and SSRP1. The N-terminal domain of Spt16 resembles an inactive aminopeptidase. How this domain contributes to the histone chaperone activity of FACT remains elusive. Here, the crystal structure of the N-terminal domain (NTD) of human Spt16 is reported at a resolution of 1.84 Å. The structure adopts an aminopeptidase-like fold similar to those of the Saccharomyces cerevisiae and Schizosaccharomyces pombe Spt16 NTDs. Isothermal titration calorimetry analyses show that human Spt16 NTD binds histones H3/H4 with low-micromolar affinity, suggesting that Spt16 NTD may contribute to histone binding in the FACT complex. Surface-residue conservation and electrostatic analysis reveal a conserved acidic patch that may be involved in histone binding.

  17. Structure of the human histone chaperone FACT Spt16 N-terminal domain

    International Nuclear Information System (INIS)

    Marcianò, G.; Huang, D. T.

    2016-01-01

    The Spt16–SSRP1 heterodimer is a histone chaperone that plays an important role in regulating chromatin assembly. Here, a crystal structure of the N-terminal domain of human Spt16 is presented and it is shown that this domain may contribute to histone binding. The histone chaperone FACT plays an important role in facilitating nucleosome assembly and disassembly during transcription. FACT is a heterodimeric complex consisting of Spt16 and SSRP1. The N-terminal domain of Spt16 resembles an inactive aminopeptidase. How this domain contributes to the histone chaperone activity of FACT remains elusive. Here, the crystal structure of the N-terminal domain (NTD) of human Spt16 is reported at a resolution of 1.84 Å. The structure adopts an aminopeptidase-like fold similar to those of the Saccharomyces cerevisiae and Schizosaccharomyces pombe Spt16 NTDs. Isothermal titration calorimetry analyses show that human Spt16 NTD binds histones H3/H4 with low-micromolar affinity, suggesting that Spt16 NTD may contribute to histone binding in the FACT complex. Surface-residue conservation and electrostatic analysis reveal a conserved acidic patch that may be involved in histone binding

  18. Pharmacokinetic, pharmacodynamic, and antihypertensive effects of the neprilysin inhibitor LCZ-696: sacubitril/valsartan.

    Science.gov (United States)

    Chrysant, Steven G

    2017-07-01

    LCZ-696, sacubitril/valsartan, is a dual-acting molecule consisting of the angiotensin II (Ang II) receptor blocker valsartan and the neprilysin (neutral endopeptidase) inhibitor AHU-377 with significant beneficial effects in patients with hypertension and heart failure (HF). Several recent studies have demonstrated a higher effectiveness of LCZ-696 compared to valsartan in the treatment of hypertension and HF. The rationale for the development and the Food and Drug Administration approval of LCZ-696 was based on the concept of an additive effect of the Ang II receptor blocker valsartan and the neutral endopeptidase (neprilysin) inhibitor AHU-377 for the treatment of hypertension and HF. The synergism from these drugs arises from the vasodilating effects of valsartan through its blockade of Ang II type 1 receptor and the action of natriuretic peptides atrial natriuretic peptide and B-type natriuretic peptide (BNP) by preventing their catabolism with neprilysin resulting in increase of cyclic guanosine monophosphate. This action of neprilysin is associated with increased natriuresis, diuresis, and systemic vasodilation, since these peptides have been shown to have potent diuretic, natriuretic, and vasodilating effects. In addition, it reduces the levels of N terminal pro-BNP. Therefore, administration of LCZ-696 results in significant reduction of wall stress from pressure and volume overload of the left ventricle as demonstrated by the reduction of N terminal pro-BNP, both significant constituents of hypertension and HF, and it is safe, well tolerated and is almost free of cough and angioedema. Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

  19. Inter-machine comparison of the termination phase and energy conversion in tokamak disruptions with runaway current plateau formation and implications for ITER

    International Nuclear Information System (INIS)

    Martín-Solís, J.R.; Loarte, A.; Hollmann, E.M.; Esposito, B.; Riccardo, V.

    2014-01-01

    The termination of the current and the loss of runaway electrons following runaway current plateau formation during disruptions have been investigated in the JET, DIII-D and FTU tokamaks. Substantial conversion of magnetic energy into runaway kinetic energy, up to ∼10 times the initial plateau runaway kinetic energy, has been inferred for the slowest current terminations. Both modelling and experiment suggest that, in present devices, the efficiency of conversion into runaway kinetic energy is determined to a great extent by the characteristic runaway loss time, τ diff , and the resistive time of the residual ohmic plasma after the disruption, τ res , increasing with the ratio τ diff /τ res . It is predicted that, in large future devices such as ITER, the generation of runaways by the avalanche mechanism will play an important role, particularly for slow runaway discharge terminations, increasing substantially the amount of energy deposited by the runaways onto the plasma-facing components by the conversion of magnetic energy of the runaway plasma into runaway kinetic energy. Estimates of the power fluxes on the beryllium plasma-facing components during runaway termination in ITER indicate that for runaway currents of up to 2 MA no melting of the components is expected. For larger runaway currents, minimization of the effects of runaway impact on the first wall requires a reduction in the kinetic energy of the runaway beam before termination and, in addition, high plasma density n e and low ohmic plasma resistance (long τ res ) to prevent large conversion of magnetic into runaway kinetic energy during slow current terminations. (paper)

  20. Au-Catalyzed Synthesis of 2-Alkylindoles from N-Arylhydroxylamines and Terminal Alkynes

    Science.gov (United States)

    Wang, Yanzhao; Ye, Longwu

    2012-01-01

    The first gold-catalyzed addition of N-arylhydroxylamines to aliphatic terminal alkynes is developed to access O-alkenyl-N-arylhydroxylamines, which undergo facile in situ sequential 3,3-rearrangements and cyclodehydrations to afford 2-alkylindoles with regiospecificity and under exceptionally mild reaction conditions. PMID:21637891

  1. Inhibition of Progenitor Dendritic Cell Maturation by Plasma from Patients with Peripartum Cardiomyopathy: Role in Pregnancy-associated Heart Disease

    Directory of Open Access Journals (Sweden)

    Jane E. Ellis

    2005-01-01

    Full Text Available Dendritic cells (DCs play dual roles in innate and adaptive immunity based on their functional maturity, and both innate and adaptive immune responses have been implicated in myocardial tissue remodeling associated with cardiomyopathies. Peripartum cardiomyopathy (PPCM is a rare disorder which affects women within one month antepartum to five months postpartum. A high occurrence of PPCM in central Haiti (1 in 300 live births provided the unique opportunity to study the relationship of immune activation and DC maturation to the etiology of this disorder. Plasma samples from two groups (n = 12 of age- and parity-matched Haitian women with or without evidence of PPCM were tested for levels of biomarkers of cardiac tissue remodeling and immune activation. Significantly elevated levels of GM-CSF, endothelin-1, proBNP and CRP and decreased levels of TGF- were measured in PPCM subjects relative to controls. Yet despite these findings, in vitro maturation of normal human cord blood derived progenitor dendritic cells (CBDCs was significantly reduced (p < 0.001 in the presence of plasma from PPCM patients relative to plasma from post-partum control subjects as determined by expression of CD80, CD86, CD83, CCR7, MHC class II and the ability of these matured CBDCs to induce allo-responses in PBMCs. These results represent the first findings linking inhibition of DC maturation to the dysregulation of normal physiologic cardiac tissue remodeling during pregnancy and the pathogenesis of PPCM.

  2. Normally-off AlGaN/GaN-based MOS-HEMT with self-terminating TMAH wet recess etching

    Science.gov (United States)

    Son, Dong-Hyeok; Jo, Young-Woo; Won, Chul-Ho; Lee, Jun-Hyeok; Seo, Jae Hwa; Lee, Sang-Heung; Lim, Jong-Won; Kim, Ji Heon; Kang, In Man; Cristoloveanu, Sorin; Lee, Jung-Hee

    2018-03-01

    Normally-off AlGaN/GaN-based MOS-HEMT has been fabricated by utilizing damage-free self-terminating tetramethyl ammonium hydroxide (TMAH) recess etching. The device exhibited a threshold voltage of +2.0 V with good uniformity, extremely small hysteresis of ∼20 mV, and maximum drain current of 210 mA/mm. The device also exhibited excellent off-state performances, such as breakdown voltage of ∼800 V with off-state leakage current as low as ∼10-12 A and high on/off current ratio (Ion/Ioff) of 1010. These excellent device performances are believed to be due to the high quality recessed surface, provided by the simple self-terminating TMAH etching.

  3. Novel determinants of H-Ras plasma membrane localization and transformation

    DEFF Research Database (Denmark)

    Willumsen, B M; Cox, A D; Solski, P A

    1996-01-01

    cysteine did not abolish palmitoylation. However, despite continued lipid modification the mutant proteins failed to bind to plasma membranes and instead accumulated on internal membranes and, importantly, were not transforming. Addition of an N-terminal myristoylation signal to these defective mutants......, or to proteins entirely lacking the C-terminal 25 residues restored both plasma membrane association and transforming activity. Thus, H-Ras does not absolutely require prenylation or palmitoylation nor indeed its hypervariable domain in order to interact with effectors that ultimately cause transformation....... However, in this native state, the C-terminus appears to provide a combination of lipids and a previously unrecognized signal for specific plasma membrane targeting that are essential for the correct localization and biological function of H-Ras....

  4. The membranotropic activity of N-terminal peptides from the pore ...

    Indian Academy of Sciences (India)

    The membranotropic activity of N-terminal peptides from the pore-forming proteins sticholysin I and II is modulated by hydrophobic and electrostatic interactions ... Center for Protein Studies, Biology Faculty, University of Havana, Havana, Cuba; Department of Applied Physics, Institute of Physics, University of São Paulo, São ...

  5. Hydroxyl Radical-Mediated Novel Modification of Peptides: N-Terminal Cyclization through the Formation of α-Ketoamide.

    Science.gov (United States)

    Lee, Seon Hwa; Kyung, Hyunsook; Yokota, Ryo; Goto, Takaaki; Oe, Tomoyuki

    2015-01-20

    The hydroxyl radical-mediated oxidation of peptides and proteins constitutes a large group of post-translational modifications that can result in structural and functional changes. These oxidations can lead to hydroxylation, sulfoxidation, or carbonylation of certain amino acid residues and cleavage of peptide bonds. In addition, hydroxyl radicals can convert the N-terminus of peptides to an α-ketoamide via abstraction of the N-terminal α-hydrogen and hydrolysis of the ketimine intermediate. In the present study, we identified N-terminal cyclization as a novel modification mediated by a hydroxyl radical. The reaction of angiotensin (Ang) II (DRVYIHPF) and the hydroxyl radical generated by the Cu(II)/ascorbic acid (AA) system or UV/hydrogen peroxide system produced N-terminal cyclized-Ang II (Ang C) and pyruvamide-Ang II (Ang P, CH3COCONH-RVYIHPF). The structure of Ang C was confirmed by mass spectrometry and comparison to an authentic standard. The subsequent incubation of isolated Ang P in the presence of Cu(II)/AA revealed that Ang P was the direct precursor of Ang C. The proposed mechanism involves the formation of a nitrogen-centered (aminyl) radical, which cyclizes to form a five-membered ring containing the alkoxy radical. The subsequent β-scission reaction of the alkoxyl radical results in the cleavage of the terminal CH3CO group. The initial aminyl radical can be stabilized by chelation to the Cu(II) ions. The affinity of Ang C toward the Ang II type 1 receptor was significantly lower than that of Ang II or Ang P. Ang C was not further metabolized by aminopeptidase A, which converts Ang II to Ang III. Hydroxyl radical-mediated N-terminal cyclization was also observed in other Ang peptides containing N-terminal alanine, arginine, valine, and amyloid β 1-11 (DAEFRHDSGYE).

  6. N-terminal region of gelsolin induces apoptosis of activated hepatic stellate cells by a caspase-dependent mechanism.

    Directory of Open Access Journals (Sweden)

    Budhaditya Mazumdar

    Full Text Available Activated hepatic stellate cells (HSCs are the major source for alteration of extracellular matrix in fibrosis and cirrhosis. Conditioned medium (CM collected from immortalized human hepatocytes (IHH have earlier been shown to be responsible for apoptosis of HSCs. In this study, we have shown that antibodies raised against a peptide derived from a linear B-cell epitope in the N-terminal region of gelsolin identified a gelsolin fragment in IHH CM. Analysis of activated stellate cell death by CM collected from Huh7 cells transfected with plasmids encoding gelsolin deletion mutants suggested that the N-terminal half of gelsolin contained sequences which were responsible for stellate cell death. Further analysis determined that this activity was restricted to a region encompassing amino acids 1-70 in the gelsolin sequence; antibody directed to an epitope within this region was able to neutralize stellate cell death. Gelsolin modulation of cell death using this fragment involved upregulation of TRAIL-R1 and TRAIL-R2, and involved caspase 3 activation by extrinsic pathway. The apoptotic activity of N-terminal gelsolin fragments was restricted to activated but not quiescent stellate cells indicating its potential application in therapeutic use as an anti-fibrotic agent. Gelsolin fragments encompassing N-terminal regions in polypeptides of different molecular sizes were detected by N-terminal peptide specific antiserum in IHH CM immunoprecipitated with chronically HCV infected patient sera, suggesting the presence of autoantibodies generated against N-terminal gelsolin fragments in patients with chronic liver disease.

  7. Roles of N- and C-terminal domains in the ligand-binding properties of cytoglobin.

    Science.gov (United States)

    Hanai, Shumpei; Tsujino, Hirofumi; Yamashita, Taku; Torii, Ryo; Sawai, Hitomi; Shiro, Yoshitsugu; Oohora, Koji; Hayashi, Takashi; Uno, Tadayuki

    2018-02-01

    Cytoglobin (Cygb) is a member of the hexacoordinated globin protein family and is expressed ubiquitously in rat and human tissues. Although Cygb is reportedly upregulated under hypoxic conditions both in vivo and in vitro, suggesting a physiological function to protect cells under hypoxic/ischemic conditions by scavenging reactive oxygen species or by signal transduction, the mechanisms associated with this function have not been fully elucidated. Recent studies comparing Cygbs among several species suggest that mammalian Cygbs show a distinctly longer C-terminal domain potentially involved in unique physiological functions. In this study, we prepared human Cygb mutants (ΔC, ΔN, and ΔNC) with either one or both terminal domains truncated and investigated the enzymatic functions and structural features by spectroscopic methods. Evaluation of the superoxide-scavenging activity between Cygb variants showed that the ΔC and ΔNC mutants exhibited slightly higher activity involving superoxide scavenging as compared with wild-type Cygb. Subsequent experiments involving ligand titration, flash photolysis, and resonance Raman spectroscopic studies suggested that the truncation of the C- and N-terminal domains resulted in less effective to dissociation constants and binding rates for carbon monoxide, respectively. Furthermore, structural stability was assessed by guanidine hydrochloride and revealed that the C-terminal domain might play a vital role in improving structure, whereas the N-terminal domain did not exert a similar effect. These findings indicated that long terminal domains could be important not only in regulating enzymatic activity but also for structural stability, and that the domains might be relevant to other hypothesized physiological functions for Cygb. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Dimeric structure of the N-terminal domain of PriB protein from Thermoanaerobacter tengcongensis solved ab initio

    Energy Technology Data Exchange (ETDEWEB)

    Liebschner, Dorothee [National Cancer Institute, Argonne National Laboratory, Argonne, IL 60439 (United States); Brzezinski, Krzysztof [National Cancer Institute, Argonne National Laboratory, Argonne, IL 60439 (United States); University of Bialystok, 15-399 Bialystok (Poland); Dauter, Miroslawa [Argonne National Laboratory, Argonne, IL 60439 (United States); Dauter, Zbigniew, E-mail: dauter@anl.gov [National Cancer Institute, Argonne National Laboratory, Argonne, IL 60439 (United States); Nowak, Marta; Kur, Józef; Olszewski, Marcin, E-mail: dauter@anl.gov [Gdansk University of Technology, 80-952 Gdansk (Poland); National Cancer Institute, Argonne National Laboratory, Argonne, IL 60439 (United States)

    2012-12-01

    The N-terminal domain of the PriB protein from the thermophilic bacterium T. tengcongensis (TtePriB) was expressed and its crystal structure has been solved at the atomic resolution of 1.09 Å by direct methods. PriB is one of the components of the bacterial primosome, which catalyzes the reactivation of stalled replication forks at sites of DNA damage. The N-terminal domain of the PriB protein from the thermophilic bacterium Thermoanaerobacter tengcongensis (TtePriB) was expressed and its crystal structure was solved at the atomic resolution of 1.09 Å by direct methods. The protein chain, which encompasses the first 104 residues of the full 220-residue protein, adopts the characteristic oligonucleotide/oligosaccharide-binding (OB) structure consisting of a five-stranded β-barrel filled with hydrophobic residues and equipped with four loops extending from the barrel. In the crystal two protomers dimerize, forming a six-stranded antiparallel β-sheet. The structure of the N-terminal OB domain of T. tengcongensis shows significant differences compared with mesophile PriBs. While in all other known structures of PriB a dimer is formed by two identical OB domains in separate chains, TtePriB contains two consecutive OB domains in one chain. However, sequence comparison of both the N-terminal and the C-terminal domains of TtePriB suggests that they have analogous structures and that the natural protein possesses a structure similar to a dimer of two N-terminal domains.

  9. Crystallization of Galectin-8 Linker Reveals Intricate Relationship between the N-terminal Tail and the Linker

    Directory of Open Access Journals (Sweden)

    Yunlong Si

    2016-12-01

    Full Text Available Galectin-8 (Gal-8 plays a significant role in normal immunological function as well as in cancer. This lectin contains two carbohydrate recognition domains (CRD connected by a peptide linker. The N-terminal CRD determines ligand binding specificity, whereas the linker has been proposed to regulate overall Gal-8 function, including multimerization and biological activity. Here, we crystallized the Gal-8 N-terminal CRD with the peptide linker using a crystallization condition that contains Ni2+. The Ni2+ ion was found to be complexed between two CRDs via crystal packing contacts. The coordination between Ni2+ and Asp25 plays an indirect role in determining the structure of β-strand F0 and in influencing the linker conformation which could not be defined due to its dynamic nature. The linker was also shortened in situ and crystallized under a different condition, leading to a higher resolution structure refined to 1.08 Å. This crystal structure allowed definition of a short portion of the linker interacting with the Gal-8 N-terminal tail via ionic interactions and hydrogen bonds. Observation of two Gal-8 N-terminal CRD structures implies that the N-terminal tail and the linker may influence each other’s conformation. In addition, under specific crystallization conditions, glycerol could replace lactose and was observed at the carbohydrate binding site. However, glycerol did not show inhibition activity in hemagglutination assay.

  10. Recomendación para la Atención Ético-Médica del Paciente Terminal

    Directory of Open Access Journals (Sweden)

    Fernando Sánchez Torres

    2002-08-01

    Full Text Available

    (Aprobada en Sesión del 18 de abril de 2002

    Pautas para el Manejo Ético-Médico del Paciente en Estado Terminal.

    En la actualidad, los avances tecnológicos en el campo de las Ciencias Médicas han hecho posible prolongar la vida de pacientes que en otras circunstancias estarían condenados a fallecer a corto plazo como consecuencia de una enfermedad o de una agresión traumática. La existencia de las llamadas Unidades de Cuidados Intensivos (UCI ha sido un factor preponderante para ello. Se trata de espacios asistenciales destinados a manejar “agresivamente” los estados considerados como “críticos“, utilizando aparatos y procedimientos de avanzada, a unos costos económicos altos, con frecuencia superiores a las posibilidades pecuniarias de muchos de los pacientes.

    Frente al valor de la vida -de la vida útil y de calidad, por supuesto-, cualquier gasto que signifique su conservación se convierte en una buena inversión. Tal principio justifica la existencia de las UCI.

    Sin embargo, no es raro que en las UCI sean aceptados y manejados por tiempo largo pacientes cuya recuperación no es posible, pese a la variada y sofisticada tecnología con que se cuenta. Se trata de individuos catalogados como “en estado terminal“, para significar con ello que su enfermedad es ineluctablemente mortal, vale decir, que la Medicina ya ha sido derrotada.

    Teniendo en cuenta lo anterior, el manejo agresivo y costoso de dichos enfermos es a todas luces injustificado, lo cual configura la llamada “distanasia” o “encarnizamiento terapéutico”, criticable desde el punto de vista científico y, con más razón, desde el punto de vista ético.

    Por no ser subsidiario de los beneficios de la medicina agresiva o intensiva, el enfermo en estado terminal se constituye en un paciente muy especial.

    Por una parte, habiendo sido desahuciado médicamente, algunos consideran que las

  11. Investigation of nitrogen atom production in Ar/N2 and He/N2 surface wave plasmas

    International Nuclear Information System (INIS)

    Tabbal, M.; Kazopoulo, M.; Christidis, T.; Isber, S.

    2000-01-01

    Full text: There is presently great interest in nitrogen plasmas for surface coating processes. Such as the deposition of nitride thin films and surface treatment of materials. Indeed, nitrogen plasmas have been used to nitride the surface of ferrous and non-ferrous materials in order to improve their surface properties such as resistance to corrosion and hardness. Moreover, the design and development of nitrogen atom sources could be essential for the synthesis of gallium nitride (GaN), a wide band-gap semiconductor whose properties have revolutionized the microelectronics and optoelectronics industries. Correlations have been established between the density of active species in the process, namely atomic nitrogen (N) produced by the discharge and GaN film properties. Thus, it is of fundamental importance to investigate the N-atom production mechanisms in such discharges. N-atom production has been studied in pure N 2 surface-wave plasmas (SWP), as a function of operating parameters, namely gas pressure and electrical power. These studies indicate that the increase in the gas temperature (T g ) limits the N-atom production. One possible way of enhancing the N 2 dissociation rate ([N]/[N 2 ]) in the plasma could be the use of gas mixtures such as Ar/N 2 or He/N 2 . the aim of this paper is to characterize an Ar/N 2 and He/N 2 surface-wave discharge (SWD) by optical emission spectroscopy (OES), in order to determine the optimal plasma conditions in terms of [N]/[N 2 ]. The plasma is generated by a radio frequency (40.68 MHz) wave launcher. The effect of mixing N 2 with Ar and He on the production of N-atoms in the plasma was investigated at varying experimental conditions, such as operating pressure (4.5 and 7.5 Torr), electrical power (40 to 120 W), at a total gas flow of 250 sccm. It was found that [N]/[N 2 ] increases with the partial pressure of Ar in the mixture by a factor of about 8 at 120W. Such an enhancement is reduced at lower incident powers. On the

  12. Copper(II) Binding Sites in N-Terminally Acetylated α-Synuclein: A Theoretical Rationalization.

    Science.gov (United States)

    Ramis, Rafael; Ortega-Castro, Joaquín; Vilanova, Bartolomé; Adrover, Miquel; Frau, Juan

    2017-08-03

    The interactions between N-terminally acetylated α-synuclein and Cu(II) at several binding sites have been studied with DFT calculations, specifically with the M06 hybrid functional and the ωB97X-D DFT-D functional. In previous experimental studies, Cu(II) was shown to bind several α-synuclein residues, including Met1-Asp2 and His50, forming square planar coordination complexes. Also, it was determined that a low-affinity binding site exists in the C-terminal domain, centered on Asp121. However, in the N-terminally acetylated protein, present in vivo, the Met1 site is blocked. In this work, we simplify the representation of the protein by modeling each experimentally found binding site as a complex between an N-terminally acetylated α-synuclein dipeptide (or several independent residues) and a Cu(II) cation, and compare the results with a number of additional, structurally analogous sites not experimentally found. This way of representing the binding sites, although extremely simple, allows us to reproduce experimental results and to provide a theoretical rationale to explain the preference of Cu(II) for certain sites, as well as explicit geometrical structures for the complexes formed. These results are important to understand the interactions between α-synuclein and Cu(II), one of the factors inducing structural changes in the protein and leading to aggregated forms of it which may play a role in neurodegeneration.

  13. La eficiencia terminal en la Educación Superior

    Directory of Open Access Journals (Sweden)

    Dr. C. Victor Millo Carmenate

    2016-04-01

    Full Text Available Se procesan los resultados de promoción de los estudian­tes de la carrera de Ingeniería Mecánica disponibles en la Secretaría General de la Facultad de Ingeniería de la Universidad de Cienfuegos entre los años 2008 al 2015 y se encuestan 35 de los 75 que abandonaron sus estudios de­finitivamente en este mismo período, con el objetivo de co­nocer desde la perspectivas de los estudiantes causas del comportamiento de varios indicadores de eficiencia e iden­tificar los factores que afectan la eficiencia terminal, para lo cual se hizo uso de métodos estadísticos y cualitativos de análisis. Se realiza una propuesta de acciones a considerar para la mejora de los indicadores de eficiencia terminal.

  14. Functional interaction between the N- and C-terminal domains of murine leukemia virus surface envelope protein

    International Nuclear Information System (INIS)

    Lu, C.-W.; Roth, Monica J.

    2003-01-01

    A series of murine leukemia viruses (MuLVs) with chimeric envelope proteins (Env) was generated to map functional interactions between the N- and the C-terminal domains of surface proteins (SU). All these chimeras have the 4070A amphotropic receptor-binding region flanked by various lengths of Moloney ecotropic N- and C-terminal Env. A charged residue, E49 (E16 on the mature protein), was identified at the N-terminals of Moloney MuLV SU that is important for the interaction with the C-terminal domain of the SU. The region that interacts with E49 was localized between junction 4 (R265 of M-MuLV Env) and junction 6 (L374 of M-MuLV Env) of SU. Sequencing the viable chimeric Env virus populations identified residues within the SU protein that improved the replication kinetics of the input chimeric Env viruses. Mutations in the C-domain of SU (G387E/R, L435I, L442P) were found to improve chimera IV4, which displayed a delayed onset of replication. The replication of AE6, containing a chimeric junction in the SU C-terminus, was improved by mutations in the N-domain (N40H, E80K), the proline-rich region (Q252R), or the transmembrane protein (L538N). Altogether, these observations provide insights into the structural elements required for Env function

  15. Proteinuria and its relation to diverse biomarkers and body mass index in chronic hemodialysis

    Directory of Open Access Journals (Sweden)

    Trimarchi H

    2013-06-01

    Full Text Available Hernán Trimarchi,1 Alexis Muryan,2 María-Soledad Raña,1 Pedro Paggi,2 Fernando Lombi,1 Mariano Forrester,1 Vanesa Pomeranz,1 Alejandra Karl,1 Mirta Alonso,2 Pablo Young,3 Mariana Dicugno2 1Department of Nephrology, 2Department of Biochemistry, 3Department of Internal Medicine Services, Hospital Británico de Buenos Aires, Buenos Aires, Argentina Background: Certain adipokines exert direct effects on proteinuria, a cardiovascular risk factor ignored in hemodialysis. We measured different adipokines according to body mass index (BMI in relation to proteinuria. Methods: Patients numbered 57: group A (GA, BMI 30, n = 20. There were no statistical differences in age, sex, time on dialysis, cause of renal failure, diabetes, hypertension, C-reactive protein, or nutritional status. Measures were taken of 24-hour diuresis and proteinuria, ultrafiltration, albumin, pro-brain natriuretic peptide (Pro-BNP, insulin, adiponectin, leptin, and ghrelin. Results: Proteinuria was significantly higher in GC versus (vs GA (1.5 g/day, range 0.30–14 vs 0.72 g/day, range 0.1–2.7; P 0.05. In GA, elevated levels of Pro-BNP, adiponectin, and ghrelin were associated with lower degrees of proteinuria. Significant correlations were found between adiponectin and leptin (ρ = -0.54, P = 0.03, and adiponectin and Pro-BNP (ρ= 0.59, P = 0.02. Though not significant, there were more diabetics in GC (GA four, GB three, GC ten. As BMI increased in GB and GC, Pro-BNP, adiponectin, and ghrelin levels decreased significantly, while proteinuria, insulin, and homeostasis model assessment of insulin resistance increased. Leptin levels were significantly elevated in GC vs GA and GB. In GC, ghrelin correlated significantly with Pro-BNP (ρ= 0.51, P = 0.03, while leptin correlation with Pro-BNP was inverse and significant in GA (ρ = -0.74, P > 0.001 and inverse and nonsignificant in GB and GC. Conclusion: In patients with BMI < 25, higher adiponectin, ghrelin, and Pro-BNP levels

  16. Evolutionary analysis of a novel zinc ribbon in the N-terminal region of threonine synthase.

    Science.gov (United States)

    Kaur, Gurmeet; Subramanian, Srikrishna

    2017-10-18

    Threonine synthase (TS) catalyzes the terminal reaction in the biosynthetic pathway of threonine and requires pyridoxal phosphate as a cofactor. TSs share a common catalytic domain with other fold type II PALP dependent enzymes. TSs are broadly grouped into two classes based on their sequence, quaternary structure, and enzyme regulation. We report the presence of a novel zinc ribbon domain in the N-terminal region preceding the catalytic core in TS. The zinc ribbon domain is present in TSs belonging to both classes. Our sequence analysis reveals that archaeal TSs possess all zinc chelating residues to bind a metal ion that are lacking in the structurally characterized homologs. Phylogenetic analysis suggests that TSs with an N-terminal zinc ribbon likely represents the ancestral state of the enzyme while TSs without a zinc ribbon must have diverged later in specific lineages. The zinc ribbon and its N- and C-terminal extensions are important for enzyme stability, activity and regulation. It is likely that the zinc ribbon domain is involved in higher order oligomerization or mediating interactions with other biomolecules leading to formation of larger metabolic complexes.

  17. Can Brain Natriuretic Peptides and Osteoprotegerin Serve As Biochemical Markers for the Detection of Aortic Pathology in Children and Adolescents with Turner Syndrome?

    Directory of Open Access Journals (Sweden)

    Meenal Mavinkurve

    2017-07-01

    Full Text Available Turner syndrome (TS is a chromosomal disorder that affects 1:2,000 females. It results from either the complete or partial loss of the X chromosome as well as other aberrations. Clinical features of TS include short stature, delayed puberty, and congenital cardiac malformations. TS children also have an increased prevalence of cardiometabolic risk factors, which predisposes them to complications like coronary artery disease, cerebrovascular-related deaths, and aortic dissection. Early cardiac imaging, such as echocardiography and cardiac magnetic resonance imaging, are recommended to detect underlying aortic pathology. However, these modalities are limited by cost, accessibility, and are operator dependent. In view of these shortcomings, alternative methods, like vascular biomarkers, are currently being explored. There are only a few studies that have examined the relationship between B-type natriuretic peptide (BNP, N-terminal pro BNP (NT pro-BNP, and osteoprotegerin (OPG and aortic disease in TS, and thus the data are only in proof-of-concept stages. Further meticulous longitudinal studies are required before BNP, NT pro-BNP, and OPG are used as vascular biomarkers for the detection of aortic disease in childhood and adolescent TS.

  18. Impact of Plasma Electron Flux on Plasma Damage-Free Sputtering of Ultrathin Tin-Doped Indium Oxide Contact Layer on p-GaN for InGaN/GaN Light-Emitting Diodes.

    Science.gov (United States)

    Son, Kwang Jeong; Kim, Tae Kyoung; Cha, Yu-Jung; Oh, Seung Kyu; You, Shin-Jae; Ryou, Jae-Hyun; Kwak, Joon Seop

    2018-02-01

    The origin of plasma-induced damage on a p -type wide-bandgap layer during the sputtering of tin-doped indium oxide (ITO) contact layers by using radiofrequency-superimposed direct current (DC) sputtering and its effects on the forward voltage and light output power (LOP) of light-emitting diodes (LEDs) with sputtered ITO transparent conductive electrodes (TCE) is systematically studied. Changing the DC power voltage from negative to positive bias reduces the forward voltages and enhances the LOP of the LEDs. The positive DC power drastically decreases the electron flux in the plasma obtained by plasma diagnostics using a cutoff probe and a Langmuir probe, suggesting that the repulsion of plasma electrons from the p -GaN surface can reduce plasma-induced damage to the p -GaN. Furthermore, electron-beam irradiation on p -GaN prior to ITO deposition significantly increases the forward voltages, showing that the plasma electrons play an important role in plasma-induced damage to the p -GaN. The plasma electrons can increase the effective barrier height at the ITO/deep-level defect (DLD) band of p -GaN by compensating DLDs, resulting in the deterioration of the forward voltage and LOP. Finally, the plasma damage-free sputtered-ITO TCE enhances the LOP of the LEDs by 20% with a low forward voltage of 2.9 V at 20 mA compared to LEDs with conventional e-beam-evaporated ITO TCE.

  19. Photoaffinity labeling of opiate (enkephalin) receptor of rat brain plasma membranes with 125I(D-Ala2, p-N3-Phe4-Met5)-enkephalin

    International Nuclear Information System (INIS)

    Yeung, C.W.T.

    1986-01-01

    A photoreactive (D-Ala 2 , p-N 3 -Phe 4 -Met 5 )enkephalin derivative was prepared, iodinated with carrier free 125 I and then purified by high performance liquid chromatography. The purified radioactive photoprobe was monoiodinated at the amino terminal tyrosine residue. This radioactive photoprobe was used to photoaffinity label plasma membranes prepared from rat brain, spinal cord and cerebellum. The photolabeled plasma membranes were analyzed by sodium dodecyl sulfate gel electrophoresis. A 46,000-daltons band was specifically photolabeled in the plasma membranes of brain and spinal cord but not in the plasma membranes from cerebellum. The photolabeling of this band was inhibited by peptides related to enkephalin by not but substance P or gastrin tetrapeptide. These data demonstrate that the labeled 46,000-daltons band is a protein of the opiate (enkephalin)receptor

  20. A non-catalytic N-terminal domain negatively influences the nucleotide exchange activity of translation elongation factor 1Bα.

    Science.gov (United States)

    Trosiuk, Tetiana V; Shalak, Vyacheslav F; Szczepanowski, Roman H; Negrutskii, Boris S; El'skaya, Anna V

    2016-02-01

    Eukaryotic translation elongation factor 1Bα (eEF1Bα) is a functional homolog of the bacterial factor EF-Ts, and is a component of the macromolecular eEF1B complex. eEF1Bα functions as a catalyst of guanine nucleotide exchange on translation elongation factor 1A (eEF1A). The C-terminal domain of eEF1Bα is necessary and sufficient for its catalytic activity, whereas the N-terminal domain interacts with eukaryotic translation elongation factor 1Bγ (eEF1Bγ) to form a tight complex. However, eEF1Bγ has been shown to enhance the catalytic activity of eEF1Bα attributed to the C-terminal domain of eEF1Bα. This suggests that the N-terminal domain of eEF1Bα may in some way influence the guanine nucleotide exchange process. We have shown that full-length recombinant eEF1Bα and its truncated forms are non-globular proteins with elongated shapes. Truncation of the N-terminal domain of eEF1Bα, which is dispensable for catalytic activity, resulted in acceleration of the rate of guanine nucleotide exchange on eEF1A compared to full-length eEF1Bα. A similar effect on the catalytic activity of eEF1Bα was observed after its interaction with eEF1Bγ. We suggest that the non-catalytic N-terminal domain of eEF1Bα may interfere with eEF1A binding to the C-terminal catalytic domain, resulting in a decrease in the overall rate of the guanine nucleotide exchange reaction. Formation of a tight complex between the eEF1Bγ and eEF1Bα N-terminal domains abolishes this inhibitory effect. © 2015 FEBS.

  1. Analysis of reverse gate leakage mechanism of AlGaN/GaN HEMTs with N2 plasma surface treatment

    Science.gov (United States)

    Liu, Hui; Zhang, Zongjing; Luo, Weijun

    2018-06-01

    The mechanism of reverse gate leakage current of AlGaN/GaN HEMTs with two different surface treatment methods are studied by using C-V, temperature dependent I-V and theoretical analysis. At the lower reverse bias region (VR >- 3.5 V), the dominant leakage current mechanism of the device with N2 plasma surface treatment is the Poole-Frenkel emission current (PF), and Trap-Assisted Tunneling current (TAT) is the principal leakage current of the device which treated by HCl:H2O solution. At the higher reverse bias region (VR current of the device with N2 plasma surface treatment is one order of magnitude smaller than the device which treated by HCl:H2O solution. This is due to the recovery of Ga-N bond in N2 plasma surface treatment together with the reduction of the shallow traps in post-gate annealing (PGA) process. The measured results agree well with the theoretical calculations and demonstrate N2 plasma surface treatment can reduce the reverse leakage current of the AlGaN/GaN HEMTs.

  2. Ribonucleocapsid Formation of SARS-COV Through Molecular Action of the N-Terminal Domain of N Protein

    Energy Technology Data Exchange (ETDEWEB)

    Saikatendu, K.S.; Joseph, J.S.; Subramanian, V.; Neuman, B.W.; Buchmeier, M.J.; Stevens, R.C.; Kuhn, P.; /Scripps Res. Inst.

    2007-07-12

    Conserved amongst all coronaviruses are four structural proteins, the matrix (M), small envelope (E) and spike (S) that are embedded in the viral membrane and the nucleocapsid phosphoprotein (N), which exists in a ribonucleoprotein complex in their lumen. The N terminal domain of coronaviral N proteins (N-NTD) provides a scaffold for RNA binding while the C-terminal domain (N-CTD) mainly acts as oligomerization modules during assembly. The C-terminus of N protein anchors it to the viral membrane by associating with M protein. We characterized the structures of N-NTD from severe acute respiratory syndrome coronavirus (SARS-CoV) in two crystal forms, at 1.17A (monoclinic) and 1.85 A (cubic) respectively, solved by molecular replacement using the homologous avian infectious bronchitis virus (IBV) structure. Flexible loops in the solution structure of SARS-CoV N-NTD are now shown to be well ordered around the beta-sheet core. The functionally important positively charged beta-hairpin protrudes out of the core and is oriented similar to that in the IBV N-NTD and is involved in crystal packing in the monoclinic form. In the cubic form, the monomers form trimeric units that stack in a helical array. Comparison of crystal packing of SARS-CoV and IBV N-NTDs suggest a common mode of RNA recognition, but probably associate differently in vivo during the formation of the ribonucleoprotein complex. Electrostatic potential distribution on the surface of homology models of related coronaviral N-NTDs hints that they employ different modes of both RNA recognition as well as oligomeric assembly, perhaps explaining why their nucleocapsids have different morphologies.

  3. Protection against β-amyloid neurotoxicity by a non-toxic endogenous N-terminal β-amyloid fragment and its active hexapeptide core sequence.

    Science.gov (United States)

    Forest, Kelly H; Alfulaij, Naghum; Arora, Komal; Taketa, Ruth; Sherrin, Tessi; Todorovic, Cedomir; Lawrence, James L M; Yoshikawa, Gene T; Ng, Ho-Leung; Hruby, Victor J; Nichols, Robert A

    2018-01-01

    High levels (μM) of beta amyloid (Aβ) oligomers are known to trigger neurotoxic effects, leading to synaptic impairment, behavioral deficits, and apoptotic cell death. The hydrophobic C-terminal domain of Aβ, together with sequences critical for oligomer formation, is essential for this neurotoxicity. However, Aβ at low levels (pM-nM) has been shown to function as a positive neuromodulator and this activity resides in the hydrophilic N-terminal domain of Aβ. An N-terminal Aβ fragment (1-15/16), found in cerebrospinal fluid, was also shown to be a highly active neuromodulator and to reverse Aβ-induced impairments of long-term potentiation. Here, we show the impact of this N-terminal Aβ fragment and a shorter hexapeptide core sequence in the Aβ fragment (Aβcore: 10-15) to protect or reverse Aβ-induced neuronal toxicity, fear memory deficits and apoptotic death. The neuroprotective effects of the N-terminal Aβ fragment and Aβcore on Aβ-induced changes in mitochondrial function, oxidative stress, and apoptotic neuronal death were demonstrated via mitochondrial membrane potential, live reactive oxygen species, DNA fragmentation and cell survival assays using a model neuroblastoma cell line (differentiated NG108-15) and mouse hippocampal neuron cultures. The protective action of the N-terminal Aβ fragment and Aβcore against spatial memory processing deficits in amyloid precursor protein/PSEN1 (5XFAD) mice was demonstrated in contextual fear conditioning. Stabilized derivatives of the N-terminal Aβcore were also shown to be fully protective against Aβ-triggered oxidative stress. Together, these findings indicate an endogenous neuroprotective role for the N-terminal Aβ fragment, while active stabilized N-terminal Aβcore derivatives offer the potential for therapeutic application. © 2017 International Society for Neurochemistry.

  4. Gestión centralizada de la iluminación en Terminal 1 del aeropuerto Barcelona-El Prat

    OpenAIRE

    Borraz Rocafull, Óscar

    2017-01-01

    Este trabajo consiste en el estudio de una gestión centralizada de iluminación en la Terminal T1 del Aeropuerto de Barcelona-El Prat. Se dan a conocer los sistemas y subsistemas del control de iluminación, con base KNX-EIB (sistema estándar de interconexión de dispositivos) y su central de gestión. También se explican los fallos encontrados al finalizar la obra de construcción de la T1 (terminada en 2009) o los sucedidos durante su operatividad. Así como mejoras para su func...

  5. N-terminally truncated forms of human cathepsin F accumulate in aggresome-like inclusions.

    Science.gov (United States)

    Jerič, Barbara; Dolenc, Iztok; Mihelič, Marko; Klarić, Martina; Zavašnik-Bergant, Tina; Gunčar, Gregor; Turk, Boris; Turk, Vito; Stoka, Veronika

    2013-10-01

    The contribution of individual cysteine cathepsins as positive mediators of programmed cell death is dependent on several factors, such as the type of stimuli, intensity and duration of the stimulus, and cell type involved. Of the eleven human cysteine cathepsins, cathepsin F is the only cathepsin that exhibits an extended N-terminal proregion, which contains a cystatin-like domain. We predicted that the wild-type human cathepsin F contains three natively disordered regions within the enzyme's propeptide and various amino acid stretches with high fibrillation propensity. Wild-type human cathepsin F and its N-terminally truncated forms, Ala(20)-Asp(484) (Δ(19)CatF), Pro(126)-Asp(484) (Δ(125)CatF), and Met(147)-Asp(484) (Δ(146)CatF) were cloned into the pcDNA3 vector and overexpressed in HEK 293T cells. Wild-type human cathepsin F displayed a clear vesicular labeling and colocalized with the LAMP2 protein, a lysosomal marker. However, all three N-terminally truncated forms of human cathepsin F were recovered as insoluble proteins, suggesting that the deletion of at least the signal peptides (Δ(19)CatF), results in protein aggregation. Noteworthy, they concentrated large perinuclear-juxtanuclear aggregates that accumulated within aggresome-like inclusions. These inclusions showed p62-positive immunoreactivity and were colocalized with the autophagy marker LC3B, but not with the LAMP2 protein. In addition, an approximately 2-3 fold increase in DEVDase activity was not sufficient to induce apoptotic cell death. These results suggested the clearance of the N-terminally truncated forms of human cathepsin F via the autophagy pathway, underlying its protective and prosurvival mechanisms. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  6. N-terminal pro-C-type natriuretic peptide in serum associated with bone destruction in patients with multiple myeloma

    DEFF Research Database (Denmark)

    Mylin, Anne K; Goetze, Jens P; Heickendorff, Lene

    2015-01-01

    AIM: To examine whether N-terminal proCNP concentrations in serum is associated with bone destruction in patients with multiple myeloma. MATERIALS & METHODS: N-terminal proCNP and biochemical bone markers were measured in 153 patients. Radiographic bone disease and skeletal-related events were...

  7. Synergy between the N-terminal and C-terminal domains of Mycobacterium tuberculosis HupB is essential for high-affinity binding, DNA supercoiling and inhibition of RecA-promoted strand exchange.

    Science.gov (United States)

    Sharadamma, N; Khan, Krishnendu; Kumar, Sandeep; Patil, K Neelakanteshwar; Hasnain, Seyed E; Muniyappa, K

    2011-09-01

    The occurrence of DNA architectural proteins containing two functional domains derived from two different architectural proteins is an interesting emerging research theme in the field of nucleoid structure and function. Mycobacterium tuberculosis HupB, unlike Escherichia coli HU, is a two-domain protein that, in the N-terminal region, shows broad sequence homology with bacterial HU. The long C-terminal extension, on the other hand, contains seven PAKK/KAAK motifs, which are characteristic of the histone H1/H5 family of proteins. In this article, we describe several aspects of HupB function, in comparison with its truncated derivatives lacking either the C-terminus or N-terminus. We found that HupB binds a variety of DNA repair and replication intermediates with K(d) values in the nanomolar range. By contrast, the N-terminal fragment of M. tuberculosis HupB (HupB(MtbN)) showed diminished DNA-binding activity, with K(d) values in the micromolar range, and the C-terminal domain was completely devoid of DNA-binding activity. Unlike HupB(MtbN) , HupB was able to constrain DNA in negative supercoils and introduce negative superhelical turns into relaxed DNA. Similarly, HupB exerted a robust inhibitory effect on DNA strand exchange promoted by cognate and noncognate RecA proteins, whereas HupB(MtbN), even at a 50-fold molar excess, had no inhibitory effect. Considered together, these results suggest that synergy between the N-terminal and C-terminal domains of HupB is essential for its DNA-binding ability, and to modulate the topological features of DNA, which has implications for processes such as DNA compaction, gene regulation, homologous recombination, and DNA repair. © 2011 The Authors Journal compilation © 2011 FEBS.

  8. High efficiency GaN-based LEDs using plasma selective treatment of p-GaN surface

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young-Bae; Naoi, Yoshiki; Sakai, Shiro [Department of Electrical and Electronic Engineering, University of Tokushima, 2-1 Minami-josanjima, Tokushima 770-8506 (Japan); Takaki, Ryohei; Sato, Hisao [Nitride Semiconductor Co., Ltd., 115-7 Itayajima, Akinokami, Seto-cho, Naruto, Tokushima 771-0360 (Japan)

    2003-11-01

    We have studied a new method of increasing the extraction efficiency of a GaN-based light-emitting diode (LED) using a plasma surface treatment. In this method, prior to the evaporation of a semitransparent p-metal, the surface of a p-GaN located beneath a p-pad is selectively exposed to a nitrogen plasma in a reactive ion etching (RIE) chamber. The electrical characteristics of the plasma treated p-GaN remarkably changes its resistivity into semi-insulator without any parasitic damage. Since the LEDs with a new method have no light absorption in a p-pad region, a higher optical power can be extracted compared to a conventional LEDs without plasma selective treatment on the p-GaN surface. (copyright 2003 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  9. Simulación de la formación de plasma en el mecanizado por electroerosión

    OpenAIRE

    Villagomez Galindo, Miguel; González Rojas, Hernan Alberto

    2017-01-01

    El proceso de mecanizado por electroerosión es una técnica de manufactura no convencional caracterizada por descargas eléctricas controladas que liberan tal cantidad de energía que es capaz de transformar en plasma el dieléctrico circundante al material conductor a mecanizar, con la consecuente sublimación del mismo, lo que provoca la remoción de material. En este trabajo se presenta la simulación de la formación de plasma debido a una sucesión de descargas eléctricas durante el p...

  10. Analysis of performance degradation in an electron heating dominant H-mode plasma after ECRH termination in EAST

    Science.gov (United States)

    Du, Hongfei; Ding, Siye; Chen, Jiale; Wang, Yifeng; Lian, Hui; Xu, Guosheng; Zhai, Xuemei; Liu, Haiqing; Zang, Qing; Lyu, Bo; Duan, Yanmin; Qian, Jinping; Gong, Xianzu

    2018-06-01

    In recent EAST experiments, significant performance degradation accompanied by a decrease of internal inductance is observed in an electron heating dominant H-mode plasma after the electron cyclotron resonance heating termination. The lower hybrid wave (LHW) deposition and effective electron heat diffusivity are calculated to explain this phenomenon. Analysis shows that the changes of LHW heating deposition rather than the increase of transport are responsible for the significant decrease in energy confinement (). The reason why the confinement degradation occurred on a long time scale could be attributed to both good local energy confinement in the core and also the dependence of LHW deposition on the magnetic shear. The electron temperature profile shows weaker stiffness in near axis region where electron heating is dominant, compared to that in large radius region. Unstable electron modes from low to high k in the core plasma have been calculated in the linear GYRO simulations, which qualitatively agree with the experimental observation. This understanding of the plasma performance degradation mechanism will help to find ways of improving the global confinement in the radio-frequency dominant scenario in EAST.

  11. The EspF N-Terminal of Enterohemorrhagic Escherichia coli O157:H7 EDL933w Imparts Stronger Toxicity Effects on HT-29 Cells than the C-Terminal.

    Science.gov (United States)

    Wang, Xiangyu; Du, Yanli; Hua, Ying; Fu, Muqing; Niu, Cong; Zhang, Bao; Zhao, Wei; Zhang, Qiwei; Wan, Chengsong

    2017-01-01

    Enterohemorrhagic Escherichia coli (EHEC) O157:H7 EspF is an important multifunctional protein that destroys the tight junctions of intestinal epithelial cells and promotes host cell apoptosis. However, its molecular mechanism remains elusive. We knocked out the espF sequence (747 bp, Δ espF ), N-terminal sequence (219 bp, Δ espF N ), and C-terminal sequence (528 bp, Δ espF C ) separately using the pKD46-mediated λ Red homologous recombination system. Then, we built the corresponding complementation strains, namely, Δ espF/pespF , Δ espF N /pespF N , and Δ espF C /pespF C by overlap PCR, which were used in infecting HT-29 cells and BALB/C mice. The level of reactive oxygen species, cell apoptosis, mitochondrial trans-membrane potential, inflammatory factors, transepithelial electrical resistance (TER), and animal mortality were evaluated by DCFH-DA, double staining of Annexin V-FITC/PI, JC-1 staining, ELISA kit, and a mouse assay. The wild-type (WT), Δ espF , Δ espF/pespF , Δ espF C , Δ espF C /pespF C , Δ espF N , and Δ espF N /pespF N groups exhibited apoptotic rates of 68.3, 27.9, 64.9, 65.7, 73.4, 41.3, and 35.3% respectively, and mean TNF-α expression levels of 428 pg/mL, 342, 466, 446, 381, 383, and 374 pg/mL, respectively. In addition, the apoptotic rates and TNF-α levels of the WT, Δ espF/pespF , and Δ espF C were significantly higher than that of Δ espF , Δ espF N , Δ espF C /pespF C , and Δ espF N /pespF N group ( p < 0.05). The N-terminal of EspF resulted in an increase in the number of apoptotic cells, TNF-α secretion, ROS generation, mitochondria apoptosis, and pathogenicity in BalB/c mice. In conclusion, the N-terminal domain of the Enterohemorrhagic E. coli O157:H7 EspF more strongly promotes apoptosis and inflammation than the C-terminal domain.

  12. Effect of estimated glomerular filtration rate on plasma concentrations of B-type natriuretic peptides measured with multiple immunoassays in elderly individuals

    DEFF Research Database (Denmark)

    Schou, M.; Alehagen, U.; Goetze, J.P.

    2009-01-01

    linear regression models. RESULTS: In univariate analyses the effect of a 10% decrease in eGFR on proBNP concentrations was a 15% (95% confidence interval 11% to 18%), 9% (5% to 13%) and 21% (14% to 28%) increase. In multivariate models the effect was a 7% (3% to 11%), 4% (2% to 6%) and 13% (4% to 20....... SETTING: 474 elderly outpatients with suspected heart failure (prevalence 13%) from the primary care. MAIN OUTCOME MEASURES: The effects of eGFR on proBNP, measured with three different immunoassays (Roche Diagnostics, Oslo and Copenhagen), and BNP (Shionogi) concentrations were evaluated by multiple...

  13. The distribution of chandelier cell axon terminals that express the GABA plasma membrane transporter GAT-1 in the human neocortex.

    Science.gov (United States)

    Inda, M C; Defelipe, J; Muñoz, A

    2007-09-01

    Chandelier cells represent a unique type of cortical GABAergic interneuron whose axon terminals (Ch-terminals) form synapses exclusively with the axon initial segments of pyramidal cells. In this study, we have used immunocytochemistry for the high-affinity plasma membrane transporter-1 (GAT-1) to analyze the distribution and density of Ch-terminals in various cytoarchitectonic and functional areas of the human neocortex. The lowest density of GAT-1-immuoreactive (-ir) Ch-terminals was detected in the primary and secondary visual (areas 17 and 18) and in the somatosensory areas (areas 3b and 1). In contrast, an intermediate density was observed in the motor area 4 and the associative frontolateral areas 45 and 46, whereas the associative frontolateral areas 9 and 10, frontal orbitary areas 11, 12, 13, 14, and 47, associative temporal areas 20, 21, 22, and 38, and cingulate areas 24 and 32 displayed the highest density of GAT-1-ir Ch-terminals. Despite these differences, the laminar distribution of GAT-1-ir Ch-terminals was similar in most cortical areas. Hence, the highest density of this transporter was observed in layer II, followed by layers III, V, VI, and IV. In most cortical areas, the density of GAT-1-ir Ch-terminals was positively correlated with the neuronal density, although a negative correlation was detected in layer III across all cortical areas. These results indicate that there are substantial differences in the distribution and density of GAT-1-ir Ch-terminals between areas and layers of the human neocortex. These differences might be related to the different functional attributes of the cortical regions examined.

  14. A pulsed plasma jet with the various Ar/N2 mixtures

    Science.gov (United States)

    Barkhordari, A.; Ganjovi, A.; Mirzaei, I.; Falahat, A.; Rostami Ravari, M. N.

    2017-12-01

    In this paper, using the Optical Emission Spectroscopy technique, the physical properties of a fabricated pulsed DBD plasma jet are studied. Ar/N2 gaseous mixture is taken as operational gas, and Ar contribution in Ar/N2 mixture is varied from 75 to 95%. Through the optical emission spectra analysis of the pulsed DBD plasma jet, the rotational, vibrational and excitation temperatures and density of electrons in plasma medium of the pulsed plasma jet are obtained. It is seen that, at the wavelength of 750.38 nm, the radiation intensity from the Ar 4p → 4 s transition increases at the higher Ar contributions in Ar/N2 mixture. It is found that, for 95% of Ar presence in the mixture, the emission intensities from argon and molecular nitrogen are higher, and the emission line intensities will increase nonlinearly. In addition, it is observed that the quenching of Ar* by N2 results in the higher intensities of N2 excited molecules. Moreover, at the higher percentages of Ar in Ar/N2 mixture, while all the plasma temperatures are increased, the plasma electron density is reduced.

  15. Synthesis of phenanthrenes through copper-catalyzed cross-coupling of N-tosylhydrazones with terminal alkynes.

    Science.gov (United States)

    Hossain, Mohammad Lokman; Ye, Fei; Liu, Zhenxing; Xia, Ying; Shi, Yi; Zhou, Lei; Zhang, Yan; Wang, Jianbo

    2014-09-19

    A novel protocol for the synthesis of phenanthrenes through the copper-catalyzed reaction of aromatic tosylhydrazones with terminal alkynes is explored. The reaction proceeds via the formation of an allene intermediate and subsequent six-π-electron cyclization-isomerization, affording phenanthrene derivatives in good yields. The transformation can be performed in two ways: (1) with N-tosylhydrazones derived from [1,1'-biphenyl]-2-carbaldehydes and terminal alkynes as the starting materials and (2) with N-tosylhydrazones derived from aromatic aldehydes and 2-alkynyl biphenyls as the starting materials. This new phenanthrene synthesis uses readily available starting materials and a cheap copper catalyst and has a wide range of functional group compatibility.

  16. Effects of body mass index and age on N-terminal pro brain natriuretic peptide are associated with glomerular filtration rate in chronic heart failure patients

    DEFF Research Database (Denmark)

    Schou, Morten; Gustafsson, Finn; Kistorp, Caroline N

    2007-01-01

    BACKGROUND: Obesity is a state characterized by glomerular hyperfiltration and age-related decreases in glomerular filtration rate (GFR). Body mass index (BMI), age, and GFR are associated with plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) in chronic heart failure...... (CHF) patients. We hypothesized that the effects of BMI and age on plasma concentrations of NT-proBNP are associated with GFR. METHODS: We obtained clinical data and laboratory test results from 345 CHF patients at the baseline visit in our heart failure clinic and examined the hypothesis using...... estimates for BMI (P = 0.3807) and age (P = 0.7238) changed markedly and became insignificant. In another model, after adjustment for GFR estimated by the 4-component Modification of Diet in Renal Disease formula (eGFR(MDRD)), the parameter estimates for age (P = 0.0674) changed markedly and became...

  17. X-ray crystal structure of the N-terminal region of Moloney murine leukemia virus integrase and its implications for viral DNA recognition: N-Terminal Region of M-MuLV Integrase

    Energy Technology Data Exchange (ETDEWEB)

    Guan, Rongjin [Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Northeast Structural Genomics Consortium, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Aiyer, Sriram [Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Cote, Marie L. [Department of Biochemistry, Robert Wood Johnson Medical School, UMDNJ, Piscataway New Jersey 08854; Xiao, Rong [Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Northeast Structural Genomics Consortium, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Jiang, Mei [Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Northeast Structural Genomics Consortium, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Acton, Thomas B. [Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Northeast Structural Genomics Consortium, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Roth, Monica J. [Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Montelione, Gaetano T. [Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Northeast Structural Genomics Consortium, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Department of Biochemistry, Robert Wood Johnson Medical School, UMDNJ, Piscataway New Jersey 08854

    2017-02-03

    The retroviral integrase (IN) carries out the integration of a dsDNA copy of the viral genome into the host DNA, an essential step for viral replication. All IN proteins have three general domains, the N-terminal domain (NTD), the catalytic core domain, and the C-terminal domain. The NTD includes an HHCC zinc finger-like motif, which is conserved in all retroviral IN proteins. Two crystal structures of Moloney murine leukemia virus (M-MuLV) IN N-terminal region (NTR) constructs that both include an N-terminal extension domain (NED, residues 1–44) and an HHCC zinc-finger NTD (residues 45–105), in two crystal forms are reported. The structures of IN NTR constructs encoding residues 1–105 (NTR1–105) and 8–105 (NTR8–105) were determined at 2.7 and 2.15 Å resolution, respectively and belong to different space groups. While both crystal forms have similar protomer structures, NTR1–105 packs as a dimer and NTR8–105 packs as a tetramer in the asymmetric unit. The structure of the NED consists of three anti-parallel β-strands and an α-helix, similar to the NED of prototype foamy virus (PFV) IN. These three β-strands form an extended β-sheet with another β-strand in the HHCC Zn2+ binding domain, which is a unique structural feature for the M-MuLV IN. The HHCC Zn2+ binding domain structure is similar to that in HIV and PFV INs, with variations within the loop regions. Differences between the PFV and MLV IN NEDs localize at regions identified to interact with the PFV LTR and are compared with established biochemical and virological data for M-MuLV. Proteins 2017; 85:647–656.

  18. Neurohormonal activation and exercise tolerance in patients supported with a continuous-flow left ventricular assist device

    DEFF Research Database (Denmark)

    Jung, Mette Holme; Goetze, Jens Peter; Boesgaard, Soeren

    2016-01-01

    BACKGROUND: Neurohormones play a key role in regulating hemodynamics in heart failure (HF) both at rest and during exercise. In contrast, little is known about the importance of neurohormonal regulation for exercise capacity in continuous-flow left ventricular assist device (CF-LVAD) patients....... The aim of this study was to assess the relation between neurohormonal activation patterns in CF-LVAD patients and exercise capacity. METHODS: Plasma concentrations of the C-terminal portion of pro-arginine vasopressin precursor (copeptin), pro-adrenomedullin (proADM), pro-B-type (proBNP) and pro......-atrial (proANP) natriuretic peptides were measured in 25 CF-LVAD patients (HeartMate II) in the morning prior to maximal cardiopulmonary exercise testing determining peak oxygen uptake (peak VO2). Quality of life (QOL) was determined by questionnaires. RESULTS: Peak VO2 was severely reduced averaging 13...

  19. The N-terminal tail of hERG contains an amphipathic α-helix that regulates channel deactivation.

    Directory of Open Access Journals (Sweden)

    Chai Ann Ng

    Full Text Available The cytoplasmic N-terminal domain of the human ether-a-go-go related gene (hERG K+ channel is critical for the slow deactivation kinetics of the channel. However, the mechanism(s by which the N-terminal domain regulates deactivation remains to be determined. Here we show that the solution NMR structure of the N-terminal 135 residues of hERG contains a previously described Per-Arnt-Sim (PAS domain (residues 26-135 as well as an amphipathic α-helix (residues 13-23 and an initial unstructured segment (residues 2-9. Deletion of residues 2-25, only the unstructured segment (residues 2-9 or replacement of the α-helix with a flexible linker all result in enhanced rates of deactivation. Thus, both the initial flexible segment and the α-helix are required but neither is sufficient to confer slow deactivation kinetics. Alanine scanning mutagenesis identified R5 and G6 in the initial flexible segment as critical for slow deactivation. Alanine mutants in the helical region had less dramatic phenotypes. We propose that the PAS domain is bound close to the central core of the channel and that the N-terminal α-helix ensures that the flexible tail is correctly orientated for interaction with the activation gating machinery to stabilize the open state of the channel.

  20. N-terminal truncation enables crystallization of the receptor-binding domain of the FedF bacterial adhesin

    Energy Technology Data Exchange (ETDEWEB)

    De Kerpel, Maia; Van Molle, Inge [Department of Ultrastructure, Vrije Universiteit Brussel (VUB), Flanders Interuniversity Institute for Biotechnology (VIB), Pleinlaan 2, 1050 Brussels (Belgium); Brys, Lea [Department of Cellular and Molecular Immunology, Vrije Universiteit Brussel (VUB), Flanders Interuniversity Institute for Biotechnology (VIB), Pleinlaan 2, 1050 Brussels (Belgium); Wyns, Lode; De Greve, Henri; Bouckaert, Julie, E-mail: bouckaej@vub.ac.be [Department of Ultrastructure, Vrije Universiteit Brussel (VUB), Flanders Interuniversity Institute for Biotechnology (VIB), Pleinlaan 2, 1050 Brussels (Belgium)

    2006-12-01

    The N-terminal receptor-binding domain of the FedF adhesin from enterotoxigenic E. coli has been crystallized. This required the deletion of its first 14 residues, which are also cleaved off naturally. FedF is the two-domain tip adhesin of F18 fimbriae from enterotoxigenic Escherichia coli. Bacterial adherence, mediated by the N-terminal receptor-binding domain of FedF to carbohydrate receptors on intestinal microvilli, causes diarrhoea and oedema disease in newly weaned piglets and induces the secretion of Shiga toxins. A truncate containing only the receptor-binding domain of FedF was found to be further cleaved at its N-terminus. Reconstruction of this N-terminal truncate rendered FedF amenable to crystallization, resulting in crystals with space group P2{sub 1}2{sub 1}2{sub 1} and unit-cell parameters a = 36.20, b = 74.64, c = 99.03 Å that diffracted to beyond 2 Å resolution. The binding specificity of FedF was screened for on a glycan array, exposing 264 glycoconjugates, to identify specific receptors for cocrystallization with FedF.

  1. N-terminal pro-brain natriuretic peptide and associated factors in the general working population: a baseline survey of the Uranosaki cohort study.

    Science.gov (United States)

    Tanaka, Atsushi; Yoshida, Hisako; Kawaguchi, Atsushi; Oyama, Jun-Ichi; Kotooka, Norihiko; Toyoda, Shigeru; Inoue, Teruo; Natsuaki, Masafumi; Node, Koichi

    2017-07-19

    Few data on clinical characteristics associated with N-terminal pro-brain natriuretic peptide (NT-proBNP) or the clinical value of measuring NT-proBNP in the working population are available. The aim of the present study was to investigate the levels of NT-proBNP and their association with clinical variables in the Japanese general working population by using baseline data from the Uranosaki cohort study. In the study, the plasma concentration of NT-proBNP and some biomarkers were measured in addition to the standard health checkups at the workplace. Questionnaires regarding health-related quality of life (HR-QOL) were also completed. A total of 2140 participants were enrolled in the study. Plasma levels of NT-proBNP were positively associated with age, female sex, systolic blood pressure, pulse pressure, prevalent hypertension, smoking habit, high-density lipoprotein cholesterol (HDL-C), and prevalent proteinuria, and negatively associated with body mass index, lipid profiles except HDL-C, uric acid, renal function, and hemoglobin. Both the plasma concentration of high-molecular weight adiponectin and that of high-sensitivity troponin T were positively and independently associated with NT-proBNP. In addition, the HR-QOL score regarding sleep disorder was independently associated with NT-proBNP. Thus, we have obtained evidence that the plasma NT-proBNP is affected by several clinical variables in the general working population.

  2. Fabrication of enhancement-mode AlGaN/GaN high electron mobility transistors using double plasma treatment

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Jong-Won, E-mail: jwlim@etri.re.kr [Photonic/Wireless Convergence Components Dept., IT Materials and Components Lab., Electronics and Telecommunications Research Institute, Daejeon 305-700 (Korea, Republic of); Ahn, Ho-Kyun; Kim, Seong-il; Kang, Dong-Min; Lee, Jong-Min; Min, Byoung-Gue; Lee, Sang-Heung; Yoon, Hyung-Sup; Ju, Chull-Won; Kim, Haecheon; Mun, Jae-Kyoung; Nam, Eun-Soo [Photonic/Wireless Convergence Components Dept., IT Materials and Components Lab., Electronics and Telecommunications Research Institute, Daejeon 305-700 (Korea, Republic of); Park, Hyung-Moo [Photonic/Wireless Convergence Components Dept., IT Materials and Components Lab., Electronics and Telecommunications Research Institute, Daejeon 305-700 (Korea, Republic of); Division of Electronics and Electrical Engineering, Dongguk University, Seoul (Korea, Republic of)

    2013-11-29

    We report the fabrication and DC and microwave characteristics of 0.5 μm AlGaN/GaN high electron mobility transistors using double plasma treatment process. Silicon nitride layers 700 and 150 Å thick were deposited by plasma-enhanced chemical vapor deposition at 260 °C to protect the device and to define the gate footprint. The double plasma process was carried out by two different etching techniques to obtain enhancement-mode AlGaN/GaN high electron mobility transistors with 0.5 μm gate lengths. The enhancement-mode AlGaN/GaN high electron mobility transistor was prepared in parallel to the depletion-mode AlGaN/GaN high electron mobility transistor device on one wafer. Completed double plasma treated 0.5 μm AlGaN/GaN high electron mobility transistor devices fabricated by dry etching exhibited a peak transconductance, gm, of 330 mS/mm, a breakdown voltage of 115 V, a current-gain cutoff frequency (f{sub T}) of 18 GHz, and a maximum oscillation frequency (f{sub max}) of 66 GHz. - Highlights: • The double plasma process was carried out by two different etching techniques. • Double plasma treated device exhibited a transconductance of 330 mS/mm. • Completed 0.5 μm gate device exhibited a current-gain cutoff frequency of 18 GHz. • The off-state breakdown voltage of 115 V for 0.5 μm gate device was obtained. • Continuous-wave output power density of 4.3 W/mm was obtained at 2.4 GHz.

  3. Fabrication of enhancement-mode AlGaN/GaN high electron mobility transistors using double plasma treatment

    International Nuclear Information System (INIS)

    Lim, Jong-Won; Ahn, Ho-Kyun; Kim, Seong-il; Kang, Dong-Min; Lee, Jong-Min; Min, Byoung-Gue; Lee, Sang-Heung; Yoon, Hyung-Sup; Ju, Chull-Won; Kim, Haecheon; Mun, Jae-Kyoung; Nam, Eun-Soo; Park, Hyung-Moo

    2013-01-01

    We report the fabrication and DC and microwave characteristics of 0.5 μm AlGaN/GaN high electron mobility transistors using double plasma treatment process. Silicon nitride layers 700 and 150 Å thick were deposited by plasma-enhanced chemical vapor deposition at 260 °C to protect the device and to define the gate footprint. The double plasma process was carried out by two different etching techniques to obtain enhancement-mode AlGaN/GaN high electron mobility transistors with 0.5 μm gate lengths. The enhancement-mode AlGaN/GaN high electron mobility transistor was prepared in parallel to the depletion-mode AlGaN/GaN high electron mobility transistor device on one wafer. Completed double plasma treated 0.5 μm AlGaN/GaN high electron mobility transistor devices fabricated by dry etching exhibited a peak transconductance, gm, of 330 mS/mm, a breakdown voltage of 115 V, a current-gain cutoff frequency (f T ) of 18 GHz, and a maximum oscillation frequency (f max ) of 66 GHz. - Highlights: • The double plasma process was carried out by two different etching techniques. • Double plasma treated device exhibited a transconductance of 330 mS/mm. • Completed 0.5 μm gate device exhibited a current-gain cutoff frequency of 18 GHz. • The off-state breakdown voltage of 115 V for 0.5 μm gate device was obtained. • Continuous-wave output power density of 4.3 W/mm was obtained at 2.4 GHz

  4. Termination unit

    Energy Technology Data Exchange (ETDEWEB)

    Traeholt, Chresten; Willen, Dag; Roden, Mark; Tolbert, Jerry C.; Lindsay, David; Fisher, Paul W.; Nielsen, Carsten Thidemann

    2016-05-03

    Cable end section comprises end-parts of N electrical phases/neutral, and a thermally-insulation envelope comprising cooling fluid. The end-parts each comprises a conductor and are arranged with phase 1 innermost, N outermost surrounded by the neutral, electrical insulation being between phases and N and neutral. The end-parts comprise contacting surfaces located sequentially along the longitudinal extension of the end-section. A termination unit has an insulating envelope connected to a cryostat, special parts at both ends comprising an adapter piece at the cable interface and a closing end-piece terminating the envelope in the end-section. The special parts houses an inlet and/or outlet for cooling fluid. The space between an inner wall of the envelope and a central opening of the cable is filled with cooling fluid. The special part at the end connecting to the cryostat houses an inlet or outlet, splitting cooling flow into cable annular flow and termination annular flow.

  5. Impact of nitrogen plasma passivation on the Al/n-Ge contact

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Shumei; Mao, Danfeng [Department of Physics, Xiamen University, Xiamen, Fujian 361005 (China); Ruan, Yujiao [Xiamen Institute of Measurement and Testing, Xiamen, Fujian 361004 (China); Xu, Yihong; Huang, Zhiwei; Huang, Wei [Department of Physics, Xiamen University, Xiamen, Fujian 361005 (China); Chen, Songyan, E-mail: sychen@xmu.edu.cn [Department of Physics, Xiamen University, Xiamen, Fujian 361005 (China); Li, Cheng; Wang, Jianyuan [Department of Physics, Xiamen University, Xiamen, Fujian 361005 (China); Tang, Dingliang [College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005 (China)

    2016-09-15

    Highlights: • A thin GeO{sub x}N{sub y} layer was formed by N{sub 2} plasma. • The principal parameters of N{sub 2} plasma treatment and additional post anneal have a great impact on the Al/n-Ge contact. • A model was proposed to explain the variation of Schottky barrier height. • The GeO{sub x}N{sub y} layer was also benefit to achieve a low leakage current density for HfO{sub 2}/Ge MOS capacitors. - Abstract: Severe Fermi level pinning at the interface of metal/n-Ge leads to the formation of a Schottky barrier. Therefore, a high contact resistance is introduced, debasing the performance of Ge devices. In this study, a Ge surface was treated by nitrogen plasma to form an ultra-thin Germanium oxynitride (GeO{sub x}N{sub y}) passivation layer. It was found that the Schottky barrier height (SBH) of metal/n-Ge contact was strongly modulated by the GeO{sub x}N{sub y} interlayer, indicating alleviation of Fermi-level pinning effect. By adjusting the principal parameters of N{sub 2} plasma treatment and additional post anneal, a Quasi-ohmic Al/n-Ge contact was achieved. Furthermore, the introduced GeO{sub x}N{sub y} layer gave extremely lower leakage current density of the gate stack for HfO{sub 2}/Ge devices. These results demonstrate that GeO{sub x}N{sub y} formed by N{sub 2} plasma would be greatly beneficial to the fabrication of the Ge-based devices.

  6. Structure of a tropomyosin N-terminal fragment at 0.98 Å resolution

    International Nuclear Information System (INIS)

    Meshcheryakov, Vladimir A.; Krieger, Inna; Kostyukova, Alla S.; Samatey, Fadel A.

    2011-01-01

    The crystal structure of the N-terminal fragment of the short nonmuscle α-tropomyosin has been determined at a resolution of 0.98 Å. Tropomyosin (TM) is an elongated two-chain protein that binds along actin filaments. Important binding sites are localized in the N-terminus of tropomyosin. The structure of the N-terminus of the long muscle α-TM has been solved by both NMR and X-ray crystallography. Only the NMR structure of the N-terminus of the short nonmuscle α-TM is available. Here, the crystal structure of the N-terminus of the short nonmuscle α-TM (αTm1bZip) at a resolution of 0.98 Å is reported, which was solved from crystals belonging to space group P3 1 with unit-cell parameters a = b = 33.00, c = 52.03 Å, α = β = 90, γ = 120°. The first five N-terminal residues are flexible and residues 6–35 form an α-helical coiled coil. The overall fold and the secondary structure of the crystal structure of αTM1bZip are highly similar to the NMR structure and the atomic coordinates of the corresponding C α atoms between the two structures superimpose with a root-mean-square deviation of 0.60 Å. The crystal structure validates the NMR structure, with the positions of the side chains being determined precisely in our structure

  7. Structure of a tropomyosin N-terminal fragment at 0.98 Å resolution

    Energy Technology Data Exchange (ETDEWEB)

    Meshcheryakov, Vladimir A. [Okinawa Institute of Science and Technology, Okinawa (Japan); Krieger, Inna [Texas A& M University, College Station, Texas (United States); Kostyukova, Alla S. [Robert Wood Johnson Medical School, Piscataway, New Jersey (United States); Samatey, Fadel A., E-mail: f.a.samatey@oist.jp [Okinawa Institute of Science and Technology, Okinawa (Japan)

    2011-09-01

    The crystal structure of the N-terminal fragment of the short nonmuscle α-tropomyosin has been determined at a resolution of 0.98 Å. Tropomyosin (TM) is an elongated two-chain protein that binds along actin filaments. Important binding sites are localized in the N-terminus of tropomyosin. The structure of the N-terminus of the long muscle α-TM has been solved by both NMR and X-ray crystallography. Only the NMR structure of the N-terminus of the short nonmuscle α-TM is available. Here, the crystal structure of the N-terminus of the short nonmuscle α-TM (αTm1bZip) at a resolution of 0.98 Å is reported, which was solved from crystals belonging to space group P3{sub 1} with unit-cell parameters a = b = 33.00, c = 52.03 Å, α = β = 90, γ = 120°. The first five N-terminal residues are flexible and residues 6–35 form an α-helical coiled coil. The overall fold and the secondary structure of the crystal structure of αTM1bZip are highly similar to the NMR structure and the atomic coordinates of the corresponding C{sup α} atoms between the two structures superimpose with a root-mean-square deviation of 0.60 Å. The crystal structure validates the NMR structure, with the positions of the side chains being determined precisely in our structure.

  8. Determination of N-methylsuccinimide and 2-hydroxy-N-methylsuccinimide in human urine and plasma.

    Science.gov (United States)

    Jönsson, B A; Akesson, B

    1997-12-19

    A method for determination of N-methylsuccinimide (MSI) and 2-hydroxy-N-methylsuccinimide (2-HMSI) in human urine and of MSI in human plasma was developed. MSI and 2-HMSI are metabolites of the widely used organic solvent N-methyl-2-pyrrolidone (NMP). MSI and 2-HMSI were purified from urine and plasma by C8 solid-phase extraction and analysed by gas chromatography-mass spectrometry in the negative-ion chemical ionisation mode. The intra-day precisions in urine were 2-6% for MSI (50 and 400 ng/ml) and 3-5% for 2-HMSI (1000 and 8000 ng/ml). For MSI in plasma it was 2% (60 and 1200 ng/ml). The between-day precisions in urine were 3-4% for MSI (100 and 1000 ng/ml) and 2-4% for 2-HMSI (10,000 and 18,000 ng/ml) and 3-4% for MSI in plasma (100 and 900 ng/ml). The recoveries from urine were 109-117% for MSI (50 and 400 ng/ml) and 81-89% for 2-HMSI (1000 and 8000 ng/ml). The recovery of MSI from plasma was 91-101% (50 and 500 ng/ml). The detection limits for MSI were 3 ng/ml in urine and 1 ng/ml in plasma and that of 2-HMSI in urine was 200 ng/ml. The method is applicable for analysis of urine and plasma samples from workers exposed to NMP.

  9. In Situ Fabrication of AlN Coating by Reactive Plasma Spraying of Al/AlN Powder

    Directory of Open Access Journals (Sweden)

    Mohammed Shahien

    2011-10-01

    Full Text Available Reactive plasma spraying is a promising technology for the in situ formation of aluminum nitride (AlN coatings. Recently, it became possible to fabricate cubic-AlN-(c-AlN based coatings through reactive plasma spraying of Al powder in an ambient atmosphere. However, it was difficult to fabricate a coating with high AlN content and suitable thickness due to the coalescence of the Al particles. In this study, the influence of using AlN additive (h-AlN to increase the AlN content of the coating and improve the reaction process was investigated. The simple mixing of Al and AlN powders was not suitable for fabricating AlN coatings through reactive plasma spraying. However, it was possible to prepare a homogenously mixed, agglomerated and dispersed Al/AlN mixture (which enabled in-flight interaction between the powder and the surrounding plasma by wet-mixing in a planetary mill. Increasing the AlN content in the mixture prevented coalescence and increased the nitride content gradually. Using 30 to 40 wt% AlN was sufficient to fabricate a thick (more than 200 µm AlN coating with high hardness (approximately 1000 Hv. The AlN additive prevented the coalescence of Al metal and enhanced post-deposition nitriding through N2 plasma irradiation by allowing the nitriding species in the plasma to impinge on a larger Al surface area. Using AlN as a feedstock additive was found to be a suitable method for fabricating AlN coatings by reactive plasma spraying. Moreover, the fabricated coatings consist of hexagonal (h-AlN, c-AlN (rock-salt and zinc-blend phases and certain oxides: aluminum oxynitride (Al5O6N, cubic sphalerite Al23O27N5 (ALON and Al2O3. The zinc-blend c-AlN and ALON phases were attributed to the transformation of the h-AlN feedstock during the reactive plasma spraying. Thus, the zinc-blend c-AlN

  10. UV laser-induced histone-DNA crosslinking proceeds via the N-terminal tails

    International Nuclear Information System (INIS)

    Stefanovski, V.; Dimitrov, S.; Angelov, D.; Keskinova, E.; Pashev, I.

    1990-01-01

    The covalent crosslinking of histones to DNA by UV laser irradiation is accomplished solely via the N-terminal part of the molecule. Irradiated isolated calfthymus nuclei are treated with clostripain. The crosslinked protein-DNA complexes are isolated and the presence of each core histone analyzed by dot-immunoassay using antibodies, specific to the central globular domain of the respective histone. The reaction is negative for all core histones i.e. the globular domain is absent. It means that this domain has not been crosslinked to DNA and, once cleaved by clostripain, it has been stripped from DNA during the centrigugation in CsCl. This peculiar property of the crosslinked procedure makes it particularly useful in addressing some yet unanswered questions concerning histone-DNA interactions, such as the interaction of the N-terminal tails with linker DNA, the effect of the transient postsynthetic histone acetylation on its interaction with DNA, etc. These questions are now under study. 1 fig., 6 refs

  11. Implementación de los Servicios Terminal Server en un Sistema Corporativo

    OpenAIRE

    PUCHALT RODRÍGUEZ, ANA ELVIRA; GÓMEZ GARCÍA, PABLO JOSÉ

    2014-01-01

    Este proyecto final de carrera presenta el diseño e implementación de los sistemas de acceso a la red y de los servicios de Terminal Server en un sistema corporativo basado en Windows Server 2008 R2. Dado que no hay posibilidad de realizar el proyecto en un sistema corporativo real, se establecerá un sistema corporativo ficticio, donde cada uno de los trabajadores obtendrá acceso a su propia sesión con sus credenciales identificadoras. En esta sesión, se tendrá acceso a determi...

  12. Antimicrobial activity of human prion protein is mediated by its N-terminal region.

    Directory of Open Access Journals (Sweden)

    Mukesh Pasupuleti

    Full Text Available BACKGROUND: Cellular prion-related protein (PrP(c is a cell-surface protein that is ubiquitously expressed in the human body. The multifunctionality of PrP(c, and presence of an exposed cationic and heparin-binding N-terminus, a feature characterizing many antimicrobial peptides, made us hypothesize that PrP(c could exert antimicrobial activity. METHODOLOGY AND PRINCIPAL FINDINGS: Intact recombinant PrP exerted antibacterial and antifungal effects at normal and low pH. Studies employing recombinant PrP and N- and C-terminally truncated variants, as well as overlapping peptide 20mers, demonstrated that the antimicrobial activity is mediated by the unstructured N-terminal part of the protein. Synthetic peptides of the N-terminus of PrP killed the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, and the Gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungus Candida parapsilosis. Fluorescence studies of peptide-treated bacteria, paired with analysis of peptide effects on liposomes, showed that the peptides exerted membrane-breaking effects similar to those seen after treatment with the "classical" human antimicrobial peptide LL-37. In contrast to LL-37, however, no marked helix induction was detected for the PrP-derived peptides in presence of negatively charged (bacteria-mimicking liposomes. PrP furthermore showed an inducible expression during wounding of human skin ex vivo and in vivo, as well as stimulation of keratinocytes with TGF-alpha in vitro. CONCLUSIONS: The demonstration of an antimicrobial activity of PrP, localisation of its activity to the N-terminal and heparin-binding region, combined with results showing an increased expression of PrP during wounding, indicate that PrPs could have a previously undisclosed role in host defense.

  13. Comparative study on nitridation and oxidation plasma interface treatment for AlGaN/GaN MIS-HEMTs with AlN gate dielectric

    Science.gov (United States)

    Zhu, Jie-Jie; Ma, Xiao-Hua; Hou, Bin; Chen, Li-Xiang; Zhu, Qing; Hao, Yue

    2017-02-01

    This paper demonstrated the comparative study on interface engineering of AlN/AlGaN/GaN metal-insulator-semiconductor high-electron-mobility transistors (MIS-HEMTs) by using plasma interface pre-treatment in various ambient gases. The 15 nm AlN gate dielectric grown by plasma-enhanced atomic layer deposition significantly suppressed the gate leakage current by about two orders of magnitude and increased the peak field-effect mobility by more than 50%. NH3/N2 nitridation plasma treatment (NPT) was used to remove the 3 nm poor-quality interfacial oxide layer and N2O/N2 oxidation plasma treatment (OPT) to improve the quality of interfacial layer, both resulting in improved dielectric/barrier interface quality, positive threshold voltage (V th) shift larger than 0.9 V, and negligible dispersion. In comparison, however, NPT led to further decrease in interface charges by 3.38 × 1012 cm-2 and an extra positive V th shift of 1.3 V. Analysis with fat field-effect transistors showed that NPT resulted in better sub-threshold characteristics and transconductance linearity for MIS-HEMTs compared with OPT. The comparative study suggested that direct removing the poor interfacial oxide layer by nitridation plasma was superior to improving the quality of interfacial layer by oxidation plasma for the interface engineering of GaN-based MIS-HEMTs.

  14. El tacto como factor de humanización en la fase terminal Tact as a humanization factor during the terminal phase

    Directory of Open Access Journals (Sweden)

    Tiberio Alvarez Echeverri

    1993-03-01

    Full Text Available

    Se hace una descripción del tacto como el sentido que aparece más precozmente durante la vida embrionaria y de su significado para el desarrollo armónico de la personalidad y como forma de comunicación Interhumana. Se discute cuándo es apropiado el tacto en las relaciones con los demás; se describen sus cualidades y niveles comunicativos. Finalmente, se destaca la importancia del sentido del tacto como una forma muy efectiva de comunicación con el enfermo en fase terminal.

    The sense of touch is the first one to appear during embryonic Life and Its significance for the armonic development of personality and as an effective mean of communication are described, as well as, the appropiateness of touching in the relationship between persons and the quality and communicative levels of tact. Finally, the relevance of tact for communicating with terminal patients is emphasized.

  15. Use of green fluorescent protein fusions to analyse the N- and C-terminal signal peptides of GPI-anchored cell wall proteins in Candida albicans.

    Science.gov (United States)

    Mao, Yuxin; Zhang, Zimei; Wong, Brian

    2003-12-01

    Glycophosphatidylinositol (GPI)-anchored proteins account for 26-35% of the Candida albicans cell wall. To understand the signals that regulate these proteins' cell surface localization, green fluorescent protein (GFP) was fused to the N- and C-termini of the C. albicans cell wall proteins (CWPs) Hwp1p, Als3p and Rbt5p. C. albicans expressing all three fusion proteins were fluorescent at the cell surface. GFP was released from membrane fractions by PI-PLC and from cell walls by beta-glucanase, which implied that GFP was GPI-anchored to the plasma membrane and then covalently attached to cell wall glucans. Twenty and 25 amino acids, respectively, from the N- and C-termini of Hwp1p were sufficient to target GFP to the cell surface. C-terminal substitutions that are permitted by the omega rules (G613D, G613N, G613S, G613A, G615S) did not interfere with GFP localization, whereas some non-permitted substitutions (G613E, G613Q, G613R, G613T and G615Q) caused GFP to accumulate in intracellular ER-like structures and others (G615C, G613N/G615C and G613D/G615C) did not. These results imply that (i) GFP fusions can be used to analyse the N- and C-terminal signal peptides of GPI-anchored CWPs, (ii) the omega amino acid in Hwp1p is G613, and (iii) C can function at the omega+2 position in C. albicans GPI-anchored proteins.

  16. ALFVÉN WAVES IN A PARTIALLY IONIZED TWO-FLUID PLASMA

    International Nuclear Information System (INIS)

    Soler, R.; Ballester, J. L.; Terradas, J.; Carbonell, M.

    2013-01-01

    Alfvén waves are a particular class of magnetohydrodynamic waves relevant in many astrophysical and laboratory plasmas. In partially ionized plasmas the dynamics of Alfvén waves is affected by the interaction between ionized and neutral species. Here we study Alfvén waves in a partially ionized plasma from the theoretical point of view using the two-fluid description. We consider that the plasma is composed of an ion-electron fluid and a neutral fluid, which interact by means of particle collisions. To keep our investigation as general as possible, we take the neutral-ion collision frequency and the ionization degree as free parameters. First, we perform a normal mode analysis. We find the modification due to neutral-ion collisions of the wave frequencies and study the temporal and spatial attenuation of the waves. In addition, we discuss the presence of cutoff values of the wavelength that constrain the existence of oscillatory standing waves in weakly ionized plasmas. Later, we go beyond the normal mode approach and solve the initial-value problem in order to study the time-dependent evolution of the wave perturbations in the two fluids. An application to Alfvén waves in the low solar atmospheric plasma is performed and the implication of partial ionization for the energy flux is discussed.

  17. The unique N-terminal zinc finger of synaptotagmin-like protein 4 reveals FYVE structure.

    Science.gov (United States)

    Miyamoto, Kazuhide; Nakatani, Arisa; Saito, Kazuki

    2017-12-01

    Synaptotagmin-like protein 4 (Slp4), expressed in human platelets, is associated with dense granule release. Slp4 is comprised of the N-terminal zinc finger, Slp homology domain, and C2 domains. We synthesized a compact construct (the Slp4N peptide) corresponding to the Slp4 N-terminal zinc finger. Herein, we have determined the solution structure of the Slp4N peptide by nuclear magnetic resonance (NMR). Furthermore, experimental, chemical modification of Cys residues revealed that the Slp4N peptide binds two zinc atoms to mediate proper folding. NMR data showed that eight Cys residues coordinate zinc atoms in a cross-brace fashion. The Simple Modular Architecture Research Tool database predicted the structure of Slp4N as a RING finger. However, the actual structure of the Slp4N peptide adopts a unique C 4 C 4 -type FYVE fold and is distinct from a RING fold. To create an artificial RING finger (ARF) with specific ubiquitin-conjugating enzyme (E2)-binding capability, cross-brace structures with eight zinc-ligating residues are needed as the scaffold. The cross-brace structure of the Slp4N peptide could be utilized as the scaffold for the design of ARFs. © 2017 The Protein Society.

  18. N-terminal domains of human DNA polymerase lambda promote primer realignment during translesion DNA synthesis

    Science.gov (United States)

    Taggart, David J.; Dayeh, Daniel M.; Fredrickson, Saul W.; Suo, Zucai

    2014-01-01

    The X-family DNA polymerases λ (Polλ) and β (Polβ) possess similar 5′-2-deoxyribose-5-phosphatelyase (dRPase) and polymerase domains. Besides these domains, Polλ also possesses a BRCA1 C-terminal (BRCT) domain and a proline-rich domain at its N terminus. However, it is unclear how these non-enzymatic domains contribute to the unique biological functions of Polλ. Here, we used primer extension assays and a newly developed high-throughput short oligonucleotide sequencing assay (HT-SOSA) to compare the efficiency of lesion bypass and fidelity of human Polβ, Polλ and two N-terminal deletion constructs of Polλ during the bypass of either an abasic site or a 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) lesion. We demonstrate that the BRCT domain of Polλ enhances the efficiency of abasic site bypass by approximately 1.6-fold. In contrast, deletion of the N-terminal domains of Polλ did not affect the efficiency of 8-oxodG bypass relative to nucleotide incorporations opposite undamaged dG. HT-SOSA analysis demonstrated that Polλ and Polβ preferentially generated −1 or −2 frameshift mutations when bypassing an abasic site and the single or double base deletion frequency was highly sequence dependent. Interestingly, the BRCT and proline-rich domains of Polλ cooperatively promoted the generation of −2 frameshift mutations when the abasic site was situated within a sequence context that was susceptible to homology-driven primer realignment. Furthermore, both N-terminal domains of Polλ increased the generation of −1 frameshift mutations during 8-oxodG bypass and influenced the frequency of substitution mutations produced by Polλ opposite the 8-oxodG lesion. Overall, our data support a model wherein the BRCT and proline-rich domains of Polλ act cooperatively to promote primer/template realignment between DNA strands of limited sequence homology. This function of the N-terminal domains may facilitate the role of Polλ as a gap-filling polymerase

  19. Effects of plasma treatment on the Ohmic characteristics of Ti/Al/Ti/Au contacts to n-AlGaN

    International Nuclear Information System (INIS)

    Cao, X. A.; Piao, H.; LeBoeuf, S. F.; Li, J.; Lin, J. Y.; Jiang, H. X.

    2006-01-01

    The effects of surface treatment using Cl 2 /BCl 3 and Ar inductive coupled plasmas on the Ohmic characteristics of Ti/Al/Ti/Au contacts to n-type Al x Ga 1-x N (x=0-0.5) were investigated. Plasma treatment significantly increased the surface conductivity of GaN and Al 0.1 Ga 0.9 N, leading to improved Ohmic behaviors of the contacts. However, it reduced the surface doping level in Al x Ga 1-x N (x≥0.3) and degraded the contact properties. Following a 900-1000 deg. C anneal, the Ti/Al/Ti/Au contacts to Al x Ga 1-x N (x=0-0.3) became truly Ohmic, with specific contact resistances of (3-7)x10 -5 Ω cm 2 , whereas the contact to Al 0.5 Ga 0.5 N remained rectifying even without the plasma treatment. X-ray photoelectron spectroscopy measurements confirmed that the Fermi level moved toward the conduction band in GaN after the plasma treatment, but it was pinned by plasma-induced deep-level states in Al 0.5 Ga 0.5 N. This study emphasizes the need to mitigate plasma damage introduced during the mesa etch step for AlGaN-based deep-UV emitters and detectors

  20. Plasma N-Glycome Signature of Down Syndrome

    NARCIS (Netherlands)

    Borelli, V.; Vanhooren, V.; Lonardi, E.; Reiding, K.R.; Capri, M.; Libert, C.; Garagnani, P.; Salvioli, S.; Franceschi, C.; Wuhrer, M.

    2015-01-01

    In recent years, plasma N-glycans have emerged as biomarkers for health and disease. Here, we studied N-glycomic changes in Down Syndrome (DS). Because of the progeroid phenotype of DS, we focused on the dissection of syndrome- and aging-associated glycomic changes, as well as the interaction

  1. Osteogenic cell differentiation on H-terminated and O-terminated nanocrystalline diamond films

    Directory of Open Access Journals (Sweden)

    Liskova J

    2015-01-01

    Full Text Available Jana Liskova,1 Oleg Babchenko,2 Marian Varga,2 Alexander Kromka,2 Daniel Hadraba,1 Zdenek Svindrych,1 Zuzana Burdikova,1 Lucie Bacakova1 1Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic; 2Institute of Physics, Academy of Sciences of the Czech Republic, Prague, Czech Republic Abstract: Nanocrystalline diamond (NCD films are promising materials for bone implant coatings because of their biocompatibility, chemical resistance, and mechanical hardness. Moreover, NCD wettability can be tailored by grafting specific atoms. The NCD films used in this study were grown on silicon substrates by microwave plasma-enhanced chemical vapor deposition and grafted by hydrogen atoms (H-termination or oxygen atoms (O-termination. Human osteoblast-like Saos-2 cells were used for biological studies on H-terminated and O-terminated NCD films. The adhesion, growth, and subsequent differentiation of the osteoblasts on NCD films were examined, and the extracellular matrix production and composition were quantified. The osteoblasts that had been cultivated on the O-terminated NCD films exhibited a higher growth rate than those grown on the H-terminated NCD films. The mature collagen fibers were detected in Saos-2 cells on both the H-terminated and O-terminated NCD films; however, the quantity of total collagen in the extracellular matrix was higher on the O-terminated NCD films, as were the amounts of calcium deposition and alkaline phosphatase activity. Nevertheless, the expression of genes for osteogenic markers – type I collagen, alkaline phosphatase, and osteocalcin – was either comparable on the H-terminated and O-terminated films or even lower on the O-terminated films. In conclusion, the higher wettability of the O-terminated NCD films is promising for adhesion and growth of osteoblasts. In addition, the O-terminated surface also seems to support the deposition of extracellular matrix proteins and extracellular matrix

  2. Peptides derived from human galectin-3 N-terminal tail interact with its carbohydrate recognition domain in a phosphorylation-dependent manner

    Energy Technology Data Exchange (ETDEWEB)

    Berbís, M. Álvaro [Chemical and Physical Biology Department, Centro de Investigaciones Biológicas, CSIC, 28040 Madrid (Spain); André, Sabine [Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians University, 80539 Munich (Germany); Cañada, F. Javier [Chemical and Physical Biology Department, Centro de Investigaciones Biológicas, CSIC, 28040 Madrid (Spain); Pipkorn, Rüdiger [Central Peptide Synthesis Unit, German Cancer Research Center, 69120 Heidelberg (Germany); Ippel, Hans [Department of Biochemistry, CARIM, University of Maastricht, Maastricht (Netherlands); Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455 (United States); Mayo, Kevin H. [Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455 (United States); Kübler, Dieter [Biomolecular Interactions, German Cancer Research Center, 69120 Heidelberg (Germany); Gabius, Hans-Joachim [Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians University, 80539 Munich (Germany); Jiménez-Barbero, Jesús, E-mail: jjbarbero@cib.csic.es [Chemical and Physical Biology Department, Centro de Investigaciones Biológicas, CSIC, 28040 Madrid (Spain)

    2014-01-03

    Highlights: •Galectin-3 is composed of a carbohydrate recognition domain and an N-terminal tail. •Synthetic peptides derived from the tail are shown to interact with the CRD. •This interaction is modulated by Ser- and Tyr-phosphorylation of the peptides. -- Abstract: Galectin-3 (Gal-3) is a multi-functional effector protein that functions in the cytoplasm and the nucleus, as well as extracellularly following non-classical secretion. Structurally, Gal-3 is unique among galectins with its carbohydrate recognition domain (CRD) attached to a rather long N-terminal tail composed mostly of collagen-like repeats (nine in the human protein) and terminating in a short non-collagenous terminal peptide sequence unique in this lectin family and not yet fully explored. Although several Ser and Tyr sites within the N-terminal tail can be phosphorylated, the physiological significance of this post-translational modification remains unclear. Here, we used a series of synthetic (phospho)peptides derived from the tail to assess phosphorylation-mediated interactions with {sup 15}N-labeled Gal-3 CRD. HSQC-derived chemical shift perturbations revealed selective interactions at the backface of the CRD that were attenuated by phosphorylation of Tyr 107 and Tyr 118, while phosphorylation of Ser 6 and Ser 12 was essential. Controls with sequence scrambling underscored inherent specificity. Our studies shed light on how phosphorylation of the N-terminal tail may impact on Gal-3 function and prompt further studies using phosphorylated full-length protein.

  3. Peptides derived from human galectin-3 N-terminal tail interact with its carbohydrate recognition domain in a phosphorylation-dependent manner

    International Nuclear Information System (INIS)

    Berbís, M. Álvaro; André, Sabine; Cañada, F. Javier; Pipkorn, Rüdiger; Ippel, Hans; Mayo, Kevin H.; Kübler, Dieter; Gabius, Hans-Joachim; Jiménez-Barbero, Jesús

    2014-01-01

    Highlights: •Galectin-3 is composed of a carbohydrate recognition domain and an N-terminal tail. •Synthetic peptides derived from the tail are shown to interact with the CRD. •This interaction is modulated by Ser- and Tyr-phosphorylation of the peptides. -- Abstract: Galectin-3 (Gal-3) is a multi-functional effector protein that functions in the cytoplasm and the nucleus, as well as extracellularly following non-classical secretion. Structurally, Gal-3 is unique among galectins with its carbohydrate recognition domain (CRD) attached to a rather long N-terminal tail composed mostly of collagen-like repeats (nine in the human protein) and terminating in a short non-collagenous terminal peptide sequence unique in this lectin family and not yet fully explored. Although several Ser and Tyr sites within the N-terminal tail can be phosphorylated, the physiological significance of this post-translational modification remains unclear. Here, we used a series of synthetic (phospho)peptides derived from the tail to assess phosphorylation-mediated interactions with 15 N-labeled Gal-3 CRD. HSQC-derived chemical shift perturbations revealed selective interactions at the backface of the CRD that were attenuated by phosphorylation of Tyr 107 and Tyr 118, while phosphorylation of Ser 6 and Ser 12 was essential. Controls with sequence scrambling underscored inherent specificity. Our studies shed light on how phosphorylation of the N-terminal tail may impact on Gal-3 function and prompt further studies using phosphorylated full-length protein

  4. Assessment of a bedside test for N-terminal pro B-type natriuretic peptide (NT-proBNP) to differentiate cardiac from non-cardiac causes of pleural effusion in cats.

    Science.gov (United States)

    Wurtinger, Gabriel; Henrich, Estelle; Hildebrandt, Nicolai; Wiedemann, Nicola; Schneider, Matthias; Hassdenteufel, Esther

    2017-12-20

    Cats with pleural effusion represent common emergencies in small animal practice. The aim of this prospective study was to investigate the diagnostic ability of a point-of-care ELISA (POC-ELISA) for the measurement of N-terminal pro B-type natriuretic peptide (NT-proBNP) to differentiate cardiac from non-cardiac disease in cats with pleural effusion. The sample material for use of this rapid test was either plasma or diluted pleural effusion. Twenty cats with moderate to severe pleural effusion were prospectively recruited. The cats were grouped into two groups, with or without congestive heart failure (CHF; N-CHF), after complete work-up. Blood and effusion were collected in EDTA tubes. Plasma and pleural effusion supernatants were transferred into stabilizer tubes and frozen. POC-ELISA for NT-proBNP was performed with plasma and diluted effusion (1:1). Quantitative NT-proBNP measurement was performed in plasma and diluted and undiluted effusions. Six cats were assigned to the CHF group. Of the 14 cats in the N-CHF group, 6 had concurrent cardiac abnormalities that were not responsible for the effusion. For the detection of CHF, the test displayed respective sensitivities and specificities of 100% and 79% in plasma and 100% and 86% in diluted pleural fluid. Receiver operating characteristic (ROC) analysis for quantitative NT-proBNP measurement of plasma and diluted and undiluted pleural effusions displayed areas under the curve of 0.98, sensitivities of 100% and specificities of 86%. The optimum cut-off was calculated at 399 pmol/l in plasma and 229 pmol/l in the diluted effusion and 467 pmol/l in the undiluted effusion. POC-ELISA for NT-proBNP in both plasma and diluted pleural effusion was suitable to differentiate cardiac from non-cardiac causes of feline pleural effusion. According to our results, use of pleural effusion is feasible, but dilution of the effusion before measurement seems to improve specificity.

  5. N-terminal pro-brain natriuretic peptide and high-sensitivity troponin T exhibit additive prognostic value for the outcome of critically ill patients.

    Science.gov (United States)

    Lenz, Max; Krychtiuk, Konstantin A; Goliasch, Georg; Distelmaier, Klaus; Wojta, Johann; Heinz, Gottfried; Speidl, Walter S

    2018-04-01

    Patients treated at medical intensive care units suffer from various pathologies and often present with elevated troponin T (TnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Both markers may reflect different forms of cardiac involvement in critical illness. Therefore, the aim of our study was to examine the synergistic prognostic potential of NT-proBNP and high-sensitivity TnT (hs)TnT in unselected critically ill patients. We included all consecutive patients admitted to our intensive care unit within one year, excluding those suffering from acute myocardial infarction or undergoing cardiac surgery and measured NT-proBNP and TnT plasma levels on the day of admission and 72 hours thereafter. Of the included 148 patients, 52% were male, mean age was of 64.2 ± 16.8 years and 30-day mortality was 33.2%. Non-survivors showed significantly higher NT-proBNP and TnT plasma levels as compared with survivors ( pvalue. This might be attributed to a difference in underlying pathomechanisms and an assessment of synergistic risk factors.

  6. A Loop Region in the N-Terminal Domain of Ebola Virus VP40 Is Important in Viral Assembly, Budding, and Egress

    Directory of Open Access Journals (Sweden)

    Emmanuel Adu-Gyamfi

    2014-10-01

    Full Text Available Ebola virus (EBOV causes viral hemorrhagic fever in humans and can have clinical fatality rates of ~60%. The EBOV genome consists of negative sense RNA that encodes seven proteins including viral protein 40 (VP40. VP40 is the major Ebola virus matrix protein and regulates assembly and egress of infectious Ebola virus particles. It is well established that VP40 assembles on the inner leaflet of the plasma membrane of human cells to regulate viral budding where VP40 can produce virus like particles (VLPs without other Ebola virus proteins present. The mechanistic details, however, of VP40 lipid-interactions and protein-protein interactions that are important for viral release remain to be elucidated. Here, we mutated a loop region in the N-terminal domain of VP40 (Lys127, Thr129, and Asn130 and find that mutations (K127A, T129A, and N130A in this loop region reduce plasma membrane localization of VP40. Additionally, using total internal reflection fluorescence microscopy and number and brightness analysis we demonstrate these mutations greatly reduce VP40 oligomerization. Lastly, VLP assays demonstrate these mutations significantly reduce VLP release from cells. Taken together, these studies identify an important loop region in VP40 that may be essential to viral egress.

  7. Interaction of the N-terminal segment of pulmonary surfactant protein SP-C with interfacial phospholipid films

    DEFF Research Database (Denmark)

    Plasencia, Inés; Keough, Kevin M W; Perez-Gil, Jesus

    2005-01-01

    Pulmonary surfactant protein SP-C is a 35-residue polypeptide composed of a hydrophobic transmembrane alpha-helix and a polycationic, palmitoylated-cysteine containing N-terminal segment. This segment is likely the only structural motif the protein projects out of the bilayer in which SP-C is ins......Pulmonary surfactant protein SP-C is a 35-residue polypeptide composed of a hydrophobic transmembrane alpha-helix and a polycationic, palmitoylated-cysteine containing N-terminal segment. This segment is likely the only structural motif the protein projects out of the bilayer in which SP...... or anionic phospholipid monolayers. The peptide expands the pi-A compression isotherms of interfacial phospholipid/peptide films, and perturbs the lipid packing of phospholipid films during compression-driven liquid-expanded to liquid-condensed lateral transitions, as observed by epifluorescence microscopy....... These results demonstrate that the sequence of the SP-C N-terminal region has intrinsic ability to interact with, insert into, and perturb the structure of zwitterionic and anionic phospholipid films, even in the absence of the palmitic chains attached to this segment in the native protein. This effect has been...

  8. The role of surface currents in plasma confinement

    International Nuclear Information System (INIS)

    Webster, Anthony J.

    2011-01-01

    During plasma instabilities, ''surface currents'' can flow at the interface between the plasma and the surrounding vacuum, and in most cases, they are a harmless symptom of the instability that is causing them. Large instabilities can lead to ''disruptions,'' an abrupt termination of the plasma with the potential to damage the machine in which it is contained. For disruptions, the correct calculation of surface currents is thought to be essential for modelling disruptions properly. Recently, however, there has been debate and disagreement about the correct way to calculate surface currents. The purpose of this paper is to clarify as simply as possible the role of surface currents for plasma confinement and to show that a commonly used representation for surface currents σ-vector with σ-vector=∇I and n-vector, I a scalar function, and n-vector the unit normal to the plasma surface, is only appropriate for the calculation of surface currents that are in magnetohydrodynamic equilibrium. Fortunately, this is the situation thought to be of most relevance for disruption calculations.

  9. Effects of plasma-induced defects on electrical characteristics of AlGaN/GaN heterostructure before and after low-temperature annealing

    International Nuclear Information System (INIS)

    Takimoto, Takuma; Takeshita, Koji; Nakamura, Seiji; Okumura, Tsugunori

    2014-01-01

    We investigated the electrical characteristics of an AlGaN/GaN heterostructure exposed to Ar plasma. In the near-surface region of the AlGaN/GaN heterostructure, we found that plasma-induced defects reduced the two-dimensional electron gas (2DEG) density and mobility at the AlGaN/GaN interface with increasing exposure time. The decrease in 2DEG density suggests that plasma-induced disordering partly extinguishes the piezo-polarization of the AlGaN layer, that the effective Schottky barrier height is increased by the introduction of negatively changed defects, or that the negatively charged defects induced during plasma exposure deactivate or compensate Si donors. In addition, we investigated the postannealing behavior of plasma-induced defects in the AlGaN/GaN heterostructure as well as in the n-GaN layer under an applied bias voltage. - Highlights: • We have investigated the electrical characteristics of the AlGaN/GaN heterostructure. • Electrons under the AlGaN/GaN interface are decreased by plasma exposure. • Post-annealing treatment with gate bias recovers the degradation caused by defects

  10. Electrically controlled wire-channel GaN/AlGaN transistor for terahertz plasma applications

    Science.gov (United States)

    Cywiński, G.; Yahniuk, I.; Kruszewski, P.; Grabowski, M.; Nowakowski-Szkudlarek, K.; Prystawko, P.; Sai, P.; Knap, W.; Simin, G. S.; Rumyantsev, S. L.

    2018-03-01

    We report on a design of fin-shaped channel GaN/AlGaN field-effect transistors developed for studying resonant terahertz plasma oscillations. Unlike common two dimensional FinFET transistor design, the gates were deposited only to the sides of the two dimensional electron gas channel, i.e., metal layers were not deposited on the top of the AlGaN. This side gate configuration allowed us to electrically control the conductivity of the channel by changing its width while keeping the carrier density and mobility virtually unchanged. Computer simulations and analytical model describe well the general shape of the characteristics. The side gate control of the channel width of these transistors allowed us to eliminate the so-called oblique plasma wave modes and paves the way towards future terahertz detectors and emitters using high quality factor plasma wave resonances.

  11. Time-dependent plasma behavior triggered by a pulsed electron gun under conditions of beam-plasma-discharge

    International Nuclear Information System (INIS)

    Szuszczewicz, E.P.; Lin, C.S.

    1982-01-01

    This chapter reports on experiments whose purpose was to simulate spaceborne applications of energetic electron guns while exploring the ''in situ'' diagnostics of time-dependent beam-plasma behavior under pulsed electron gun conditions. Beam-plasma-discharge (BPD), the BPD afterglow that exists after gun-pulse termination, and the plasma decay process are considered. It is concluded that there is a rapid enhancement in plasma density as the gas turns on; that during the pulse-ON time a quasi-steady-state BPD can be maintained with characteristics identical with its dc counterpart; that in the period immediately following gun-pulse termination the plasma loss process is dominated by cross-field radial diffusion; and that the afterglow plasma is within + or -10% of being an isodensity contour

  12. Caracterización de las necesidades psicosociales del enfermo oncológico terminal Characterization of the psychosocial needs of oncological terminal patients

    Directory of Open Access Journals (Sweden)

    María de los Angeles Garrido Pérez

    2012-08-01

    Full Text Available Introducción: a pesar del desarrollo alcanzado en la medicina, se han incrementado las enfermedades crónicas degenerativas y malignas y con ellas el aumento de los enfermos terminales. Este estudio tuvo como objetivo principal la identificación de las necesidades psicosociales de los enfermos oncológicos en situación terminal del policlínico José Martí del municipio de Camagüey que se encontraban ingresados en el hogar durante el año 2011. Material y métodos: se les aplicó una encuesta a 50 pacientes para valorar comportamiento de la comunicación sobre la enfermedad tanto con el médico como con sus familiares, así como la satisfacción ante el tratamiento médico, acompañamiento familiar y atención recibida por el equipo de salud. Los datos obtenidos fueron procesados de forma computarizada mediante el empleo de métodos de estadística descriptiva, los mismos se expresaron en forma de tablas. Resultados y Discusión: el análisis de los resultados indicó que el 90 % de los enfermos habla poco del tema con el médico que lo atiende; asimismo, el 84 % de los pacientes terminales conversa poco con la familia acerca de la enfermedad y sus complicaciones. El 100 % de los pacientes mostraron satisfacción con la atención recibida. La relación con los integrantes del equipo de cuidados paliativos, el 100 % de los encuestados lo calificó como bueno. Conclusiones: aunque hay aspectos del bienestar psicosocial de estos enfermos que pueden considerarse de nivel satisfactorio existen otros que requieren un mejor enfoque tanto por los pacientes, como por el personal médico.Introduction: Despite the development reached in the field of medicine, degenerative and malignant chronic diseases have increased, and with them, the number of terminal patients. The main objective of this work was to identify the psychosocial needs of the oncological terminal patients that had been hospitalized in 2011, at José Martí polyclinic in the

  13. Structure and assembly properties of the N-terminal domain of the prion Ure2p in isolation and in its natural context.

    Directory of Open Access Journals (Sweden)

    Luc Bousset

    Full Text Available BACKGROUND: The aggregation of the baker's yeast prion Ure2p is at the origin of the [URE3] trait. The Q- and N-rich N-terminal part of the protein is believed to drive Ure2p assembly into fibrils of amyloid nature and the fibrillar forms of full-length Ure2p and its N-terminal part generated in vitro have been shown to induce [URE3] occurrence when introduced into yeast cells. This has led to the view that the fibrillar form of the N-terminal part of the protein is sufficient for the recruitment of constitutive Ure2p and that it imprints its amyloid structure to full-length Ure2p. RESULTS: Here we generate a set of Ure2p N-terminal fragments, document their assembly and structural properties and compare them to that of full-length Ure2p. We identify the minimal region critical for the assembly of Ure2p N-terminal part into amyloids and show that such fibrils are unable to seed the assembly of full length Ure2p unlike fibrils made of intact Ure2p. CONCLUSION: Our results clearly indicate that fibrillar Ure2p shares no structural similarities with the amyloid fibrils made of Ure2p N-terminal part. Our results further suggest that the induction of [URE3] by fibrils made of full-length Ure2p is likely the consequence of fibrils growth by depletion of cytosolic Ure2p while it is the consequence of de novo formation of prion particles following, for example, titration within the cells of a specific set of molecular chaperones when fibrils made of Ure2p N-terminal domain are introduced within the cytoplasm.

  14. An N-terminal peptide extension results in efficient expression, but not secretion, of a synthetic horseradish peroxidase gene in transgenic tobacco.

    Science.gov (United States)

    Kis, Mihaly; Burbridge, Emma; Brock, Ian W; Heggie, Laura; Dix, Philip J; Kavanagh, Tony A

    2004-03-01

    Native horseradish (Armoracia rusticana) peroxidase, HRP (EC 1.11.1.7), isoenzyme C is synthesized with N-terminal and C-terminal peptide extensions, believed to be associated with protein targeting. This study aimed to explore the specific functions of these extensions, and to generate transgenic plants with expression patterns suitable for exploring the role of peroxidase in plant development and defence. Transgenic Nicotiana tabacum (tobacco) plants expressing different versions of a synthetic horseradish peroxidase, HRP, isoenzyme C gene were constructed. The gene was engineered to include additional sequences coding for either the natural N-terminal or the C-terminal extension or both. These constructs were placed under the control of a constitutive promoter (CaMV-35S) or the tobacco RUBISCO-SSU light inducible promoter (SSU) and introduced into tobacco using Agrobacterium-mediated transformation. To study the effects of the N- and C-terminal extensions, the localization of recombinant peroxidase was determined using biochemical and molecular techniques. Transgenic tobacco plants can exhibit a ten-fold increase in peroxidase activity compared with wild-type tobacco levels, and the majority of this activity is located in the symplast. The N-terminal extension is essential for the production of high levels of recombinant protein, while the C-terminal extension has little effect. Differences in levels of enzyme activity and recombinant protein are reflected in transcript levels. There is no evidence to support either preferential secretion or vacuolar targeting of recombinant peroxidase in this heterologous expression system. This leads us to question the postulated targeting roles of these peptide extensions. The N-terminal extension is essential for high level expression and appears to influence transcript stability or translational efficiency. Plants have been generated with greatly elevated cytosolic peroxidase activity, and smaller increases in apoplastic

  15. Structure of the N-terminal region of Haemophilus Influenzae HI0017: Implications for function

    International Nuclear Information System (INIS)

    Yu Liping; Mack, Jamey; Hajduk, Phil; Fesik, Stephen W.

    2001-01-01

    Haemophilus influenzae is a gram-negative pathogen that causes infections ranging from asymptomatic colonization of the human upper respiratory tract to serious invasive diseases such as meningitis. Although the genome of Haemophilus influenzae has been completely sequenced, the structure and function of many of these proteins are unknown. HI0017 is one of these uncharacterized proteins. Here we describe the three-dimensional solution structure of the N-terminal portion of HI0017 as determined by NMR spectroscopy. The structure consists of a five-stranded antiparallel β-sheet and two short α-helices. It is similar to the C-terminal domain of Diphtheria toxin repressor (DtxR). The C-terminal portion of HI0017 has an amino acid sequence that closely resembles pyruvate formate-lyase - an enzyme that converts pyruvate and CoA into acetyl-CoA and formate by a radical mechanism. Based on structural and sequence comparisons, we propose that the C-terminus of HI0017 functions as an enzyme with a glycyl radical mechanism, while the N-terminus participates in protein/protein interactions involving an activase (iron-sulfur protein) and/or the substrate

  16. Structure of the N-terminal region of Haemophilus Influenzae HI0017: Implications for function

    Energy Technology Data Exchange (ETDEWEB)

    Yu Liping; Mack, Jamey; Hajduk, Phil; Fesik, Stephen W. [Abbott Laboratories, Pharmaceutical Discovery Division, D46Y, AP10/LL (United States)

    2001-06-15

    Haemophilus influenzae is a gram-negative pathogen that causes infections ranging from asymptomatic colonization of the human upper respiratory tract to serious invasive diseases such as meningitis. Although the genome of Haemophilus influenzae has been completely sequenced, the structure and function of many of these proteins are unknown. HI0017 is one of these uncharacterized proteins. Here we describe the three-dimensional solution structure of the N-terminal portion of HI0017 as determined by NMR spectroscopy. The structure consists of a five-stranded antiparallel {beta}-sheet and two short {alpha}-helices. It is similar to the C-terminal domain of Diphtheria toxin repressor (DtxR). The C-terminal portion of HI0017 has an amino acid sequence that closely resembles pyruvate formate-lyase - an enzyme that converts pyruvate and CoA into acetyl-CoA and formate by a radical mechanism. Based on structural and sequence comparisons, we propose that the C-terminus of HI0017 functions as an enzyme with a glycyl radical mechanism, while the N-terminus participates in protein/protein interactions involving an activase (iron-sulfur protein) and/or the substrate.

  17. Abl N-terminal Cap stabilization of SH3 domain dynamics†

    OpenAIRE

    Chen, Shugui; Dumitrescu, Teodora Pene; Smithgall, Thomas E.; Engen, John R.

    2008-01-01

    Crystal structures and other biochemical data indicate that the N-terminal cap (NCap) region of the Abelson tyrosine kinase (c-Abl) is important for maintaining the downregulated conformation of the kinase domain. The exact contributions that NCap makes in stabilizing the various intramolecular interactions within c-Abl are less clear. While the NCap appears important for locking the SH3/SH2 domains to the back of the kinase domain, there may be other more subtle elements of regulation. Hydro...

  18. Controlling the Plasma-Polymerization Process of N-Vinyl-2-pyrrolidone

    DEFF Research Database (Denmark)

    Norrman, Kion; Winther-Jensen, Bjørn

    2005-01-01

    N-vinyl-2-pyrrolidone was plasma-polymerized on glass substrates using a pulsed AC plasma. Pulsed AC plasma produces a chemical surface structure different from that produced by conventional RF plasma; this is ascribed to the different power regimes used. A high degree of control over the structure...... of the chemical surface was obtained using pulsed AC plasma, as shown by ToF-SIMS. It is demonstrated how the experimental conditions to some extent control the chemical structure of the plasma-polymerized film, e.g., film thickness, density of post-plasma-polymerized oligomeric chains, and the density of intact...

  19. Directed evolution of the TALE N-terminal domain for recognition of all 5' bases.

    Science.gov (United States)

    Lamb, Brian M; Mercer, Andrew C; Barbas, Carlos F

    2013-11-01

    Transcription activator-like effector (TALE) proteins can be designed to bind virtually any DNA sequence. General guidelines for design of TALE DNA-binding domains suggest that the 5'-most base of the DNA sequence bound by the TALE (the N0 base) should be a thymine. We quantified the N0 requirement by analysis of the activities of TALE transcription factors (TALE-TF), TALE recombinases (TALE-R) and TALE nucleases (TALENs) with each DNA base at this position. In the absence of a 5' T, we observed decreases in TALE activity up to >1000-fold in TALE-TF activity, up to 100-fold in TALE-R activity and up to 10-fold reduction in TALEN activity compared with target sequences containing a 5' T. To develop TALE architectures that recognize all possible N0 bases, we used structure-guided library design coupled with TALE-R activity selections to evolve novel TALE N-terminal domains to accommodate any N0 base. A G-selective domain and broadly reactive domains were isolated and characterized. The engineered TALE domains selected in the TALE-R format demonstrated modularity and were active in TALE-TF and TALEN architectures. Evolved N-terminal domains provide effective and unconstrained TALE-based targeting of any DNA sequence as TALE binding proteins and designer enzymes.

  20. On the terminal homologation of physiologically active peptides as a means of increasing stability in human serum--neurotensin, opiorphin, B27-KK10 epitope, NPY.

    Science.gov (United States)

    Seebach, Dieter; Lukaszuk, Aneta; Patora-Komisarska, Krystyna; Podwysocka, Dominika; Gardiner, James; Ebert, Marc-Olivier; Reubi, Jean Claude; Cescato, Renzo; Waser, Beatrice; Gmeiner, Peter; Hübner, Harald; Rougeot, Catherine

    2011-05-01

    The terminal homologation by CH(2) insertion into the peptides mentioned in the title is described. This involves replacement of the N-terminal amino acid residue by a β(2) - and of the C-terminal amino acid residue by a β(3) -homo-amino acid moiety (β(2) hXaa and β(3) hXaa, resp.; Fig. 1). In this way, the structure of the peptide chain from the N-terminal to the C-terminal stereogenic center is identical, and the modified peptide is protected against cleavage by exopeptidases (Figs. 2 and 3). Neurotensin (NT; 1) and its C-terminal fragment NT(8-13) are ligands of the G-protein-coupled receptors (GPCR) NT1, NT2, NT3, and NT analogs are promising tools to be used in cancer diagnostics and therapy. The affinities of homologated NT analogs, 2b-2e, for NT1 and NT2 receptors were determined by using cell homogenates and tumor tissues (Table 1); in the latter experiments, the affinities for the NT1 receptor are more or less the same as those of NT (0.5-1.3 vs. 0.6 nM). At the same time, one of the homologated NT analogs, 2c, survives in human plasma for 7 days at 37° (Fig. 6). An NMR analysis of NT(8-13) (Tables 2 and 4, and Fig. 8) reveals that this N-terminal NT fragment folds to a turn in CD(3) OH. - In the case of the human analgesic opiorphin (3a), a pentapeptide, and of the HIV-derived B27-KK10 (4a), a decapeptide, terminal homologation (→3b and 4b, resp.) led to a 7- and 70-fold half-life increase in plasma (Fig. 9). With N-terminally homologated NPY, 5c, we were not able to determine serum stability; the peptide consisting of 36 amino acid residues is subject to cleavage by endopetidases. Three of the homologated compounds, 2b, 2c, and 5c, were shown to be agonists (Fig. 7 and 11). A comparison of terminal homologation with other stability-increasing terminal modifications of peptides is performed (Fig. 5), and possible applications of the neurotensin analogs, described herein, are discussed. Copyright © 2011 Verlag Helvetica Chimica

  1. Molecular cloning and biologically active production of IpaD N-terminal region.

    Science.gov (United States)

    Hesaraki, Mahdi; Saadati, Mojtaba; Honari, Hossein; Olad, Gholamreza; Heiat, Mohammad; Malaei, Fatemeh; Ranjbar, Reza

    2013-07-01

    Shigella is known as pathogenic intestinal bacteria in high dispersion and pathogenic bacteria due to invasive plasmid antigen (Ipa). So far, a number of Ipa proteins have been studied to introduce a new candidate vaccine. Here, for the first time, we examined whether the N-terminal region of IpaD(72-162) could be a proper candidate for Shigella vaccine. Initially, the DNA sequence coding N-terminal region was isolated by PCR from Shigella dysenteriae type I and cloned into pET-28a expression vector. Then, the heterologous protein was expressed, optimized and purified by affinity Ni-NTA column. Western blot analysis using, His-tag and IpaD(72-162) polyclonal antibodies, confirmed the purity and specificity of the recombinant protein, respectively. Subsequently, the high immunogenicity of the antigen was shown by ELISA. The results of the sereny test in Guinea pigs showed that IpaD(72-162) provides a protective system against Shigella flexneri 5a and S. dysenteriae type I. Copyright © 2013. Published by Elsevier Ltd.

  2. Effect of N-Terminal Acylation on the Activity of Myostatin Inhibitory Peptides.

    Science.gov (United States)

    Takayama, Kentaro; Nakamura, Akari; Rentier, Cédric; Mino, Yusaku; Asari, Tomo; Saga, Yusuke; Taguchi, Akihiro; Yakushiji, Fumika; Hayashi, Yoshio

    2016-04-19

    Inhibition of myostatin, which negatively regulates skeletal muscle growth, is a promising strategy for the treatment of muscle atrophic disorders, such as muscular dystrophy, cachexia and sarcopenia. Recently, we identified peptide A (H-WRQNTRYSRIEAIKIQILSKLRL-NH2 ), the 23-amino-acid minimum myostatin inhibitory peptide derived from mouse myostatin prodomain, and highlighted the importance of its N-terminal tryptophan residue for the effective inhibition. In this study, we synthesized a series of acylated peptide derivatives focused on the tryptophan residue to develop potent myostatin inhibitors. As a result of the investigation, a more potent derivative of peptide A was successfully identified in which the N-terminal tryptophan residue is replaced with a 2-naphthyloxyacetyl moiety to give an inhibitory peptide three times (1.19±0.11 μm) more potent than parent peptide A (3.53±0.25 μm). This peptide could prove useful as a new starting point for the development of improved inhibitory peptides. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Suppression of cell death by the secretory form of N-terminal ERC/mesothelin.

    Science.gov (United States)

    Wang, Tegexibaiyin; Kajino, Kazunori; Abe, Masaaki; Tan, Ke; Maruo, Masumi; Sun, Guodong; Hagiwara, Yoshiaki; Maeda, Masahiro; Hino, Okio

    2010-08-01

    ERC/mesothelin is highly expressed in malignant mesothelioma, pancreatic cancer, and ovarian cancer. It is cleaved to a 30 kDa N-terminal secretory form (N-ERC) and a 40 kDa C-terminal membranous form (C-ERC). Several functions have been reported for full-length ERC (full-ERC) and C-ERC/mesothelin, such as in cell adhesion and invasion, stimulation of cell proliferation, and the suppression of cell death. However, there have been no studies to date on the function of secretory N-ERC, despite the fact that it is abundantly secreted into the sera of mesothelioma patients. In this study, we investigated whether N-ERC could function as a secretory factor to stimulate tumor progression. Full-, N, or C-ERC was overexpressed in the human hepatocellular carcinoma cell line Huh7 that lacks endogenous expression of ERC/mesothelin. Changes in the rates of cell proliferation and cell death were determined, and the state of signal transducers was examined using various endpoints: total cell counts, trypan blue exclusion rate, BrdU incorporation rate, TUNEL assay, and the phosphorylation of ERK1/2 and Stat3. In cells overexpressing N-ERC, phosphorylation of ERK1/2 was enhanced and the rate of cell death decreased, leading to the increase of cell number. The culture medium containing the secretory N-ERC also had the activity to increase the number of cells. Our data suggested that one of the full-ERC functions reported previously was mediated by the secretory N-ERC.

  4. Comparison of usefulness of N-terminal pro-brain natriuretic peptide as an independent predictor of cardiac function among admission cardiac serum biomarkers in patients with anterior wall versus nonanterior wall ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

    Science.gov (United States)

    Haeck, Joost D E; Verouden, Niels J W; Kuijt, Wichert J; Koch, Karel T; Van Straalen, Jan P; Fischer, Johan; Groenink, Maarten; Bilodeau, Luc; Tijssen, Jan G P; Krucoff, Mitchell W; De Winter, Robbert J

    2010-04-15

    The purpose of the present study was to determine the prognostic value of N-terminal pro-brain natriuretic peptide (NT-pro-BNP), among other serum biomarkers, on cardiac magnetic resonance (CMR) imaging parameters of cardiac function and infarct size in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. We measured NT-pro-BNP, cardiac troponin T, creatinine kinase-MB fraction, high-sensitivity C-reactive protein, and creatinine on the patients' arrival at the catheterization laboratory in 206 patients with ST-segment elevation myocardial infarction. The NT-pro-BNP levels were divided into quartiles and correlated with left ventricular function and infarct size measured by CMR imaging at 4 to 6 months. Compared to the lower quartiles, patients with nonanterior wall myocardial infarction in the highest quartile of NT-pro-BNP (> or = 260 pg/ml) more often had a greater left ventricular end-systolic volume (68 vs 39 ml/m(2), p pro-BNP level of > or = 260 pg/ml was the strongest independent predictor of left ventricular ejection fraction in patients with nonanterior wall myocardial infarction compared to the other serum biomarkers (beta = -5.8; p = 0.019). In conclusion, in patients with nonanterior wall myocardial infarction undergoing primary percutaneous coronary intervention, an admission NT-pro-BNP level of > or = 260 pg/ml was a strong, independent predictor of left ventricular function assessed by CMR imaging at follow-up. Our findings suggest that NT-pro-BNP, a widely available biomarker, might be helpful in the early risk stratification of patients with nonanterior wall myocardial infarction. Copyright 2010 Elsevier Inc. All rights reserved.

  5. Specificity of Plasma Membrane Targeting by the Rous Sarcoma Virus Gag Protein

    OpenAIRE

    Scheifele, Lisa Z.; Rhoads, Jonathan D.; Parent, Leslie J.

    2003-01-01

    Budding of C-type retroviruses begins when the viral Gag polyprotein is directed to the plasma membrane by an N-terminal membrane-binding (M) domain. While dispersed basic amino acids within the M domain are critical for stable membrane association and consequent particle assembly, additional residues or motifs may be required for specific plasma membrane targeting and binding. We have identified an assembly-defective Rous sarcoma virus (RSV) Gag mutant that retains significant membrane affin...

  6. Membrane fusion by VAMP3 and plasma membrane t-SNAREs

    International Nuclear Information System (INIS)

    Hu Chuan; Hardee, Deborah; Minnear, Fred

    2007-01-01

    Pairing of SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins on vesicles (v-SNAREs) and SNARE proteins on target membranes (t-SNAREs) mediates intracellular membrane fusion. VAMP3/cellubrevin is a v-SNARE that resides in recycling endosomes and endosome-derived transport vesicles. VAMP3 has been implicated in recycling of transferrin receptors, secretion of α-granules in platelets, and membrane trafficking during cell migration. Using a cell fusion assay, we examined membrane fusion capacity of the ternary complexes formed by VAMP3 and plasma membrane t-SNAREs syntaxin1, syntaxin4, SNAP-23 and SNAP-25. VAMP3 forms fusogenic pairing with t-SNARE complexes syntaxin1/SNAP-25, syntaxin1/SNAP-23 and syntaxin4/SNAP-25, but not with syntaxin4/SNAP-23. Deletion of the N-terminal domain of syntaxin4 enhanced membrane fusion more than two fold, indicating that the N-terminal domain negatively regulates membrane fusion. Differential membrane fusion capacities of the ternary v-/t-SNARE complexes suggest that transport vesicles containing VAMP3 have distinct membrane fusion kinetics with domains of the plasma membrane that present different t-SNARE proteins

  7. The N-Terminal of Aquareovirus NS80 Is Required for Interacting with Viral Proteins and Viral Replication.

    Directory of Open Access Journals (Sweden)

    Jie Zhang

    Full Text Available Reovirus replication and assembly occurs within viral inclusion bodies that formed in specific intracellular compartments of cytoplasm in infected cells. Previous study indicated that aquareovirus NS80 is able to form inclusion bodies, and also can retain viral proteins within its inclusions. To better understand how NS80 performed in viral replication and assembly, the functional regions of NS80 associated with other viral proteins in aquareovirus replication were investigated in this study. Deletion mutational analysis and rotavirus NSP5-based protein association platform were used to detect association regions. Immunofluorescence images indicated that different N-terminal regions of NS80 could associate with viral proteins VP1, VP4, VP6 and NS38. Further co-immunoprecipitation analysis confirmed the interaction between VP1, VP4, VP6 or NS38 with different regions covering the N-terminal amino acid (aa, 1-471 of NS80, respectively. Moreover, removal of NS80 N-terminal sequences required for interaction with proteins VP1, VP4, VP6 or NS38 not only prevented the capacity of NS80 to support viral replication in NS80 shRNA-based replication complementation assays, but also inhibited the expression of aquareovirus proteins, suggesting that N-terminal regions of NS80 are necessary for viral replication. These results provided a foundational basis for further understanding the role of NS80 in viral replication and assembly during aquareovirus infection.

  8. Functionalization of alkyne-terminated thermally hydrocarbonized porous silicon nanoparticles with targeting peptides and antifouling polymers: effect on the human plasma protein adsorption.

    Science.gov (United States)

    Wang, Chang-Fang; Mäkilä, Ermei M; Bonduelle, Colin; Rytkönen, Jussi; Raula, Janne; Almeida, Sérgio; Närvänen, Ale; Salonen, Jarno J; Lecommandoux, Sebastien; Hirvonen, Jouni T; Santos, Hélder A

    2015-01-28

    Porous silicon (PSi) nanomaterials combine a high drug loading capacity and tunable surface chemistry with various surface modifications to meet the requirements for biomedical applications. In this work, alkyne-terminated thermally hydrocarbonized porous silicon (THCPSi) nanoparticles were fabricated and postmodified using five bioactive molecules (targeting peptides and antifouling polymers) via a single-step click chemistry to modulate the bioactivity of the THCPSi nanoparticles, such as enhancing the cellular uptake and reducing the plasma protein association. The size of the nanoparticles after modification was increased from 176 to 180-220 nm. Dextran 40 kDa modified THCPSi nanoparticles showed the highest stability in aqueous buffer. Both peptide- and polymer-functionalized THCPSi nanoparticles showed an extensive cellular uptake which was dependent on the functionalized moieties presented on the surface of the nanoparticles. The plasma protein adsorption study showed that the surface modification with different peptides or polymers induced different protein association profiles. Dextran 40 kDa functionalized THCPSi nanoparticles presented the least protein association. Overall, these results demonstrate that the "click" conjugation of the biomolecules onto the alkyne-terminated THCPSi nanoparticles is a versatile and simple approach to modulate the surface chemistry, which has high potential for biomedical applications.

  9. Molecular dissection of the C-terminal regulatory domain of the plant plasma membrane H+-ATPase AHA2: Mapping of residues that when altered give rise to an activated enzyme

    DEFF Research Database (Denmark)

    Axelsen, K.B.; Venema, K.; Jah, T.

    1999-01-01

    in an extension of the C-terminus unique to plant H+-ATPases, Alteration of residues in both regions led to increased binding of yeast 14-3-3 protein to the plasma membrane of transformed cells. Taken together, our data suggest that modification of residues in two regions of the C-terminal regulatory domain......The plasma membrane H+-ATPase is a proton pump belonging to the P-type ATPase superfamily and is important for nutrient acquisition in plants, The H+-ATPase is controlled by an autoinhibitory C-terminal regulatory domain and is activated by 14-3-3 proteins which bind to this part of the enzyme......+-ATPase. The enzymes were characterized by their ability to promote growth in acidic conditions and to promote H+ extrusion from intact cells, both of which are measures of plasma membrane H+-ATPase activity, and were also characterized with respect to kinetic properties such as affinity for H+ and ATP. Residues...

  10. Structural Insight into the Critical Role of the N-Terminal Region in the Catalytic Activity of Dual-Specificity Phosphatase 26.

    Directory of Open Access Journals (Sweden)

    Eun-Young Won

    Full Text Available Human dual-specificity phosphatase 26 (DUSP26 is a novel target for anticancer therapy because its dephosphorylation of the p53 tumor suppressor regulates the apoptosis of cancer cells. DUSP26 inhibition results in neuroblastoma cell cytotoxicity through p53-mediated apoptosis. Despite the previous structural studies of DUSP26 catalytic domain (residues 61-211, DUSP26-C, the high-resolution structure of its catalytically active form has not been resolved. In this study, we determined the crystal structure of a catalytically active form of DUSP26 (residues 39-211, DUSP26-N with an additional N-terminal region at 2.0 Å resolution. Unlike the C-terminal domain-swapped dimeric structure of DUSP26-C, the DUSP26-N (C152S monomer adopts a fold-back conformation of the C-terminal α8-helix and has an additional α1-helix in the N-terminal region. Consistent with the canonically active conformation of its protein tyrosine phosphate-binding loop (PTP loop observed in the structure, the phosphatase assay results demonstrated that DUSP26-N has significantly higher catalytic activity than DUSP26-C. Furthermore, size exclusion chromatography-multiangle laser scattering (SEC-MALS measurements showed that DUSP26-N (C152S exists as a monomer in solution. Notably, the crystal structure of DUSP26-N (C152S revealed that the N-terminal region of DUSP26-N (C152S serves a scaffolding role by positioning the surrounding α7-α8 loop for interaction with the PTP-loop through formation of an extensive hydrogen bond network, which seems to be critical in making the PTP-loop conformation competent for phosphatase activity. Our study provides the first high-resolution structure of a catalytically active form of DUSP26, which will contribute to the structure-based rational design of novel DUSP26-targeting anticancer therapeutics.

  11. Spectroanalytical investigations on inductively coupled N2/Ar and Ar/Ar high frequency plasmas

    International Nuclear Information System (INIS)

    Malinowski, P.; Mazurkiewicz, M.; Nickel, H.

    1981-03-01

    In order to improve the detection limits of trace elements in corrosion products of metallic materials, the inductively coupled plasma excitation source (ICP) was applied for spectroscopic analysis. Besides optimizing the working conditions for the mentioned materials, the fundamental research clearing the excitation processes in ICP was carried out. Basicly, two plasma systems were investigated: the nitrogen cooled N 2 /Ar- and pure Ar/Ar-plasma. The computed detection limits for 8 chosen elements are between 0.1 and 50 μg ml -1 in both plasmas. The advantage of ion lines was clearly present; in N 2 /Ar-plasma it was larger than in Ar/Ar-plasma. The excitation temperatures measured with help of ArI, FeI and ZnI lines rise with increasing power and decreasing distance from the induction coil. The distribution of Zn excitation temperature in N 2 /Ar-plasma as well as the measured N + 2 rotational and CN vibrational temperatures indicate, that the toroidal structure of Ar/Ar-plasma is not analogue to the N 2 /Ar-plasma. The values of the various excitation temperatures (Ar, Fe, Zn) and the differences between the excitation, vibration, rotation and ionization temperatures (Tsub(i) > Tsub(n) = Tsub(vib) > Tsub(rot)) indicate an absence of thermal equilibrium in the concerned system. (orig.)

  12. Dual N- and C-terminal helices are required for endoplasmic reticulum and lipid droplet association of alcohol acetyltransferases in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Jyun-Liang Lin

    Full Text Available In the yeast Saccharomyces cerevisiae two alcohol acetyltransferases (AATases, Atf1 and Atf2, condense short chain alcohols with acetyl-CoA to produce volatile acetate esters. Such esters are, in large part, responsible for the distinctive flavors and aromas of fermented beverages including beer, wine, and sake. Atf1 and Atf2 localize to the endoplasmic reticulum (ER and Atf1 is known to localize to lipid droplets (LDs. The mechanism and function of these localizations are unknown. Here, we investigate potential mechanisms of Atf1 and Atf2 membrane association. Segments of the N- and C-terminal domains of Atf1 (residues 24-41 and 508-525, respectively are predicted to be amphipathic helices. Truncations of these helices revealed that the terminal domains are essential for ER and LD association. Moreover, mutations of the basic or hydrophobic residues in the N-terminal helix and hydrophobic residues in the C-terminal helix disrupted ER association and subsequent sorting from the ER to LDs. Similar amphipathic helices are found at both ends of Atf2, enabling ER and LD association. As was the case with Atf1, mutations to the N- and C-terminal helices of Atf2 prevented membrane association. Sequence comparison of the AATases from Saccharomyces, non-Saccharomyces yeast (K. lactis and P. anomala and fruits species (C. melo and S. lycopersicum showed that only AATases from Saccharomyces evolved terminal amphipathic helices. Heterologous expression of these orthologs in S. cerevisiae revealed that the absence of terminal amphipathic helices eliminates LD association. Combined, the results of this study suggest a common mechanism of membrane association for AATases via dual N- and C-terminal amphipathic helices.

  13. Glycosylation of the N-terminal potential N-glycosylation sites in the human α1,3-fucosyltransferase V and -VI (hFucTV and -VI)

    DEFF Research Database (Denmark)

    Christensen, Lise Lotte; Bross, Peter Gerd; Ørntoft, Torben Falck

    2000-01-01

    Human alpha1,3-fucosyltransferase V and -VI (hFucTV and -VI) each contain four potential N-glycosylation sites (hFucTV: Asn60, Asn105, Asn167 and Asn198 and hFucTVI: Asn46, Asn91, Asn153 and Asn184). Glycosylation of the two N-terminal potential N-glycosylation sites (hFucTV: Asn60, Asn105 and h......FucTVI: Asn46 and Asn91) have never been studied in detail. In the present study, we have analysed the glycosylation of these potential N-glycosylation sites. Initially, we compared the molecular mass of hFucTV and -VI expressed in COS-7 cells treated with tunicamycin with the mass of the proteins...... in untreated cells. The difference in molecular mass between the proteins in treated and untreated cells corresponded to the presence of at least three N-linked glycans. We then made a series of mutants, in which the asparagine residues in the N-terminal potential N-glycosylation sites were replaced...

  14. The N-terminal-truncated recombinant fibrin(ogen)olytic serine protease improves its functional property, demonstrates in vivo anticoagulant and plasma defibrinogenation activity as well as pre-clinical safety in rodent model.

    Science.gov (United States)

    Bora, Bandana; Gogoi, Debananda; Tripathy, Debabrata; Kurkalang, Sillarine; Ramani, Sheetal; Chatterjee, Anupam; Mukherjee, Ashis K

    2018-05-01

    An N-terminal truncated fibrino(geno)lytic serine protease gene encoding a ~42kDa protein from Bacillus cereus strain AB01 was produced by error prone PCR, cloned into pET19b vector, and expressed in E5 coli BL21 DE3 cells. The deletion of 24 amino acid residues from N-terminal of wild-type Bacifrinase improves the catalytic activity of [Bacifrinase (ΔN24)]. The anticoagulant potency of [Bacifrinase (ΔN24)] was comparable to Nattokinase and Warfarin and results showed that its anticoagulant action is contributed by progressive defibrinogenation and antiplatelet activities. Nonetheless, at the tested concentration of 2.0μM [Bacifrinase (ΔN24)] did not show in vitro cytotoxicity or chromosomal aberrations on human embryonic kidney cells-293 (HEK-293) and human peripheral blood lymphocytes (HPBL) cells. [Bacifrinase (ΔN24)], at a dose of 2mg/kg, did not show toxicity, adverse pharmacological effects, tissue necrosis or hemorrhagic effect after 72h of its administration in Swiss albino mice. However, at the tested doses of 0.125 to 0.5mg/kg, it demonstrated significant in anticoagulant effect as well as defibrinogenation after 6h of administration in mice. We propose that [Bacifrinase (ΔN24)] may serve as prototype for the development of potent drug to prevent hyperfibrinogenemia related disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Detailed study of the plasma-activated catalytic generation of ammonia in N2-H2 plasmas

    Science.gov (United States)

    van Helden, J. H.; Wagemans, W.; Yagci, G.; Zijlmans, R. A. B.; Schram, D. C.; Engeln, R.; Lombardi, G.; Stancu, G. D.; Röpcke, J.

    2007-02-01

    We investigated the efficiency and formation mechanism of ammonia generation in recombining plasmas generated from mixtures of N2 and H2 under various plasma conditions. In contrast to the Haber-Bosch process, in which the molecules are dissociated on a catalytic surface, under these plasma conditions the precursor molecules, N2 and H2, are already dissociated in the gas phase. Surfaces are thus exposed to large fluxes of atomic N and H radicals. The ammonia production turns out to be strongly dependent on the fluxes of atomic N and H radicals to the surface. By optimizing the atomic N and H fluxes to the surface using an atomic nitrogen and hydrogen source ammonia can be formed efficiently, i.e., more than 10% of the total background pressure is measured to be ammonia. The results obtained show a strong similarity with results reported in literature, which were explained by the production of ammonia at the surface by stepwise addition reactions between adsorbed nitrogen and hydrogen containing radicals at the surface and incoming N and H containing radicals. Furthermore, our results indicate that the ammonia production is independent of wall material. The high fluxes of N and H radicals in our experiments result in a passivated surface, and the actual chemistry, leading to the formation of ammonia, takes place in an additional layer on top of this passivated surface.

  16. Involvement of the N-terminal unique domain of Chk tyrosine kinase in Chk-induced tyrosine phosphorylation in the nucleus

    International Nuclear Information System (INIS)

    Nakayama, Yuji; Kawana, Akiko; Igarashi, Asae; Yamaguchi, Naoto

    2006-01-01

    Chk tyrosine kinase phosphorylates Src-family kinases and suppresses their kinase activity. We recently showed that Chk localizes to the nucleus as well as the cytoplasm and inhibits cell proliferation. In this study, we explored the role of the N-terminal unique domain of Chk in nuclear localization and Chk-induced tyrosine phosphorylation in the nucleus. In situ binding experiments showed that the N-terminal domain of Chk was associated with the nucleus and the nuclear matrix. The presence of the N-terminal domain of Chk led to a fourfold increase in cell population exhibiting Chk-induced tyrosine phosphorylation in the nucleus. Expression of Chk but not kinase-deficient Chk induced tyrosine phosphorylation of a variety of proteins ranging from 23 kDa to ∼200 kDa, especially in Triton X-100-insoluble fraction that included chromatin and the nuclear matrix. Intriguingly, in situ subnuclear fractionations revealed that Chk induced tyrosine phosphorylation of proteins that were associated with the nuclear matrix. These results suggest that various unidentified substrates of Chk, besides Src-family kinases, may be present in the nucleus. Thus, our findings indicate that the importance of the N-terminal domain to Chk-induced tyrosine phosphorylation in the nucleus, implicating that these nuclear tyrosine-phosphorylated proteins may contribute to inhibition of cell proliferation

  17. Hiperplasia linfoide de íleon terminal, presentación de un caso

    Directory of Open Access Journals (Sweden)

    Arley Fajardo Ochoa

    2014-08-01

    Full Text Available Se presenta el caso de un adolescente masculino de 16 años de edad que acudió a la consulta por dolor abdominal recurrente, localizado en la fosa ilíaca derecha, el cual había recibido tratamiento sintomático con antiespasmódicos y antiparasitarios sin lograr mejoría del dolor, por lo que fue remitido a la consulta de Gastroenterología donde se le realizaron exámenes complementarios que evidenciaron la existencia de una patología en el íleon terminal, se remitió al Instituto de Gastroenterología, donde se le realizó una colonoscopia y se le diagnosticó una hiperplasia linfoide severa de Ileon terminal que con el tratamiento higiénico dietético, se logró disminuir la frecuencia y la intensidad del dolor, sin embargo en las colonoscopías evolutivas se observó un incremento en la intensidad y la extensión de la hiperplasia por lo que se le indicaron exámenes endoscópicos e histológicos cada seis meses, llama la atención que a pesar de la severidad del cuadro, nunca se ha observado ningún episodio de sangrado digestivo que es la forma de presentación más frecuente de esta entidad

  18. Plasma-assisted ohmic contact for AlGaN/GaN heterostructure field-effect transistors

    International Nuclear Information System (INIS)

    Zhang, Jiaqi; Wang, Lei; Wang, Qingpeng; Jiang, Ying; Li, Liuan; Ao, Jin-Ping; Zhu, Huichao

    2016-01-01

    An Al-based ohmic process assisted by an inductively coupled plasma (ICP) recess treatment is proposed for AlGaN/GaN heterostructure field-effect transistors (HFETs) to realize ohmic contact, which is only needed to anneal at 500 °C. The recess treatment was done with SiCl 4 plasma with 100 W ICP power for 20 s and annealing at 575 °C for 1 min. Under these conditions, contact resistance of 0.52 Ωmm was confirmed. To suppress the ball-up phenomenon and improve the surface morphology, an Al/TiN structure was also fabricated with the same conditions. The contact resistance was further improved to 0.30 Ωmm. By using this plasma-assisted ohmic process, a gate-first HFET was fabricated. The device showed high drain current density and high transconductance. The leakage current of the TiN-gate device decreased to 10 −9 A, which was 5 orders of magnitude lower than that of the device annealed at 800 °C. The results showed that the low-temperature ohmic contact process assisted by ICP treatment is promising for the fabrication of gate-first and self-aligned gate HFETs. (paper)

  19. The N-terminal domain of the repressor of Staphylococcus aureus phage Φ11 possesses an unusual dimerization ability and DNA binding affinity.

    Directory of Open Access Journals (Sweden)

    Anindya Biswas

    Full Text Available Bacteriophage Φ11 uses Staphylococcus aureus as its host and, like lambdoid phages, harbors three homologous operators in between its two divergently oriented repressor genes. None of the repressors of Φ11, however, showed binding to all three operators, even at high concentrations. To understand why the DNA binding mechanism of Φ11 repressors does not match that of lambdoid phage repressors, we studied the N-terminal domain of the Φ11 lysogenic repressor, as it harbors a putative helix-turn-helix motif. Our data revealed that the secondary and tertiary structures of the N-terminal domain were different from those of the full-length repressor. Nonetheless, the N-terminal domain was able to dimerize and bind to the operators similar to the intact repressor. In addition, the operator base specificity, binding stoichiometry, and binding mechanism of this domain were nearly identical to those of the whole repressor. The binding affinities of the repressor and its N-terminal domain were reduced to a similar extent when the temperature was increased to 42°C. Both proteins also adequately dislodged a RNA polymerase from a Φ11 DNA fragment carrying two operators and a promoter. Unlike the intact repressor, the binding of the N-terminal domain to two adjacent operator sites was not cooperative in nature. Taken together, we suggest that the dimerization and DNA binding abilities of the N-terminal domain of the Φ11 repressor are distinct from those of the DNA binding domains of other phage repressors.

  20. Crystal Structure of the Full-Length Feline Immunodeficiency Virus Capsid Protein Shows an N-Terminal β-Hairpin in the Absence of N-Terminal Proline

    Directory of Open Access Journals (Sweden)

    Christelle Folio

    2017-11-01

    Full Text Available Feline immunodeficiency virus (FIV is a member of the Retroviridae family. It is the causative agent of an acquired immunodeficiency syndrome (AIDS in cats and wild felines. Its capsid protein (CA drives the assembly of the viral particle, which is a critical step in the viral replication cycle. Here, the first atomic structure of full-length FIV CA to 1.67 Å resolution is determined. The crystallized protein exhibits an original tetrameric assembly, composed of dimers which are stabilized by an intermolecular disulfide bridge induced by the crystallogenesis conditions. The FIV CA displays a standard α-helical CA topology with two domains, separated by a linker shorter than other retroviral CAs. The β-hairpin motif at its amino terminal end, which interacts with nucleotides in HIV-1, is unusually long in FIV CA. Interestingly, this functional β-motif is formed in this construct in the absence of the conserved N-terminal proline. The FIV CA exhibits a cis Arg–Pro bond in the CypA-binding loop, which is absent in known structures of lentiviral CAs. This structure represents the first tri-dimensional structure of a functional, full-length FIV CA.

  1. Autocatalytic activity and substrate specificity of the pestivirus N-terminal protease N{sup pro}

    Energy Technology Data Exchange (ETDEWEB)

    Gottipati, Keerthi; Acholi, Sudheer [Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, The University of Texas Medical Branch, Galveston, TX 77555-0647 (United States); Ruggli, Nicolas [Institute of Virology and Immunology, CH-3147 Mittelhäusern (Switzerland); Choi, Kyung H., E-mail: kychoi@utmb.edu [Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, The University of Texas Medical Branch, Galveston, TX 77555-0647 (United States)

    2014-03-15

    Pestivirus N{sup pro} is the first protein translated in the viral polypeptide, and cleaves itself off co-translationally generating the N-terminus of the core protein. Once released, N{sup pro} blocks the host's interferon response by inducing degradation of interferon regulatory factor-3. N{sup pro'}s intracellular autocatalytic activity and lack of trans-activity have hampered in vitro cleavage studies to establish its substrate specificity and the roles of individual residues. We constructed N{sup pro}-GFP fusion proteins that carry the authentic cleavage site and determined the autoproteolytic activities of N{sup pro} proteins containing substitutions at the predicted catalytic sites Glu22 and Cys69, at Arg100 that forms a salt bridge with Glu22, and at the cleavage site Cys168. Contrary to previous reports, we show that N{sup pro'}s catalytic activity does not involve Glu22, which may instead be involved in protein stability. Furthermore, N{sup pro} does not have specificity for Cys168 at the cleavage site even though this residue is conserved throughout the pestivirus genus. - Highlights: • N{sup pro'}s autoproteolysis is studied using N{sup pro}-GFP fusion proteins. • N-terminal 17 amino acids are dispensable without loss of protease activity. • The putative catalytic residue Glu22 is not involved in protease catalysis. • No specificity for Cys168 at the cleavage site despite evolutionary conservation. • N{sup pro} prefers small amino acids with non-branched beta carbons at the P1 position.

  2. Electric field measurements on plasma bullets in N2 using four-wave mixing

    NARCIS (Netherlands)

    van der Schans, M.; Böhm, P.; Nijdam, S.; IJzerman, W.L.; Czarnetzki, U.

    2015-01-01

    Atmospheric pressure plasma jets driven by pulsed DC or kHz AC voltages typically consist of discrete guided ionisation waves called plasma bullets. In this work, the electric field of plasma bullets generated in a pulsed DC jet with N2 as feed gas is investigated. Electric field measurements in N2

  3. Solution structure of the N-terminal domain of a replication restart primosome factor, PriC, in Escherichia coli

    Science.gov (United States)

    Aramaki, Takahiko; Abe, Yoshito; Katayama, Tsutomu; Ueda, Tadashi

    2013-01-01

    In eubacterial organisms, the oriC-independent primosome plays an essential role in replication restart after the dissociation of the replication DNA-protein complex by DNA damage. PriC is a key protein component in the replication restart primosome. Our recent study suggested that PriC is divided into two domains: an N-terminal and a C-terminal domain. In the present study, we determined the solution structure of the N-terminal domain, whose structure and function have remained unknown until now. The revealed structure was composed of three helices and one extended loop. We also observed chemical shift changes in the heteronuclear NMR spectrum and oligomerization in the presence of ssDNA. These abilities may contribute to the PriC-ssDNA complex, which is important for the replication restart primosome. PMID:23868391

  4. Potential safe termination by injection of polypropylene pellets in JET

    International Nuclear Information System (INIS)

    Schmidt, G.L.; Ali-Arshad, S.; Bartlett, D.

    1995-01-01

    Thermal energy and the magnetic field energy associated with the plasma current must be dissipated safely when a tokamak discharge is terminated in a disruption. Magnetic energy can be dissipated by impurity radiation if position control is maintained. Prior to the dissipation of magnetic energy, thermal energy is usually conducted to the plasma contact points on a 1ms time scale in a thermal quench. A resistive, highly radiating plasma formed prior to the thermal quench, might dissipate both the thermal and magnetic energy by radiation minimizing damage due to local deposition. High speed injection of a low Z material can produce a resistive, highly radiating plasma on a 1ms time scale. Neon has recently been used in such an application on JT60-U. A large carbon pellet producing dilution temperatures < 1 keV is a possible alternative. This paper summarizes the results of an initial experiment performed in JET using carbon injected at high speed, as a 6mm polypropylene pellet, to investigate this potential approach to a safe plasma termination

  5. Energy Considerations for Plasma-Assisted N-Fixation Reactions

    Directory of Open Access Journals (Sweden)

    Aikaterini Anastasopoulou

    2014-09-01

    Full Text Available In a time of increasing concerns about the immense energy consumption and poor environmental performance of contemporary processes in the chemical industry, there is great need to develop novel sustainable technologies that enhance energy efficiency. There is abundant chemical literature on process innovations (laboratory-scale around the plasma reactor itself, which, naturally, is the essential part to be intensified to achieve a satisfactory process. In essence, a plasma process needs attention beyond reaction engineering towards the process integration side and also with strong electrical engineering focus. In this mini-review, we have detailed our future focus on the process and energy intensification of plasma-based N-fixation. Three focal points are mainly stressed throughout the review: (I the integration of renewable energy; (II the power supply system of plasma reactors and (III process design of industrial plasma-assisted nitrogen fixation. These different enabling strategies will be set in a holistic and synergetic picture so as to improve process performance.

  6. FUNCTIONAL-ANALYSIS OF THE N-TERMINAL PREPEPTIDES OF WATERMELON MITOCHONDRIAL AND GLYOXYSOMAL MALATE-DEHYDROGENASES

    NARCIS (Netherlands)

    LEHNERER, M; KEIZERGUNNIK, [No Value; VEENHUIS, M; GIETL, C

    1994-01-01

    Mitochondrial and glyoxysomal malate dehydrogenase (mMDH; gMDH; L-malate : NAD(+) oxidoreductase; EC 1.1.1.37) of watermelon (Citrullus vulgaris) cotyledons are synthesized with N-terminal cleavable presequences which are shown to specify sorting of the two proteins. The two presequences differ in

  7. Fluorine-plasma surface treatment for gate forward leakage current reduction in AlGaN/GaN HEMTs

    International Nuclear Information System (INIS)

    Chen Wanjun; Zhang Jing; Zhang Bo; Chen, Kevin Jing

    2013-01-01

    The gate forward leakage current in AlGaN/GaN high electron mobility transistors (HEMTs) is investigated. It is shown that the current which originated from the forward biased Schottky-gate contributed to the gate forward leakage current. Therefore, a fluorine-plasma surface treatment is presented to induce the negative ions into the AlGaN layer which results in a higher metal—semiconductor barrier. Consequently, the gate forward leakage current shrinks. Experimental results confirm that the gate forward leakage current is decreased by one order magnitude lower than that of HEMT device without plasma treatment. In addition, the DC characteristics of the HEMT device with plasma treatment have been studied. (semiconductor devices)

  8. Improving cell penetration of helical peptides stabilized by N-terminal crosslinked aspartic acids.

    Science.gov (United States)

    Zhao, Hui; Jiang, Yanhong; Tian, Yuan; Yang, Dan; Qin, Xuan; Li, Zigang

    2017-01-04

    Cell penetration and nucleus translocation efficiency are important for the cellular activities of peptide therapeutics. For helical peptides stabilized by N-terminal crosslinked aspartic acid, correlations between their penetration efficiency/nucleus translocation and physicochemical properties were studied. An increase in hydrophobicity and isoelectric point will promote cellular uptake and nucleus translocation of stabilized helices.

  9. Preparation and Analysis of N-Terminal Chemokine Receptor Sulfopeptides Using Tyrosylprotein Sulfotransferase Enzymes.

    Science.gov (United States)

    Seibert, Christoph; Sanfiz, Anthony; Sakmar, Thomas P; Veldkamp, Christopher T

    2016-01-01

    In most chemokine receptors, one or multiple tyrosine residues have been identified within the receptor N-terminal domain that are, at least partially, modified by posttranslational tyrosine sulfation. For example, tyrosine sulfation has been demonstrated for Tyr-3, -10, -14, and -15 of CCR5, for Tyr-3, -14, and -15 of CCR8, and for Tyr-7, -12, and -21 of CXCR4. While there is evidence for several chemokine receptors that tyrosine sulfation is required for optimal interaction with the chemokine ligands, the precise role of tyrosine sulfation for chemokine receptor function remains unclear. Furthermore, the function of the chemokine receptor N-terminal domain in chemokine binding and receptor activation is also not well understood. Sulfotyrosine peptides corresponding to the chemokine receptor N-termini are valuable tools to address these important questions both in structural and functional studies. However, due to the lability of the sulfotyrosine modification, these peptides are difficult to obtain using standard peptide chemistry methods. In this chapter, we provide methods to prepare sulfotyrosine peptides by enzymatic in vitro sulfation of peptides using purified recombinant tyrosylprotein sulfotransferase (TPST) enzymes. In addition, we also discuss alternative approaches for the generation of sulfotyrosine peptides and methods for sulfopeptide analysis. © 2016 Elsevier Inc. All rights reserved.

  10. Investigation of enhancement-mode AlGaN/GaN nanowire channel high-electron-mobility transistor with oxygen-containing plasma treatment

    Science.gov (United States)

    He, Yunlong; Wang, Chong; Mi, Minhan; Zhang, Meng; Zhu, Qing; Zhang, Peng; Wu, Ji; Zhang, Hengshuang; Zheng, Xuefeng; Yang, Ling; Duan, Xiaoling; Ma, Xiaohua; Hao, Yue

    2017-05-01

    A novel enhancement-mode (E-mode) AlGaN/GaN high-electron-mobility transistor (HEMT) has been fabricated, by combining nanowire channel (NC) structure fabrication and N2O (or O2) plasma treatment. A comparison of two NC-HEMTs with different plasma treatments has been made. The NC-HEMT with N2O plasma treatment shows an output current of 610 mA/mm and a peak transconductance of 450 mS/mm. The DIBL of the NC-HEMT with N2O plasma treatment is as low as 2 mV/V, and an SS of 70 mV/decade is achieved. The device exhibits an intrinsic current gain cutoff frequency f T of 19 GHz and a maximum oscillation frequency f max of 58 GHz.

  11. Plasma-column instabilities in a reversed-field pinch without a shell

    Energy Technology Data Exchange (ETDEWEB)

    Schmid, P.G.

    1988-01-01

    Plasma column instabilities in a Reversed Field Pinch (RFP) without a shell were investigated in the Colorado Reversatron RFP. The Reversatron RFP (aspect ration R/a = 50 cm/8cm) is a toroidal plasma containment device consisting of a vacuum chamber, a thick conducting shell, modular shells, magnetic field producing coils and diagnostics to characterize the plasma. RFP discharges were set up in the Reversatron in three different experimental configurations: with a thick conducting shell, with a modular shell and with no shell. In two of the configurations, a shell enclosed the plasma column to provide some plasma stability. A vertical magnetic field provided equilibrium in experiments without a shell. Data from discharges without a shell indicated that the plasma duration was greatly reduced and the plasma resistance increased compared to the discharges with a thick shell. Plasma position probes indicated large plasma centriod displacements corresponding to a n = 1 and a n = 3 kink coincident with the peak of the plasma current and the start of a discharge termination phase. The modular shell lengthened the discharge duration and lowered the plasma resistance to values intermediate between the plasma with a thick shell and the plasma with no shell. The modular shell suppressed the large plasma column displacements observed in the RFP plasma without a shell.

  12. Plasma-column instabilities in a reversed-field pinch without a shell

    International Nuclear Information System (INIS)

    Schmid, P.G.

    1988-01-01

    Plasma column instabilities in a Reversed Field Pinch (RFP) without a shell were investigated in the Colorado Reversatron RFP. The Reversatron RFP (aspect ration R/a = 50 cm/8cm) is a toroidal plasma containment device consisting of a vacuum chamber, a thick conducting shell, modular shells, magnetic field producing coils and diagnostics to characterize the plasma. RFP discharges were set up in the Reversatron in three different experimental configurations: with a thick conducting shell, with a modular shell and with no shell. In two of the configurations, a shell enclosed the plasma column to provide some plasma stability. A vertical magnetic field provided equilibrium in experiments without a shell. Data from discharges without a shell indicated that the plasma duration was greatly reduced and the plasma resistance increased compared to the discharges with a thick shell. Plasma position probes indicated large plasma centriod displacements corresponding to a n = 1 and a n = 3 kink coincident with the peak of the plasma current and the start of a discharge termination phase. The modular shell lengthened the discharge duration and lowered the plasma resistance to values intermediate between the plasma with a thick shell and the plasma with no shell. The modular shell suppressed the large plasma column displacements observed in the RFP plasma without a shell

  13. Structure of a C-terminal AHNAK peptide in a 1:2:2 complex with S100A10 and an acetylated N-terminal peptide of annexin A2

    International Nuclear Information System (INIS)

    Ozorowski, Gabriel; Milton, Saskia; Luecke, Hartmut

    2013-01-01

    Structure of a 20-amino-acid peptide of AHNAK bound asymmetrically to the AnxA2–S100A10A heterotetramer (1:2:2 symmetry) provides insights into the atomic level interactions that govern this membrane-repair scaffolding complex. AHNAK, a large 629 kDa protein, has been implicated in membrane repair, and the annexin A2–S100A10 heterotetramer [(p11) 2 (AnxA2) 2 )] has high affinity for several regions of its 1002-amino-acid C-terminal domain. (p11) 2 (AnxA2) 2 is often localized near the plasma membrane, and this C2-symmetric platform is proposed to be involved in the bridging of membrane vesicles and trafficking of proteins to the plasma membrane. All three proteins co-localize at the intracellular face of the plasma membrane in a Ca 2+ -dependent manner. The binding of AHNAK to (p11) 2 (AnxA2) 2 has been studied previously, and a minimal binding motif has been mapped to a 20-amino-acid peptide corresponding to residues 5654–5673 of the AHNAK C-terminal domain. Here, the 2.5 Å resolution crystal structure of this 20-amino-acid peptide of AHNAK bound to the AnxA2–S100A10 heterotetramer (1:2:2 symmetry) is presented, which confirms the asymmetric arrangement first described by Rezvanpour and coworkers and explains why the binding motif has high affinity for (p11) 2 (AnxA2) 2 . Binding of AHNAK to the surface of (p11) 2 (AnxA2) 2 is governed by several hydrophobic interactions between side chains of AHNAK and pockets on S100A10. The pockets are large enough to accommodate a variety of hydrophobic side chains, allowing the consensus sequence to be more general. Additionally, the various hydrogen bonds formed between the AHNAK peptide and (p11) 2 (AnxA2) 2 most often involve backbone atoms of AHNAK; as a result, the side chains, particularly those that point away from S100A10/AnxA2 towards the solvent, are largely interchangeable. While the structure-based consensus sequence allows interactions with various stretches of the AHNAK C-terminal domain, comparison

  14. Two-temperature transport coefficients of SF6–N2 plasma

    International Nuclear Information System (INIS)

    Yang, Fei; Chen, Zhexin; Wu, Yi; Rong, Mingzhe; Wang, Chunlin; Guo, Anxiang; Liu, Zirui

    2015-01-01

    Sulfur hexafluoride (SF 6 ) is widely adopted in electric power industry, especially in high-voltage circuit breakers and gas-insulated switchgear. However, the use of SF 6 is limited by its high liquidation temperature and high global warming potential. Recently, research shows SF 6 –N 2 mixture, which shows environmental friendliness and good electrical properties, may be a feasible substitute for pure SF 6 . This paper is devoted to the calculation of and transport coefficients of SF 6 –N 2 mixture under both LTE (local thermodynamic equilibrium) and non-LTE condition. The two–temperature mass action law was used to determine the composition. The transport coefficients were calculated by classical Chapman–Enskog method simplified by Devoto. The thermophysical properties are presented for electron temperatures of 300–40 000 K, ratios of electron to heavy species temperature of 1–10 and N 2 mole fraction of 0%–100% at atmospheric pressure. The ionization processes under both LTE and non-LTE have been discussed. The results show that deviations from local thermodynamic equilibrium significantly affect the properties of SF 6 –N 2 plasma, especially before the plasma is fully ionized. The different influence of N 2 on properties for SF 6 –N 2 plasma in and out of LTE has been found. The results will serve as reliable reference data for computational simulation of the behavior of SF 6 –N 2 plasmas

  15. Proyecto básico de adecuación y ampliación de una terminal de almacenamiento y distribución de combustible a buques

    OpenAIRE

    Fernández Hinojosa, María Isabel

    2018-01-01

    El objeto de este proyecto es la definición básica de una planta de almacenamiento de productos petrolíferos no inflamables con punto de inflamación superior a 55ºC (Clase C) y 98.000 m3 de capacidad que permita llevar a cabo la solicitud de permisos y licencias necesarios para su posterior construcción. La capacidad total se alcanzará a partir de la adaptación de la terminal existente de 30.000 m3,que estaba destinada al manejo de aceites vegetales, y de la construcción ...

  16. Autoantibodies to N-terminally truncated GAD improve clinical phenotyping of individuals with adult-onset diabetes: Action LADA 12.

    Science.gov (United States)

    Achenbach, Peter; Hawa, Mohammed I; Krause, Stephanie; Lampasona, Vito; Jerram, Samuel T; Williams, Alistair J K; Bonifacio, Ezio; Ziegler, Anette G; Leslie, R David

    2018-04-04

    Adult-onset type 1 diabetes, in which the 65 kDa isoform of GAD (GAD65) is a major autoantigen, has a broad clinical phenotype encompassing variable need for insulin therapy. This study aimed to evaluate whether autoantibodies against N-terminally truncated GAD65 more closely defined a type 1 diabetes phenotype associated with insulin therapy. Of 1114 participants with adult-onset diabetes from the Action LADA (latent autoimmune diabetes in adults) study with sufficient sera, we selected those designated type 1 (n = 511) or type 2 diabetes (n = 603) and retested the samples in radiobinding assays for human full-length GAD65 autoantibodies (f-GADA) and N-terminally truncated (amino acids 96-585) GAD65 autoantibodies (t-GADA). Individuals' clinical phenotypes were analysed according to antibody binding patterns. Overall, 478 individuals were f-GADA-positive, 431 were t-GADA-positive and 628 were negative in both assays. Risk of insulin treatment was augmented in t-GADA-positive individuals (OR 4.69 [95% CI 3.57, 6.17]) compared with f-GADA-positive individuals (OR 3.86 [95% CI 2.95, 5.06]), irrespective of diabetes duration. Of 55 individuals who were f-GADA-positive but t-GADA-negative, i.e. with antibody binding restricted to the N-terminus of GAD65, the phenotype was similar to type 2 diabetes with low risk of progression to insulin treatment. Compared with these individuals with N-terminal GAD65-restricted GADA, t-GADA-positive individuals were younger at diagnosis (p = 0.005), leaner (p N-terminally truncated GAD65 autoantibodies is associated with the clinical phenotype of autoimmune type 1 diabetes and predicts insulin therapy.

  17. Atomic layer deposition of AlN for thin membranes using trimethylaluminum and H2/N2 plasma

    International Nuclear Information System (INIS)

    Goerke, Sebastian; Ziegler, Mario; Ihring, Andreas; Dellith, Jan; Undisz, Andreas; Diegel, Marco; Anders, Solveig; Huebner, Uwe; Rettenmayr, Markus; Meyer, Hans-Georg

    2015-01-01

    Highlights: • AlN films grown at 150 °C by ALD using trimethylaluminum and H 2 /N 2 -plasma. • Nearly stoichiometric AlN films (ratio Al:N = 0.938), polycrystalline by XRD/TEM. • Refractive index of n = 1.908 and low thermal conductivity of κ = 1.66 W/(m K). • Free-standing AlN membranes mechanically stable and buckling free (tensile strain). • Membrane patterning by focused ion beam etching possible. - Abstract: Aluminum nitride (AlN) thin films with thicknesses from 20 to 100 nm were deposited on silicon, amorphous silica, silicon nitride, and vitreous carbon by plasma enhanced atomic layer deposition (PE-ALD). Trimethylaluminum (TMA) and a H 2 /N 2 plasma mixture were used as precursors. We investigated the influence of deposition temperature and plasma parameters on the growth characteristics and the film properties of AlN. Stable PE-ALD growth conditions were obtained from 150 °C to the highest tested temperature of 300 °C. The growth rate, refractive index, and thickness homogeneity on 4″ wafers were determined by spectroscopic ellipsometry. X-ray diffraction (XRD), high-resolution transmission electron microscopy (HRTEM) and Rutherford backscattering spectrometry (RBS) were carried out to analyze crystallinity and composition of the films. Furthermore, the thermal conductivity and the film stress were determined. The stress was sufficiently low to fabricate mechanically stable free-standing AlN membranes with lateral dimensions of up to 2.2 × 2.2 mm 2 . The membranes were patterned with focused ion beam etching. Thus, these AlN membranes qualify as dielectric support material for a variety of potential applications

  18. Structure of a double hexamer of the Pyrococcus furiosus minichromosome maintenance protein N-terminal domain

    Energy Technology Data Exchange (ETDEWEB)

    Meagher, Martin; Enemark, Eric J.

    2016-06-22

    The crystal structure of the N-terminal domain of thePyrococcus furiosusminichromosome maintenance (MCM) protein as a double hexamer is described. The MCM complex is a ring-shaped helicase that unwinds DNA at the replication fork of eukaryotes and archaea. Prior to replication initiation, the MCM complex assembles as an inactive double hexamer at specific sites of DNA. The presented structure is highly consistent with previous MCM double-hexamer structures and shows two MCM hexamers with a head-to-head interaction mediated by the N-terminal domain. Minor differences include a diminished head-to-head interaction and a slightly reduced inter-hexamer rotation.

  19. Radioimmunoassay and characterization of atrial natriuretic peptide in human plasma

    International Nuclear Information System (INIS)

    Yandle, T.G.; Espiner, E.A.; Nicholls, M.G.; Duff, H.

    1986-01-01

    A RIA for alpha-human atrial natriuretic peptide (alpha hANP) in plasma was developed and used to study the immunoreactive components secreted by the heart and circulating in peripheral venous plasma. The assay used [125I]diiodotyrosyl-alpha hANP, purified by high pressure liquid chromatography (HPLC), and a C-terminal-specific antiserum purchased from Peninsula Laboratories. Serial dilution curves of coronary sinus plasma samples were parallel with the standard curve, but significant nonparallelism was found in peripheral plasma samples of low immunoreactivity. When plasma was extracted using C-18 Sep-Pak cartridges, serial dilution curves from both coronary sinus and peripheral plasma samples were parallel to the standard curve. Although values for plasma samples assayed before and after extraction agreed closely (r = 0.99; n = 76), immunoreactive ANP in unextracted plasma was consistently greater (70-79 pmol/liter) than in extracts of plasma, suggesting non-specific interference by a component in plasma when assayed without extraction. Mean plasma immunoreactive ANP in 19 normal subjects consuming a normal salt intake was 14 +/- 1 (+/- SE) pmol/liter. In 5 normal men, increasing dietary sodium intake from 10 to 200 mmol sodium/day was associated with a 2-fold increment in ANP levels, and similar changes accompanied acute sodium loading using iv saline. Elevated values were found in patients with congestive heart failure (mean, 58 pmol/liter; range, 0-200; n = 9), chronic renal failure (mean, 118 pmol/liter; range, 30-290; n = 8), and primary aldosteronism (range, 32-90 pmol/liter; n = 3). HPLC and gel chromatographic analysis of the immunoreactive material found in coronary sinus plasma extracts showed that a large amount of the material eluted in the position of alpha hANP

  20. A prawn core histone 4: derivation of N- and C-terminal peptides and their antimicrobial properties, molecular characterization and mRNA transcription.

    Science.gov (United States)

    Chaurasia, Mukesh Kumar; Palanisamy, Rajesh; Bhatt, Prasanth; Kumaresan, Venkatesh; Gnanam, Annie J; Pasupuleti, Mukesh; Kasi, Marimuthu; Harikrishnan, Ramaswamy; Arockiaraj, Jesu

    2015-01-01

    This study investigates the complete molecular characterization including bioinformatics characterization, gene expression, synthesis of N and C terminal peptides and their antimicrobial activity of the core histone 4 (H4) from freshwater giant prawn Macrobrachium rosenbergii (Mr). A cDNA encoding MrH4 was identified from the constructed cDNA library of M. rosenbergii during screening and the sequence was obtained using internal sequencing primers. The MrH4 coding region possesses a polypeptide of 103 amino acids with a calculated molecular weight of 11kDa and an isoelectric point of 11.5. The bioinformatics analysis showed that the MrH4 polypeptide contains a H4 signature at (15)GAKRH(19). Multiple sequence alignment of MrH4 showed that the N-terminal (21-42) and C-terminal (87-101) antimicrobial peptide regions and the pentapeptide or H4 signature (15-19) are highly conserved including in humans. The phylogenetic tree formed two separate clades of vertebrate and invertebrate H4, wherein MrH4 was located within the arthropod monophyletic clade of invertebrate H4 groups. Three-dimensional model of MrH4 was established using I-TASSER program and the model was validated using Ramachandran plot analysis. Schiffer-Edmundson helical wheel modeling was used to predict the helix propensity of N (21-42) and C (87-101) terminal derived Mr peptides. The highest gene expression was observed in gills and is induced by viral [white spot syndrome baculovirus (WSBV) and M. rosenbergii nodovirus (MrNV)] and bacterial (Aeromonas hydrophila and Vibrio harveyi) infections. The N and C terminal peptides were synthesized and their antimicrobial and hemolytic properties were examined. Both peptides showed activity against the tested Gram negative and Gram positive bacteria; however, the highest activity was noticed against Gram negative bacteria. Among the two peptides used in this study, C-terminal peptide yielded better results than the N-terminal peptide. Therefore, C terminal

  1. The AAA+ ATPase TRIP13 remodels HORMA domains through N-terminal engagement and unfolding

    Energy Technology Data Exchange (ETDEWEB)

    Ye, Qiaozhen; Kim, Dong Hyun; Dereli, Ihsan; Rosenberg, Scott C.; Hagemann, Goetz; Herzog, Franz; Tóth, Attila; Cleveland, Don W.; Corbett, Kevin D.

    2017-06-28

    Proteins of the conserved HORMA domain family, including the spindle assembly checkpoint protein MAD2 and the meiotic HORMADs, assemble into signaling complexes by binding short peptides termed “closure motifs”. The AAA+ ATPase TRIP13 regulates both MAD2 and meiotic HORMADs by disassembling these HORMA domain–closure motif complexes, but its mechanisms of substrate recognition and remodeling are unknown. Here, we combine X-ray crystallography and crosslinking mass spectrometry to outline how TRIP13 recognizes MAD2 with the help of the adapter protein p31comet. We show that p31comet binding to the TRIP13 N-terminal domain positions the disordered MAD2 N-terminus for engagement by the TRIP13 “pore loops”, which then unfold MAD2 in the presence of ATP. N-terminal truncation of MAD2 renders it refractory to TRIP13 action in vitro, and in cells causes spindle assembly checkpoint defects consistent with loss of TRIP13 function. Similar truncation of HORMAD1 in mouse spermatocytes compromises its TRIP13-mediated removal from meiotic chromosomes, highlighting a conserved mechanism for recognition and disassembly of HORMA domain–closure motif complexes by TRIP13.

  2. Band termination in the N=Z nucleus 44Ti

    International Nuclear Information System (INIS)

    Ur, C.A.; Lenzi, S.M.; Martinez-Pinedo, G.

    1998-01-01

    Nuclei in the vicinity of the middle of the 1f 7/2 shell show strong prolate deformation at low spins resulting in rotational-like band structures. With increasing angular momentum the structure of these nuclei evolves through triaxial and spherical shapes. Recently, band terminating states corresponding to fully aligned configurations of valence nucleons in the f 7/2 shell have been reported. Further increase of the angular momentum can be achieved by particle excitations on the higher shell. This will result in high energy γ-ray transitions as it was observed in 50 Cr. We have investigated the structure of 44 Ti up to the band termination. Excited states in 44 Ti have been populated via the 28 Si + 24 Mg at 110 MeV beam energy. The target consisted of ∼0.5 mg/cm 2 of 24 Mg deposited on a gold backing. Gamma-rays were detected with the GASP multidetector array composed by 40 HPGe Compton-suppressed detectors and the inner ball built of 80 BGO detectors. The preliminary level scheme of 44 Ti, as determined in our work, is presented. This nucleus has 2 valence protons and 2 valence neutrons filling the f 7/2 shell. The band terminating state corresponding to their total alignment is the 12 + state. Several γ-rays transitions above this state have been identified. Also, we have identified two negative parity bands strongly connected to the yrast positive parity structure. Such structures have also been observed in other two even-even N=Z nuclei in the f 7/2 shell, namely, 44 Cr and 52 Fe, but they were less populated. The structure of 44 Ti is also interesting from the point of view of the cross-conjugate symmetry. Comparing the level structure of 44 Ti and the one of its cross-conjugate nucleus at the other end of the shell, 52 Fe, it can be noticed that up to spin 10ℎ their structure is very similar, but in 44 Ti the band terminating state 12 + is not below the 10 + state as in the case of 52 Fe. This was related to a reminiscent degree of collectivity in the

  3. The N-terminal domain of human DNA helicase Rtel1 contains a redox active iron-sulfur cluster.

    Science.gov (United States)

    Landry, Aaron P; Ding, Huangen

    2014-01-01

    Human telomere length regulator Rtel1 is a superfamily II DNA helicase and is essential for maintaining proper length of telomeres in chromosomes. Here we report that the N-terminal domain of human Rtel1 (RtelN) expressed in Escherichia coli cells produces a protein that contains a redox active iron-sulfur cluster with the redox midpoint potential of -248 ± 10 mV (pH 8.0). The iron-sulfur cluster in RtelN is sensitive to hydrogen peroxide and nitric oxide, indicating that reactive oxygen/nitrogen species may modulate the DNA helicase activity of Rtel1 via modification of its iron-sulfur cluster. Purified RtelN retains a weak binding affinity for the single-stranded (ss) and double-stranded (ds) DNA in vitro. However, modification of the iron-sulfur cluster by hydrogen peroxide or nitric oxide does not significantly affect the DNA binding activity of RtelN, suggesting that the iron-sulfur cluster is not directly involved in the DNA interaction in the N-terminal domain of Rtel1.

  4. The N-Terminal Domain of Human DNA Helicase Rtel1 Contains a Redox Active Iron-Sulfur Cluster

    Directory of Open Access Journals (Sweden)

    Aaron P. Landry

    2014-01-01

    Full Text Available Human telomere length regulator Rtel1 is a superfamily II DNA helicase and is essential for maintaining proper length of telomeres in chromosomes. Here we report that the N-terminal domain of human Rtel1 (RtelN expressed in Escherichia coli cells produces a protein that contains a redox active iron-sulfur cluster with the redox midpoint potential of −248 ± 10 mV (pH 8.0. The iron-sulfur cluster in RtelN is sensitive to hydrogen peroxide and nitric oxide, indicating that reactive oxygen/nitrogen species may modulate the DNA helicase activity of Rtel1 via modification of its iron-sulfur cluster. Purified RtelN retains a weak binding affinity for the single-stranded (ss and double-stranded (ds DNA in vitro. However, modification of the iron-sulfur cluster by hydrogen peroxide or nitric oxide does not significantly affect the DNA binding activity of RtelN, suggesting that the iron-sulfur cluster is not directly involved in the DNA interaction in the N-terminal domain of Rtel1.

  5. The Herpes Simplex Virus Protein pUL31 Escorts Nucleocapsids to Sites of Nuclear Egress, a Process Coordinated by Its N-Terminal Domain.

    Directory of Open Access Journals (Sweden)

    Christina Funk

    2015-06-01

    Full Text Available Progeny capsids of herpesviruses leave the nucleus by budding through the nuclear envelope. Two viral proteins, the membrane protein pUL34 and the nucleo-phosphoprotein pUL31 form the nuclear egress complex that is required for capsid egress out of the nucleus. All pUL31 orthologs are composed of a diverse N-terminal domain with 1 to 3 basic patches and a conserved C-terminal domain. To decipher the functions of the N-terminal domain, we have generated several Herpes simplex virus mutants and show here that the N-terminal domain of pUL31 is essential with basic patches being critical for viral propagation. pUL31 and pUL34 entered the nucleus independently of each other via separate routes and the N-terminal domain of pUL31 was required to prevent their premature interaction in the cytoplasm. Unexpectedly, a classical bipartite nuclear localization signal embedded in this domain was not required for nuclear import of pUL31. In the nucleus, pUL31 associated with the nuclear envelope and newly formed capsids. Viral mutants lacking the N-terminal domain or with its basic patches neutralized still associated with nucleocapsids but were unable to translocate them to the nuclear envelope. Replacing the authentic basic patches with a novel artificial one resulted in HSV1(17+Lox-UL31-hbpmp1mp2, that was viable but delayed in nuclear egress and compromised in viral production. Thus, while the C-terminal domain of pUL31 is sufficient for the interaction with nucleocapsids, the N-terminal domain was essential for capsid translocation to sites of nuclear egress and a coordinated interaction with pUL34. Our data indicate an orchestrated sequence of events with pUL31 binding to nucleocapsids and escorting them to the inner nuclear envelope. We propose a common mechanism for herpesviral nuclear egress: pUL31 is required for intranuclear translocation of nucleocapsids and subsequent interaction with pUL34 thereby coupling capsid maturation with primary

  6. Comparison of gate dielectric plasma damage from plasma-enhanced atomic layer deposited and magnetron sputtered TiN metal gates

    Energy Technology Data Exchange (ETDEWEB)

    Brennan, Christopher J.; Neumann, Christopher M.; Vitale, Steven A., E-mail: steven.vitale@ll.mit.edu [Lincoln Laboratory, Massachusetts Institute of Technology, Lexington, Massachusetts 02420 (United States)

    2015-07-28

    Fully depleted silicon-on-insulator transistors were fabricated using two different metal gate deposition mechanisms to compare plasma damage effects on gate oxide quality. Devices fabricated with both plasma-enhanced atomic-layer-deposited (PE-ALD) TiN gates and magnetron plasma sputtered TiN gates showed very good electrostatics and short-channel characteristics. However, the gate oxide quality was markedly better for PE-ALD TiN. A significant reduction in interface state density was inferred from capacitance-voltage measurements as well as a 1200× reduction in gate leakage current. A high-power magnetron plasma source produces a much higher energetic ion and vacuum ultra-violet (VUV) photon flux to the wafer compared to a low-power inductively coupled PE-ALD source. The ion and VUV photons produce defect states in the bulk of the gate oxide as well as at the oxide-silicon interface, causing higher leakage and potential reliability degradation.

  7. Locus-specific detection of HLA-DQ and -DR antigens by antibodies against synthetic N-terminal octapeptides of the beta chain

    DEFF Research Database (Denmark)

    Deufel, T; Grove, A; Kofod, Hans

    1985-01-01

    Antibodies against synthetic peptides representing the class-II antigen HLA-DR and -DQ beta chain N-terminal sequences were prepared in rabbits. The two octapeptides only share two amino acids and enzyme-linked immuno-assays showed the antisera only to bind to its own antigen. Both peptide antisera...... chains of HLA-DR and -DQ have been prepared by the preparation by the production of antibodies against the N-terminal sequences of each polypeptide....

  8. Directed evolution of the TALE N-terminal domain for recognition of all 5′ bases

    Science.gov (United States)

    Lamb, Brian M.; Mercer, Andrew C.; Barbas, Carlos F.

    2013-01-01

    Transcription activator-like effector (TALE) proteins can be designed to bind virtually any DNA sequence. General guidelines for design of TALE DNA-binding domains suggest that the 5′-most base of the DNA sequence bound by the TALE (the N0 base) should be a thymine. We quantified the N0 requirement by analysis of the activities of TALE transcription factors (TALE-TF), TALE recombinases (TALE-R) and TALE nucleases (TALENs) with each DNA base at this position. In the absence of a 5′ T, we observed decreases in TALE activity up to >1000-fold in TALE-TF activity, up to 100-fold in TALE-R activity and up to 10-fold reduction in TALEN activity compared with target sequences containing a 5′ T. To develop TALE architectures that recognize all possible N0 bases, we used structure-guided library design coupled with TALE-R activity selections to evolve novel TALE N-terminal domains to accommodate any N0 base. A G-selective domain and broadly reactive domains were isolated and characterized. The engineered TALE domains selected in the TALE-R format demonstrated modularity and were active in TALE-TF and TALEN architectures. Evolved N-terminal domains provide effective and unconstrained TALE-based targeting of any DNA sequence as TALE binding proteins and designer enzymes. PMID:23980031

  9. N-terminal amphipathic helix as a trigger of hemolytic activity in antimicrobial peptides: a case study in latarcins.

    Science.gov (United States)

    Polyansky, Anton A; Vassilevski, Alexander A; Volynsky, Pavel E; Vorontsova, Olga V; Samsonova, Olga V; Egorova, Natalya S; Krylov, Nicolay A; Feofanov, Alexei V; Arseniev, Alexander S; Grishin, Eugene V; Efremov, Roman G

    2009-07-21

    In silico structural analyses of sets of alpha-helical antimicrobial peptides (AMPs) are performed. Differences between hemolytic and non-hemolytic AMPs are revealed in organization of their N-terminal region. A parameter related to hydrophobicity of the N-terminal part is proposed as a measure of the peptide propensity to exhibit hemolytic and other unwanted cytotoxic activities. Based on the information acquired, a rational approach for selective removal of these properties in AMPs is suggested. A proof of concept is gained through engineering specific mutations that resulted in elimination of the hemolytic activity of AMPs (latarcins) while leaving the beneficial antimicrobial effect intact.

  10. Pro–A-Type Natriuretic Peptide, Proadrenomedullin, and N-Terminal Pro–B-Type Natriuretic Peptide Used in a Multimarker Strategy in Primary Health Care in Risk Assessment of Patients With Symptoms of Heart Failure

    DEFF Research Database (Denmark)

    Alehagen, Urban; Dahlström, Ulf; Rehfeld, Jens F

    2013-01-01

    Use of new biomarkers in the handling of heart failure patients has been advocated in the literature, but most often in hospital-based populations. Therefore, we wanted to evaluate whether plasma measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP), midregional pro-A-type...... natriuretic peptide (MR-proANP), and midregional proadrenomedullin (MR-proADM), individually or combined, gives prognostic information regarding cardiovascular and all-cause mortality that could motivate use in elderly patients presenting with symptoms suggestive of heart failure in primary health care....

  11. The EspF N-Terminal of Enterohemorrhagic Escherichia coli O157:H7 EDL933w Imparts Stronger Toxicity Effects on HT-29 Cells than the C-Terminal

    Directory of Open Access Journals (Sweden)

    Xiangyu Wang

    2017-09-01

    Full Text Available Enterohemorrhagic Escherichia coli (EHEC O157:H7 EspF is an important multifunctional protein that destroys the tight junctions of intestinal epithelial cells and promotes host cell apoptosis. However, its molecular mechanism remains elusive. We knocked out the espF sequence (747 bp, ΔespF, N-terminal sequence (219 bp, ΔespFN, and C-terminal sequence (528 bp, ΔespFC separately using the pKD46-mediated λ Red homologous recombination system. Then, we built the corresponding complementation strains, namely, ΔespF/pespF, ΔespFN/pespFN, and ΔespFC/pespFC by overlap PCR, which were used in infecting HT-29 cells and BALB/C mice. The level of reactive oxygen species, cell apoptosis, mitochondrial trans-membrane potential, inflammatory factors, transepithelial electrical resistance (TER, and animal mortality were evaluated by DCFH-DA, double staining of Annexin V-FITC/PI, JC-1 staining, ELISA kit, and a mouse assay. The wild-type (WT, ΔespF, ΔespF/pespF, ΔespFC, ΔespFC/pespFC, ΔespFN, and ΔespFN/pespFN groups exhibited apoptotic rates of 68.3, 27.9, 64.9, 65.7, 73.4, 41.3, and 35.3% respectively, and mean TNF-α expression levels of 428 pg/mL, 342, 466, 446, 381, 383, and 374 pg/mL, respectively. In addition, the apoptotic rates and TNF-α levels of the WT, ΔespF/pespF, and ΔespFC were significantly higher than that of ΔespF, ΔespFN, ΔespFC/pespFC, and ΔespFN/pespFN group (p < 0.05. The N-terminal of EspF resulted in an increase in the number of apoptotic cells, TNF-α secretion, ROS generation, mitochondria apoptosis, and pathogenicity in BalB/c mice. In conclusion, the N-terminal domain of the Enterohemorrhagic E. coli O157:H7 EspF more strongly promotes apoptosis and inflammation than the C-terminal domain.

  12. Specificity of N-terminal methionyl peptidase: analysis by site-directed mutagenesis

    International Nuclear Information System (INIS)

    Kasper, T.J.; Boissel, J.P.; Bunn, H.F.

    1987-01-01

    The start site of eukaryotic translation is normally an AUG codon. The corresponding N-terminal methionine is most often removed when the nascent chain reaches about 30 residues. Data from a survey of 1764 eukaryotic protein sequences suggest that the residue adjacent to the initiator Met determines Met cleavage. In order to investigate the mechanism of this reaction, the authors have prepared oligonucleotide-directed mutants of human β-globin from gapped heteroduplexes of a T3/T7 plasmid containing a globin cDNA clone. To date, the authors have produced mutants encoding for 15 of 19 possible amino acid replacements at position 1 in the β-globin chain. These mutants have been confirmed by dideoxy sequencing, transcribed in vitro, and translated in a rabbit reticulocyte lysate in the presence of 35 S-methionine. Labeled translation products were then isolated by cation exchange HPLC, and tryptic peptides were analyzed by RP-HPLC. Thus far, this structural analysis has shown that for β-1 Val, Ala, and Ser, the initiator Met is cleaved, whereas for β-1 Lys, Met, Glu, Trp, Asn, Tyr, and Glu, initiator Met is retained. For β-1 Leu initiator Met is cleaved with a frequency of about 50%. These results are consistent with the data obtained from the previous survey. The expression of site-directed mutants in a cell-free system can also be used to investigate other N-terminal processing events, such as acetylation and myristylation

  13. Characterization of niphatenones that inhibit androgen receptor N-terminal domain.

    Directory of Open Access Journals (Sweden)

    Carmen A Banuelos

    Full Text Available Androgen ablation therapy causes a temporary reduction in tumor burden in patients with advanced prostate cancer. Unfortunately the malignancy will return to form lethal castration-recurrent prostate cancer (CRPC. The androgen receptor (AR remains transcriptionally active in CRPC in spite of castrate levels of androgens in the blood. AR transcriptional activity resides in its N-terminal domain (NTD. Possible mechanisms of continued AR transcriptional activity may include, at least in part, expression of constitutively active splice variants of AR that lack the C-terminal ligand-binding domain (LBD. Current therapies that target the AR LBD, would not be effective against these AR variants. Currently no drugs are clinically available that target the AR NTD which should be effective against these AR variants as well as full-length AR. Niphatenones were originally isolated and identified in active extracts from Niphates digitalis marine sponge. Here we begin to characterize the mechanism of niphatenones in blocking AR transcriptional activity. Both enantiomers had similar IC50 values of 6 µM for inhibiting the full-length AR in a functional transcriptional assay. However, (S-niphatenone had significantly better activity against the AR NTD compared to (R-niphatenone. Consistent with niphatenones binding to and inhibiting transactivation of AR NTD, niphatenones inhibited AR splice variant. Niphatenone did not affect the transcriptional activity of the related progesterone receptor, but slightly decreased glucocorticoid receptor (GR activity and covalently bound to GR activation function-1 (AF-1 region. Niphatenone blocked N/C interactions of AR without altering either AR protein levels or its intracellular localization in response to androgen. Alkylation with glutathione suggests that niphatenones are not a feasible scaffold for further drug development.

  14. Upregulation of α7 Nicotinic Receptors by Acetylcholinesterase C-Terminal Peptides

    Science.gov (United States)

    Bond, Cherie E.; Zimmermann, Martina; Greenfield, Susan A.

    2009-01-01

    Background The alpha-7 nicotinic acetylcholine receptor (α7-nAChR) is well known as a potent calcium ionophore that, in the brain, has been implicated in excitotoxicity and hence in the underlying mechanisms of neurodegenerative disorders such as Alzheimer's disease. Previous research implied that the activity of this receptor may be modified by exposure to a peptide fragment derived from the C-terminal region of the enzyme acetylcholinesterase. This investigation was undertaken to determine if the functional changes observed could be attributed to peptide binding interaction with the α7-nAChR, or peptide modulation of receptor expression. Methodology/Principal Findings This study provides evidence that two peptides derived from the C-terminus of acetylcholinesterase, not only selectively displace specific bungarotoxin binding at the α7-nAChR, but also alter receptor binding properties for its familiar ligands, including the alternative endogenous agonist choline. Of more long-term significance, these peptides also induce upregulation of α7-nAChR mRNA and protein expression, as well as enhancing receptor trafficking to the plasma membrane. Conclusions/Significance The results reported here demonstrate a hitherto unknown relationship between the α7-nAChR and the non-enzymatic functions of acetylcholinesterase, mediated independently by its C-terminal domain. Such an interaction may prove valuable as a pharmacological tool, prompting new approaches for understanding, and combating, the process of neurodegeneration. PMID:19287501

  15. Novel Insights into Structure-Activity Relationships of N-Terminally Modified PACE4 Inhibitors.

    Science.gov (United States)

    Kwiatkowska, Anna; Couture, Frédéric; Levesque, Christine; Ly, Kévin; Beauchemin, Sophie; Desjardins, Roxane; Neugebauer, Witold; Dory, Yves L; Day, Robert

    2016-02-04

    PACE4 plays important roles in prostate cancer cell proliferation. The inhibition of this enzyme has been shown to slow prostate cancer progression and is emerging as a promising therapeutic strategy. In previous work, we developed a highly potent and selective PACE4 inhibitor, the multi-Leu (ML) peptide, an octapeptide with the sequence Ac-LLLLRVKR-NH2 . Here, with the objective of developing a useful compound for in vivo administration, we investigate the effect of N-terminal modifications. The inhibitory activity, toxicity, stability, and cell penetration properties of the resulting analogues were studied and compared to the unmodified inhibitor. Our results show that the incorporation of a polyethylene glycol (PEG) moiety leads to a loss of antiproliferative activity, whereas the attachment of a lipid chain preserves or improves it. However, the lipidated peptides are significantly more toxic when compared with their unmodified counterparts. Therefore, the best results were achieved not by the N-terminal extension but by the protection of both ends with the d-Leu residue and 4-amidinobenzylamide, which yielded the most stable inhibitor, with an excellent activity and toxicity profile. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Interaction of N-terminal peptide analogues of the Na+,K+-ATPase with membranes

    DEFF Research Database (Denmark)

    Nguyen, Khoa; Garcia, Alvaro; Sani, Marc Antoine

    2018-01-01

    phosphatidylserine) in the surrounding membrane. Furthermore, to isolate which segments of the N-terminus could be involved in membrane binding, we chemically synthesized N-terminal fragments of various lengths. Based on a combination of results from RH421 UV/visible absorbance measurements and solid-state 31P and 2...

  17. Study of ultrasound-assisted radio-frequency plasma discharges in n-dodecane

    Science.gov (United States)

    Camerotto, Elisabeth; De Schepper, Peter; Nikiforov, Anton Y.; Brems, Steven; Shamiryan, Denis; Boullart, Werner; Leys, Christophe; De Gendt, Stefan

    2012-10-01

    This paper investigates the generation of a stable plasma phase in a liquid hydrocarbon (n-dodecane) by means of ultrasound (US) and radio-frequency (RF) or electromagnetic radiation. It is demonstrated for the first time that ultrasonic aided RF plasma discharges can be generated in a liquid. Plasma discharges are obtained for different gas mixtures at a pressure of 12 kPa and at low ignition powers (100 W for RF and 2.4 W cm-2 for US). Direct carbon deposition from the liquid precursor on Cu, Ni, SiO2 and Si substrates has been obtained and no apparent compositional or structural difference among the substrate materials was observed. Characterization of the deposited solid phase revealed an amorphous structure. In addition, structural changes in the liquid precursor after plasma treatment have been analysed. Optical emission spectroscopy (OES) allowed the estimation of several plasma characteristic temperatures. The plasma excitation temperature was estimated to be about 2.3-2.4 eV. The rotational and vibrational temperatures of the discharge in n-dodecane with Ar as a feed gas were 1400 K and 6500 K, respectively. In Ar/O2 plasma, an increased rotational (1630 K) and vibrational temperature (7200 K) were obtained.

  18. Método de eliminación de trihalometanos y/o contaminantes emergentes mediante plasma

    OpenAIRE

    Erra Serrabasa, Pilar; Jover Comas, Eric; Molina Mansilla, Ricardo; Bertrán Serra, Enric; Bayona Termens, Josep María; Reyes Contreras, Carolina

    2009-01-01

    Método de eliminación de trihalometanos y/o contaminantes emergentes mediante plasma. Se describe un método de eliminación de trihalometanos y contaminantes refractarios en medios acuosos mediante la aplicación directa de plasma para conseguir la degradación de los compuestos contaminantes presentes en el agua.

  19. N-terminal protein processing: A comparative proteogenomic analysis

    Energy Technology Data Exchange (ETDEWEB)

    Bonissone, Stefano; Gupta, Nitin; Romine, Margaret F.; Bradshaw, Ralph A.; Pevzner, Pavel A.

    2013-01-01

    N-Terminal Methionine Excision (NME) is a universally conserved mechanism with the same specificity across all life forms that removes the first Methionine in proteins when the second residue is Gly, Ala, Ser, Cys, Thr, Pro, or Val. In spite of its necessity for proper cell functioning, the functional role of NME remains unclear. In 1988, Arfin and Bradshaw connected NME with the N-end protein degradation rule and postulated that the role of NME is to expose the stabilizing residues with the goal to resist protein degradation. While this explanation (that treats 7 stabilizing residues in the same manner) has become the de facto dogma of NME, comparative proteogenomics analysis of NME tells a different story. We suggest that the primary role of NME is to expose only two (rather than seven) amino acids Ala and Ser for post-translational modifications (e.g., acetylation) rather than to regulate protein degradation. We argue that, contrary to the existing view, NME is not crucially important for proteins with 5 other stabilizing residue at the 2nd positions that are merely bystanders (their function is not affected by NME) that become exposed to NME because their sizes are comparable or smaller than the size of Ala and Ser.

  20. Plasma balls in large-N gauge theories and localized black holes

    International Nuclear Information System (INIS)

    Aharony, Ofer; Minwalla, Shiraz; Wiseman, Toby

    2006-01-01

    We argue for the existence of plasma balls-metastable, nearly homogeneous lumps of gluon plasma at just above the deconfinement energy density-in a class of large-N confining gauge theories that undergo first-order deconfinement transitions. Plasma balls decay over a time scale of order N 2 by thermally radiating hadrons at the deconfinement temperature. In gauge theories that have a dual description that is well approximated by a theory of gravity in a warped geometry, we propose that plasma balls map to a family of classically stable finite-energy black holes localized in the IR. We present a conjecture for the qualitative nature of large-mass black holes in such backgrounds and numerically construct these black holes in a particular class of warped geometries. These black holes have novel properties; in particular, their temperature approaches a nonzero constant value at large mass. Black holes dual to plasma balls shrink as they decay by Hawking radiation; towards the end of this process, they resemble ten-dimensional Schwarzschild black holes, which we propose are dual to small plasma balls. Our work may find practical applications in the study of the physics of localized black holes from a dual viewpoint

  1. The metalloid arsenite induces nuclear export of Id3 possibly via binding to the N-terminal cysteine residues

    International Nuclear Information System (INIS)

    Kurooka, Hisanori; Sugai, Manabu; Mori, Kentaro; Yokota, Yoshifumi

    2013-01-01

    Highlights: •Sodium arsenite induces cytoplasmic accumulation of Id3. •Arsenite binds to closely spaced N-terminal cysteine residues of Id3. •N-terminal cysteines are essential for arsenite-induced nuclear export of Id3. •Nuclear export of Id3 counteracts its transcriptional repression activity. -- Abstract: Ids are versatile transcriptional repressors that regulate cell proliferation and differentiation, and appropriate subcellular localization of the Id proteins is important for their functions. We previously identified distinct functional nuclear export signals (NESs) in Id1 and Id2, but no active NES has been reported in Id3. In this study, we found that treatment with the stress-inducing metalloid arsenite led to the accumulation of GFP-tagged Id3 in the cytoplasm. Cytoplasmic accumulation was impaired by a mutation in the Id3 NES-like sequence resembling the Id1 NES, located at the end of the HLH domain. It was also blocked by co-treatment with the CRM1-specific nuclear export inhibitor leptomycin B (LMB), but not with the inhibitors for mitogen-activated protein kinases (MAPKs). Importantly, we showed that the closely spaced N-terminal cysteine residues of Id3 interacted with the arsenic derivative phenylarsine oxide (PAO) and were essential for the arsenite-induced cytoplasmic accumulation, suggesting that arsenite induces the CRM1-dependent nuclear export of Id3 via binding to the N-terminal cysteines. Finally, we demonstrated that Id3 significantly repressed arsenite-stimulated transcription of the immediate-early gene Egr-1 and that this repression activity was inversely correlated with the arsenite-induced nuclear export. Our results imply that Id3 may be involved in the biological action of arsenite

  2. The N-terminal region of eukaryotic translation initiation factor 5A signals to nuclear localization of the protein

    International Nuclear Information System (INIS)

    Parreiras-e-Silva, Lucas T.; Gomes, Marcelo D.; Oliveira, Eduardo B.; Costa-Neto, Claudio M.

    2007-01-01

    The eukaryotic translation initiation factor 5A (eIF5A) is a ubiquitous protein of eukaryotic and archaeal organisms which undergoes hypusination, a unique post-translational modification. We have generated a polyclonal antibody against murine eIF5A, which in immunocytochemical assays in B16-F10 cells revealed that the endogenous protein is preferentially localized to the nuclear region. We therefore analyzed possible structural features present in eIF5A proteins that could be responsible for that characteristic. Multiple sequence alignment analysis of eIF5A proteins from different eukaryotic and archaeal organisms showed that the former sequences have an extended N-terminal segment. We have then performed in silico prediction analyses and constructed different truncated forms of murine eIF5A to verify any possible role that the N-terminal extension might have in determining the subcellular localization of the eIF5A in eukaryotic organisms. Our results indicate that the N-terminal extension of the eukaryotic eIF5A contributes in signaling this protein to nuclear localization, despite of bearing no structural similarity with classical nuclear localization signals

  3. The heparin-binding site in tetranectin is located in the N-terminal region and binding does not involve the carbohydrate recognition domain.

    Science.gov (United States)

    Lorentsen, R H; Graversen, J H; Caterer, N R; Thogersen, H C; Etzerodt, M

    2000-04-01

    Tetranectin is a homotrimeric plasma and extracellular-matrix protein that binds plasminogen and complex sulphated polysaccharides including heparin. In terms of primary and tertiary structure, tetranectin is related to the collectin family of Ca(2+)-binding C-type lectins. Tetranectin is encoded in three exons. Exon 3 encodes the carbohydrate recognition domain, which binds to kringle 4 in plasminogen at low levels of Ca(2+). Exon 2 encodes an alpha-helix, which is necessary and sufficient to govern the trimerization of tetranectin by assembling into a triple-helical coiled-coil structural element. Here we show that the heparin-binding site in tetranectin resides not in the carbohydrate recognition domain but within the N-terminal region, comprising the 16 amino acid residues encoded by exon 1. In particular, the lysine residues in the decapeptide segment KPKKIVNAKK (tetranectin residues 6-15) are shown to be of primary importance in heparin binding.

  4. LeCPK1, a Calcium-Dependent Protein Kinase from Tomato. Plasma Membrane Targeting and Biochemical Characterization1

    Science.gov (United States)

    Rutschmann, Frank; Stalder, Urs; Piotrowski, Markus; Oecking, Claudia; Schaller, Andreas

    2002-01-01

    The cDNA of LeCPK1, a calcium-dependent protein kinase, was cloned from tomato (Lycopersicon esculentum Mill.). LeCPK1 was expressed in Escherichia coli and purified from bacterial extracts. The recombinant protein was shown to be a functional protein kinase using a synthetic peptide as the substrate (syntide-2, Km = 85 μm). Autophosphorylation of LeCPK1 was observed on threonine and serine residues, one of which was identified as serine-439. Kinase activity was shown to be Ca2+ dependent and required the C-terminal, calmodulin-like domain of LeCPK1. Two classes of high- and low-affinity Ca2+-binding sites were observed, exhibiting dissociation constants of 0.6 and 55 μm, respectively. LeCPK1 was found to phosphorylate the regulatory C-terminal domain of the plasma membrane H+-ATPase in vitro. A potential role in the regulation of proton pump activity is corroborated by the apparent colocalization of the plasma membrane H+-ATPase and LeCPK1 in vivo. Upon transient expression in suspension-cultured cells, a C-terminal fusion of LeCPK1 with the green fluorescent protein was targeted to the plasma membrane. Myristoylation of the LeCPK1 N terminus was found to be required for plasma membrane targeting. PMID:12011347

  5. Nonthermal Radiation Processes in Interplanetary Plasmas

    Science.gov (United States)

    Chian, A. C. L.

    1990-11-01

    RESUMEN. En la interacci6n de haces de electrones energeticos con plasmas interplanetarios, se excitan ondas intensas de Langmuir debido a inestabilidad del haz de plasma. Las ondas Langmuir a su vez interaccio nan con fluctuaciones de densidad de baja frecuencia para producir radiaciones. Si la longitud de las ondas de Langmujr exceden las condicio nes del umbral, se puede efectuar la conversi5n de modo no lineal a on- das electromagneticas a traves de inestabilidades parametricas. As se puede excitar en un plasma inestabilidades parametricas electromagneticas impulsadas por ondas intensas de Langmuir: (1) inestabilidades de decaimiento/fusi5n electromagnetica impulsadas por una bomba de Lang- muir que viaja; (2) inestabilidades dobles electromagneticas de decai- miento/fusi5n impulsadas por dos bombas de Langrnuir directamente opues- tas; y (3) inestabilidades de dos corrientes oscilatorias electromagne- ticas impulsadas por dos bombas de Langmuir de corrientes contrarias. Se concluye que las inestabilidades parametricas electromagneticas in- ducidas por las ondas de Langmuir son las fuentes posibles de radiacio- nes no termicas en plasmas interplanetarios. ABSTRACT: Nonthermal radio emissions near the local electron plasma frequency have been detected in various regions of interplanetary plasmas: solar wind, upstream of planetary bow shock, and heliopause. Energetic electron beams accelerated by solar flares, planetary bow shocks, and the terminal shock of heliosphere provide the energy source for these radio emissions. Thus, it is expected that similar nonthermal radiation processes may be responsible for the generation of these radio emissions. As energetic electron beams interact with interplanetary plasmas, intense Langmuir waves are excited due to a beam-plasma instability. The Langmuir waves then interact with low-frequency density fluctuations to produce radiations near the local electron plasma frequency. If Langmuir waves are of sufficiently large

  6. Structure of a C-terminal AHNAK peptide in a 1:2:2 complex with S100A10 and an acetylated N-terminal peptide of annexin A2

    Energy Technology Data Exchange (ETDEWEB)

    Ozorowski, Gabriel [University of California, Irvine, Irvine, CA 92697-3900 (United States); University of California, Irvine, Irvine, CA 92697-3900 (United States); Milton, Saskia [University of California, Irvine, Irvine, CA 92697-3900 (United States); Luecke, Hartmut, E-mail: hudel@uci.edu [University of California, Irvine, Irvine, CA 92697-3900 (United States); University of California, Irvine, Irvine, CA 92697-3900 (United States); University of California, Irvine, Irvine, CA 92697 (United States); University of California, Irvine, Irvine, CA 92697 (United States)

    2013-01-01

    Structure of a 20-amino-acid peptide of AHNAK bound asymmetrically to the AnxA2–S100A10A heterotetramer (1:2:2 symmetry) provides insights into the atomic level interactions that govern this membrane-repair scaffolding complex. AHNAK, a large 629 kDa protein, has been implicated in membrane repair, and the annexin A2–S100A10 heterotetramer [(p11){sub 2}(AnxA2){sub 2})] has high affinity for several regions of its 1002-amino-acid C-terminal domain. (p11){sub 2}(AnxA2){sub 2} is often localized near the plasma membrane, and this C2-symmetric platform is proposed to be involved in the bridging of membrane vesicles and trafficking of proteins to the plasma membrane. All three proteins co-localize at the intracellular face of the plasma membrane in a Ca{sup 2+}-dependent manner. The binding of AHNAK to (p11){sub 2}(AnxA2){sub 2} has been studied previously, and a minimal binding motif has been mapped to a 20-amino-acid peptide corresponding to residues 5654–5673 of the AHNAK C-terminal domain. Here, the 2.5 Å resolution crystal structure of this 20-amino-acid peptide of AHNAK bound to the AnxA2–S100A10 heterotetramer (1:2:2 symmetry) is presented, which confirms the asymmetric arrangement first described by Rezvanpour and coworkers and explains why the binding motif has high affinity for (p11){sub 2}(AnxA2){sub 2}. Binding of AHNAK to the surface of (p11){sub 2}(AnxA2){sub 2} is governed by several hydrophobic interactions between side chains of AHNAK and pockets on S100A10. The pockets are large enough to accommodate a variety of hydrophobic side chains, allowing the consensus sequence to be more general. Additionally, the various hydrogen bonds formed between the AHNAK peptide and (p11){sub 2}(AnxA2){sub 2} most often involve backbone atoms of AHNAK; as a result, the side chains, particularly those that point away from S100A10/AnxA2 towards the solvent, are largely interchangeable. While the structure-based consensus sequence allows interactions with various

  7. Designing a Long Acting Erythropoietin by Fusing Three Carboxyl-Terminal Peptides of Human Chorionic Gonadotropin β Subunit to the N-Terminal and C-Terminal Coding Sequence

    Directory of Open Access Journals (Sweden)

    Fuad Fares

    2011-01-01

    Full Text Available A new analog of EPO was designed by fusing one and two CTPs to the N-terminal and C-terminal ends of EPO (EPO-(CTP3, respectively. This analog was expressed and secreted efficiently in CHO cells. The in vitro test shows that the activity of EPO-(CTP3 in TFI-1 cell proliferation assay is similar to that of EPO-WT and commercial rHEPO. However, in vivo studies indicated that treatment once a week with EPO-(CTP3 (15 μg/kg dramatically increased (~8 folds haematocrit as it was compared to rHuEPO. Moreover, it was found that EPO-(CTP3 is more effective than rHuEPO and Aranesp in increasing reticulocyte number in mice blood. The detected circulatory half-lives of rHuEPO, Aranesp, and EPO-(CTP3 following IV injection of 20 IU were 4.4, 10.8, and 13.1 h, respectively. These data established the rational for using this chimera as a long-acting EPO analog in clinics. The therapeutic efficacy of EPO-CTP analog needs to be established in higher animals and in human clinical trials.

  8. The influence of (n-n')-mixing processes in He*(n)+He(1s2) collisions on He*(n) atoms' populations in weakly ionized helium plasmas

    International Nuclear Information System (INIS)

    Mihajlov, A.A.; Ignjatovic, Lj.M.; Sreckovic, V.A.; Djuric, Z.

    2008-01-01

    The results of semi-classical calculations of rate coefficients of (n-n ' )-mixing processes due to collisions of Rydberg atoms He*(n) with He(1s 2 ) atoms are presented. It is assumed that these processes are caused by the resonant energy exchange within the electron component of He*(n)+He collision system. The method is realized through the numerical simulation of the (n-n ' )-mixing processes, and is applied for calculations of the corresponding rate coefficients. The calculations are performed for the principal quantum numbers n,n ' in ranges 4≤n ' ≤10, and the atom and electron temperatures, T a ,T e , in domains 5000K≤T a ≤T e ≤20000K. It is shown that the (n-n ' )-mixing processes can significantly influence the populations of Rydberg atoms in non-equilibrium weakly ionized helium plasmas with ionization degree ∼10 -4 . Therefore, these processes have to be included in the appropriate models of such plasmas

  9. The DnaA N-terminal domain interacts with Hda to facilitate replicase clamp-mediated inactivation of DnaA.

    Science.gov (United States)

    Su'etsugu, Masayuki; Harada, Yuji; Keyamura, Kenji; Matsunaga, Chika; Kasho, Kazutoshi; Abe, Yoshito; Ueda, Tadashi; Katayama, Tsutomu

    2013-12-01

    DnaA activity for replication initiation of the Escherichia coli chromosome is negatively regulated by feedback from the DNA-loaded form of the replicase clamp. In this process, called RIDA (regulatory inactivation of DnaA), ATP-bound DnaA transiently assembles into a complex consisting of Hda and the DNA-clamp, which promotes inter-AAA+ domain association between Hda and DnaA and stimulates hydrolysis of DnaA-bound ATP, producing inactive ADP-DnaA. Using a truncated DnaA mutant, we previously demonstrated that the DnaA N-terminal domain is involved in RIDA. However, the precise role of the N-terminal domain in RIDA has remained largely unclear. Here, we used an in vitro reconstituted system to demonstrate that the Asn-44 residue in the N-terminal domain of DnaA is crucial for RIDA but not for replication initiation. Moreover, an assay termed PDAX (pull-down after cross-linking) revealed an unstable interaction between a DnaA-N44A mutant and Hda. In vivo, this mutant exhibited an increase in the cellular level of ATP-bound DnaA. These results establish a model in which interaction between DnaA Asn-44 and Hda stabilizes the association between the AAA+ domains of DnaA and Hda to facilitate DnaA-ATP hydrolysis during RIDA. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

  10. Three-Terminal Amorphous Silicon Solar Cells

    Directory of Open Access Journals (Sweden)

    Cheng-Hung Tai

    2011-01-01

    Full Text Available Many defects exist within amorphous silicon since it is not crystalline. This provides recombination centers, thus reducing the efficiency of a typical a-Si solar cell. A new structure is presented in this paper: a three-terminal a-Si solar cell. The new back-to-back p-i-n/n-i-p structure increased the average electric field in a solar cell. A typical a-Si p-i-n solar cell was also simulated for comparison using the same thickness and material parameters. The 0.28 μm-thick three-terminal a-Si solar cell achieved an efficiency of 11.4%, while the efficiency of a typical a-Si p-i-n solar cell was 9.0%. Furthermore, an efficiency of 11.7% was achieved by thickness optimization of the three-terminal solar cell.

  11. Dietary (n-6 : n-3 Fatty Acids Alter Plasma and Tissue Fatty Acid Composition in Pregnant Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Amira Abdulbari Kassem

    2012-01-01

    Full Text Available The objective of this paper is to study the effects of varying dietary levels of n-6 : n-3 fatty acid ratio on plasma and tissue fatty acid composition in rat. The treatment groups included control rats fed chow diet only, rats fed 50% soybean oil (SBO: 50% cod liver oil (CLO (1 : 1, 84% SBO: 16% CLO (6 : 1, 96% SBO: 4% CLO (30 : 1. Blood samples were taken at day 15 of pregnancy, and the plasma and tissue were analyzed for fatty acid profile. The n-3 PUFA in plasma of Diet 1 : 1 group was significantly higher than the other diet groups, while the total n-6 PUFA in plasma was significantly higher in Diet 30 : 1 group as compared to the control and Diet 1 : 1 groups. The Diet 1 : 1 group showed significantly greater percentages of total n-3 PUFA and docosahexaenoic acid in adipose and liver tissue, and this clearly reflected the contribution of n-3 fatty acids from CLO. The total n-6 PUFA, linoleic acid, and arachidonic acid were significantly difference in Diet 30 : 1 as compared to Diet 1 : 1 and control group. These results demonstrated that the dietary ratio of n-6 : n-3 fatty acid ratio significantly affected plasma and tissue fatty acids profile in pregnant rat.

  12. Dietary (n-6 : n-3) fatty acids alter plasma and tissue fatty acid composition in pregnant Sprague Dawley rats.

    Science.gov (United States)

    Kassem, Amira Abdulbari; Abu Bakar, Md Zuki; Yong Meng, Goh; Mustapha, Noordin Mohamed

    2012-01-01

    The objective of this paper is to study the effects of varying dietary levels of n-6 : n-3 fatty acid ratio on plasma and tissue fatty acid composition in rat. The treatment groups included control rats fed chow diet only, rats fed 50% soybean oil (SBO): 50% cod liver oil (CLO) (1 : 1), 84% SBO: 16% CLO (6 : 1), 96% SBO: 4% CLO (30 : 1). Blood samples were taken at day 15 of pregnancy, and the plasma and tissue were analyzed for fatty acid profile. The n-3 PUFA in plasma of Diet 1 : 1 group was significantly higher than the other diet groups, while the total n-6 PUFA in plasma was significantly higher in Diet 30 : 1 group as compared to the control and Diet 1 : 1 groups. The Diet 1 : 1 group showed significantly greater percentages of total n-3 PUFA and docosahexaenoic acid in adipose and liver tissue, and this clearly reflected the contribution of n-3 fatty acids from CLO. The total n-6 PUFA, linoleic acid, and arachidonic acid were significantly difference in Diet 30 : 1 as compared to Diet 1 : 1 and control group. These results demonstrated that the dietary ratio of n-6 : n-3 fatty acid ratio significantly affected plasma and tissue fatty acids profile in pregnant rat.

  13. Dietary (n-6 : n-3) Fatty Acids Alter Plasma and Tissue Fatty Acid Composition in Pregnant Sprague Dawley Rats

    Science.gov (United States)

    Kassem, Amira Abdulbari; Abu Bakar, Md Zuki; Yong Meng, Goh; Mustapha, Noordin Mohamed

    2012-01-01

    The objective of this paper is to study the effects of varying dietary levels of n-6 : n-3 fatty acid ratio on plasma and tissue fatty acid composition in rat. The treatment groups included control rats fed chow diet only, rats fed 50% soybean oil (SBO): 50% cod liver oil (CLO) (1 : 1), 84% SBO: 16% CLO (6 : 1), 96% SBO: 4% CLO (30 : 1). Blood samples were taken at day 15 of pregnancy, and the plasma and tissue were analyzed for fatty acid profile. The n-3 PUFA in plasma of Diet 1 : 1 group was significantly higher than the other diet groups, while the total n-6 PUFA in plasma was significantly higher in Diet 30 : 1 group as compared to the control and Diet 1 : 1 groups. The Diet 1 : 1 group showed significantly greater percentages of total n-3 PUFA and docosahexaenoic acid in adipose and liver tissue, and this clearly reflected the contribution of n-3 fatty acids from CLO. The total n-6 PUFA, linoleic acid, and arachidonic acid were significantly difference in Diet 30 : 1 as compared to Diet 1 : 1 and control group. These results demonstrated that the dietary ratio of n-6 : n-3 fatty acid ratio significantly affected plasma and tissue fatty acids profile in pregnant rat. PMID:22489205

  14. Optical and electrical characterization of n-GaAs surfaces passivated by N{sub 2}-H{sub 2} plasma

    Energy Technology Data Exchange (ETDEWEB)

    Augelli, V.; Ligonzo, T.; Minafra, A.; Schiavulli, L.; Capozzi, V. E-mail: capozzi@ba.infn.it; Perna, G.; Ambrico, M.; Losurdo, M

    2003-05-01

    The passivation of GaAs (1 0 0) surface has been performed by using remote N{sub 2}-H{sub 2} (3% in H{sub 2}) RF plasma nitridation. The samples, consisting of n-doped GaAs wafers, show photoluminescence enhancement when the nitridation time and exposure to the plasma are in a narrow temporal window, so that a very thin (about 10 A) GaN layer is deposited on the GaAs surface. Pure N{sub 2} nitridation does not provide an efficient passivation, because it results in GaN layers with As and AsN{sub x} segregation at the GaN/GaAs interface. Increase of Au-GaAs Schottky barrier with the insertion of GaN interlayer and improvement of current-voltage characteristic have been observed.

  15. Stability of AlGaN/GaN heterostructures after hydrogen plasma treatment

    Czech Academy of Sciences Publication Activity Database

    Babchenko, O.; Dzuba, J.; Lalinský, T.; Vojs, M.; Vincze, A.; Ižák, Tibor; Vanko, G.

    2017-01-01

    Roč. 395, Feb (2017), s. 92-97 ISSN 0169-4332 R&D Projects: GA ČR(CZ) GP14-16549P Grant - others:AV ČR(CZ) SAV-16-02 Program:Bilaterální spolupráce Institutional support: RVO:68378271 Keywords : AIGaN/GaN heterostructure * hydrogen plasma * SIMS * TLM * HEMT Subject RIV: BM - Solid Matter Physics ; Magnetism OBOR OECD: Condensed matter physics (including formerly solid state physics, supercond.) Impact factor: 3.387, year: 2016

  16. Survey of compressions in the SW (1 AU), and after termination shock at Voyager (in sheath & LISM)

    Science.gov (United States)

    Berdichevsky, D. B.

    2017-12-01

    Examples of the plasma compression as it is observed in the solar wind at 1 AU with the suite of instruments in the SC Wind, and after the termination shock with both Voyager SC, as well as with Voyager 1 in the local interstellar medium (LISM) are presented. The work will focus on similarities and differences in the observations at the different locations. At priory is fair to mention that the 4 regions differ in several aspects. At 1 AU the solar wind (SW) flow is mostly alfvenic. In the sheath after the termination shock the possibly subsonic solar wind is mostly compressional but fluctuation modes in scales of one hour are much less observed at Voyager 1 than at Voyager 2 path. Finally Burlaga and Ness1 documented the nature of the compressional flow in the `depletion' layer at the start of the LISM as well later in this medium, showing the low plasma-beta character of this LISM region in Voyager 1 path. 1Burlaga L.F., and N. Ness, ApJ, 784, 146 (14pp), 2014.

  17. Low-n shear Alfven spectra in axisymmetric toroidal plasmas

    International Nuclear Information System (INIS)

    Cheng, C.Z.; Chance, M.S.

    1985-11-01

    In toroidal plasmas, the toroidal magnetic field is nonuniform over a magnetic surface and causes coupling of different poloidal harmonics. It is shown both analytically and numerically that the toroidicity not only breaks up the shear Alfven continuous spectrum, but also creates new, discrete, toroidicity-induced shear Alfven eigenmodes with frequencies inside the continuum gaps. Potential applications of the low-n toroidicity-induced shear Alfven eigenmodes on plasma heating and instabilities are addressed. 17 refs., 4 figs

  18. Diagnosis of invasive candidiasis by enzyme-linked immunosorbent assay using the N-terminal fragment of Candida albicans hyphal wall protein 1

    Directory of Open Access Journals (Sweden)

    Pontón José

    2007-04-01

    Full Text Available Abstract Background The diagnosis of invasive candidiasis is difficult because there are no specific clinical manifestations of the disease and colonization and infection are difficult to distinguish. In the last decade, much effort has been made to develop reliable tests for rapid diagnosis of invasive candidiasis, but none of them have found widespread clinical use. Results Antibodies against a recombinant N-terminal fragment of the Candida albicans germ tube-specific antigen hyphal wall protein 1 (Hwp1 generated in Escherichia coli were detected by both immunoblotting and ELISA tests in a group of 36 hematological or Intensive Care Unit patients with invasive candidiasis and in a group of 45 control patients at high risk for the mycosis who did not have clinical or microbiological data to document invasive candidiasis. Results were compared with an immunofluorescence test to detect antibodies to C. albicans germ tubes (CAGT. The sensitivity, specificity, positive and negative predictive values of a diagnostic test based on the detection of antibodies against the N-terminal fragment of Hwp1 by immunoblotting were 27.8 %, 95.6 %, 83.3 % and 62.3 %, respectively. Detection of antibodies to the N-terminal fragment of Hwp1 by ELISA increased the sensitivity (88.9 % and the negative predictive value (90.2 % but slightly decreased the specificity (82.6 % and positive predictive values (80 %. The kinetics of antibody response to the N-terminal fragment of Hwp1 by ELISA was very similar to that observed by detecting antibodies to CAGT. Conclusion An ELISA test to detect antibodies against a recombinant N-terminal fragment of the C. albicans germ tube cell wall antigen Hwp1 allows the diagnosis of invasive candidiasis with similar results to those obtained by detecting antibodies to CAGT but without the need of treating the sera to adsorb the antibodies against the cell wall surface of the blastospore.

  19. A Three-Step Atomic Layer Deposition Process for SiN x Using Si2Cl6, CH3NH2, and N2 Plasma.

    Science.gov (United States)

    Ovanesyan, Rafaiel A; Hausmann, Dennis M; Agarwal, Sumit

    2018-06-06

    We report a novel three-step SiN x atomic layer deposition (ALD) process using Si 2 Cl 6 , CH 3 NH 2 , and N 2 plasma. In a two-step process, nonhydrogenated chlorosilanes such as Si 2 Cl 6 with N 2 plasmas lead to poor-quality SiN x films that oxidize rapidly. The intermediate CH 3 NH 2 step was therefore introduced in the ALD cycle to replace the NH 3 plasma step with a N 2 plasma, while using Si 2 Cl 6 as the Si precursor. This three-step process lowers the atomic H content and improves the film conformality on high-aspect-ratio nanostructures as Si-N-Si bonds are formed during a thermal CH 3 NH 2 step in addition to the N 2 plasma step. During ALD, the reactive surface sites were monitored using in situ surface infrared spectroscopy. Our infrared spectra show that, on the post-N 2 plasma-treated SiN x surface, Si 2 Cl 6 reacts primarily with the surface -NH 2 species to form surface -SiCl x ( x = 1, 2, or 3) bonds, which are the reactive sites during the CH 3 NH 2 cycle. In the N 2 plasma step, reactive -NH 2 surface species are created because of the surface H available from the -CH 3 groups. At 400 °C, the SiN x films have a growth per cycle of ∼0.9 Å with ∼12 atomic percent H. The films grown on high-aspect-ratio nanostructures have a conformality of ∼90%.

  20. Changes in regional plasma extravasation in rats following endotoxin infusion

    International Nuclear Information System (INIS)

    van Lambalgen, A.A.; van den Bos, G.C.; Thijs, L.G.

    1987-01-01

    Regional differences in plasma extravasation during endotoxin shock in rats and a possible relationship with changes in regional blood flow were studied with radioactive isotopes ( 125 I-HSA, 51Cr-labeled red blood cells, microspheres) in anesthetized rats (pentobarbital). Shock was induced by intravenous infusion of endotoxin (Eschericia coli; 10 mg X kg-1) for 60 min (starting at t = 0); at t = 120 min, the experiments were terminated. These rats (n = 8) were compared with time-matched control rats (n = 8). A third group (rats killed 7.5 min after injection of 125 I-HSA, i.e., no extravasation; n = 8) served as baseline. The amount of plasma extravasated in 2 hr of endotoxin shock was significantly increased over control values in skin (by 67%), colon (88%), skeletal muscle (105%), stomach (230%), pancreas (300%), and diaphragm (1300%). Losses of 125 I-HSA into intestinal lumen and peritoneal cavity had also increased over control values by 146 and 380%, respectively. Blood flow was compromised in most organs except heart and diaphragm. Extravasation when normalized for total plasma supply was correlated with total blood supply; the more the blood supply decreased, the higher the normalized extravasation. In the diaphragm, however, blood supply and plasma leakage increased together. Decreased blood supply and plasma extravasation may be related but they could also be simultaneously occurring independent phenomena with a common origin

  1. AlN Surface Passivation of GaN-Based High Electron Mobility Transistors by Plasma-Enhanced Atomic Layer Deposition.

    Science.gov (United States)

    Tzou, An-Jye; Chu, Kuo-Hsiung; Lin, I-Feng; Østreng, Erik; Fang, Yung-Sheng; Wu, Xiao-Peng; Wu, Bo-Wei; Shen, Chang-Hong; Shieh, Jia-Ming; Yeh, Wen-Kuan; Chang, Chun-Yen; Kuo, Hao-Chung

    2017-12-01

    We report a low current collapse GaN-based high electron mobility transistor (HEMT) with an excellent thermal stability at 150 °C. The AlN was grown by N 2 -based plasma enhanced atomic layer deposition (PEALD) and shown a refractive index of 1.94 at 633 nm of wavelength. Prior to deposit AlN on III-nitrides, the H 2 /NH 3 plasma pre-treatment led to remove the native gallium oxide. The X-ray photoelectron spectroscopy (XPS) spectroscopy confirmed that the native oxide can be effectively decomposed by hydrogen plasma. Following the in situ ALD-AlN passivation, the surface traps can be eliminated and corresponding to a 22.1% of current collapse with quiescent drain bias (V DSQ ) at 40 V. Furthermore, the high temperature measurement exhibited a shift-free threshold voltage (V th ), corresponding to a 40.2% of current collapse at 150 °C. The thermal stable HEMT enabled a breakdown voltage (BV) to 687 V at high temperature, promising a good thermal reliability under high power operation.

  2. AlN Surface Passivation of GaN-Based High Electron Mobility Transistors by Plasma-Enhanced Atomic Layer Deposition

    Science.gov (United States)

    Tzou, An-Jye; Chu, Kuo-Hsiung; Lin, I.-Feng; Østreng, Erik; Fang, Yung-Sheng; Wu, Xiao-Peng; Wu, Bo-Wei; Shen, Chang-Hong; Shieh, Jia-Ming; Yeh, Wen-Kuan; Chang, Chun-Yen; Kuo, Hao-Chung

    2017-04-01

    We report a low current collapse GaN-based high electron mobility transistor (HEMT) with an excellent thermal stability at 150 °C. The AlN was grown by N2-based plasma enhanced atomic layer deposition (PEALD) and shown a refractive index of 1.94 at 633 nm of wavelength. Prior to deposit AlN on III-nitrides, the H2/NH3 plasma pre-treatment led to remove the native gallium oxide. The X-ray photoelectron spectroscopy (XPS) spectroscopy confirmed that the native oxide can be effectively decomposed by hydrogen plasma. Following the in situ ALD-AlN passivation, the surface traps can be eliminated and corresponding to a 22.1% of current collapse with quiescent drain bias ( V DSQ) at 40 V. Furthermore, the high temperature measurement exhibited a shift-free threshold voltage ( V th), corresponding to a 40.2% of current collapse at 150 °C. The thermal stable HEMT enabled a breakdown voltage (BV) to 687 V at high temperature, promising a good thermal reliability under high power operation.

  3. The N-terminal segment of pulmonary surfactant lipopeptide SP-C has intrinsic propensity to interact with and perturb phospholipid bilayers

    DEFF Research Database (Denmark)

    Plasencia, Inés; Rivas, Luis; Keough, Kevin M W

    2004-01-01

    aggregation, and leakage of the aqueous content of the vesicles. The lipid-peptide interaction includes a significant hydrophobic component for both zwitterionic and anionic membranes, although the interaction with phosphatidylglycerol bilayers is also electrostatic in nature. The effects of the SP-C N......-terminal peptides on the membrane structure are mediated by significant perturbations of the packing order and mobility of phospholipid acyl chain segments deep in the bilayer, as detected by differential scanning calorimetry and spin-label ESR. These results suggest that the N-terminal region of SP-C, even...

  4. Nickel Ligation of the N-Terminal Amine of HypA Is Required for Urease Maturation in Helicobacter pylori.

    Science.gov (United States)

    Hu, Heidi Q; Johnson, Ryan C; Merrell, D Scott; Maroney, Michael J

    2017-02-28

    The human pathogen Helicobacter pylori requires nickel for colonization of the acidic environment of the stomach. HypA, a Ni metallochaperone that is typically associated with hydrogenase maturation, is also required for urease maturation and acid survival of H. pylori. There are two proposed Ni site structures for HypA; one is a paramagnetic six-coordinate site characterized by X-ray absorption spectroscopy (XAS) in unmodified HypA, while another is a diamagnetic four-coordinate planar site characterized by solution nuclear magnetic resonance in an N-terminally modified HypA construct. To determine the role of the N-terminal amine in Ni binding of HypA, an N-terminal extension variant, L2*-HypA, in which a leucine residue was inserted into the second position of the amino acid sequence in the proposed Ni-binding motif, was characterized in vitro and in vivo. Structural characterization of the Ni site using XAS showed a coordination change from six-coordinate in wild-type HypA (WT-HypA) to five-coordinate pyramidal in L2*-HypA, which was accompanied by the loss of two N/O donor protein ligands and the addition of an exogenous bromide ligand from the buffer. The magnetic properties of the Ni sites in WT-HypA compared to those of the Ni sites in L2*-HypA confirmed that a spin-state change from high to low spin accompanied this change in structure. The L2*-HypA H. pylori strain was shown to be acid sensitive and deficient in urease activity in vivo. In vitro characterization showed that L2*-HypA did not disrupt the HypA-UreE interaction that is essential for urease maturation but was at least 20-fold weaker in Ni binding than WT-HypA. Characterization of the L2*-HypA variant clearly demonstrates that the N-terminal amine of HypA is involved in proper Ni coordination and is necessary for urease activity and acid survival.

  5. Untangling spider silk evolution with spidroin terminal domains

    Directory of Open Access Journals (Sweden)

    Garb Jessica E

    2010-08-01

    Full Text Available Abstract Background Spidroins are a unique family of large, structural proteins that make up the bulk of spider silk fibers. Due to the highly variable nature of their repetitive sequences, spidroin evolutionary relationships have principally been determined from their non-repetitive carboxy (C-terminal domains, though they offer limited character data. The few known spidroin amino (N-terminal domains have been difficult to obtain, but potentially contain critical phylogenetic information for reconstructing the diversification of spider silks. Here we used silk gland expression data (ESTs from highly divergent species to evaluate the functional significance and phylogenetic utility of spidroin N-terminal domains. Results We report 11 additional spidroin N-termini found by sequencing ~1,900 silk gland cDNAs from nine spider species that shared a common ancestor > 240 million years ago. In contrast to their hyper-variable repetitive regions, spidroin N-terminal domains have retained striking similarities in sequence identity, predicted secondary structure, and hydrophobicity. Through separate and combined phylogenetic analyses of N-terminal domains and their corresponding C-termini, we find that combined analysis produces the most resolved trees and that N-termini contribute more support and less conflict than the C-termini. These analyses show that paralogs largely group by silk gland type, except for the major ampullate spidroins. Moreover, spidroin structural motifs associated with superior tensile strength arose early in the history of this gene family, whereas a motif conferring greater extensibility convergently evolved in two distantly related paralogs. Conclusions A non-repetitive N-terminal domain appears to be a universal attribute of spidroin proteins, likely retained from the origin of spider silk production. Since this time, spidroin N-termini have maintained several features, consistent with this domain playing a key role in silk

  6. Ultra-Sensitive NT-proBNP Quantification for Early Detection of Risk Factors Leading to Heart Failure

    Directory of Open Access Journals (Sweden)

    Keum-Soo Song

    2017-09-01

    Full Text Available Cardiovascular diseases such as acute myocardial infarction and heart failure accounted for the death of 17.5 million people (31% of all global deaths in 2015. Monitoring the level of circulating N-terminal proBNP (NT-proBNP is crucial for the detection of people at risk of heart failure. In this article, we describe a novel ultra-sensitive NT-proBNP test (us-NT-proBNP that allows the quantification of circulating NT-proBNP in 30 min at 25 °C in the linear detection range of 7.0–600 pg/mL. It is a first report on the application of a fluorescence bead labeled detection antibody, DNA-guided detection method, and glass fiber membrane platform for the quantification of NT-proBNP in clinical samples. Limit of blank, limit of detection, and limit of quantification were 2.0 pg/mL, 3.7 pg/mL, and 7 pg/mL, respectively. The coefficient of variation was found to be less than 10% in the entire detection range of 7–600 pg/mL. The test demonstrated specificity for NT-proBNP without interferences from bilirubin, intra-lipid, biotin, and hemoglobin. The serial dilution test for plasma samples containing various NT-proBNP levels showed the linear decrement in concentration with the regression coefficient of 0.980–0.998. These results indicate that us-NT-proBNP test does not suffer from the interference of the plasma components for the measurement of NT-proBNP in clinical samples.

  7. Identification of succinimide sites in proteins by N-terminal sequence analysis after alkaline hydroxylamine cleavage.

    Science.gov (United States)

    Kwong, M. Y.; Harris, R. J.

    1994-01-01

    Under favorable conditions, Asp or Asn residues can undergo rearrangement to a succinimide (cyclic imide), which may also serve as an intermediate for deamidation and/or isoaspartate formation. Direct identification of such succinimides by peptide mapping is hampered by their lability at neutral and alkaline pH. We determined that incubation in 2 M hydroxylamine, 0.2 M Tris buffer, pH 9, for 2 h at 45 degrees C will specifically cleave on the C-terminal side of succinimides without cleavage at Asn-Gly bonds; yields are typically approximately 50%. N-terminal sequence analysis can then be used to identify an internal sequence generated by cleavage of the succinimide, hence identifying the succinimide site. PMID:8142891

  8. Characteristics of N-doped TiO{sub 2} nanotube arrays by N{sub 2}-plasma for visible light-driven photocatalysis

    Energy Technology Data Exchange (ETDEWEB)

    Liu Xu [College of Chemical Engineering, Sichuan University, Chengdu 610065 (China); Liu Zhongqing, E-mail: 301zql@vip.sina.com [College of Chemical Engineering, Sichuan University, Chengdu 610065 (China); Zheng Jian; Yan Xin; Li Dandan; Chen Si [College of Chemical Engineering, Sichuan University, Chengdu 610065 (China); Chu Wei, E-mail: chuwei1965_scu@yahoo.com [College of Chemical Engineering, Sichuan University, Chengdu 610065 (China)

    2011-10-13

    Highlights: > A new pathway is provided to prepare N-doped TiO2 nanotube arrays using N{sub 2}-plasma treatment. > N{sub 2}-plasma treatment did not wreck the structure of nanotube arrays. > Nitrogen doping promoted the phase transition to rutile phase at low annealing temperatures > Nitrogen doping narrow band gap of TiO{sub 2} and improve the photocatalytic activity of samples. - Abstract: N-doped TiO{sub 2} nanotube arrays were prepared by electrochemical anode oxidation of Ti foil followed by treatment with N{sub 2}-plasma and subsequent annealed under Ar atmosphere. The morphologies, composition and optical properties of N-doped TiO{sub 2} nanotube arrays were characterized using field-emission scanning electron microscope (FE-SEM), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction spectrometer (XRD), Photoluminescence (PL) and UV-vis diffusion reflection spectroscopy (UV-vis DRS). Methylene blue (MB) solution was utilized as the degradation model to evaluate the photocatalytic activity of the samples under visible light irradiation. The results suggested N{sub 2}-plasma treatment created doping of nitrogen onto the surface of photoelectrodes successfully and the N-doped TiO{sub 2} nanotube arrays display a significantly enhancement of the photocatalytic activity comparing with the pure TiO{sub 2} nanotube arrays under the visible light irradiation.

  9. Superficial disposition of the N-terminal region of the surfactant protein SP-C and the absence of specific SP-B-SP-C interactions in phospholipid bilayers

    DEFF Research Database (Denmark)

    Plasencia, I; Cruz, A; Casals, C

    2001-01-01

    . The fluorescence emission spectrum of Dns-SP-C in phospholipid bilayers is similar to the spectrum of dansyl-phosphatidylethanolamine, and indicates that the N-terminal end of the protein is located at the surface of the membranes and is exposed to the aqueous environment. In membranes containing...... phosphatidylglycerol (PG), the fluorescence of Dns-SP-C shows a 3-fold increase with respect to the fluorescence of phosphatidylcholine (PC), suggesting that electrostatic lipid-protein interactions induce important effects on the structure and disposition of the N-terminal segment of the protein in these membranes...... of the N-terminal segment of the protein into less polar environments that originate during protein lateral segregation. This suggests that conformation and interactions of the N-terminal segment of SP-C could be important in regulating the lateral distribution of the protein in surfactant bilayers...

  10. Circulating forms of immunoreactive parathyroid hormone-related protein for identifying patients with humoral hypercalcemia of malignancy. A comparative study with C-terminal (109-141)- and N-terminal (1-86)-region-specific PTHrP radioassay

    International Nuclear Information System (INIS)

    Suehiro, Mitsuko; Murakami, Minoru; Fukuchi, Minoru

    1994-01-01

    We evaluated the circulating forms of immunoreactive parathyroid hormone-related protein(PTHrP) in 115 healthy subjects and 122 patients with malignant diseases by using radioassay systems (RAS) specific for the C-terminal (109-141) fragment of PTHrP (C-RAS) and for the N-terminal(1-86) (N-RAS). PTHrP levels in healthy controls ranged from 1.5 to 38.2 (mean: 24.5) pmol/L with the C-RAS and from 0.9 to 2.5 (mean: 1.7) pmol/L with the N-RAS. The ratio of circulating N-terminal fragment (N) to C-terminal fragment (C) of PTHrP was calculated to be about 1 : 14.4 in the healthy subjects. Of the 122 patients with malignant diseases, 40 (32.8%) had circulating PTHrP levels undetectable with the N-RAS, but only 11 (9.0%) patients had levels undetectable with the C-RAS. Of the former 122 patients, 41 (33.6%) had high PTHrP as determined with the C-RAS, and 10 (8.2%) had high PTHrP as determined with the N-RAS. The former of these included only 8 (19.5%) humoral hypercalcemia malignancy(HHM) patients, while the latter included 8 (80.0%) HHM patients. The circulating N to C ratio was about 1 : 70.7 in the HHM patients. The N and C obtained with the different RASs showed a close correlation (r=0.86). The values also showed a close correlation with serum Ca; r=0.75 for C-RAS and r=0.81 for N-RAS. In addition, the correlation between the PTHrP reading obtained with the different RASs and serum Cr were: r=0.42 with C-RAS and r=0.26 with N-RAS. The circulating form of immunoreactive PTHrP fragments is therefore comprised mainly of PTHrP (109-141). In contrast, circulating concentrations of the PTHrP (1-86) fragment are very low, but detection of the PTHrP (1-86) fragment with the N-RAS is a more useful indicator of HHM with fewer false positive results and is less likely to be influenced by renal function than the detection of the PHPrP (109-141) fragment with C-RAS. (author)

  11. [Usefulness of brain natriuretic propeptide in the diagnosis and management of patent ductus arteriosus].

    Science.gov (United States)

    Montaner Ramón, Alicia; Galve Pradel, Zenaida; Fernández Espuelas, Cristina; Jiménez Montañés, Lorenzo; Samper Villagrasa, María Pilar; Rite Gracia, Segundo

    2017-06-01

    Patent ductus arteriosus (PDA) is a prevalent condition in preterm infants, and may be related to increased morbidity and mortality in the most immature newborns. Recent studies have examined the usefulness of brain natriuretic propeptide (proBNP) in the diagnosis of this pathology. The aim of the study was to evaluate the diagnostic efficacy of proBNP as a marker of hemodynamic overload in PDA. A retrospective study was conducted on preterm infants less than 32 weeks of gestation and/or weight less than 1500 grams. Echocardiogram and determination of proBNP levels were performed on all patients. Comparison was made by subgroups according to the presence of PDA and their haemodynamic characteristics. Of the 60 patients enrolled, 71.7% had PDA, of which 86% had haemodynamically significant patent ductus arteriosus (HS-PDA). All of them, but one, received medical treatment with ibuprofen or acetaminophen. Surgical closure was required in 29.7% of HS-PDA. Higher values of proBNP were found in patients with HS-PDA (33338±34494.47pg/mL; p=.000) compared with patients with closed or non-haemodynamically significant ductus arteriosus. Higher values were also found in patients who required surgical closure of PDA (30596.8±14910.9; p=.004). A greater decrease inproBNP levels was found in the group of patients which duct closure after pharmacological treatment (68±24.69% vs -12.22±99.4%; p=.030). ProBNP cutoff-level for HS-PDA was calculated by ROC curve and it was 9321.5pg/mL (Specificity: 100%, Sensitivity: 94.6%). ProBNP levels are related to the presence or absence of haemodynamically significant patent ductus arteriosus; and its variations with treatment response. High values are also related to the need for surgical closure of PDA. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. PARTICLE ACCELERATION AT THE HELIOSPHERIC TERMINATION SHOCK WITH A STOCHASTIC SHOCK OBLIQUITY APPROACH

    International Nuclear Information System (INIS)

    Arthur, Aaron D.; Le Roux, Jakobus A.

    2013-01-01

    Observations by the plasma and magnetic field instruments on board the Voyager 2 spacecraft suggest that the termination shock is weak with a compression ratio of ∼2. However, this is contrary to the observations of accelerated particle spectra at the termination shock, where standard diffusive shock acceleration theory predicts a compression ratio closer to ∼2.9. Using our focused transport model, we investigate pickup proton acceleration at a stationary spherical termination shock with a moderately strong compression ratio of 2.8 to include both the subshock and precursor. We show that for the particle energies observed by the Voyager 2 Low Energy Charged Particle (LECP) instrument, pickup protons will have effective length scales of diffusion that are larger than the combined subshock and precursor termination shock structure observed. As a result, the particles will experience a total effective termination shock compression ratio that is larger than values inferred by the plasma and magnetic field instruments for the subshock and similar to the value predicted by diffusive shock acceleration theory. Furthermore, using a stochastically varying magnetic field angle, we are able to qualitatively reproduce the multiple power-law structure observed for the LECP spectra downstream of the termination shock

  13. PrP N-terminal domain triggers PrPSc-like aggregation of Dpl

    International Nuclear Information System (INIS)

    Erlich, Paul; Cesbron, Jean-Yves; Lemaire-Vieille, Catherine; Curt, Aurelie; Andrieu, Jean-Pierre; Schoehn, Guy; Jamin, Marc; Gagnon, Jean

    2008-01-01

    Transmissible spongiform encephalopathies are fatal neurodegenerative disorders thought to be transmitted by self-perpetuating conformational conversion of a neuronal membrane glycoprotein (PrP C , for 'cellular prion protein') into an abnormal state (PrP Sc , for 'scrapie prion protein'). Doppel (Dpl) is a protein that shares significant biochemical and structural homology with PrP C . In contrast to its homologue PrP C , Dpl is unable to participate in prion disease progression or to achieve an abnormal PrP Sc -like state. We have constructed a chimeric mouse protein, composed of the N-terminal domain of PrP C (residues 23-125) and the C-terminal part of Dpl (residues 58-157). This chimeric protein displays PrP-like biochemical and structural features; when incubated in presence of NaCl, the α-helical monomer forms soluble β-sheet-rich oligomers which acquire partial resistance to pepsin proteolysis in vitro, as do PrP oligomers. Moreover, the presence of aggregates akin to protofibrils is observed in soluble oligomeric species by electron microscopy

  14. Temperature dependence on plasma-induced damage and chemical reactions in GaN etching processes using chlorine plasma

    Science.gov (United States)

    Liu, Zecheng; Ishikawa, Kenji; Imamura, Masato; Tsutsumi, Takayoshi; Kondo, Hiroki; Oda, Osamu; Sekine, Makoto; Hori, Masaru

    2018-06-01

    Plasma-induced damage (PID) on GaN was optimally reduced by high-temperature chlorine plasma etching. Energetic ion bombardments primarily induced PID involving stoichiometry, surface roughness, and photoluminescence (PL) degradation. Chemical reactions under ultraviolet (UV) irradiation and chlorine radical exposure at temperatures higher than 400 °C can be controlled by taking into account the synergism of simultaneous photon and radical irradiations to effectively reduce PID.

  15. Plasmas for the low-temperature growth of high-quality GaN films by molecular beam epitaxy and remote plasma MOCVD

    Energy Technology Data Exchange (ETDEWEB)

    Losurdo, M.; Capezzuto, P.; Bruno, G. [Plasmachemistry Research Center, CNR, Bari (Italy); Namkoong, G.; Doolittle, W.A.; Brown, A.S. [Georgia Inst. of Tech., Atlanta (United States). School of Electrical and Computer Engineering, Microelectronic Research Center

    2002-03-16

    GaN heteroepitaxial growth on sapphire (0001) substrates was carried out by both radio-frequency (rf) remote plasma metalorganic chemical vapor deposition (RP-MOCVD) and molecular beam epitaxy (MBE). A multistep growth process including substrate plasma cleaning and nitridation, buffer growth, its subsequent annealing and epilayer growth was used. In order to achieve a better understanding of the GaN growth, in-situ real time investigation of the surface chemistry is performed for all the steps using the conventional reflection high-energy electron spectroscopy (RHEED) during the MBE process, while laser reflectance interferometry (LRI) and spectroscopic ellipsometry (SE), which do not require UHV conditions, are used for the monitoring of the RP-MOCVD process. The chemistry of the rf N{sub 2} plasma sapphire nitridation and its effect on the epilayer growth and quality are discussed in both MBE and RP-MOCVD. (orig.)

  16. Effects of varying levels of n-6:n-3 fatty acid ratio on plasma fatty acid ...

    African Journals Online (AJOL)

    This study investigated the effects of varying dietary levels of n-6:n-3 fatty acid ratio on plasma fatty acid composition and prostanoid synthesis in pregnant rats. Four groups consisting of seven rats per group of non pregnant rats were fed diets with either a very low n-6:n-3 ratio of 50% soybean oil (SBO): 50% cod liver oil ...

  17. Role of N-terminal 28-amino-acid region of Rhizopus oryzae lipase in directing proteins to secretory pathway of Aspergillus oryzae.

    Science.gov (United States)

    Hama, Shinji; Tamalampudi, Sriappareddy; Shindo, Naoki; Numata, Takao; Yamaji, Hideki; Fukuda, Hideki; Kondo, Akihiko

    2008-07-01

    To develop a new approach for improving heterologous protein production in Aspergillus oryzae, we focused on the functional role of the N-terminal region of Rhizopus oryzae lipase (ROL). Several N-terminal deletion variants of ROL were expressed in A. oryzae. Interestingly, a segment of 28 amino acids from the C-terminal region of the propeptide (N28) was found to be critical for secretion of ROL into the culture medium. To further investigate the role of N28, the ROL secretory process was visualized in vivo using ROL-green fluorescent protein (GFP) fusion proteins. In cells producing ROL with N28, fluorescence observations showed that the fusion proteins are transported through endoplasmic reticulum (ER), Golgi, and cell wall, which is one of the typical secretory processes in a eukaryotic cell. Because the expression of the mature ROL-GFP fusion protein induced fluorescence accumulation without its translocation into the ER, N28 is considered to play a crucial role in protein transport. When N28 was inserted between the secretion signal and GFP, fluorescence observations showed that GFP, which is originally a cytoplasmic protein, was efficiently translocated into the ER of A. oryzae, resulting in an enhanced secretion of mature GFP after proteolytic cleavage of N28. These findings suggest that N28 facilitates protein translocation into ER and can be a promising candidate for improving heterologous protein production in A. oryzae.

  18. The 18-kilodalton Chlamydia trachomatis histone H1-like protein (Hc1) contains a potential N-terminal dimerization site and a C-terminal nucleic acid-binding domain

    DEFF Research Database (Denmark)

    Pedersen, Lotte Bang; Birkelund, S; Holm, A

    1996-01-01

    The Chlamydia trachomatis histone H1-like protein (Hc1) is a DNA-binding protein specific for the metabolically inactive chlamydial developmental form, the elementary body. Hc1 induces DNA condensation in Escherichia coli and is a strong inhibitor of transcription and translation. These effects may......-hydroxysuccinimide ester), purified recombinant Hc1 was found to form dimers. The dimerization site was located in the N-terminal part of Hc1 (Hc1(2-57)). Moreover, circular dichroism measurements indicated an overall alpha-helical structure of this region. By using limited proteolysis, Southwestern blotting, and gel...... retardation assays, Hc1(53-125) was shown to contain a domain capable of binding both DNA and RNA. Under the same conditions, Hc1(2-57) had no nucleic acid-binding activity. Electron microscopy of Hc1-DNA and Hc1(53-125)-DNA complexes revealed differences suggesting that the N-terminal part of Hc1 may affect...

  19. Diacylglycerol Acyltransferase 1 Is Regulated by Its N-Terminal Domain in Response to Allosteric Effectors.

    Science.gov (United States)

    Caldo, Kristian Mark P; Acedo, Jeella Z; Panigrahi, Rashmi; Vederas, John C; Weselake, Randall J; Lemieux, M Joanne

    2017-10-01

    Diacylglycerol acyltransferase 1 (DGAT1) is an integral membrane enzyme catalyzing the final and committed step in the acyl-coenzyme A (CoA)-dependent biosynthesis of triacylglycerol (TAG). The biochemical regulation of TAG assembly remains one of the least understood areas of primary metabolism to date. Here, we report that the hydrophilic N-terminal domain of Brassica napus DGAT1 (BnaDGAT1 1-113 ) regulates activity based on acyl-CoA/CoA levels. The N-terminal domain is not necessary for acyltransferase activity and is composed of an intrinsically disordered region and a folded segment. We show that the disordered region has an autoinhibitory function and a dimerization interface, which appears to mediate positive cooperativity, whereas the folded segment of the cytosolic region was found to have an allosteric site for acyl-CoA/CoA. Under increasing acyl-CoA levels, the binding of acyl-CoA with this noncatalytic site facilitates homotropic allosteric activation. Enzyme activation, on the other hand, is prevented under limiting acyl-CoA conditions (low acyl-CoA-to-CoA ratio), whereby CoA acts as a noncompetitive feedback inhibitor through interaction with the same folded segment. The three-dimensional NMR solution structure of the allosteric site revealed an α-helix with a loop connecting a coil fragment. The conserved amino acid residues in the loop interacting with CoA were identified, revealing details of this important regulatory element for allosteric regulation. Based on these results, a model is proposed illustrating the role of the N-terminal domain of BnaDGAT1 as a positive and negative modulator of TAG biosynthesis. © 2017 American Society of Plant Biologists. All Rights Reserved.

  20. Predictive value of N-terminal pro-brain natriuretic peptide in severe sepsis and septic shock.

    Science.gov (United States)

    Varpula, Marjut; Pulkki, Kari; Karlsson, Sari; Ruokonen, Esko; Pettilä, Ville

    2007-05-01

    The aim of this study was to evaluate the predictive value of N-terminal pro-brain natriuretic peptide (NT-proBNP) on mortality in a large, unselected patient population with severe sepsis and septic shock. Prospective observational cohort study about incidence and prognosis of sepsis in 24 intensive care units in Finland (the FINNSEPSIS study). A total of 254 patients with severe sepsis or septic shock. After informed consent, the blood tests for NT-proBNP analyses were drawn on the day of admission and 72 hrs thereafter. Patients' demographic data were collected, and intensive care unit and hospital mortality and basic hemodynamic and laboratory data were recorded daily. NT-proBNP levels at admission were significantly higher in hospital nonsurvivors (median, 7908 pg/mL) compared with survivors (median, 3479 pg/mL; p = .002), and the difference remained after 72 hrs (p = .002). The receiver operating characteristic curves of admission and 72-hr NT-proBNP levels for hospital mortality resulted in area under the curve values of 0.631 (95% confidence interval, 0.549-0.712; p = .002) and 0.648 (95% confidence interval, 0.554-0.741; p = .002), respectively. In logistic regression analyses, NT-proBNP values at 72 hrs after inclusion and Simplified Acute Physiology Score for the first 24 hrs were independent predictors of hospital mortality. Pulmonary artery occlusion pressure (p < .001), plasma creatinine clearance (p = .001), platelet count (p = .03), and positive blood culture (p = .04) had an independent effect on first-day NT-proBNP values, whereas after 72 hrs, only plasma creatinine clearance (p < .001) was significant in linear regression analysis. NT-proBNP values are frequently increased in severe sepsis and septic shock. Values are significantly higher in nonsurvivors than survivors. NT-proBNP on day 3 in the intensive care unit is an independent prognostic marker of mortality in severe sepsis.

  1. N-terminal prolactin-derived fragments, vasoinhibins, are proapoptoptic and antiproliferative in the anterior pituitary.

    Science.gov (United States)

    Ferraris, Jimena; Radl, Daniela Betiana; Zárate, Sandra; Jaita, Gabriela; Eijo, Guadalupe; Zaldivar, Verónica; Clapp, Carmen; Seilicovich, Adriana; Pisera, Daniel

    2011-01-01

    The anterior pituitary is under a constant cell turnover modulated by gonadal steroids. In the rat, an increase in the rate of apoptosis occurs at proestrus whereas a peak of proliferation takes place at estrus. At proestrus, concomitant with the maximum rate of apoptosis, a peak in circulating levels of prolactin is observed. Prolactin can be cleaved to different N-terminal fragments, vasoinhibins, which are proapoptotic and antiproliferative factors for endothelial cells. It was reported that a 16 kDa vasoinhibin is produced in the rat anterior pituitary by cathepsin D. In the present study we investigated the anterior pituitary production of N-terminal prolactin-derived fragments along the estrous cycle and the involvement of estrogens in this process. In addition, we studied the effects of a recombinant vasoinhibin, 16 kDa prolactin, on anterior pituitary apoptosis and proliferation. We observed by Western Blot that N-terminal prolactin-derived fragments production in the anterior pituitary was higher at proestrus with respect to diestrus and that the content and release of these prolactin forms from anterior pituitary cells in culture were increased by estradiol. A recombinant preparation of 16 kDa prolactin induced apoptosis (determined by TUNEL assay and flow cytometry) of cultured anterior pituitary cells and lactotropes from ovariectomized rats only in the presence of estradiol, as previously reported for other proapoptotic factors in the anterior pituitary. In addition, 16 kDa prolactin decreased forskolin-induced proliferation (evaluated by BrdU incorporation) of rat total anterior pituitary cells and lactotropes in culture and decreased the proportion of cells in S-phase of the cell cycle (determined by flow cytometry). In conclusion, our study indicates that the anterior pituitary production of 16 kDa prolactin is variable along the estrous cycle and increased by estrogens. The antiproliferative and estradiol-dependent proapoptotic actions of this

  2. N-terminal prolactin-derived fragments, vasoinhibins, are proapoptoptic and antiproliferative in the anterior pituitary.

    Directory of Open Access Journals (Sweden)

    Jimena Ferraris

    Full Text Available The anterior pituitary is under a constant cell turnover modulated by gonadal steroids. In the rat, an increase in the rate of apoptosis occurs at proestrus whereas a peak of proliferation takes place at estrus. At proestrus, concomitant with the maximum rate of apoptosis, a peak in circulating levels of prolactin is observed. Prolactin can be cleaved to different N-terminal fragments, vasoinhibins, which are proapoptotic and antiproliferative factors for endothelial cells. It was reported that a 16 kDa vasoinhibin is produced in the rat anterior pituitary by cathepsin D. In the present study we investigated the anterior pituitary production of N-terminal prolactin-derived fragments along the estrous cycle and the involvement of estrogens in this process. In addition, we studied the effects of a recombinant vasoinhibin, 16 kDa prolactin, on anterior pituitary apoptosis and proliferation. We observed by Western Blot that N-terminal prolactin-derived fragments production in the anterior pituitary was higher at proestrus with respect to diestrus and that the content and release of these prolactin forms from anterior pituitary cells in culture were increased by estradiol. A recombinant preparation of 16 kDa prolactin induced apoptosis (determined by TUNEL assay and flow cytometry of cultured anterior pituitary cells and lactotropes from ovariectomized rats only in the presence of estradiol, as previously reported for other proapoptotic factors in the anterior pituitary. In addition, 16 kDa prolactin decreased forskolin-induced proliferation (evaluated by BrdU incorporation of rat total anterior pituitary cells and lactotropes in culture and decreased the proportion of cells in S-phase of the cell cycle (determined by flow cytometry. In conclusion, our study indicates that the anterior pituitary production of 16 kDa prolactin is variable along the estrous cycle and increased by estrogens. The antiproliferative and estradiol-dependent proapoptotic

  3. N-terminally truncated GADD34 proteins are convenient translation enhancers in a human cell-derived in vitro protein synthesis system.

    Science.gov (United States)

    Mikami, Satoshi; Kobayashi, Tominari; Machida, Kodai; Masutani, Mamiko; Yokoyama, Shigeyuki; Imataka, Hiroaki

    2010-07-01

    Human cell-derived in vitro protein synthesis systems are useful for the production of recombinant proteins. Productivity can be increased by supplementation with GADD34, a protein that is difficult to express in and purify from E. coli. Deletion of the N-terminal 120 or 240 amino acids of GADD34 improves recovery of this protein from E. coli without compromising its ability to boost protein synthesis in an in vitro protein synthesis system. The use of N-terminally truncated GADD34 proteins in place of full-length GADD34 should improve the utility of human cell-based cell-free protein synthesis systems.

  4. Control of N/N2 species ratio in NO plasma for p-type doping of ZnO

    International Nuclear Information System (INIS)

    Chen Xingyou; Zhang Zhenzhong; Jiang Mingming; Wang Shuangpeng; Li Binghui; Shan Chongxin; Liu Lei; Zhao Dongxu; Shen Dezhen; Yao Bin

    2011-01-01

    Nitrogen-doped ZnO thin films were grown on c-plane sapphire (Al 2 O 3 ) substrates via plasma-assisted molecular beam epitaxy using plasma activated nitric oxide (NO) as the oxygen source and dopant. X-ray diffraction measurements indicate that a small NO flux benefits the crystal quality of the thin films. Hall effect measurements indicate that the electron density of the ZnO films decreases gradually with decreasing NO flux, and the conduction reverses to p-type at a certain flux. Optical emission spectra indicate that the N atom content in the NO plasma increases with decreasing NO flux, and the origin of this is discussed. X-ray photoelectron spectroscopy measurements demonstrate that the number of N atom occupied O sites in the ZnO lattice increases correspondingly.

  5. Long-chain n-3 polyunsaturated fatty acids in plasma in British meat-eating, vegetarian, and vegan men.

    Science.gov (United States)

    Rosell, Magdalena S; Lloyd-Wright, Zouë; Appleby, Paul N; Sanders, Thomas A B; Allen, Naomi E; Key, Timothy J

    2005-08-01

    Plasma concentrations of long-chain n-3 polyunsaturated fatty acids are lower in vegetarians and in vegans than in omnivores. No data are available on whether these concentrations differ between long- and short-term vegetarians and vegans. We compared plasma fatty acid composition in meat-eaters, vegetarians, and vegans and examined whether the proportions of eicosapentaenoic acid (20:5n-3; EPA), docosapentaenoic acid (22:5n-3; DPA), and docosahexaenoic acid (22:6n-3; DHA) were related to the subjects' duration of adherence to their diets or to the proportions of plasma linoleic acid (18:2n-6; LA) and alpha-linolenic acid (18:3n-3; ALA). The present cross-sectional study included 196 meat-eating, 231 vegetarian, and 232 vegan men in the United Kingdom. Information on anthropometry, diet, and smoking habits was obtained through a questionnaire. Total fatty acid composition in plasma was measured. The proportions of plasma EPA and DHA were lower in the vegetarians and in the vegans than in the meat-eaters, whereas only small differences were seen for DPA. Plasma EPA, DPA, and DHA proportions were not significantly associated with the duration of time since the subjects became vegetarian or vegan, which ranged from 20 y. In the vegetarians and the vegans, plasma DHA was inversely correlated with plasma LA. The proportions of plasma long-chain n-3 fatty acids were not significantly affected by the duration of adherence to a vegetarian or vegan diet. This finding suggests that when animal foods are wholly excluded from the diet, the endogenous production of EPA and DHA results in low but stable plasma concentrations of these fatty acids.

  6. Autocatalytic activity and substrate specificity of the pestivirus N-terminal protease Npro

    International Nuclear Information System (INIS)

    Gottipati, Keerthi; Acholi, Sudheer; Ruggli, Nicolas; Choi, Kyung H.

    2014-01-01

    Pestivirus N pro is the first protein translated in the viral polypeptide, and cleaves itself off co-translationally generating the N-terminus of the core protein. Once released, N pro blocks the host's interferon response by inducing degradation of interferon regulatory factor-3. N pro' s intracellular autocatalytic activity and lack of trans-activity have hampered in vitro cleavage studies to establish its substrate specificity and the roles of individual residues. We constructed N pro -GFP fusion proteins that carry the authentic cleavage site and determined the autoproteolytic activities of N pro proteins containing substitutions at the predicted catalytic sites Glu22 and Cys69, at Arg100 that forms a salt bridge with Glu22, and at the cleavage site Cys168. Contrary to previous reports, we show that N pro' s catalytic activity does not involve Glu22, which may instead be involved in protein stability. Furthermore, N pro does not have specificity for Cys168 at the cleavage site even though this residue is conserved throughout the pestivirus genus. - Highlights: • N pro' s autoproteolysis is studied using N pro -GFP fusion proteins. • N-terminal 17 amino acids are dispensable without loss of protease activity. • The putative catalytic residue Glu22 is not involved in protease catalysis. • No specificity for Cys168 at the cleavage site despite evolutionary conservation. • N pro prefers small amino acids with non-branched beta carbons at the P1 position

  7. Dependence of Lunar Surface Charging on Solar Wind Plasma Conditions and Solar Irradiation

    Science.gov (United States)

    Stubbs, T. J.; Farrell, W. M.; Halekas, J. S.; Burchill, J. K.; Collier, M. R.; Zimmerman, M. I.; Vondrak, R. R.; Delory, G. T.; Pfaff, R. F.

    2014-01-01

    The surface of the Moon is electrically charged by exposure to solar radiation on its dayside, as well as by the continuous flux of charged particles from the various plasma environments that surround it. An electric potential develops between the lunar surface and ambient plasma, which manifests itself in a near-surface plasma sheath with a scale height of order the Debye length. This study investigates surface charging on the lunar dayside and near-terminator regions in the solar wind, for which the dominant current sources are usually from the pohotoemission of electrons, J(sub p), and the collection of plasma electrons J(sub e) and ions J(sub i). These currents are dependent on the following six parameters: plasma concentration n(sub 0), electron temperature T(sub e), ion temperature T(sub i), bulk flow velocity V, photoemission current at normal incidence J(sub P0), and photo electron temperature T(sub p). Using a numerical model, derived from a set of eleven basic assumptions, the influence of these six parameters on surface charging - characterized by the equilibrium surface potential, Debye length, and surface electric field - is investigated as a function of solar zenith angle. Overall, T(sub e) is the most important parameter, especially near the terminator, while J(sub P0) and T(sub p) dominate over most of the dayside.

  8. Ar plasma induced deep levels in epitaxial n-GaAs

    International Nuclear Information System (INIS)

    Venter, A.; Nyamhere, C.; Botha, J. R.; Auret, F. D.; Janse van Rensburg, P. J.; Meyer, W. E.; Coelho, S. M. M.; Kolkovsky, V. l.

    2012-01-01

    Ar plasma etching of n-type (Si doped) GaAs introduces several electron traps (E c - 0.04 eV, E c - 0.07 eV, E c - 0.19 eV, E c - 0.31 eV, E c - 0.53 eV, and E c - 0.61 eV). The trap, E c - 0.04 eV, labelled E1' and having a trap signature similar to irradiation induced defect E1, appears to be metastable. E c - 0.31 eV and E c - 0.61 eV are metastable too and they are similar to the M3/M4 defect configuration present in hydrogen plasma exposed n-GaAs.

  9. The growth of axially modulated p–n GaN nanowires by plasma-enhanced chemical vapor deposition

    International Nuclear Information System (INIS)

    Wu, Tung-Hsien; Hong, Franklin Chau-Nan

    2013-01-01

    Due to the n-type characteristics of intrinsic gallium nitride, p-type gallium nitride (GaN) is more difficult to synthesize than n-type gallium nitride in forming the p–n junctions for optoelectronic applications. For the growth of the p-type gallium nitride, magnesium is used as the dopant. The Mg-doped GaN nanowires (NWs) have been synthesized on (111)-oriented n + -silicon substrates by plasma-enhanced chemical vapor deposition. The scanning electron microscope images showed that the GaN NWs were bent at high Mg doping levels, and the transmission electron microscope characterization indicated that single-crystalline GaN NWs grew along < 0001 > orientation. As shown by energy dispersive spectroscopy, the Mg doping levels in GaN NWs increased with increasing partial pressure of magnesium nitride, which was employed as the dopant precursor for p-GaN NW growth. Photoluminescence measurements suggested the presence of both p- and n‐type GaN NWs. Furthermore, the GaN NWs with axial p–n junctions were aligned between either two-Ni or two-Al electrodes by applying alternating current voltages. The current–voltage characteristics have confirmed the formation of axial p–n junctions in GaN nanowires. - Highlights: ► Grow axially modulated GaN nanowires by plasma-enhanced chemical vapor deposition ► Control the Mg concentration of GaN nanowires by tuning Mg 3 N 2 temperature ► Align the GaN nanowires by applying alternating current voltages between electrodes

  10. Hydropyrolysis of n-Hexane and Toluene to Acetylene in Rotating-Arc Plasma

    Directory of Open Access Journals (Sweden)

    Jie Ma

    2017-07-01

    Full Text Available Thermal plasma pyrolysis is a powerful technology for converting waste or low-value materials to valuable gaseous hydrocarbons. This paper presents for the first time the hydropyrolysis of n-hexane and toluene in a rotating-arc plasma reactor. Effects of the mole ratio of H/C in the feed, power input and magnetic induction were investigated to evaluate the reaction performance. A lower H/C ratio could lead to a lower yield of C2H2 and lower specific energy consumption, and there existed an optimum range of power input for both n-hexane and toluene pyrolysis within the investigated range. The yield of C2H2 in n-hexane and toluene pyrolysis could reach 85% and 68%, respectively, with respective specific energy consumption (SEC of 13.8 kWh/kg·C2H2 and 19.9 kWh/kg·C2H2. Compared with the results reported in literature, the rotating-arc plasma process showed higher C2H2 yield and lower energy consumption, which is attributed to the better initial mixing of the reactant with the hot plasma gas and the more uniform temperature distribution.

  11. Plasma performance, boundary studies and first experiments with ICRH in TEXTOR

    International Nuclear Information System (INIS)

    Waidmann, G.; Bay, H.L.; Bertschinger, G.

    1985-01-01

    The TEXTOR plasma serves as a test bed for plasma/wall interaction studies and ICRH experiments. Reproducible and long-lasting discharges with soft termination were generated in the internal disruptive mode. The operational regime for Ohmic heating is shown in a 1/q versus n-barsub(e)R/Bsub(T) diagram. A comparison of electrical conductivity derived from current density measurements with calculated values favours neoclassical theory. A pump limiter installed on TEXTOR demonstrated a particle removal rate of 6x10 20 particles per second out of the boundary layer. It could decrease the central electron density by 50%. The pump limiter was used to control fuelling and recycling characteristics of stable discharges. First experiments with additional ICRH showed a strong influence on the plasma boundary and scrape-off layer. The interaction of the radiofrequency with the boundary layer at present limits the power input to the plasma. Plasma boundary parameters have been measured by optical methods combined with neutral particle beams. (author)

  12. Modeling Plasma-based CO2 and CH4 Conversion in Mixtures with N2, O2 and H2O: the Bigger Plasma Chemistry Picture

    KAUST Repository

    Wang, Weizong

    2018-01-18

    Due to the unique properties of plasma technology, its use in gas conversion applications is gaining significant interest around the globe. Plasma-based CO2 and CH4 conversion have become major research areas. Many investigations have already been performed regarding the single component gases, i.e. CO2 splitting and CH4 reforming, as well as for two component mixtures, i.e. dry reforming of methane (CO2/CH4), partial oxidation of methane (CH4/O2), artificial photosynthesis (CO2/H2O), CO2 hydrogenation (CO2/H2), and even first steps towards the influence of N2 impurities have been taken, i.e. CO2/N2 and CH4/N2. In this feature article we briefly discuss the advances made in literature for these different steps from a plasma chemistry modeling point of view. Subsequently, we present a comprehensive plasma chemistry set, combining the knowledge gathered in this field so far, and supported with extensive experimental data. This set can be used for chemical kinetics plasma modeling for all possible combinations of CO2, CH4, N2, O2 and H2O, to investigate the bigger picture of the underlying plasmachemical pathways for these mixtures in a dielectric barrier discharge plasma. This is extremely valuable for the optimization of existing plasma-based CO2 conversion and CH4 reforming processes, as well as for investigating the influence of N2, O2 and H2O on these processes, and even to support plasma-based multi-reforming processes.

  13. Prediction of the Chemoreflex Gain by Common Clinical Variables in Heart Failure.

    Directory of Open Access Journals (Sweden)

    Gianluca Mirizzi

    Full Text Available Peripheral and central chemoreflex sensitivity, assessed by the hypoxic or hypercapnic ventilatory response (HVR and HCVR, respectively, is enhanced in heart failure (HF patients, is involved in the pathophysiology of the disease, and is under investigation as a potential therapeutic target. Chemoreflex sensitivity assessment is however demanding and, therefore, not easily applicable in the clinical setting. We aimed at evaluating whether common clinical variables, broadly obtained by routine clinical and instrumental evaluation, could predict increased HVR and HCVR.191 patients with systolic HF (left ventricular ejection fraction--LVEF--<50% underwent chemoreflex assessment by rebreathing technique to assess HVR and HCVR. All patients underwent clinical and neurohormonal evaluation, comprising: echocardiogram, cardiopulmonary exercise test (CPET, daytime cardiorespiratory monitoring for breathing pattern evaluation. Regarding HVR, multivariate penalized logistic regression, Bayesian Model Averaging (BMA logistic regression and random forest analysis identified, as predictors, the presence of periodic breathing and increased slope of the relation between ventilation and carbon dioxide production (VE/VCO2 during exercise. Again, the above-mentioned statistical tools identified as HCVR predictors plasma levels of N-terminal fragment of proBNP and VE/VCO2 slope.In HF patients, the simple assessment of breathing pattern, alongside with ventilatory efficiency during exercise and natriuretic peptides levels identifies a subset of patients presenting with increased chemoreflex sensitivity to either hypoxia or hypercapnia.

  14. Caracterización de un plasma pulsado utilizado para producir recubrimientos de TiN, por medio de espectroscopía óptica de emisión

    OpenAIRE

    Restrepo Parra, Elisabeth

    2001-01-01

    En este trabajo se realiza la caracterización de un plasma pulsado utilizado para la producción de recubrimientos duros de TiN, utilizando técnicas de espectroscopía óptica de emisión. Con el fin de realizar esta caracterización se han calculado la temperatura y la densidad electrónica de dicho plasma. El cálculo de la temperatura electrónica se realiza suponiendo que esta es diferente de la temperatura de excitación de los átomos, esto nos permite modificar el método más convencional, co...

  15. Depletion of the human N-terminal acetyltransferase hNaa30 disrupts Golgi integrity and ARFRP1 localization.

    Science.gov (United States)

    Starheim, Kristian K; Kalvik, Thomas V; Bjørkøy, Geir; Arnesen, Thomas

    2017-04-30

    The organization of the Golgi apparatus (GA) is tightly regulated. Golgi stack scattering is observed in cellular processes such as apoptosis and mitosis, and has also been associated with disruption of cellular lipid metabolism and neurodegenerative diseases. Our studies show that depletion of the human N-α-acetyltransferase 30 (hNaa30) induces fragmentation of the Golgi stack in HeLa and CAL-62 cell lines. The GA associated GTPase ADP ribosylation factor related protein 1 (ARFRP1) was previously shown to require N-terminal acetylation for membrane association and based on its N-terminal sequence, it is likely to be a substrate of hNaa30. ARFRP1 is involved in endosome-to- trans -Golgi network (TGN) traffic. We observed that ARFRP1 shifted from a predominantly cis -Golgi and TGN localization to localizing both Golgi and non-Golgi vesicular structures in hNaa30-depleted cells. However, we did not observe loss of membrane association of ARFRP1. We conclude that hNaa30 depletion induces Golgi scattering and induces aberrant ARFRP1 Golgi localization. © 2017 The Author(s).

  16. Fatty acids bind tightly to the N-terminal domain of angiopoietin-like protein 4 and modulate its interaction with lipoprotein lipase.

    Science.gov (United States)

    Robal, Terje; Larsson, Mikael; Martin, Miina; Olivecrona, Gunilla; Lookene, Aivar

    2012-08-24

    Angiopoietin-like protein 4 (Angptl4), a potent regulator of plasma triglyceride metabolism, binds to lipoprotein lipase (LPL) through its N-terminal coiled-coil domain (ccd-Angptl4) inducing dissociation of the dimeric enzyme to inactive monomers. In this study, we demonstrate that fatty acids reduce the inactivation of LPL by Angptl4. This was the case both with ccd-Angptl4 and full-length Angptl4, and the effect was seen in human plasma or in the presence of albumin. The effect decreased in the sequence oleic acid > palmitic acid > myristic acid > linoleic acid > linolenic acid. Surface plasmon resonance, isothermal titration calorimetry, fluorescence, and chromatography measurements revealed that fatty acids bind with high affinity to ccd-Angptl4. The interactions were characterized by fast association and slow dissociation rates, indicating formation of stable complexes. The highest affinity for ccd-Angptl4 was detected for oleic acid with a subnanomolar equilibrium dissociation constant (K(d)). The K(d) values for palmitic and myristic acid were in the nanomolar range. Linoleic and linolenic acid bound with much lower affinity. On binding of fatty acids, ccd-Angptl4 underwent conformational changes resulting in a decreased helical content, weakened structural stability, dissociation of oligomers, and altered fluorescence properties of the Trp-38 residue that is located close to the putative LPL-binding region. Based on these results, we propose that fatty acids play an important role in modulating the effects of Angptl4.

  17. Intrafamiliar clinical variability of circumferential skin creases Kunze type caused by a novel heterozygous mutation of N-terminal TUBB gene.

    Science.gov (United States)

    Dentici, M L; Terracciano, A; Bellacchio, E; Capolino, R; Novelli, A; Digilio, M C; Dallapiccola, B

    2018-02-10

    Circumferential skin creases Kunze type (CSC-KT; OMIM 156610, 616734) is a rare disorder characterized by folding of excess skin, which leads to ringed creases, known as Michelin Tire Baby Syndrome (MTBS). CSC-KT patients also exhibit facial dysmorphism, growth retardation, intellectual disability (ID) and multiple congenital malformations. Recently, 2 heterozygous mutations in TUBB gene and 4 mutations (both homozygous and heterozygous) in MAPRE2 gene were identified in 3 and 4 CSC-KT patients, respectively. In the 3 TUBB gene-related CSC-KT patients, all mutations fall in the N-terminal gene domain and were de novo. Mutations in the C-terminal of TUBB gene have been associated to microcephaly and structural brain malformation, in the absence of CSC-KT features. We report a 9-year-old boy with a diagnosis of CSC-KT based on MTBS, facial dysmorphism, microcephaly, severe ID, cortical atrophy and corpus callosum hypoplasia. Sanger sequencing identified a novel heterozygous c.218T>C (p.Met73Thr) mutation in the N-terminal of TUBB gene, that was inherited from the mother affected by isolated MTBS. This is the first report of inherited TUBB gene-related CSC-KT resulting from a novel heterozygous mutation in the N-terminal domain. Present data support the role of TUBB mutations in CSC-KT and definitely includes CSC-KT syndrome within the tubulinopathies. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Accumulation of fluorine in CF4 plasma-treated AlGaN/GaN heterostructure interface: An experimental investigation

    International Nuclear Information System (INIS)

    Basu, Anirban; Adesida, Ilesanmi

    2009-01-01

    The impact of CF 4 plasma treatment on the transport properties of the two dimensional electron gas (2DEG) in AlGaN/GaN heterostrustures has been studied. Systematic Hall measurements of the plasma-treated samples show a large degradation in mobility and sheet concentration, which can be partially recovered with short-duration rapid thermal annealing. Further annealing progressively degrades both mobility and sheet concentration. Secondary ion mass spectrometry of the heterostructure reveals accumulation of fluorine at the AlGaN/GaN interface close to the 2DEG channel as a result of annealing. Following our systematic electrical and analytical studies of the behavior of fluorine incorporated into the heterostructure epilayer due to bombardment, a vacancy-mediated postannealing redistribution of fluorine has been proposed

  19. Reactive physical vapor deposition of TixAlyN: Integrated plasma-surface modeling characterization

    International Nuclear Information System (INIS)

    Zhang Da; Schaeffer, J.K.

    2004-01-01

    Reactive physical vapor deposition (RPVD) has been widely applied in the microelectronic industry for producing thin films. Fundamental understanding of RPVD mechanisms is needed for successful process development due to the high sensitivity of film properties on process conditions. An integrated plasma equipment-target nitridation modeling infrastructure for RPVD has therefore been developed to provide mechanistic insights and assist optimal process design. The target nitridation model computes target nitride coverage based on self-consistently derived plasma characteristics from the plasma equipment model; target sputter yields needed in the plasma equipment model are also self-consistently derived taking into account the yield-suppressing effect from nitridation. The integrated modeling infrastructure has been applied to investigating RPVD processing with a Ti 0.8 Al 0.2 compound target and an Ar/N 2 gas supply. It has been found that the process produces athermal metal neutrals as the primary deposition precursor. The metal stoichiometry in the deposited film is close to the target composition due to the predominance of athermal species in the flux that reaches the substrate. Correlations between process parameters (N 2 flow, target power), plasma characteristics, surface conditions, and deposition kinetics have been studied with the model. The deposition process is characterized by two regimes when the N 2 flow rate is varied. When N 2 is dilute relative to argon, target nitride coverage increases rapidly with increasing N 2 flow. The sputter yield and deposition rate consequently decrease. For less dilute N 2 mixtures, the sputter yield and deposition rate are stable due to the saturation of target nitridation. With increasing target power, the electron density increases nearly linearly while the variation of N generation is much smaller. Target nitridation and its suppression of the sputter yield saturate at high N 2 flow rendering these parameters

  20. Transformation mechanism of n-butyl terminated Si nanoparticles embedded into Si1-xCx nanocomposites mixed with Si nanoparticles and C atoms

    International Nuclear Information System (INIS)

    Shin, J.W.; Oh, D.H.; Kim, T.W.; Cho, W.J.

    2009-01-01

    Bright-field transmission electron microscopy (TEM) images, high-resolution TEM (HRTEM) images, and fast-Fourier transformed electron-diffraction patterns showed that n-butyl terminated Si nanoparticles were aggregated. The formation of Si 1-x C x nanocomposites was mixed with Si nanoparticles and C atoms embedded in a SiO 2 layer due to the diffusion of C atoms from n-butyl termination shells into aggregated Si nanoparticles. Atomic force microscopy (AFM) images showed that the Si 1-x C x nanocomposites mixed with Si nanoparticles and C atoms existed in almost all regions of the SiO 2 layer. The formation mechanism of Si nanoparticles and the transformation mechanism of n-butyl terminated Si nanoparticles embedded into Si 1-x C x nanocomposites mixed with Si nanoparticles and C atoms are described on the basis of the TEM, HRTEM, and AFM results. These results can help to improve the understanding of the formation mechanism of Si nanoparticles.

  1. Two-temperature transport coefficients of SF{sub 6}–N{sub 2} plasma

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Fei; Chen, Zhexin; Wu, Yi, E-mail: wuyic51@mail.xjtu.edu.cn; Rong, Mingzhe; Wang, Chunlin [State Key Laboratory of Electrical Insulation and Power Equipment, School of Electrical Engineering, Xi' an Jiaotong University, Xi' an 710049 (China); Guo, Anxiang; Liu, Zirui [Electric Power Research Institute of State Grid Shaanxi Electric Power Company, Xian (China)

    2015-10-15

    Sulfur hexafluoride (SF{sub 6}) is widely adopted in electric power industry, especially in high-voltage circuit breakers and gas-insulated switchgear. However, the use of SF{sub 6} is limited by its high liquidation temperature and high global warming potential. Recently, research shows SF{sub 6}–N{sub 2} mixture, which shows environmental friendliness and good electrical properties, may be a feasible substitute for pure SF{sub 6}. This paper is devoted to the calculation of and transport coefficients of SF{sub 6}–N{sub 2} mixture under both LTE (local thermodynamic equilibrium) and non-LTE condition. The two–temperature mass action law was used to determine the composition. The transport coefficients were calculated by classical Chapman–Enskog method simplified by Devoto. The thermophysical properties are presented for electron temperatures of 300–40 000 K, ratios of electron to heavy species temperature of 1–10 and N{sub 2} mole fraction of 0%–100% at atmospheric pressure. The ionization processes under both LTE and non-LTE have been discussed. The results show that deviations from local thermodynamic equilibrium significantly affect the properties of SF{sub 6}–N{sub 2} plasma, especially before the plasma is fully ionized. The different influence of N{sub 2} on properties for SF{sub 6}–N{sub 2} plasma in and out of LTE has been found. The results will serve as reliable reference data for computational simulation of the behavior of SF{sub 6}–N{sub 2} plasmas.

  2. Fabrication and Characterization of GaN-Based Two Terminal Devices for Liquid Sensing

    Energy Technology Data Exchange (ETDEWEB)

    Jeat, Wang Soo; Abidin, Mastura Shafinaz Zainal; Hashim, Abdul Manaf; Rahman, Shaharin Fadzli Abd; Sharifabad, Maneea Eizadi; Mustafa, Farahiyah; Rahman, Abdul Rahim Abdul [Material Innovations and Nanoelectronics Research Group, Faculty of Electrical Engineering, Universiti Teknologi Malaysia, 81310 Skudai, Johor (Malaysia); Qindeel, Rabia [Department of Physics, Faculty of Science, Universiti Teknologi Malaysia, 81310 Skudai, Johor (Malaysia); Omar, Nurul Afzan, E-mail: manaf@fke.utm.my [Telekom Research and Development, TM Innovation Centre, 63000 Cyberjaya (Malaysia)

    2011-02-15

    Gallium Nitride (GaN) based materials are highly suitable for liquid-phase sensor applications due to their chemical stability and high internal piezoelectric polarization. The sensitivity of GaN surfaces in aqueous solutions and polar liquids has been investigated. For this purpose, two terminal devices fabricated on bulk Si doped-GaN structures and undoped-AlGaN/GaN heterostructures with unpassivated open area are used to measure the responses to the changes of the H{sup +} concentration in aqueous solutions and the dipole moment in polar liquids. The I-V characteristics show that the devices are able to distinguish the variations of pH. It is observed that the drain current decreases linearly with pH for both device structures. Evaluating the sensitivity in aqueous solutions at V{sub DS} = 2V, a quite large current change is obtained for both structures. For the response to polar liquids, it is also found that the drain current decreases with the dipole moments. The results indicate that both devices are capable of distinguishing molecules with different dipole moments.

  3. NUMERICAL SIMULATION OF THE MELTING OF PARTICLES INJECTED IN A PLASMA JET SIMULACIÓN NUMÉRICA DE LA FUSIÓN DE PARTÍCULAS INYECTADAS EN UN JET DE PLASMA

    Directory of Open Access Journals (Sweden)

    Jorge Romero Rojas

    2009-12-01

    Full Text Available This work presents the numerical simulation of the melting process of a particle injected in a plasma jet. The plasma process is nowadays applied to produce thin coatings on metal mechanical components with the aim of improving the surface resistance to different phenomena such as corrosion, temperature or wear. In this work we studied the heat transfer including phase-change of a bi-layer particle composed of a metallic iron core coated with ceramic alumina, inside a plasma jet. The model accounted for the environmental conditions along the particle path. The numerical simulation of this problem was performed via a temperature-based phase-change finite element formulation. The results obtained with this methodology satisfactorily described the melting process of the particle. Particularly, the results of the present work illustrate the phase change evolution in a bi-layer particle during its motion in the plasma jet. Moreover, the numerical trends agreed with those previously reported in the literature and computed with a finite volume enthalpy based formulation.Este trabajo presenta la simulación numérica de la fusión de una partícula inyectada en un jet de plasma. Este proceso es hoy en día aplicado para producir capas o recubrimientos delgados sobre componentes mecánicos metálicos, con el objetivo de mejorar su resistencia superficial frente a diferentes fenómenos tales como corrosión, temperatura y desgaste. En este trabajo se estudió la transferencia de calor incluyendo cambio de fase, de una partícula bimaterial compuesta por un centro metálico de hierro recubierto por una capa protectora de alúmina cerámica, dentro de un jet de plasma. El modelo numérico tomó en cuenta las condiciones ambientales a lo largo de toda su trayectoria en el jet. La simulación numérica de este problema fue realizada mediante una formulación de elementos finitos con cambio de fase que retiene como variable única la temperatura. Los

  4. Non-linear collective phenomena in dusty plasmas

    International Nuclear Information System (INIS)

    Tsytovich, V N; Morfill, G E

    2004-01-01

    Dusty plasmas are unusual states of matter where the interactions between the dust grains can be collective and are not a sum of all pair particle interactions. This state of matter is appropriate to form non-linear dissipative collective self-organized structures. It is found that the potential around the grains can be over-screened leading to a new phenomenon-collective attraction of pairs of large charge grains of equal sign. The grain clouds can self-contract and their collapse is terminated at distances where the interaction becomes repulsive. The homogeneous dusty plasma distribution is universally unstable to form structures. The potential of the collective attraction is proportional to the square of the dimensionless parameter P = n d Z d /n i , where n d and n i are the average dust and ion densities, respectively, and Z d is the dust charge in units of electron charge. The collective attraction is determined by finite grain size and by the presence of absorption of plasma flux on grains. The physics of attraction is related to the space charge accumulation caused by collective flux disturbances. The collective attraction operates for systems with size larger than the mean free path for ion-dust absorption, the condition met in many existing low temperature dusty plasma experiments, in edge plasmas of fusion devices and in space dusty plasmas. The collective attraction exceeds the previously known non-collective attraction such as shadow attraction or wake attraction. The collective attraction can be responsible for pairing of dust grains (this process is completely classical in contrast to the known pairing in superconductivity) and can serve as the main process for the formation of more complicated dust complexes up to dust-plasma crystals. The equilibrium structures formed by collective attraction have universal properties and can exist in a limited domain of parameters (similar to the equilibrium balance known for stars). The balance conditions for

  5. Ar plasma induced deep levels in epitaxial n-GaAs

    Energy Technology Data Exchange (ETDEWEB)

    Venter, A.; Nyamhere, C.; Botha, J. R. [Department of Physics, Nelson Mandela Metropolitan University, PO Box 77000, Port Elizabeth 6031 (South Africa); Auret, F. D.; Janse van Rensburg, P. J.; Meyer, W. E.; Coelho, S. M. M. [Department of Physics, University of the Pretoria, Lynnwood Road, Pretoria 0002 (South Africa); Kolkovsky, V. l. [Technische Universitaet, Dresden, 01062 Dresden (Germany)

    2012-01-01

    Ar plasma etching of n-type (Si doped) GaAs introduces several electron traps (E{sub c} - 0.04 eV, E{sub c} - 0.07 eV, E{sub c} - 0.19 eV, E{sub c} - 0.31 eV, E{sub c} - 0.53 eV, and E{sub c} - 0.61 eV). The trap, E{sub c} - 0.04 eV, labelled E1' and having a trap signature similar to irradiation induced defect E1, appears to be metastable. E{sub c} - 0.31 eV and E{sub c} - 0.61 eV are metastable too and they are similar to the M3/M4 defect configuration present in hydrogen plasma exposed n-GaAs.

  6. Isolation and N-terminal sequencing of a novel cadmium-binding protein from Boletus edulis

    Science.gov (United States)

    Collin-Hansen, C.; Andersen, R. A.; Steinnes, E.

    2003-05-01

    A Cd-binding protein was isolated from the popular edible mushroom Boletus edulis, which is a hyperaccumulator of both Cd and Hg. Wild-growing samples of B. edulis were collected from soils rich in Cd. Cd radiotracer was added to the crude protein preparation obtained from ethanol precipitation of heat-treated cytosol. Proteins were then further separated in two consecutive steps; gel filtration and anion exchange chromatography. In both steps the Cd radiotracer profile showed only one distinct peak, which corresponded well with the profiles of endogenous Cd obtained by atomic absorption spectrophotometry (AAS). Concentrations of the essential elements Cu and Zn were low in the protein fractions high in Cd. N-terminal sequencing performed on the Cd-binding protein fractions revealed a protein with a novel amino acid sequence, which contained aromatic amino acids as well as proline. Both the N-terminal sequencing and spectrofluorimetric analysis with EDTA and ABD-F (4-aminosulfonyl-7-fluoro-2, 1, 3-benzoxadiazole) failed to detect cysteine in the Cd-binding fractions. These findings conclude that the novel protein does not belong to the metallothionein family. The results suggest a role for the protein in Cd transport and storage, and they are of importance in view of toxicology and food chemistry, but also for environmental protection.

  7. Understanding the growth of micro and nano-crystalline AlN by thermal plasma process

    Science.gov (United States)

    Kanhe, Nilesh S.; Nawale, Ashok B.; Gawade, Rupesh L.; Puranik, Vedavati G.; Bhoraskar, Sudha V.; Das, Asoka K.; Mathe, Vikas L.

    2012-01-01

    We report the studies related to the growth of crystalline AlN in a DC thermal plasma reactor, operated by a transferred arc plasma torch. The reactor is capable of producing the nanoparticles of Al and AlN depending on the composition of the reacting gas. Al and AlN micro crystals are formed at the anode placed on the graphite and nano crystalline Al and AlN gets deposited on the inner surface of the plasma reactor. X-ray diffraction, Raman spectroscopy analysis, single crystal X-ray diffraction and TGA-DTA techniques are used to infer the purity of post process crystals as a hexagonal AlN. The average particle size using SEM was found to be around 30 μm. The morphology of nanoparticles of Al and AlN, nucleated by gas phase condensation in a homogeneous medium were studied by transmission electron microscopy analysis. The particle ranged in size between 15 and 80 nm in diameter. The possible growth mechanism of crystalline AlN at the anode has been explained on the basis of non-equilibrium processes in the core of the plasma and steep temperature gradient near its periphery. The gas phase species of AlN and various constituent were computed using Murphy code based on minimization of free energy. The process provides 50% yield of microcrystalline AlN and remaining of Al at anode and that of nanocrystalline h-AlN and c-Al collected from the walls of the chamber is about 33% and 67%, respectively.

  8. Relation between N-terminal pro-brain natriuretic peptide and cardiac remodeling and function assessed by cardiovascular magnetic resonance imaging in patients with arrhythmogenic right ventricular cardiomyopathy.

    Science.gov (United States)

    Cheng, Huaibing; Lu, Minjie; Hou, Cuihong; Chen, Xuhua; Wang, Jing; Yin, Gang; Chu, Jianmin; Zhang, Shu; Prasad, Sanjay K; Pu, Jielin; Zhao, Shihua

    2015-02-01

    Although N-terminal pro-brain natriuretic peptide (NT-proBNP) is a useful screening test of impaired right ventricular (RV) function in conditions affecting the right-sided cardiac muscle, the role of NT-proBNP remains unclear in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). This study was designed to clarify the relation between the plasma NT-proBNP level and the RV function evaluated by cardiovascular magnetic resonance (CMR) imaging. We selected 56 patients with confirmed ARVC only when their blood specimens for NT-proBNP measurements were collected within 48 hours of a CMR scan. The NT-proBNP level was significantly higher in patients with RV dysfunction than in patients without RV dysfunction (median of 655.3 [interquartile range 556.4 to 870.0] vs 347.0 [interquartile range 308.0 to 456.2] pmol/L, p rights reserved.

  9. Study of heat and synchrotron radiation transport in fusion tokamak plasmas. Application to the modelling of steady state and fast burn termination scenarios for the international experimental fusion reactor ITER

    International Nuclear Information System (INIS)

    Villar Colome, J.

    1997-12-01

    The aim of this thesis is to give a global scope of the problem of energy transport within a thermonuclear plasma in the context of its power balance and the implications when modelling ITER operating scenarios. This is made in two phases. First, by furnishing new elements to the existing models of heat and synchrotron radiation transport in a thermonuclear plasma. Second, by applying the improved models to plasma engineering studies of ITER operating scenarios. The scenarios modelled are the steady state operating point and the transient that appears to have the biggest technological implications: the fast burn termination. The conduction-convection losses are modelled through the energy confinement time. This parameter is empirically obtained from the existing experimental data, since the underlying mechanisms are not well understood. In chapter 2 an expression for the energy confinement time is semi-analytically deduced from the Rebut-Lallia-Watkins local transport model. The current estimates of the synchrotron radiation losses are made with expressions of the dimensionless transparency factor deduced from a 0-dimensional cylindrical model proposed by Trubnikov in 1979. In chapter 3 realistic hypothesis for the cases of cylindrical and toroidal geometry are included in the model to deduce compact explicit expressions for the fast numerical computation of the synchrotron radiation losses. Numerical applications are provided for the cylindrical case. The results are checked against the existing models. In chapter 4, the nominal operating point of ITER and its thermal stability is studied by means of a 0-dimensional burn model of the thermonuclear plasma in ignition. This model is deduced by the elements furnished by the plasma particle and power balance. Possible heat overloading on the plasma facing components may provoke severe structural damage, implying potential safety problems related to tritium inventory and metal activation. In chapter 5, the assessment

  10. Study of heat and synchrotron radiation transport in fusion tokamak plasmas. Application to the modelling of steady state and fast burn termination scenarios for the international experimental fusion reactor ITER

    Energy Technology Data Exchange (ETDEWEB)

    Villar Colome, J. [Association Euratom-CEA, Centre d`Etudes de Cadarache, 13 - Saint-Paul-lez-Durance (France). Dept. de Recherches sur la Fusion Controlee]|[Universitat Polytechnica de Catalunya (Spain)

    1997-12-01

    The aim of this thesis is to give a global scope of the problem of energy transport within a thermonuclear plasma in the context of its power balance and the implications when modelling ITER operating scenarios. This is made in two phases. First, by furnishing new elements to the existing models of heat and synchrotron radiation transport in a thermonuclear plasma. Second, by applying the improved models to plasma engineering studies of ITER operating scenarios. The scenarios modelled are the steady state operating point and the transient that appears to have the biggest technological implications: the fast burn termination. The conduction-convection losses are modelled through the energy confinement time. This parameter is empirically obtained from the existing experimental data, since the underlying mechanisms are not well understood. In chapter 2 an expression for the energy confinement time is semi-analytically deduced from the Rebut-Lallia-Watkins local transport model. The current estimates of the synchrotron radiation losses are made with expressions of the dimensionless transparency factor deduced from a 0-dimensional cylindrical model proposed by Trubnikov in 1979. In chapter 3 realistic hypothesis for the cases of cylindrical and toroidal geometry are included in the model to deduce compact explicit expressions for the fast numerical computation of the synchrotron radiation losses. Numerical applications are provided for the cylindrical case. The results are checked against the existing models. In chapter 4, the nominal operating point of ITER and its thermal stability is studied by means of a 0-dimensional burn model of the thermonuclear plasma in ignition. This model is deduced by the elements furnished by the plasma particle and power balance. Possible heat overloading on the plasma facing components may provoke severe structural damage, implying potential safety problems related to tritium inventory and metal activation. In chapter 5, the assessment

  11. Plasma membrane calcium ATPases and related disorders.

    Science.gov (United States)

    Giacomello, Marta; De Mario, Agnese; Scarlatti, Chiara; Primerano, Simona; Carafoli, Ernesto

    2013-03-01

    The plasma membrane Ca(2+) ATPases (PMCA pumps) cooperate with other transport systems in the plasma membrane and in the organelles in the regulation of cell Ca(2+). They have high Ca(2+) affinity and are thus the fine tuners of cytosolic Ca(2+). They belong to the superfamily of P-type ATPases: their four basic isoforms share the essential properties of the reaction cycle and the general membrane topography motif of 10 transmembrane domains and three large cytosolic units. However they also differ in other important properties, e.g., tissue distribution and regulatory mechanisms. Their chief regulator is calmodulin, that removes their C-terminal cytosolic tail from autoinhibitory binding sites next to the active site of the pump, restoring activity. The number of pump isoforms is increased to over 30 by alternative splicing of the transcripts at a N-terminal site (site A) and at site C within the C-terminal calmodulin binding domain: the splice variants are tissue specific and developmentally regulated. The importance of PMCAs in the maintenance of cellular Ca(2+) homeostasis is underlined by the disease phenotypes, genetic or acquired, caused by their malfunction. Non-genetic PMCA deficiencies have long been considered possible causative factors in disease conditions as important as cancer, hypertension, or neurodegeneration. Those of genetic origin are better characterized: some have now been discovered in humans as well. They concern all four PMCA isoforms, and range from cardiac dysfunctions, to deafness, to hypertension, to cerebellar ataxia. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Restricted N-terminal truncation of cardiac troponin T: a novel mechanism for functional adaptation to energetic crisis.

    Science.gov (United States)

    Feng, Han-Zhong; Biesiadecki, Brandon J; Yu, Zhi-Bin; Hossain, M Moazzem; Jin, J-P

    2008-07-15

    The N-terminal variable region of cardiac troponin T (TnT) is a regulatory structure that can be selectively removed during myocardial ischaemia reperfusion by mu-calpain proteolysis. Here we investigated the pathophysiological significance of this post-translational modification that removes amino acids 1-71 of cardiac TnT. Working heart preparations were employed to study rat acute myocardial infarction and transgenic mouse hearts over-expressing the N-terminal truncated cardiac TnT (cTnT-ND). Ex vivo myocardial infarction by ligation of the left anterior descending coronary artery induced heart failure and produced cTnT-ND not only in the infarct but also in remote zones, including the right ventricular free wall, indicating a whole organ response in the absence of systemic neurohumoral mechanisms. Left ventricular pressure overload in mouse working hearts produced increased cTnT-ND in both ventricles, suggesting a role of haemodynamic stress in triggering an acute whole organ proteolytic regulation. Transgenic mouse hearts in which the endogenous intact cardiac TnT was partially replaced by cTnT-ND showed lowered contractile velocity. When afterload increased from 55 mmHg to 90 mmHg, stroke volume decreased in the wild type but not in the transgenic mouse hearts. Correspondingly, the left ventricular rapid-ejection time of the transgenic mouse hearts was significantly longer than that of wild type hearts, especially at high afterload. The restricted deletion of the N-terminal variable region of cardiac troponin T demonstrates a novel mechanism by which the thin filament regulation adapts to sustain cardiac function under stress conditions.

  13. The EBNA-2 N-Terminal Transactivation Domain Folds into a Dimeric Structure Required for Target Gene Activation.

    Directory of Open Access Journals (Sweden)

    Anders Friberg

    2015-05-01

    Full Text Available Epstein-Barr virus (EBV is a γ-herpesvirus that may cause infectious mononucleosis in young adults. In addition, epidemiological and molecular evidence links EBV to the pathogenesis of lymphoid and epithelial malignancies. EBV has the unique ability to transform resting B cells into permanently proliferating, latently infected lymphoblastoid cell lines. Epstein-Barr virus nuclear antigen 2 (EBNA-2 is a key regulator of viral and cellular gene expression for this transformation process. The N-terminal region of EBNA-2 comprising residues 1-58 appears to mediate multiple molecular functions including self-association and transactivation. However, it remains to be determined if the N-terminus of EBNA-2 directly provides these functions or if these activities merely depend on the dimerization involving the N-terminal domain. To address this issue, we determined the three-dimensional structure of the EBNA-2 N-terminal dimerization (END domain by heteronuclear NMR-spectroscopy. The END domain monomer comprises a small fold of four β-strands and an α-helix which form a parallel dimer by interaction of two β-strands from each protomer. A structure-guided mutational analysis showed that hydrophobic residues in the dimer interface are required for self-association in vitro. Importantly, these interface mutants also displayed severely impaired self-association and transactivation in vivo. Moreover, mutations of solvent-exposed residues or deletion of the α-helix do not impair dimerization but strongly affect the functional activity, suggesting that the EBNA-2 dimer presents a surface that mediates functionally important intra- and/or intermolecular interactions. Our study shows that the END domain is a novel dimerization fold that is essential for functional activity. Since this specific fold is a unique feature of EBNA-2 it might provide a novel target for anti-viral therapeutics.

  14. Mechanism of laser and rf plasma in vibrational nonequilibrium CO-N2 gas mixture

    International Nuclear Information System (INIS)

    Lou Guofeng; Adamovich, Igor V.

    2009-01-01

    This paper investigates the mechanism of plasma created by focused CO laser and rf electric field. The plasma is created in a CO/N 2 environment, at a total pressure of 600 torr. Ionization of the gases occurs by an associative ionization mechanism, in collisions of two highly vibrationally excited molecules. These highly vibrationally excited states are populated by resonance absorption of the CO radiation followed by anharmonic vibration-vibration (V-V) pumping. Moreover N 2 also becomes vibrationally excited due to collisions with vibrationally excited CO. The coupled rf reduced electric field E/N is sufficiently low to prevent electron impact ionization that may create plasma individually, so when a subbreakdown rf field is applied to the plasma, collisions between the free electrons heated by the field and the diatomic species create additional vibrational excitation both in the region occupied by the CO laser beam and outside of the laser beam region. The numerical results show plasma created in both regions (in and out of the CO laser beam region) with the associative ionization mechanism. This suggests a method for creating a stable nonequilibrium plasma. The calculation result is verified by comparison the synthetic spectrum to a measured one.

  15. Association of N-terminal pro-brain natriuretic peptide with cognitive function and depression in elderly people with type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Insa Feinkohl

    Full Text Available Type 2 diabetes mellitus is associated with risk of congestive heart failure (CHF, cognitive dysfunction and depression. CHF itself is linked both to poor cognition and depression. The ventricular N-terminal pro-brain natriuretic peptide (NT-proBNP is a marker of CHF, suggesting potential as a marker for cognitive impairment and/or depression. This was tested in the Edinburgh Type 2 Diabetes Study (ET2DS.Cross-sectional analysis of 1066 men and women aged 60-75 with type 2 diabetes. Results from seven neuropsychological tests were combined in a standardised general cognitive ability factor, 'g'. A vocabulary-based test estimated pre-morbid cognitive ability. The Hospital Anxiety and Depression Scale (HADS assessed possible depression. After adjustment for age and sex, raised plasma NT-proBNP was weakly associated with lower 'g' and higher depression scores (ß -0.09, 95% CI -0.13 to -0.03, p = 0.004 and ß 0.08, 95% CI 0.04 to 0.12, p0.05 for 'g'; β 0.03, 95% CI -0.02 to 0.07, p>0.05 for depression scores.Raised plasma NT-proBNP was weakly but statistically significantly associated with poorer cognitive function and depression. The prospective phases of the ET2DS will help determine whether or not NT-proBNP can be considered a risk marker for subsequent cognitive impairment and incident depression and whether it provides additional information over and above traditional risk factors for these conditions.

  16. The N-terminal domains of Vps3 and Vps8 are critical for localization and function of the CORVET tethering complex on endosomes.

    Directory of Open Access Journals (Sweden)

    Nadine Epp

    Full Text Available Endosomal biogenesis depends on multiple fusion and fission events. For fusion, the heterohexameric CORVET complex as an effector of the endosomal Rab5/Vps21 GTPase has a central function in the initial tethering event. Here, we show that the CORVET-specific Vps3 and Vps8 subunits, which interact with Rab5/Vps21, require their N-terminal domains for localization and function. Surprisingly, CORVET may lack either one of the two N-terminal domains, but not both, to promote protein sorting via the endosome. The dually truncated complex mislocalizes to the cytosol and is impaired in endocytic protein sorting, but not in assembly. Furthermore, the endosomal localization can be rescued by overexpression of Vps21 or one of the truncated CORVET subunits, even though CORVET assembly is not impaired by loss of the N-terminal domains or in strains lacking all endosomal Rab5s and Ypt7. We thus conclude that CORVET requires only its C-terminal domains for assembly and has beyond its putative β-propeller domains additional binding sites for endosomes, which could be important to bind Vps21 and other endosome-specific factors for efficient endosome tethering.

  17. Efficient adhesion-based plasma membrane isolation for cell surface N-glycan analysis.

    Science.gov (United States)

    Mun, Ji-Young; Lee, Kyung Jin; Seo, Hoon; Sung, Min-Sun; Cho, Yee Sook; Lee, Seung-Goo; Kwon, Ohsuk; Oh, Doo-Byoung

    2013-08-06

    Glycans, which decorate cell surfaces, play crucial roles in various physiological events involving cell surface recognition. Despite the importance of surface glycans, most analyses have been performed using total cells or whole membranes rather than plasma membranes due to difficulties related to isolation. In the present study, we employed an adhesion-based method for plasma membrane isolation to analyze N-glycans on cell surfaces. Cells were attached to polylysine-coated glass plates and then ruptured by hypotonic pressure. After washing to remove intracellular organelles, only a plasma membrane fraction remained attached to the plates, as confirmed by fluorescence imaging using organelle-specific probes. The plate was directly treated with trypsin to digest and detach the glycoproteins from the plasma membrane. From the resulting glycopeptides, N-glycans were released and analyzed using MALDI-TOF mass spectrometry and HPLC. When N-glycan profiles obtained by this method were compared to those by other methods, the amount of high-mannose type glycans mainly contaminated from the endoplasmic reticulum was dramatically reduced, which enabled the efficient detection of complex type glycans present on the cell surface. Moreover, this method was successfully used to analyze the increase of high-mannose glycans on the surface as induced by a mannosidase inhibitor treatment.

  18. Accessibility of the Shine-Dalgarno sequence dictates N-terminal codon bias in E. coli

    OpenAIRE

    Shakhnovich, Eugene; Zhang, Wenli; Yan, Jin; Adkar, Bharat; Jacobs, William; Bhattacharyya, Sanchari; Adkar, Bharat

    2018-01-01

    Despite considerable efforts, no physical mechanism has been shown to explain N-terminal codon bias in prokaryotic genomes. Using a systematic study of synonymous substitutions in two endogenous E. coli genes, we show that interactions between the coding region and the upstream Shine-Dalgarno (SD) sequence modulate the efficiency of translation initiation, affecting both intracellular mRNA and protein levels due to the inherent coupling of transcription and translation in E. coli. We further ...

  19. Plasma-deposited a-C(N) H films

    CERN Document Server

    Franceschini, D E

    2000-01-01

    The growth behaviour, film structure and mechanical properties of plasma-deposited amorphous hydrogenated carbon-nitrogen films are shortly reviewed. The effect of nitrogen-containing gas addition to the deposition to the hydrocarbon atmospheres used is discussed, considering the modifications observed in the chemical composition growth kinetics, carbon atom hybridisation and chemical bonding arrangements of a-C(N):H films. The overall structure behaviour is correlated to the variation of the mechanical properties.

  20. Control of N/N{sub 2} species ratio in NO plasma for p-type doping of ZnO

    Energy Technology Data Exchange (ETDEWEB)

    Chen Xingyou [Key Laboratory of Excited State Processes and Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, 3888 Dongnanhu Road, Changchun, 130033 (China); Graduate School of the Chinese Academy of Sciences, Beijing 100049 (China); Zhang Zhenzhong; Jiang Mingming; Wang Shuangpeng; Li Binghui; Shan Chongxin; Liu Lei; Zhao Dongxu; Shen Dezhen [Key Laboratory of Excited State Processes and Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, 3888 Dongnanhu Road, Changchun, 130033 (China); Yao Bin [State Key Laboratory of Superhard Materials and College of Physics, Jilin University, Changchun 130023 (China)

    2011-09-01

    Nitrogen-doped ZnO thin films were grown on c-plane sapphire (Al{sub 2}O{sub 3}) substrates via plasma-assisted molecular beam epitaxy using plasma activated nitric oxide (NO) as the oxygen source and dopant. X-ray diffraction measurements indicate that a small NO flux benefits the crystal quality of the thin films. Hall effect measurements indicate that the electron density of the ZnO films decreases gradually with decreasing NO flux, and the conduction reverses to p-type at a certain flux. Optical emission spectra indicate that the N atom content in the NO plasma increases with decreasing NO flux, and the origin of this is discussed. X-ray photoelectron spectroscopy measurements demonstrate that the number of N atom occupied O sites in the ZnO lattice increases correspondingly.

  1. Prediction of drug terminal half-life and terminal volume of distribution after intravenous dosing based on drug clearance, steady-state volume of distribution, and physiological parameters of the body.

    Science.gov (United States)

    Berezhkovskiy, Leonid M

    2013-02-01

    The steady state, V(ss), terminal volume of distribution, V(β), and the terminal half-life, t(1/2), are commonly obtained from the drug plasma concentration-time profile, C(p)(t), following intravenous dosing. Unlike V(ss) that can be calculated based on the physicochemical properties of drugs considering the equilibrium partitioning between plasma and organ tissues, t(1/2) and V(β) cannot be calculated that way because they depend on the rates of drug transfer between blood and tissues. Considering the physiological pharmacokinetic model pertinent to the terminal phase of drug elimination, a novel equation that calculates t(1/2) (and consequently V(β)) was derived. It turns out that V(ss), the total body clearance, Cl, equilibrium blood-plasma concentration ratio, r; and the physiological parameters of the body such as cardiac output, and blood and tissue volumes are sufficient for determination of terminal kinetics. Calculation of t(1/2) by the obtained equation appears to be in good agreement with the experimentally observed vales of this parameter in pharmacokinetic studies in rat, monkey, dog, and human. The equation for the determination of the pre-exponent of the terminal phase of C(p)(t) is also found. The obtained equation allows to predict t(1/2) in human assuming that V(ss) and Cl were either obtained by allometric scaling or, respectively, calculated in silico or based on in vitro drug stability measurements. For compounds that have high clearance, the derived equation may be applied to calculate r just using the routine data on Cl, V(ss), and t(1/2), rather than doing the in vitro assay to measure this parameter. Copyright © 2012 Wiley Periodicals, Inc.

  2. Deposition of Al N and Ti N thin films on substrates of stainless steel SS304 using plasma focus device

    International Nuclear Information System (INIS)

    Al-Hawat, Sh.; Soukieh, M.; Abou Kharoub, M.; Al-Sadat, W.

    2006-06-01

    A 2.8 kJ plasma focus device was used to deposit thin films of aluminium nitride Al N and titanium nitride Ti N on a stainless steel 394 substrate, in order to improve its surface properties. The deposition process was carried out using various number of nitrogen plasma shots at pressures 0.5-0.75 mbar and at different sample's distances from the anode. The plasma diagnostics was achieved using the voltage and current signals recorded by a voltage divider and Rogovskii coil to determine the temperature and plasma density. The surface hardness of SS-304 was increased by about 50% after plasma coating and the thickness of the coated layers was about 1-2μm. This study shows that the hardness is increased with increasing the number of shots and decreased with the distance from the anode. The coated layers were characterized and a qualitative understanding of the deposition process was given. (author)

  3. Impacts of recessed gate and fluoride-based plasma treatment approaches toward normally-off AlGaN/GaN HEMT.

    Science.gov (United States)

    Heo, Jun-Woo; Kim, Young-Jin; Kim, Hyun-Seok

    2014-12-01

    We report two approaches to fabricating high performance normally-off AIGaN/GaN high-electron mobility transistors (HEMTs). The fabrication techniques employed were based on recessed-metal-insulator-semiconductor (MIS) gate and recessed fluoride-based plasma treatment. They were selectively applied to the area under the gate electrode to deplete the two-dimensional electron gas (2-DEG) density. We found that the recessed gate structure was effective in shifting the threshold voltage by controlling the etching depth of gate region to reduce the AIGaN layer thickness to less than 8 nm. Likewise, the CF4 plasma treatment effectively incorporated negatively charged fluorine ions into the thin AIGaN barrier so that the threshold voltage shifted to higher positive values. In addition to the increased threshold voltage, experimental results showed a maximum drain current and a maximum transconductance of 315 mA/mm and 100 mS/mm, respectively, for the recessed-MIS gate HEMT, and 340 mA/mm and 330 mS/mm, respectively, for the fluoride-based plasma treated HEMT.

  4. Critical structural and functional roles for the N-terminal insertion sequence in surfactant protein B analogs.

    Directory of Open Access Journals (Sweden)

    Frans J Walther

    2010-01-01

    Full Text Available Surfactant protein B (SP-B; 79 residues belongs to the saposin protein superfamily, and plays functional roles in lung surfactant. The disulfide cross-linked, N- and C-terminal domains of SP-B have been theoretically predicted to fold as charged, amphipathic helices, suggesting their participation in surfactant activities. Earlier structural studies with Mini-B, a disulfide-linked construct based on the N- and C-terminal regions of SP-B (i.e., approximately residues 8-25 and 63-78, confirmed that these neighboring domains are helical; moreover, Mini-B retains critical in vitro and in vivo surfactant functions of the native protein. Here, we perform similar analyses on a Super Mini-B construct that has native SP-B residues (1-7 attached to the N-terminus of Mini-B, to test whether the N-terminal sequence is also involved in surfactant activity.FTIR spectra of Mini-B and Super Mini-B in either lipids or lipid-mimics indicated that these peptides share similar conformations, with primary alpha-helix and secondary beta-sheet and loop-turns. Gel electrophoresis demonstrated that Super Mini-B was dimeric in SDS detergent-polyacrylamide, while Mini-B was monomeric. Surface plasmon resonance (SPR, predictive aggregation algorithms, and molecular dynamics (MD and docking simulations further suggested a preliminary model for dimeric Super Mini-B, in which monomers self-associate to form a dimer peptide with a "saposin-like" fold. Similar to native SP-B, both Mini-B and Super Mini-B exhibit in vitro activity with spread films showing near-zero minimum surface tension during cycling using captive bubble surfactometry. In vivo, Super Mini-B demonstrates oxygenation and dynamic compliance that are greater than Mini-B and compare favorably to full-length SP-B.Super Mini-B shows enhanced surfactant activity, probably due to the self-assembly of monomer peptide into dimer Super Mini-B that mimics the functions and putative structure of native SP-B.

  5. Safety analyses for transient behavior of plasma and in-vessel components during plasma abnormal events in fusion reactor

    International Nuclear Information System (INIS)

    Honda, Takuro; Okazaki, Takashi; Bartels, H.W.; Uckan, N.A.; Seki, Yasushi.

    1997-01-01

    Safety analyses on plasma abnormal events have been performed using a hybrid code of a plasma dynamics model and a heat transfer model of in-vessel components. Several abnormal events, e.g., increase in fueling rate, were selected for the International Thermonuclear Experimental Reactor (ITER) and transient behavior of the plasma and the invessel components during the events was analyzed. The physics model for safety analysis was conservatively prepared. In most cases, the plasma is terminated by a disruption or it returns to the original operation point. When the energy confinement improves by a factor of 2.0 in the steady state, which is a hypothetical assumption under the present plasma data, the maximum fusion power reaches about 3.3 GW at about 3.6 s and the plasma is terminated due to a disruption. However, the results obtained in this study show the confinement boundary of ITER can be kept almost intact during the abnormal plasma transients, as long as the cooling system works normally. Several parametric studies are needed to comprehend the overpower transient including structure behavior, since many uncertainties are connected to the filed of the plasma physics. And, future work will need to discuss the burn control scenario considering confinement mode transition, system specifications, experimental plans and safety regulations, etc. to confirm the safety related to the plasma anomaly. (author)

  6. The structure of standing Alfvén waves in a dipole magnetosphere with moving plasma

    Directory of Open Access Journals (Sweden)

    D. A. Kozlov

    2006-03-01

    Full Text Available The structure and spectrum of standing Alfvén waves were theoretically investigated in a dipole magnetosphere with moving plasma. Plasma motion was simulated with its azimuthal rotation. The model's scope allowed for describing a transition from the inner plasmasphere at rest to the outer magnetosphere with convecting plasma and, through the magnetopause, to the moving plasma of the solar wind. Solutions were found to equations describing longitudinal and transverse (those formed, respectively, along field lines and across magnetic shells structures of standing Alfvén waves with high azimuthal wave numbers m>>1. Spectra were constructed for a number of first harmonics of poloidal and toroidal standing Alfvén waves inside the magnetosphere. For charged particles with velocities greatly exceeding the velocity of the background plasma, an effective parallel wave component of the electric field appears in the region occupied by such waves. This results in structured high-energy-particle flows and in the appearance of multiband aurorae. The transverse structure of the standing Alfvén waves' basic harmonic was shown to be analogous to the structure of a discrete auroral arc.

  7. [Optical emission analyses of N2/TMG ECR plasma for deposition of GaN film].

    Science.gov (United States)

    Fu, Si-Lie; Wang, Chun-An; Chen, Jun-Fang

    2013-04-01

    The optical emission spectroscopy of hybrid N2/trimethylgallium (TMG) plasma in an ECR-PECVD system was investigated. The results indicate that the TMG gas is strongly dissociated into Ga*, CH and H even under self-heating condition. Ga species and nitrogen molecule in metastable state are dominant in hybrid ECR plasma. The concentration of metastable nitrogen molecule increases with the microwave power. On the other hand, the concentration of excited nitrogen molecules and of nitrogen ion decreases when the microwave power is higher than 400 W.

  8. Intrinsic structural differences in the N-terminal segment of pulmonary surfactant protein SP-C from different species

    DEFF Research Database (Denmark)

    Plasencia, I; Rivas, L; Casals, C

    2001-01-01

    Predictive studies suggest that the known sequences of the N-terminal segment of surfactant protein SP-C from animal species have an intrinsic tendency to form beta-turns, but there are important differences on the probable location of these motifs in different SP-C species. Our hypothesis...

  9. Raman scattering and Rutherford backscattering studies on InN films grown by plasma-assisted molecular beam epitaxy

    International Nuclear Information System (INIS)

    Chung, Yee Ling; Peng Xingyu; Liao, Ying Chieh; Yao Shude; Chen, Li Chyong; Chen, Kuei Hsien; Feng, Zhe Chuan

    2011-01-01

    A series of InN thin films was grown on sapphire substrates via plasma-assisted molecular beam epitaxy (PA-MBE) with different nitrogen plasma power. Various characterization techniques, including Hall, photoluminescence, Raman scattering and Rutherford backscattering, have been employed to study these InN films. Good crystalline wurtzite structures have been identified for all PA-MBE grown InN films on sapphire substrate, which have narrower XRD wurtzite (0002) peaks, showed c-axis Raman scattering allowed longitudinal optical (LO) modes of A 1 and E 1 plus E 2 symmetry, and very weak backscattering forbidden transverse optical (TO) modes. The lower plasma power can lead to the lower carrier concentration, to have the InN film close to intrinsic material with the PL emission below 0.70 eV. With increasing the plasma power, high carrier concentration beyond 1 x 10 20 cm -3 can be obtained, keeping good crystalline perfection. Rutherford backscattering confirmed most of InN films keeping stoichiometrical In/N ratios and only with higher plasma power of 400 W leaded to obvious surface effect and interdiffusion between the substrate and InN film.

  10. Changes in plasma calcium and in radiocalcium kinetics after termination of 5-week infusions of synthetic parathyroid peptide in dogs

    International Nuclear Information System (INIS)

    Stevenson, R.W.; Parsons, J.A.; Podbesek, R.D.; Reeve, J.

    1983-01-01

    Nine dogs were infused at constant rates with the synthetic parathyroid peptide hPTH 1-34 (initially sc) to produce consistent hypercalcaemia. Over the final week, the infusions were iv. Radioisotopic tracers were injected iv 30 days (5 dogs) and 2 days (9 dogs) before the infusions were suddenly terminated. In 5 dogs, complete urine collections were obtained via a bladder catheter over 8 h beginning 2 h before stopping the infusions. Cessation of treatment caused small rises in the urinary Ca: creatinine ratio. Plasma calcium levels fell by a mean of 0.44 mmol/l, of which total urine calcium excretion only accounted for 55%. Immediately after the PTH infusions were stopped, consistent but transient increases were seen in the ratio of ''new'' 47 Ca to ''old'' 45 Ca label, suggesting inflow of 40 Ca of high 47 Ca specific activity from a fairly rapidly exchangeable bone pool. These data confirm and extend previous evidence that the immediate response of the calcium equilibrium between bone and bloodstream to rapid changes in plasma PTH concentrations in the supra-physiological ranges is paradoxical relative to the classical later response. (author)

  11. Characterization of an extensin-modifying metalloprotease: N-terminal processing and substrate cleavage pattern of Pectobacterium carotovorum Prt1

    DEFF Research Database (Denmark)

    Feng, Tao; Nyffenegger, Christian; Højrup, Peter

    2014-01-01

    Compared to other plant cell wall-degrading enzymes, proteases are less well understood. In this study, the extracellular metalloprotease Prt1 from Pectobacterium carotovorum (formerly Erwinia carotovora) was expressed in Escherichia coli and characterized with respect to N-terminal processing...

  12. Loss of Nat4 and its associated histone H4 N-terminal acetylation mediates calorie restriction-induced longevity.

    Science.gov (United States)

    Molina-Serrano, Diego; Schiza, Vassia; Demosthenous, Christis; Stavrou, Emmanouil; Oppelt, Jan; Kyriakou, Dimitris; Liu, Wei; Zisser, Gertrude; Bergler, Helmut; Dang, Weiwei; Kirmizis, Antonis

    2016-12-01

    Changes in histone modifications are an attractive model through which environmental signals, such as diet, could be integrated in the cell for regulating its lifespan. However, evidence linking dietary interventions with specific alterations in histone modifications that subsequently affect lifespan remains elusive. We show here that deletion of histone N-alpha-terminal acetyltransferase Nat4 and loss of its associated H4 N-terminal acetylation (N-acH4) extend yeast replicative lifespan. Notably, nat4Δ-induced longevity is epistatic to the effects of calorie restriction (CR). Consistent with this, (i) Nat4 expression is downregulated and the levels of N-acH4 within chromatin are reduced upon CR, (ii) constitutive expression of Nat4 and maintenance of N-acH4 levels reduces the extension of lifespan mediated by CR, and (iii) transcriptome analysis indicates that nat4Δ largely mimics the effects of CR, especially in the induction of stress-response genes. We further show that nicotinamidase Pnc1, which is typically upregulated under CR, is required for nat4Δ-mediated longevity. Collectively, these findings establish histone N-acH4 as a regulator of cellular lifespan that links CR to increased stress resistance and longevity. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

  13. Nickel Ligation of the N-Terminal Amine of HypA Is Required for Urease Maturation in Helicobacter pylori

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Heidi Q. [Department; Johnson, Ryan C. [Microbiology; Merrell, D. Scott [Microbiology; Maroney, Michael J. [Department

    2017-02-17

    The human pathogen Helicobacter pylori requires nickel for colonization of the acidic environment of the stomach. HypA, a Ni metallochaperone that is typically associated with hydrogenase maturation, is also required for urease maturation and acid survival of H. pylori. There are two proposed Ni site structures for HypA; one is a paramagnetic six-coordinate site characterized by X-ray absorption spectroscopy (XAS) in unmodified HypA, while another is a diamagnetic four-coordinate planar site characterized by solution nuclear magnetic resonance in an N-terminally modified HypA construct. To determine the role of the N-terminal amine in Ni binding of HypA, an N-terminal extension variant, L2*-HypA, in which a leucine residue was inserted into the second position of the amino acid sequence in the proposed Ni-binding motif, was characterized in vitro and in vivo. Structural characterization of the Ni site using XAS showed a coordination change from six-coordinate in wild-type HypA (WT-HypA) to five-coordinate pyramidal in L2*-HypA, which was accompanied by the loss of two N/O donor protein ligands and the addition of an exogenous bromide ligand from the buffer. The magnetic properties of the Ni sites in WT-HypA compared to those of the Ni sites in L2*-HypA confirmed that a spin-state change from high to low spin accompanied this change in structure. The L2*-HypA H. pylori strain was shown to be acid sensitive and deficient in urease activity in vivo. In vitro characterization showed that L2*-HypA did not disrupt the HypA–UreE interaction that is essential for urease maturation but was at least 20-fold weaker in Ni binding than WT-HypA. Characterization of the L2*-HypA variant clearly demonstrates that the N-terminal amine of HypA is involved in proper Ni coordination and is necessary for urease activity and acid survival.

  14. Studies on Nanocrystalline TiN Coatings Prepared by Reactive Plasma Spraying

    Directory of Open Access Journals (Sweden)

    Dong Yanchun

    2008-01-01

    Full Text Available Titanium nitride (TiN coatings with nanostructure were prepared on the surface of 45 steel (Fe-0.45%C via reactive plasma spraying (denoted as RPS Ti powders using spraying gun with self-made reactive chamber. The microstructural characterization, phases constitute, grain size, microhardness, and wear resistance of TiN coatings were systematically investigated. The grain size was obtained through calculation using the Scherrer formula and observed by TEM. The results of X-ray diffraction and electron diffraction indicated that the TiN is main phase of the TiN coating. The forming mechanism of the nano-TiN was characterized by analyzing the SEM morphologies of surface of TiN coating and TiN drops sprayed on the surface of glass, and observing the temperature and velocity of plasma jet using Spray Watch. The tribological properties of the coating under nonlubricated condition were tested and compared with those of the AISI M2 high-speed steel and Al2O3 coating. The results have shown that the RPS TiN coating presents better wear resistance than the M2 high-speed steel and Al2O3 coating under nonlubricated condition. The microhardness of the cross-section and longitudinal section of the TiN coating was tested. The highest hardness of the cross-section of TiN coating is 1735.43HV100 g.

  15. The predictive value of plasma biomarkers in discharged heart failure patients: role of plasma NT-proBNP.

    Science.gov (United States)

    Leto, Laura; Testa, Marzia; Feola, Mauro

    2016-04-01

    Natriuretic peptides (NPs) have demonstrated their value to support clinical diagnosis of heart failure (HF); furthermore they are also studied for their prognostic role using them to guide appropriate management strategies. The present review gathers available evidence on prognostic role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients hospitalized for acute decompensated heart failure (ADHF). We searched Medline for English-language studies with the sequent key-words: "acute heart failure/acute decompensated heart failure", "NT-proBNP/N-terminal pro-B type natriuretic peptide" and "prognosis/mortality/readmission". Almost 30 studies were included. NT-proBNP plasma levels at admission are strongly associated with all-cause short-term mortality (2-3 months), mid-term (6-11 months) or long- term mortality (more than one year) of follow-up. Regarding the prognostic power on cardiac death fewer data are available with uncertain results. NT-proBNP at discharge demonstrated its prognostic role for all-cause mortality at mid and long-term follow-up. The relation between NT-proBNP at discharge and cardiovascular mortality or composite end-point is under investigation. A decrease in NT-proBNP values during hospitalization provided prognostic prospects mainly for cardiovascular mortality and HF readmission. A 30% variation in NT-proBNP levels during in-hospital stay seemed to be an optimal cut-off for prognostic role. SNT-proBNP plasma levels proved to have a strong correlation with all-cause mortality, cardiovascular mortality, morbidity and composite outcomes in patients discharged after an ADHF. A better definition of the correct time of serial measurements and the cut-off values might be the challenge for the future investigations.

  16. Implication of the oligomeric state of the N-terminal PTX3 domain in cumulus matrix assembly.

    Science.gov (United States)

    Ievoli, Elena; Lindstedt, Ragnar; Inforzato, Antonio; Camaioni, Antonella; Palone, Francesca; Day, Anthony J; Mantovani, Alberto; Salvatori, Giovanni; Salustri, Antonietta

    2011-06-01

    Pentraxin 3 (PTX3) plays a key role in the formation of the hyaluronan-rich matrix of the cumulus oophorus surrounding ovulated eggs that is required for successful fertilization and female fertility. PTX3 is a multimeric protein consisting of eight identical protomers held together by a combination of non-covalent interactions and disulfide bonds. Recent findings suggest that the oligomeric status of PTX3 is important for stabilizing the cumulus matrix. Because the role of PTX3 in the cumulus resides in the unique N-terminal sequence of the protomer, we investigated further this issue by testing the ability of distinct Cys/Ser mutants of recombinant N-terminal region of PTX3 (N(_)PTX3) with different oligomeric arrangement to promote in vitro normal expansion in cumuli from Ptx3-null mice. Here we report that the dimer of the N(_)PTX3 is unable to rescue cumulus matrix organization, and that the tetrameric assembly of the protein is the minimal oligomeric state required for accomplishing this function. We have previously demonstrated that PTX3 binds to HCs of IαI and TSG-6, which are essential for cumulus matrix formation and able to interact with hyaluronan. Interestingly, here we show by solid-phase binding experiments that the dimer of the N(_)PTX3 retains the ability to bind to both IαI and TSG-6, suggesting that the octameric structure of PTX3 provides multiple binding sites for each of these ligands. These findings support the hypothesis that PTX3 contributes to cumulus matrix organization by cross-linking HA polymers through interactions with multiple HCs of IαI and/or TSG-6. The N-terminal PTX3 tetrameric oligomerization was recently reported to be also required for recognition and inhibition of FGF2. Given that this growth factor has been detected in the mammalian preovulatory follicle, we wondered whether FGF2 negatively influences cumulus expansion and PTX3 may also serve in vivo to antagonize its activity. We found that a molar excess of FGF2, above

  17. Antigenicity and Immunogenicity of RV144 Vaccine AIDSVAX Clade E Envelope Immunogen Is Enhanced by a gp120 N-Terminal Deletion

    Science.gov (United States)

    Liao, Hua-Xin; Tomaras, Georgia D.; Bonsignori, Mattia; Tsao, Chun-Yen; Hwang, Kwan-Ki; Chen, Haiyan; Lloyd, Krissey E.; Bowman, Cindy; Sutherland, Laura; Jeffries, Thomas L.; Kozink, Daniel M.; Stewart, Shelley; Anasti, Kara; Jaeger, Frederick H.; Parks, Robert; Yates, Nicole L.; Overman, R. Glenn; Sinangil, Faruk; Berman, Phillip W.; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Karasavva, Nicos; Rerks-Ngarm, Supachai; Kim, Jerome H.; Michael, Nelson L.; Zolla-Pazner, Susan; Santra, Sampa; Letvin, Norman L.; Harrison, Stephen C.

    2013-01-01

    An immune correlates analysis of the RV144 HIV-1 vaccine trial revealed that antibody responses to the gp120 V1/V2 region correlated inversely with infection risk. The RV144 protein immunogens (A244-rp120 and MN-rgp120) were modified by an N-terminal 11-amino-acid deletion (Δ11) and addition of a herpes simplex virus (HSV) gD protein-derived tag (gD). We investigated the effects of these modifications on gp120 expression, antigenicity, and immunogenicity by comparing unmodified A244 gp120 with both Δ11 deletion and gD tag and with Δ11 only. Analysis of A244 gp120, with or without Δ11 or gD, demonstrated that the Δ11 deletion, without the addition of gD, was sufficient for enhanced antigenicity to gp120 C1 region, conformational V2, and V1/V2 gp120 conformational epitopes. RV144 vaccinee serum IgGs bound more avidly to A244 gp120 Δ11 than to the unmodified gp120, and their binding was blocked by C1, V2, and V1/V2 antibodies. Rhesus macaques immunized with the three different forms of A244 gp120 proteins gave similar levels of gp120 antibody titers, although higher antibody titers developed earlier in A244 Δ11 gp120-immunized animals. Conformational V1/V2 monoclonal antibodies (MAbs) gave significantly higher levels of blocking of plasma IgG from A244 Δ11 gp120-immunized animals than IgG from animals immunized with unmodified A244 gp120, thus indicating a qualitative difference in the V1/V2 antibodies induced by A244 Δ11 gp120. These results demonstrate that deletion of N-terminal residues in the RV144 A244 gp120 immunogen improves both envelope antigenicity and immunogenicity. PMID:23175357

  18. Efficient sortase-mediated N-terminal labeling of TEV protease cleaved recombinant proteins.

    Science.gov (United States)

    Sarpong, Kwabena; Bose, Ron

    2017-03-15

    A major challenge in attaching fluorophores or other handles to proteins is the availability of a site-specific labeling strategy that provides stoichiometric modification without compromising protein integrity. We developed a simple approach that combines TEV protease cleavage, sortase modification and affinity purification to N-terminally label proteins. To achieve stoichiometrically-labeled protein, we included a short affinity tag in the fluorophore-containing peptide for post-labeling purification of the modified protein. This strategy can be easily applied to any recombinant protein with a TEV site and we demonstrate this on Epidermal Growth Factor Receptor (EGFR) and Membrane Scaffold Protein (MSP) constructs. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Data to DecisionsTerminate, Tolerate, Transfer, or Treat

    Science.gov (United States)

    2016-07-25

    and resources.  Degradation of current capability continues. Transfer – Opportunities and Consequences:  Requires a surgical knowledge of what...I N S T I T U T E F O R D E F E N S E A N A L Y S E S Data to Decisions—Terminate, Tolerate, Transfer , or Treat Laura A...Data to Decisions—Terminate, Tolerate, Transfer , or Treat For more information Laura Odell(lodell@ida.org, 703-845-2009 The Department

  20. Ionic interaction of myosin loop 2 with residues located beyond the N-terminal part of actin probed by chemical cross-linking.

    Science.gov (United States)

    Pliszka, Barbara; Martin, Brian M; Karczewska, Emilia

    2008-02-01

    To probe ionic contacts of skeletal muscle myosin with negatively charged residues located beyond the N-terminal part of actin, myosin subfragment 1 (S1) and actin split by ECP32 protease (ECP-actin) were cross-linked with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC). We have found that unmodified S1 can be cross-linked not only to the N-terminal part, but also to the C-terminal 36 kDa fragment of ECP-actin. Subsequent experiments performed on S1 cleaved by elastase or trypsin indicate that the cross-linking site in S1 is located within loop 2. This site is composed of Lys-636 and Lys-637 and can interact with negatively charged residues of the 36 kDa actin fragment, most probably with Glu-99 and Glu-100. Cross-links are formed both in the absence and presence of MgATP.P(i) analog, although the addition of nucleotide decreases the efficiency of the cross-linking reaction.

  1. Biotransformation of endorphins by a synaptosomal plasma membrane preparation of rat brain and by human serum

    NARCIS (Netherlands)

    Burbach, J.P.H.; Loeber, J.G.; Verhoef, J.; Kloet, E.R. de; Wied, D. de

    1979-01-01

    β-Endorphin (β-LPH 61–91), γ-endorphin (61–77), des-tyrosine-γ-endorphin (62–77), α-endorphin (61–76), and β-LPH 61–69 either labeled with [125I] at the N-terminal 61-tyrosine residue or unlabeled were incubated with a crude synaptosomal plasma membrane fraction of rat brain or in human serum. At

  2. N-terminal peptides from unprocessed prion proteins enter cells by macropinocytosis

    International Nuclear Information System (INIS)

    Magzoub, Mazin; Sandgren, Staffan; Lundberg, Pontus; Oglecka, Kamila; Lilja, Johanna; Wittrup, Anders; Goeran Eriksson, L.E.; Langel, Ulo; Belting, Mattias; Graeslund, Astrid

    2006-01-01

    A peptide derived from the N-terminus of the unprocessed bovine prion protein (bPrPp), incorporating the hydrophobic signal sequence (residues 1-24) and a basic domain (KKRPKP, residues 25-30), internalizes into mammalian cells, even when coupled to a sizeable cargo, and therefore functions as a cell-penetrating peptide (CPP). Confocal microscopy and co-localization studies indicate that the internalization of bPrPp is mainly through macropinocytosis, a fluid-phase endocytosis process, initiated by binding to cell-surface proteoglycans. Electron microscopy studies show internalized bPrPp-DNA-gold complexes residing in endosomal vesicles. bPrPp induces expression of a complexed luciferase-encoding DNA plasmid, demonstrating the peptide's ability to transport the cargo across the endosomal membrane and into the cytosol and nucleus. The novel CPP activity of the unprocessed N-terminal domain of PrP could be important for the retrotranslocation of partly processed PrP and for PrP trafficking inside or between cells, with implications for the infectivity associated with prion diseases

  3. Characterization of DC magnetron plasma in Ar/Kr/N2 mixture during deposition of (Cr,Al)N coating

    International Nuclear Information System (INIS)

    Bobzin, K; Bagcivan, N; Theiß, S; Brugnara, R; Bibinov, N; Awakowicz, P

    2017-01-01

    Reactive sputter deposition of (Cr,Al)N coatings in DC magnetron plasmas containing Ar/Kr/N 2 mixtures is characterized by applying a combination of voltage–current measurement, optical emission spectroscopy (OES) and numerical simulation. Theoretical and experimental methods supplement each other and their combination permits us to obtain the most reliable information about the processes by physical vapor deposition. Gas temperature ( T g ) and plasma parameters, namely electron density n e and electron temperature T e are determined by spatial resolved measurements of molecular nitrogen photoemission. Steady-state densities of Cr and Al atoms are measured using OES. The sputtering of Cr and Al atoms is simulated using the TRIDYN code, measured electric current and applied voltage. Transport of sputtered atoms through the plasma volume is simulated by adopting a Monte-Carlo code. In order to quantify the ‘poisoning’ of the target surface with nitrogen, simulated steady state densities of Al and Cr atoms at different states of poisoning and at different distances from the target are compared with the measured densities. In addition, simulated fluxes of Cr and Al atoms to the substrate are compared with the measured deposition rates of the (Cr,Al)N coating. (paper)

  4. Plasma phospholipid long-chain n-3 polyunsaturated fatty acids and body weight change

    DEFF Research Database (Denmark)

    Jakobsen, Marianne Uhre; Dethlefsen, Claus; Due, Karen Margrete

    2011-01-01

    We investigated the association between the proportion of long-chain n-3 polyunsaturated fatty acids (PUFA) in plasma phospholipids from blood samples drawn at enrollment and subsequent change in body weight. Sex, age, and BMI were considered as potential effect modifiers.......We investigated the association between the proportion of long-chain n-3 polyunsaturated fatty acids (PUFA) in plasma phospholipids from blood samples drawn at enrollment and subsequent change in body weight. Sex, age, and BMI were considered as potential effect modifiers....

  5. N-terminal amino acid sequence of Bacillus licheniformis alpha-amylase: comparison with Bacillus amyloliquefaciens and Bacillus subtilis Enzymes.

    OpenAIRE

    Kuhn, H; Fietzek, P P; Lampen, J O

    1982-01-01

    The thermostable, liquefying alpha-amylase from Bacillus licheniformis was immunologically cross-reactive with the thermolabile, liquefying alpha-amylase from Bacillus amyloliquefaciens. Their N-terminal amino acid sequences showed extensive homology with each other, but not with the saccharifying alpha-amylases of Bacillus subtilis.

  6. Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study

    NARCIS (Netherlands)

    Forouhi, N.G.; Imamura, Fumiaki; Sharp, S.J.; Koulman, A.; Schulze, M.B.; Feskens, E.J.M.

    2016-01-01

    Background
    Whether and how n-3 and n-6 polyunsaturated fatty acids (PUFAs) are related to type 2 diabetes (T2D) is debated. Objectively measured plasma PUFAs can help to clarify these associations.

    Methods and Findings
    Plasma phospholipid PUFAs were measured by gas chromatography

  7. Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes : The EPIC-InterAct Case-Cohort Study

    NARCIS (Netherlands)

    Forouhi, Nita G.; Imamura, Fumiaki; Sharp, Stephen J.; Koulman, Albert; Schulze, Matthias B.; Zheng, Jusheng; Ye, Zheng; Sluijs, Ivonne; Guevara, Marcela; Huerta, José María; Kröger, Janine; Wang, Laura Yun; Summerhill, Keith; Griffin, Julian L.; Feskens, Edith J M; Affret, Aurélie; Amiano, Pilar; Boeing, Heiner; Dow, Courtney; Fagherazzi, Guy; Franks, Paul W.; Gonzalez, Carlos; Kaaks, Rudolf; Key, Timothy J.; Khaw, Kay Tee; Kühn, Tilman; Mortensen, Lotte Maxild; Nilsson, Peter M.; Overvad, Kim; Pala, Valeria; Palli, Domenico; Panico, Salvatore; Quirós, J. Ramón; Rodriguez-Barranco, Miguel; Rolandsson, Olov; Sacerdote, Carlotta; Scalbert, Augustin; Slimani, Nadia; Spijkerman, Annemieke M W; Tjonneland, Anne; Tormo, Maria Jose; Tumino, Rosario; van der A, Daphne L.; van der Schouw, Yvonne T.; Langenberg, Claudia; Riboli, Elio; Wareham, Nicholas J.

    2016-01-01

    Background: Whether and how n-3 and n-6 polyunsaturated fatty acids (PUFAs) are related to type 2 diabetes (T2D) is debated. Objectively measured plasma PUFAs can help to clarify these associations. Methods and Findings: Plasma phospholipid PUFAs were measured by gas chromatography among 12,132

  8. 75 FR 49510 - Credit Watch Termination Initiative

    Science.gov (United States)

    2010-08-13

    ... DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT [Docket No. FR-5411-N-02] Credit Watch Termination Initiative AGENCY: Office of the Assistant Secretary for Housing--Federal Housing Commissioner, HUD. ACTION... FHA Credit Watch Termination Initiative. This notice includes a list of mortgagees which have had...

  9. 75 FR 17944 - Credit Watch Termination Initiative

    Science.gov (United States)

    2010-04-08

    ... DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT [Docket No. FR-5411-N-01] Credit Watch Termination Initiative AGENCY: Office of the Assistant Secretary for Housing--Federal Housing Commissioner, HUD. ACTION... FHA Credit Watch Termination Initiative. This notice includes a list of mortgagees which have had...

  10. Changes in Cytokines and Aggrecan ARGS Neoepitope in Synovial Fluid and Serum and in C-Terminal Crosslinking Telopeptide of Type II Collagen and N-Terminal Crosslinking Telopeptide of Type I Collagen in Urine Over Five Years After Anterior Cruciate Ligament Rupture

    DEFF Research Database (Denmark)

    Struglics, André; Larsson, Staffan; Kumahashi, Nobuyuki

    2015-01-01

    OBJECTIVE: To prospectively monitor levels of proinflammatory cytokines and aggrecan ARGS neoepitope in synovial fluid and serum as well as levels of C-terminal crosslinking telopeptide of type II collagen (CTX-II) and N-terminal crosslinking telopeptide of type I collagen (NTX-I) in urine after ...

  11. The carboxy-terminal αN helix of the archaeal XerA tyrosine recombinase is a molecular switch to control site-specific recombination.

    Science.gov (United States)

    Serre, Marie-Claude; El Arnaout, Toufic; Brooks, Mark A; Durand, Dominique; Lisboa, Johnny; Lazar, Noureddine; Raynal, Bertrand; van Tilbeurgh, Herman; Quevillon-Cheruel, Sophie

    2013-01-01

    Tyrosine recombinases are conserved in the three kingdoms of life. Here we present the first crystal structure of a full-length archaeal tyrosine recombinase, XerA from Pyrococcus abyssi, at 3.0 Å resolution. In the absence of DNA substrate XerA crystallizes as a dimer where each monomer displays a tertiary structure similar to that of DNA-bound Tyr-recombinases. Active sites are assembled in the absence of dif except for the catalytic Tyr, which is extruded and located equidistant from each active site within the dimer. Using XerA active site mutants we demonstrate that XerA follows the classical cis-cleavage reaction, suggesting rearrangements of the C-terminal domain upon DNA binding. Surprisingly, XerA C-terminal αN helices dock in cis in a groove that, in bacterial tyrosine recombinases, accommodates in trans αN helices of neighbour monomers in the Holliday junction intermediates. Deletion of the XerA C-terminal αN helix does not impair cleavage of suicide substrates but prevents recombination catalysis. We propose that the enzymatic cycle of XerA involves the switch of the αN helix from cis to trans packing, leading to (i) repositioning of the catalytic Tyr in the active site in cis and (ii) dimer stabilisation via αN contacts in trans between monomers.

  12. The carboxy-terminal αN helix of the archaeal XerA tyrosine recombinase is a molecular switch to control site-specific recombination.

    Directory of Open Access Journals (Sweden)

    Marie-Claude Serre

    Full Text Available Tyrosine recombinases are conserved in the three kingdoms of life. Here we present the first crystal structure of a full-length archaeal tyrosine recombinase, XerA from Pyrococcus abyssi, at 3.0 Å resolution. In the absence of DNA substrate XerA crystallizes as a dimer where each monomer displays a tertiary structure similar to that of DNA-bound Tyr-recombinases. Active sites are assembled in the absence of dif except for the catalytic Tyr, which is extruded and located equidistant from each active site within the dimer. Using XerA active site mutants we demonstrate that XerA follows the classical cis-cleavage reaction, suggesting rearrangements of the C-terminal domain upon DNA binding. Surprisingly, XerA C-terminal αN helices dock in cis in a groove that, in bacterial tyrosine recombinases, accommodates in trans αN helices of neighbour monomers in the Holliday junction intermediates. Deletion of the XerA C-terminal αN helix does not impair cleavage of suicide substrates but prevents recombination catalysis. We propose that the enzymatic cycle of XerA involves the switch of the αN helix from cis to trans packing, leading to (i repositioning of the catalytic Tyr in the active site in cis and (ii dimer stabilisation via αN contacts in trans between monomers.

  13. Effect of CO on NO and N2O conversions in nonthermal argon plasma

    International Nuclear Information System (INIS)

    Zhao Guibing; Argyle, Morris D.; Radosz, Maciej

    2006-01-01

    200-600 ppm of CO inhibit NO conversion in nonthermal Ar plasma, but do not produce N 2 O. However, 1.01% of CO has no effect on NO conversion, but produces N 2 O. In general, N 2 O conversion in Ar plasma decreases with increasing CO concentration. These experimental results cannot be explained by charge transfer reactions of Ar + . Selectivity analysis of all excited states of Ar possibly contributing to NO x conversion without and with CO suggests that only Ar( 3 P 2 ) contributes to NO x conversion and CO dissociation. A kinetic model of 43 reactions is required to model NO conversion or N 2 O conversion in Ar without CO, whereas 81 reactions are required to model NO conversion and N 2 O conversion in Ar with CO. At constant gas pressure, a single set of model parameters can predict NO conversion or N 2 O conversion without and with CO. All experimental results can be explained using a reaction mechanism in which excited neutral states of Ar are the only active species, which supports the conclusion that cations have a negligible impact on these nonthermal plasma reactions

  14. Diagnostics of N2 Ar plasma mixture excited in a 13.56 MHz hollow cathode discharge system: application to remote plasma treatment of polyamide surface

    Science.gov (United States)

    Saloum, S.; Naddaf, M.; Alkhaled, B.

    2008-02-01

    N2-x% Ar plasma gas mixture, generated in a hollow cathode RF discharge system, has been characterized by both optical emission spectroscopy (OES) and double Langmuir probe, as a function of experimental parameters: total pressure (5-33 Pa), and different fractions of argon (7 <= x <= 80), at a constant applied RF power of 300 W. N2 dissociation degree has been investigated qualitatively by both the actinometry method and the ratio I_N/I_{N_2} of the atomic nitrogen line emission intensity at 672.3 nm to the vibrational band (0-0) of the N2 second positive system at 337.1 nm. Both methods showed that the increase in argon fraction enhances the dissociation of N2, with a maximum at x = 50 for the pressure of 5 Pa, although the two methods give two opposite trends as a function of total pressure. Spectroscopic measurements showed that the vibrational temperature of the N2 second positive system increases with both argon fraction and total pressure increase, it lies between 4900 and 12 300 K. Langmuir probe measurements showed that, in the remote zone, the electron temperature falls in the range 1.57-1.75 eV, the N_{2}^{+} density varies between 5 × 109 and 1.4 × 1010 cm-3 and that both the plasma ionization degree and electron temperature increase towards the source. In addition, the process of plasma-polyamide (PA) surface interaction, in the remote plasma zone, has been studied through OES analysis during plasma treatment of PA to monitor the possible emissions due to the polymer etching. An increase in atomic nitrogen line (672.3 nm) intensity is obtained, atomic carbon line (833.52 nm) and the band emission (0-0) from the CN (B 2Σ+-X 2Σ+) violet system were observed. The PA surface modification has been confirmed through the improvement of its hydrophilic character as the water contact angle measured after the plasma treatment significantly decreased.

  15. Diagnostics of N2-Ar plasma mixture excited in a 13.56 MHz hollow cathode discharge system: application to remote plasma treatment of polyamide surface

    International Nuclear Information System (INIS)

    Saloum, S; Naddaf, M; Alkhaled, B

    2008-01-01

    N 2 -x% Ar plasma gas mixture, generated in a hollow cathode RF discharge system, has been characterized by both optical emission spectroscopy (OES) and double Langmuir probe, as a function of experimental parameters: total pressure (5-33 Pa), and different fractions of argon (7 ≤ x ≤ 80), at a constant applied RF power of 300 W. N 2 dissociation degree has been investigated qualitatively by both the actinometry method and the ratio I N /I N 2 of the atomic nitrogen line emission intensity at 672.3 nm to the vibrational band (0-0) of the N 2 second positive system at 337.1 nm. Both methods showed that the increase in argon fraction enhances the dissociation of N 2 , with a maximum at x = 50 for the pressure of 5 Pa, although the two methods give two opposite trends as a function of total pressure. Spectroscopic measurements showed that the vibrational temperature of the N 2 second positive system increases with both argon fraction and total pressure increase, it lies between 4900 and 12 300 K. Langmuir probe measurements showed that, in the remote zone, the electron temperature falls in the range 1.57-1.75 eV, the N 2 + density varies between 5 x 10 9 and 1.4 x 10 10 cm -3 and that both the plasma ionization degree and electron temperature increase towards the source. In addition, the process of plasma-polyamide (PA) surface interaction, in the remote plasma zone, has been studied through OES analysis during plasma treatment of PA to monitor the possible emissions due to the polymer etching. An increase in atomic nitrogen line (672.3 nm) intensity is obtained, atomic carbon line (833.52 nm) and the band emission (0-0) from the CN (B 2 Σ + -X 2 Σ + ) violet system were observed. The PA surface modification has been confirmed through the improvement of its hydrophilic character as the water contact angle measured after the plasma treatment significantly decreased

  16. The influence of (n-n{sup '})-mixing processes in He*(n)+He(1s{sup 2}) collisions on He*(n) atoms' populations in weakly ionized helium plasmas

    Energy Technology Data Exchange (ETDEWEB)

    Mihajlov, A.A. [Institute of Physics, P.O. Box 57, 11001 Belgrade (Serbia and Montenegro); Ignjatovic, Lj.M. [Institute of Physics, P.O. Box 57, 11001 Belgrade (Serbia)], E-mail: ljuba@phy.bg.ac.yu; Sreckovic, V.A. [Institute of Physics, P.O. Box 57, 11001 Belgrade (Serbia); Djuric, Z. [Silvaco Data Systems, Compass Point, St Ives PE27 5JL (United Kingdom)

    2008-03-15

    The results of semi-classical calculations of rate coefficients of (n-n{sup '})-mixing processes due to collisions of Rydberg atoms He*(n) with He(1s{sup 2}) atoms are presented. It is assumed that these processes are caused by the resonant energy exchange within the electron component of He*(n)+He collision system. The method is realized through the numerical simulation of the (n-n{sup '})-mixing processes, and is applied for calculations of the corresponding rate coefficients. The calculations are performed for the principal quantum numbers n,n{sup '} in ranges 4{<=}n{sup '}{<=}10, and the atom and electron temperatures, T{sub a},T{sub e}, in domains 5000K{<=}T{sub a}{<=}T{sub e}{<=}20000K. It is shown that the (n-n{sup '})-mixing processes can significantly influence the populations of Rydberg atoms in non-equilibrium weakly ionized helium plasmas with ionization degree {approx}10{sup -4}. Therefore, these processes have to be included in the appropriate models of such plasmas.

  17. dc-Hydrogen plasma induced defects in bulk n-Ge

    Energy Technology Data Exchange (ETDEWEB)

    Nyamhere, C., E-mail: cloud.nyamhere@nmmu.ac.za [Department of Physics, Nelson Mandela Metropolitan University, PO Box 77000, Port Elizabeth 6031 (South Africa); Venter, A.; Murape, D.M. [Department of Physics, Nelson Mandela Metropolitan University, PO Box 77000, Port Elizabeth 6031 (South Africa); Auret, F.D.; Coelho, S.M.M. [Department of Physics, University of the Pretoria, Lynnwood Road, Pretoria 0002 (South Africa); Botha, J.R. [Department of Physics, Nelson Mandela Metropolitan University, PO Box 77000, Port Elizabeth 6031 (South Africa)

    2012-08-01

    Bulk antimony doped germanium (n-Ge) has been exposed to a dc-hydrogen plasma. Capacitance-voltage depth profiles revealed extensive near surface passivation of the shallow donors as evidenced by {approx}a 1.5 orders of magnitude reduction in the free carrier concentration up to depth of {approx}3.2 {mu}m. DLTS and Laplace-DLTS revealed a prominent electron trap 0.30 eV below the conduction (E{sub C} -0.30 eV). The concentration of this trap increased with plasma exposure time. The depth profile for this defect suggested a uniform distribution up to 1.2 {mu}m. Annealing studies show that this trap, attributed to a hydrogen-related complex, is stable up to 200 Degree-Sign C. Hole traps, or vacancy-antimony centers, common in this material after high energy particle irradiation, were not observed after plasma exposure, an indication that this process does not create Frenkel (V-I) pairs.

  18. dc-Hydrogen plasma induced defects in bulk n-Ge

    International Nuclear Information System (INIS)

    Nyamhere, C.; Venter, A.; Murape, D.M.; Auret, F.D.; Coelho, S.M.M.; Botha, J.R.

    2012-01-01

    Bulk antimony doped germanium (n-Ge) has been exposed to a dc-hydrogen plasma. Capacitance-voltage depth profiles revealed extensive near surface passivation of the shallow donors as evidenced by ∼a 1.5 orders of magnitude reduction in the free carrier concentration up to depth of ∼3.2 μm. DLTS and Laplace-DLTS revealed a prominent electron trap 0.30 eV below the conduction (E C -0.30 eV). The concentration of this trap increased with plasma exposure time. The depth profile for this defect suggested a uniform distribution up to 1.2 μm. Annealing studies show that this trap, attributed to a hydrogen-related complex, is stable up to 200 °C. Hole traps, or vacancy-antimony centers, common in this material after high energy particle irradiation, were not observed after plasma exposure, an indication that this process does not create Frenkel (V-I) pairs.

  19. Cutting edge: HLA-B27 acquires many N-terminal dibasic peptides: coupling cytosolic peptide stability to antigen presentation

    NARCIS (Netherlands)

    Herberts, Carla A.; Neijssen, Joost J.; de Haan, Jolanda; Janssen, Lennert; Drijfhout, Jan Wouter; Reits, Eric A.; Neefjes, Jacques J.

    2006-01-01

    Ag presentation by MHC class I is a highly inefficient process because cytosolic peptidases destroy most peptides after proteasomal generation. Various mechanisms shape the MHC class I peptidome. We define a new one: intracellular peptide stability. Peptides with two N-terminal basic amino acids are

  20. Abl N-terminal cap stabilization of SH3 domain dynamics.

    Science.gov (United States)

    Chen, Shugui; Dumitrescu, Teodora Pene; Smithgall, Thomas E; Engen, John R

    2008-05-27

    Crystal structures and other biochemical data indicate that the N-terminal cap (NCap) region of the Abelson tyrosine kinase (c-Abl) is important for maintaining the downregulated conformation of the kinase domain. The exact contributions that the NCap makes in stabilizing the various intramolecular interactions within c-Abl are less clear. While the NCap appears to be important for locking the SH3 and SH2 domains to the back of the kinase domain, there may be other more subtle elements of regulation. Hydrogen exchange (HX) and mass spectrometry (MS) were used to determine if the NCap contributes to intramolecular interactions involving the Abl SH3 domain. Under physiological conditions, the Abl SH3 domain underwent partial unfolding and its unfolding half-life was slowed during binding to the SH2 kinase linker, providing a unique assay for testing NCap-induced stabilization of the SH3 domain in various constructs. The results showed that the NCap stabilizes the dynamics of the SH3 domain in certain constructs but does not increase the relative affinity of the SH3 domain for the native SH2 kinase linker. The stabilization effect was absent in constructs of just the NCap and SH3 but was obvious when the SH2 domain and the SH2 kinase linker were present. These results suggest that interactions between the NCap and the SH3 domain can contribute to c-Abl stabilization in constructs that contain at least the SH2 domain, an effect that may partially compensate for the absence of the negative regulatory C-terminal tail found in the related Src family of kinases.

  1. Calcium Occupancy of N-terminal Sites within Calmodulin Induces Inhibition of the Ryanodine Receptor Calcium Release Channel

    Energy Technology Data Exchange (ETDEWEB)

    Boschek, Curt B; Jones, Terry E; Squier, Thomas C; Bigelow, Diana J

    2007-08-01

    Calmodulin (CaM) regulates calcium release from intracellular stores in skeletal muscle through its association with the ryanodine receptor (RyR1) calcium release channel, where CaM association enhances channel opening at resting calcium levels and its closing at micromolar calcium levels associated with muscle contraction. A high-affinity CaM-binding sequence (RyRp) has been identified in RyR1, which corresponds to a 30-residue sequence (i.e., K3614 – N3643) located within the central portion of the primary sequence. However, it is currently unclear whether the identified CaM-binding sequence a) senses calcium over the physiological range of calcium-concentrations associated with RyR1 regulation or b) plays a structural role unrelated to the calcium-dependent modulation of RyR1 function. Therefore, we have measured the calcium-dependent activation of the individual domains of CaM in association with RyRp and their relationship to the CaM-dependent regulation of RyR1. These measurements utilize an engineered CaM, permitting the site-specific incorporation of N-(1-pyrene) maleimide at either T34C (PyN-CaM) or T110C (PyC-CaM) in the N- and C-domains, respectively. Consistent with prior measurements, we observe a high-affinity association between both apo- and calcium-activated CaM and RyRp. Upon association with RyRp, fluorescence changes in PyN-CaM or PyC-CaM permit the measurement of the calcium-activation of these individual domains. Fluorescence changes upon calcium-activation of PyC-CaM in association with RyRp are indicative of high-affinity calcium-dependent activation of the C-terminal domain of CaM bound to RyRp at resting calcium levels and the activation of the N-terminal domain at levels of calcium associated cellular activation. In comparison, occupancy of calcium-binding sites in the N-domain of CaM mirrors the calcium-dependence of RyR1 inhibition observed at activating calcium levels, where [Ca]1/2 = 4.3 0.4 μM, suggesting a direct regulation of Ry

  2. The Heliospheric Termination Shock

    Science.gov (United States)

    Jokipii, J. R.

    2013-06-01

    The heliospheric termination shock is a vast, spheroidal shock wave marking the transition from the supersonic solar wind to the slower flow in the heliosheath, in response to the pressure of the interstellar medium. It is one of the most-important boundaries in the outer heliosphere. It affects energetic particles strongly and for this reason is a significant factor in the effects of the Sun on Galactic cosmic rays. This paper summarizes the general properties and overall large-scale structure and motions of the termination shock. Observations over the past several years, both in situ and remote, have dramatically revised our understanding of the shock. The consensus now is that the shock is quite blunt, is with the front, blunt side canted at an angle to the flow direction of the local interstellar plasma relative to the Sun, and is dynamical and turbulent. Much of this new understanding has come from remote observations of energetic charged particles interacting with the shock, radio waves and radiation backscattered from interstellar neutral atoms. The observations and the implications are discussed.

  3. Crystal Structure of the N-terminal Domain of the Group B Streptococcus Alpha C Protein

    Energy Technology Data Exchange (ETDEWEB)

    Auperin,T.; Bolduc, G.; Baron, M.; Heroux, A.; Filman, D.; Madoff, L.; Hogle, J.

    2005-01-01

    Group B Streptococcus (GBS) is the leading cause of bacterial pneumonia, sepsis, and meningitis among neonates and an important cause of morbidity among pregnant women and immunocompromised adults. Invasive diseases due to GBS are attributed to the ability of the pathogen to translocate across human epithelial surfaces. The alpha C protein (ACP) has been identified as an invasin that plays a role in internalization and translocation of GBS across epithelial cells. The soluble N-terminal domain of ACP (NtACP) blocks the internalization of GBS. We determined the 1.86-{angstrom} resolution crystal structure of NtACP comprising residues Ser{sup 52} through Leu{sup 225} of the full-length ACP. NtACP has two domains, an N-terminal {beta}-sandwich and a C-terminal three-helix bundle. Structural and topological alignments reveal that the {beta}-sandwich shares structural elements with the type III fibronectin fold (FnIII), but includes structural elaborations that make it unique. We have identified a potential integrin-binding motif consisting of Lys-Thr-Asp{sup 146}, Arg{sup 110}, and Asp{sup 118}. A similar arrangement of charged residues has been described in other invasins. ACP shows a heparin binding activity that requires NtACP. We propose a possible heparin-binding site, including one surface of the three-helix bundle, and nearby portions of the sandwich and repeat domains. We have validated this prediction using assays of the heparin binding and cell-adhesion properties of engineered fragments of ACP. This is the first crystal structure of a member of the highly conserved Gram-positive surface alpha-like protein family, and it will enable the internalization mechanism of GBS to be dissected at the atomic level.

  4. Three-dimensional structure of N-terminal domain of DnaB helicase and helicase-primase interactions in Helicobacter pylori.

    Directory of Open Access Journals (Sweden)

    Tara Kashav

    2009-10-01

    Full Text Available Replication initiation is a crucial step in genome duplication and homohexameric DnaB helicase plays a central role in the replication initiation process by unwinding the duplex DNA and interacting with several other proteins during the process of replication. N-terminal domain of DnaB is critical for helicase activity and for DnaG primase interactions. We present here the crystal structure of the N-terminal domain (NTD of H. pylori DnaB (HpDnaB helicase at 2.2 A resolution and compare the structural differences among helicases and correlate with the functional differences. The structural details of NTD suggest that the linker region between NTD and C-terminal helicase domain plays a vital role in accurate assembly of NTD dimers. The sequence analysis of the linker regions from several helicases reveals that they should form four helix bundles. We also report the characterization of H. pylori DnaG primase and study the helicase-primase interactions, where HpDnaG primase stimulates DNA unwinding activity of HpDnaB suggesting presence of helicase-primase cohort at the replication fork. The protein-protein interaction study of C-terminal domain of primase and different deletion constructs of helicase suggests that linker is essential for proper conformation of NTD to interact strongly with HpDnaG. The surface charge distribution on the primase binding surface of NTDs of various helicases suggests that DnaB-DnaG interaction and stability of the complex is most probably charge dependent. Structure of the linker and helicase-primase interactions indicate that HpDnaB differs greatly from E.coli DnaB despite both belong to gram negative bacteria.

  5. BNP molecular forms and processing by the cardiac serine protease corin.

    Science.gov (United States)

    Ichiki, Tomoko; Huntley, Brenda K; Burnett, John C

    2013-01-01

    The cardiac hormone, B-type natriuretic peptide (BNP), is one of human natriuretic peptides which possesses cardiorenal protective actions and is used as a therapeutic and a biomarker for heart failure (HF). Its prohormone, proBNP1_108, is processed by the proNPs convertases, corin or furin, to inactive NT-proBNP1_76 and active BNP1-32. Paradoxically, circulating NT-proBNP and BNP are elevated in HF leading to the use of BNP as a sensitive and predictive marker of HF. This paradox may be explained by the "nonspecific" nature of conventional assays and/or a relative deficiency state of "active BNP" as characterized by an increase in inactive proBNP_108 and a decrease in active BNP1-32. Therefore, understanding the regulation of proBNP1_108 processing and the role of the convertase corin may be important in understanding the physiology of HF. Corin is expressed in heart and kidney and may play an important role in regulating blood pressure and remodeling of the heart. The processing of proBNP1_108 by corin may be controlled by O-linked glycosylation of proBNP1-108. A potential impairment of proBNP1lo8 processing in HF may be linked to dysregulation of the convertase corin, which may offer therapeutic opportunities to control proBNPlo0s processing and its activation in HF.

  6. Elevated Plasma C-Terminal Endothelin-1 Precursor Fragment Concentrations Are Associated with Less Anxiety in Patients with Cardiovascular Risk Factors. Results from the Observational DIAST-CHF Study.

    Science.gov (United States)

    Meyer, Thomas; Chavanon, Mira-Lynn; Herrrmann-Lingen, Christoph; Roggenthien, Maren; Nolte, Kathleen; Pieske, Burkert; Wachter, Rolf; Edelmann, Frank

    2015-01-01

    The role of endothelin-1 (ET-1) in the neurobiology of anxiety is unknown, therefore, we assessed in the observational multicenter DIAST-CHF study whether the C-terminal ET-1 precursor fragment (CT-proET-1) is linked to anxiety. Plasma concentrations of CT-proET-1 were measured in a total of 1,410 patients presenting with cardiovascular risk factors (mean age 66.91±8.2 years, 49.3% males, mean left ventricular ejection fraction 60.0±8.2%) who had completed the Hospital Anxiety and Depression Scale (HADS) questionnaire. Among the total study cohort (n = 1,410), there were 118 subjects (8.4%) with an HADS anxiety score above the cut-off level of 11 suggestive of clinically relevant anxiety. Plasma CT-proET-1 levels were significantly lower in the group of anxious patients as compared to non-anxious patients (p = 0.013). In regression models adjusted for sex, age, systolic blood pressure, and diameters of left atrium and ventricle, plasma CT-proET-1 was again linked to anxiety (Exp(β) = 0.247, 95%-confidence interval [95%-CI] = 0.067-0.914, p = 0.036). Given the high prevalence of depressive disorders in anxious patients, we additionally included the HADS depression score as an independent variable in the models and found that CT-proET-1 remained a significant predictor of anxiety, independent of comorbid depression (Exp(β) = 0.114, 95%-CI = 0.023-0.566, p = 0.008). Our data from a population-based study in outpatients with cardiovascular risk factors revealed that circulating CT-proET-1 levels are negatively associated with anxiety. Further investigations are required to clarify the putative anxiolytic effect of ET-1 or its precursor molecules in humans and to decipher its mechanistic pathways.

  7. Elevated Plasma C-Terminal Endothelin-1 Precursor Fragment Concentrations Are Associated with Less Anxiety in Patients with Cardiovascular Risk Factors. Results from the Observational DIAST-CHF Study.

    Directory of Open Access Journals (Sweden)

    Thomas Meyer

    Full Text Available The role of endothelin-1 (ET-1 in the neurobiology of anxiety is unknown, therefore, we assessed in the observational multicenter DIAST-CHF study whether the C-terminal ET-1 precursor fragment (CT-proET-1 is linked to anxiety.Plasma concentrations of CT-proET-1 were measured in a total of 1,410 patients presenting with cardiovascular risk factors (mean age 66.91±8.2 years, 49.3% males, mean left ventricular ejection fraction 60.0±8.2% who had completed the Hospital Anxiety and Depression Scale (HADS questionnaire.Among the total study cohort (n = 1,410, there were 118 subjects (8.4% with an HADS anxiety score above the cut-off level of 11 suggestive of clinically relevant anxiety. Plasma CT-proET-1 levels were significantly lower in the group of anxious patients as compared to non-anxious patients (p = 0.013. In regression models adjusted for sex, age, systolic blood pressure, and diameters of left atrium and ventricle, plasma CT-proET-1 was again linked to anxiety (Exp(β = 0.247, 95%-confidence interval [95%-CI] = 0.067-0.914, p = 0.036. Given the high prevalence of depressive disorders in anxious patients, we additionally included the HADS depression score as an independent variable in the models and found that CT-proET-1 remained a significant predictor of anxiety, independent of comorbid depression (Exp(β = 0.114, 95%-CI = 0.023-0.566, p = 0.008.Our data from a population-based study in outpatients with cardiovascular risk factors revealed that circulating CT-proET-1 levels are negatively associated with anxiety. Further investigations are required to clarify the putative anxiolytic effect of ET-1 or its precursor molecules in humans and to decipher its mechanistic pathways.

  8. Scandium Terminal Imido Chemistry.

    Science.gov (United States)

    Lu, Erli; Chu, Jiaxiang; Chen, Yaofeng

    2018-02-20

    Research into transition metal complexes bearing multiply bonded main-group ligands has developed into a thriving and fruitful field over the past half century. These complexes, featuring terminal M═E/M≡E (M = transition metal; E = main-group element) multiple bonds, exhibit unique structural properties as well as rich reactivity, which render them attractive targets for inorganic/organometallic chemists as well as indispensable tools for organic/catalytic chemists. This fact has been highlighted by their widespread applications in organic synthesis, for example, as olefin metathesis catalysts. In the ongoing renaissance of transition metal-ligand multiple-bonding chemistry, there have been reports of M═E/M≡E interactions for the majority of the metallic elements of the periodic table, even some actinide metals. In stark contrast, the largest subgroup of the periodic table, rare-earth metals (Ln = Sc, Y, and lanthanides), have been excluded from this upsurge. Indeed, the synthesis of terminal Ln═E/Ln≡E multiple-bonding species lagged behind that of the transition metal and actinide congeners for decades. Although these species had been pursued since the discovery of a rare-earth metal bridging imide in 1991, such a terminal (nonpincer/bridging hapticities) Ln═E/Ln≡E bond species was not obtained until 2010. The scarcity is mainly attributed to the energy mismatch between the frontier orbitals of the metal and the ligand atoms. This renders the putative terminal Ln═E/Ln≡E bonds extremely reactive, thus resulting in the formation of aggregates and/or reaction with the ligand/environment, quenching the multiple-bond character. In 2010, the stalemate was broken by the isolation and structural characterization of the first rare-earth metal terminal imide-a scandium terminal imide-by our group. The double-bond character of the Sc═N bond was unequivocally confirmed by single-crystal X-ray diffraction. Theoretical investigations revealed the presence

  9. Magnetic properties of Co-N films deposited by ECR nitrogen/argon plasma with DC negative-biased Co target

    Energy Technology Data Exchange (ETDEWEB)

    Li, H.; Zhang, Y.C.; Yang, K.; Liu, H.X.; Zhu, X.D., E-mail: xdzhu@ustc.edu.cn; Zhou, H.Y.

    2017-06-01

    Highlights: • A new method of synthesizing Co-N films containing Co{sub 4}N phase. • Tunable magnetic properties achieved in ECR plasma CVD. • The change of magnetic properties is related to atoms mobility on substrate and the concentration of active species in plasma vapor. - Abstract: By introducing DC negative-biased Co target in the Electron Cyclotron Resonance (ECR) nitrogen/argon plasma, the Co-N films containing Co{sub 4}N phase were synthesized on Si(100) substrate. Effects of processing parameters on magnetic properties of the films are investigated. It is found that magnetic properties of Co-N films vary with N{sub 2}/Ar flow ratio, substrate temperature, and target biasing voltage. The saturation magnetization M{sub s} decreased by increasing the N{sub 2}/Ar gas flow ratio or decreasing target biasing voltage, while the coercive field H{sub c} increased, which is ascribed to the variation of relative concentration for N or Co active species in plasma vapor. The magnetic properties present complex dependency with growth temperature, which is related to the atom mobility on the substrate affected by the growth temperature. This study exhibits a potential of ECR plasma chemical vapor deposition to synthesize the interstitial compounds and tune magnetic properties of films.

  10. Aging and the shape of cognitive change before death: terminal decline or terminal drop?

    Science.gov (United States)

    MacDonald, Stuart W S; Hultsch, David F; Dixon, Roger A

    2011-05-01

    Relative to typical age-related cognitive decrements, the terms "terminal decline" and "terminal drop" refer to the phenomenon of increased cognitive decline in proximity to death. Given that these terms are not necessarily synonymous, we examined the important theoretical distinction between the two alternative trajectories or shapes of changes they imply. We used 12-year (5-wave) data from the Victoria Longitudinal Study to directly test whether pre-death cognitive decrements follow a terminal decline (generally gradual) or a terminal drop (more abrupt) shape. Pre-death trajectories of cognitive decline for n=265 decedents (Mage = 72.67 years, SD = 6.44) were examined separately for 5 key cognitive constructs (verbal speed, working memory, episodic memory, semantic memory, and crystallized ability). Several classes of linear mixed models evaluated whether cognitive decline increased per additional year closer to death. Findings indicated that the shape of pre-death cognitive change was predominantly characterized by decline that is steeper as compared with typical aging-related change, but still best described as slow and steady decline, especially as compared with precipitous drop. The present findings suggest that terminal decline and terminal drop trajectories may not be mutually exclusive but could rather reflect distinct developmental trajectories within the same individual.

  11. The C-Terminal RpoN Domain of sigma54 Forms an unpredictedHelix-Turn-Helix Motif Similar to domains of sigma70

    Energy Technology Data Exchange (ETDEWEB)

    Doucleff, Michaeleen; Malak, Lawrence T.; Pelton, Jeffrey G.; Wemmer, David E.

    2005-11-01

    The ''{delta}'' subunit of prokaryotic RNA-polymerase allows gene-specific transcription initiation. Two {sigma} families have been identified, {sigma}{sup 70} and {sigma}{sup 54}, which use distinct mechanisms to initiate transcription and share no detectable sequence homology. Although the {sigma}{sup 70}-type factors have been well characterized structurally by x-ray crystallography, no high-resolution structural information is available for the {sigma}{sup 54}-type factors. Here we present the NMR derived structure of the C-terminal domain of {sigma}{sup 54} from Aquifex aeolicus. This domain (Thr323 to Gly389), which contains the highly conserved RpoN box sequence, consists of a poorly structured N-terminal tail followed by a three-helix bundle, which is surprisingly similar to domains of the {sigma}{sup 70}-type proteins. Residues of the RpoN box, which have previously been shown to be critical for DNA binding, form the second helix of an unpredicted helix-turn-helix motif. This structure's homology with other DNA binding proteins, combined with previous biochemical data, suggest how the C-terminal domain of {sigma}{sup 54} binds to DNA.

  12. Features of the Env leader protein and the N-terminal Gag domain of feline foamy virus important for virus morphogenesis

    International Nuclear Information System (INIS)

    Geiselhart, Verena; Schwantes, Astrid; Bastone, Patrizia; Frech, Matthias; Loechelt, Martin

    2003-01-01

    Previous studies have shown that foamy virus (FV) particle budding, especially the involvement of the viral Env glycoprotein, is different from that of other (ortho) retroviruses: the N-terminal Env leader protein Elp is a constituent of released FV particles. A defined sequence in Elp required for particle budding binds to the MA domain of Gag. To extend these findings, we show that feline FV Elp is a membrane-anchored protein with the N-terminus located inside the particle. Thus, the internal/cytoplasmic domain of Elp has the correct topology for interacting with Gag during budding. In addition to Elp, an Elp-related protein of about 9 kDa was shown to be virion associated and is probably generated by cellular signal peptidases. Besides the function of Elp binding, the N-terminal domain of Gag was shown to be required for proper localization of feline FV Gag to the cytoplasm and the perinuclear/nuclear region

  13. Characterization of plasma etching damage on p-type GaN using Schottky diodes

    International Nuclear Information System (INIS)

    Kato, M.; Mikamo, K.; Ichimura, M.; Kanechika, M.; Ishiguro, O.; Kachi, T.

    2008-01-01

    The plasma etching damage in p-type GaN has been characterized. From current-voltage and capacitance-voltage characteristics of Schottky diodes, it was revealed that inductively coupled plasma (ICP) etching causes an increase in series resistance of the Schottky diodes and compensation of acceptors in p-type GaN. We investigated deep levels near the valence band of p-type GaN using current deep level transient spectroscopy (DLTS), and no deep level originating from the ICP etching damage was observed. On the other hand, by capacitance DLTS measurements for n-type GaN, we observed an increase in concentration of a donor-type defect with an activation energy of 0.25 eV after the ICP etching. The origin of this defect would be due to nitrogen vacancies. We also observed this defect by photocapacitance measurements for ICP-etched p-type GaN. For both n- and p-type GaN, we found that the low bias power ICP etching is effective to reduce the concentration of this defect introduced by the high bias power ICP etching

  14. In situ x-ray photoelectron spectroscopy and capacitance voltage characterization of plasma treatments for Al{sub 2}O{sub 3}/AlGaN/GaN stacks

    Energy Technology Data Exchange (ETDEWEB)

    Qin, Xiaoye; Lucero, Antonio; Azcatl, Angelica; Kim, Jiyoung; Wallace, Robert M. [Department of Materials Science and Engineering, University of Texas at Dallas, Richardson, Texas 75080 (United States)

    2014-07-07

    We investigate the Al{sub 2}O{sub 3}/AlGaN/GaN metal-oxide-semiconductor structure pretreated by O{sub 2} anneals, N{sub 2} remote plasma, and forming gas remote plasma prior to atomic layer deposition of Al{sub 2}O{sub 3} using in situ X-ray photoelectron spectroscopy, low energy electron diffraction, and capacitance- voltage measurements. Plasma pretreatments reduce the Ga-oxide/oxynitride formation and the interface state density, while inducing a threshold voltage instability.

  15. Surface reactions during low-k etching using H2/N2 plasma

    International Nuclear Information System (INIS)

    Fukasawa, Masanaga; Tatsumi, Tetsuya; Oshima, Keiji; Nagahata, Kazunori; Uchida, Saburo; Takashima, Seigo; Hori, Masaru; Kamide, Yukihiro

    2008-01-01

    We investigated the relationship between the hard mask faceting that occurs during organic low-k etching and the ion energy distribution function of a capacitively coupled plasma reactor. We minimized the hard mask faceting by precisely controlling the ion energy. This precise control was obtained by selecting the optimum bottom frequency and bias power. We measured the amount of damage done to a SiOCH film exposed to H 2 /N 2 plasma in order to find the H 2 /N 2 ratio at which the plasma caused the least damage. The amount of moisture uptake by the damaged SiOCH film is the dominant factor controlling the dielectric constant increase (Δk). To suppress Δk, the incident ion species and ion energies have to be precisely controlled. This reduces the number of adsorption sites in the bulk SiOCH and maintains the hydrophobic surface that suppresses water permeation during air exposure

  16. n-Butyrate inhibits Jun NH(2)-terminal kinase activation and cytokine transcription in mast cells

    International Nuclear Information System (INIS)

    Diakos, Christos; Prieschl, Eva E.; Saeemann, Marcus D.; Boehmig, Georg A.; Csonga, Robert; Sobanov, Yury; Baumruker, Thomas; Zlabinger, Gerhard J.

    2006-01-01

    Mast cells are well known to contribute to type I allergic conditions but only recently have been brought in association with chronic relapsing/remitting autoimmune diseases such as celiac disease and ulcerative colitis. Since the bacterial metabolite n-butyrate is considered to counteract intestinal inflammation we investigated the effects of this short chain fatty acid on mast cell activation. Using RNAse protection assays and reporter gene technology we show that n-butyrate downregulates TNF-α transcription. This correlates with an impaired activation of the Jun NH(2)-terminal kinase (JNK) but not other MAP kinases such as ERK and p38 that are largely unaffected by n-butyrate. As a consequence, we observed a decreased nuclear activity of AP-1 and NF-AT transcription factors. These results indicate that n-butyrate inhibits critical inflammatory mediators in mast cells by relatively selectively targeting the JNK signalling

  17. An “ohmic-first” self-terminating gate-recess technique for normally-off Al2O3/GaN MOSFET

    Science.gov (United States)

    Wang, Hongyue; Wang, Jinyan; Li, Mengjun; He, Yandong; Wang, Maojun; Yu, Min; Wu, Wengang; Zhou, Yang; Dai, Gang

    2018-04-01

    In this article, an ohmic-first AlGaN/GaN self-terminating gate-recess etching technique was demonstrated where ohmic contact formation is ahead of gate-recess-etching/gate-dielectric-deposition (GRE/GDD) process. The ohmic contact exhibits few degradations after the self-terminating gate-recess process. Besides, when comparing with that using the conventional fabrication process, the fabricated device using the ohmic-first fabrication process shows a better gate dielectric quality in terms of more than 3 orders lower forward gate leakage current, more than twice higher reverse breakdown voltage as well as better stability. Based on this proposed technique, the normally-off Al2O3/GaN MOSFET exhibits a threshold voltage (V th) of ˜1.8 V, a maximum drain current of ˜328 mA/mm, a forward gate leakage current of ˜10-6 A/mm and an off-state breakdown voltage of 218 V at room temperature. Meanwhile, high temperature characteristics of the device was also evaluated and small variations (˜7.6%) of the threshold voltage was confirmed up to 300 °C.

  18. The N-terminal cleavage of chondromodulin-I in growth-plate cartilage at the hypertrophic and calcified zones during bone development.

    Directory of Open Access Journals (Sweden)

    Shigenori Miura

    Full Text Available Chondromodulin-I (ChM-I is a 20-25 kDa anti-angiogenic glycoprotein in cartilage matrix. In the present study, we identified a novel 14-kDa species of ChM-I by immunoblotting, and purified it by immunoprecipitation with a newly raised monoclonal antibody against ChM-I. The N-terminal amino acid sequencing indicated that it was an N-terminal truncated form of ChM-I generated by the proteolytic cleavage at Asp37-Asp38. This 14-kDa ChM-I was shown by the modified Boyden chamber assay to have very little inhibitory activity on the VEGF-A-induced migration of vascular endothelial cells in contrast to the intact 20-25 kDa form of ChM-I (ID50 = 8 nM. Immunohistochemistry suggested that 20-25 kDa ChM-I was exclusively localized in the avascular zones, i.e. the resting, proliferating, and prehypertrophic zones, of the cartilaginous molds of developing long bone, whereas the 14-kDa form of ChM-I was found in hypertrophic and calcified zones. Immunoblotting demonstrated that mature growth-plate chondrocytes isolated from rat costal cartilage actively secrete ChM-I almost exclusively as the intact 20-25 kDa form into the medium in primary culture. Taken together, our results suggest that intact 20-25 kDa ChM-I is stored as a component of extracellular matrix in the avascular cartilage zones, but it is inactivated by a single N-terminal proteolytic cleavage in the hypertrophic zone of growth-plate cartilage.

  19. Unbiased Selective Isolation of Protein N-Terminal Peptides from Complex Proteome Samples Using Phospho Tagging PTAG) and TiO2-based Depletion

    NARCIS (Netherlands)

    Mommen, G.P.M.; Waterbeemd, van de B.; Meiring, H.D.; Kersten, G.; Heck, A.J.R.; Jong, de A.P.J.M.

    2012-01-01

    A positional proteomics strategy for global N-proteome analysis is presented based on phospho tagging (PTAG) of internal peptides followed by depletion by titanium dioxide (TiO2) affinity chromatography. Therefore, N-terminal and lysine amino groups are initially completely dimethylated with

  20. Effects of pressure profile and plasma shaping on the n=1 internal kink mode in JT-60/JT-60U pellet fuelled plasmas

    International Nuclear Information System (INIS)

    Ozeki, Takahisa; Azumi, Masafumi

    1990-10-01

    The stability of the n=1 internal kink mode in a tokamak is numerically analyzed for plasmas with a centrally peaked pressure profile. These studies are carried out with the strongly peaked pressure inside the q=1 surface, which is based on the experimentally observed plasmas by means of injections of hydrogen-ice pellets in JT-60 tokamak. The effects of peaked pressure and shaping, i.e., elongation and triangularity, are also studied for JT-60U tokamak. The plasma with the strongly peaked pressure profile has higher critical value of poloidal beta defined within the q=1 surface than that with a parabolic pressure profile. Though the beta limit reduces with the increase of the elongation, the plasma with the peaked pressure profile has larger improvement due to the triangularity than that with the parabolic pressure profile. To access the second stability of the n=1 internal kink mode, the plasma with a flat pressure profile and the large minor radius of the q=1 surface is effective. (author)

  1. Hexa-histidin tag position influences disulfide structure but not binding behavior of in vitro folded N-terminal domain of rat corticotropin-releasing factor receptor type 2a

    OpenAIRE

    Klose, Jana; Wendt, Norbert; Kubald, Sybille; Krause, Eberhard; Fechner, Klaus; Beyermann, Michael; Bienert, Michael; Rudolph, Rainer; Rothemund, Sven

    2004-01-01

    The oxidative folding, particularly the arrangement of disulfide bonds of recombinant extracellular N-terminal domains of the corticotropin-releasing factor receptor type 2a bearing five cysteines (C2 to C6), was investigated. Depending on the position of a His-tag, two types of disulfide patterns were found. In the case of an N-terminal His-tag, the disulfide bonds C2–C3 and C4–C6 were found, leaving C5 free, whereas the C-terminal position of the His-tag led to the disulfide pattern C2–C5 a...

  2. Al2O3 dielectric layers on H-terminated diamond: Controlling surface conductivity

    Science.gov (United States)

    Yang, Yu; Koeck, Franz A.; Dutta, Maitreya; Wang, Xingye; Chowdhury, Srabanti; Nemanich, Robert J.

    2017-10-01

    This study investigates how the surface conductivity of H-terminated diamond can be preserved and stabilized by using a dielectric layer with an in situ post-deposition treatment. Thin layers of Al2O3 were grown by plasma enhanced atomic layer deposition (PEALD) on H-terminated undoped diamond (100) surfaces. The changes of the hole accumulation layer were monitored by correlating the binding energy of the diamond C 1s core level with electrical measurements. The initial PEALD of 1 nm Al2O3 resulted in an increase of the C 1s core level binding energy consistent with a reduction of the surface hole accumulation and a reduction of the surface conductivity. A hydrogen plasma step restored the C 1s binding energy to the value of the conductive surface, and the resistance of the diamond surface was found to be within the range for surface transfer doping. Further, the PEALD growth did not appear to degrade the surface conductive layer according to the position of the C 1s core level and electrical measurements. This work provides insight into the approaches to establish and control the two-dimensional hole-accumulation layer of the H-terminated diamond and improve the stability and performance of H-terminated diamond electronic devices.

  3. Unusual chemical properties of N-terminal histidine residues of glucagon and vasoactive intestinal peptide

    International Nuclear Information System (INIS)

    Hefford, M.A.; Evans, R.M.; Oda, G.; Kaplan, H.

    1985-01-01

    An N-terminal histidine residue of a protein or peptide has two functional groups, viz., an alpha-amino group and an imidazole group. A new procedure, based on the competitive labeling approach described by Duggleby and Kaplan has been developed by which the chemical reactivity of each functional group in such a residue can be determined as a function of pH. Only very small amounts of material are required, which makes it possible to determine the chemical properties in dilute solution or in proteins and polypeptides that can be obtained in only minute quantities. With this approach, the reactivity of the alpha-amino group of histidylglycine toward 1-fluoro-2,4-dinitrobenzene gave an apparent pK /sub a/ value of 7.64 +/- 0.07 at 37 degrees C, in good agreement with a value of 7.69 +/- 0.02 obtained by acid-base titration. However, the reactivity of the imidazole function gave an apparent pK /sub a/ value of 7.16 +/- 0.07 as compared to the pK /sub a/ value of 5.85 +/- 0.01 obtained by acid-base titration. Similarly, in glucagon and vasoactive intestinal peptide (VIP), apparent pKa values of 7.60 +/- 0.04 and 7.88 +/- 0.18, respectively, were obtained for the alpha-amino of their N-terminal histidine, and pKa values of 7.43 +/- 0.09 and 7.59 +/- 0.18 were obtained for the imidazole function

  4. Characterization of the N-terminal segment used by the barley yellow dwarf virus movement protein to promote interaction with the nuclear membrane of host plant cells.

    Science.gov (United States)

    Dennison, Sarah Rachel; Harris, Frederick; Brandenburg, Klaus; Phoenix, David Andrew

    2007-11-01

    The barley yellow dwarf virus movement protein (BYDV-MP) requires its N-terminal sequence to promote the transport of viral RNA into the nuclear compartment of host plant cells. Here, graphical analysis predicts that this sequence would form a membrane interactive amphiphilic alpha-helix. Confirming this prediction, NT1, a peptide homologue of the BYDV-MP N-terminal sequence, was found to be alpha-helical (65%) in the presence of vesicles mimics of the nuclear membrane. The peptide increased the fluidity of these nuclear membrane mimics (rise in wavenumber of circa 0.5-1.0 cm(-1)) and induced surface pressure changes of 2 mN m(-1) in lipid monolayers with corresponding compositions. Taken with isotherm analysis these results suggest that BYDV-MP forms an N-terminal amphiphilic alpha-helix, which partitions into the nuclear membrane primarily through thermodynamically stable associations with the membrane lipid headgroup region. We speculate that these associations may play a role in targeting of the nuclear membrane by BYDM-MP.

  5. Mouse Hepatitis Virus Strain A59 and Blocking Antireceptor Monoclonal Antibody Bind to the N-Terminal Domain of Cellular Receptor

    Science.gov (United States)

    Dveksler, Gabriela S.; Pensiero, Michael N.; Dieffenbach, Carl W.; Cardellichio, Christine B.; Basile, Alexis A.; Elia, Patrick E.; Holmes, Kathryn V.

    1993-03-01

    Mouse hepatitis virus (MHV) strain A59 uses as cellular receptors members of the carcinoembryonic antigen family in the immunoglobulin superfamily. Recombinant receptor proteins with deletions of whole or partial immunoglobulin domains were used to identify the regions of receptor glycoprotein recognized by virus and by antireceptor monoclonal antibody CC1, which blocks infection of murine cells. Monoclonal antibody CC1 and MHV-A59 virions bound only to recombinant proteins containing the entire first domain of MHV receptor. To determine which of the proteins could serve as functional virus receptors, receptor-negative hamster cells were transfected with recombinant deletion clones and then challenged with MHV-A59 virions. Receptor activity required the entire N-terminal domain with either the second or the fourth domain and the transmembrane and cytoplasmic domains. Recombinant proteins lacking the first domain or its C-terminal portion did not serve as viral receptors. Thus, like other virus receptors in the immunoglobulin superfamily, including CD4, poliovirus receptor, and intercellular adhesion molecule 1, the N-terminal domain of MHV receptor is recognized by the virus and the blocking monoclonal antibody.

  6. H+-ATPase activity from storage tissue of Beta vulgaris. IV. N,N'-dicyclohexylcarbodiimide binding and inhibition of the plasma membrane H+-ATPase

    International Nuclear Information System (INIS)

    Oleski, N.A.; Bennett, A.B.

    1987-01-01

    The molecular weight and isoelectric point of the plasma membrane H + -ATPase from red beet storage tissue were determined using N,N'-dicyclohexylcarbodiimide (DCCD) and a H + -ATPase antibody. When plasma membrane vesicles were incubated with 20 micromolar [ 14 C]-DCCD at 0 0 C, a single 97,000 dalton protein was visualized on a fluorography of a sodium dodecyl sulfate polyacrylamide gel. A close correlation between [ 14 C]DCCD labeling of the 97,000 dalton protein and the extent of ATPase inhibition over a range of DCCD concentration suggests that this 97,000 dalton protein is a component of the plasma membrane H + -ATPase. An antibody raised against the plasma membrane H + -ATPase of Neurospora crassa cross-reacted with the 97,000 dalton DCCD-binding protein, further supporting the identity of this protein. Immunoblots of two-dimensional gels of red beet plasma membrane vesicles indicated the isoelectric point of the H + -ATPase to be 6.5

  7. The Tip of the Four N-Terminal α-Helices of Clostridium sordellii Lethal Toxin Contains the Interaction Site with Membrane Phosphatidylserine Facilitating Small GTPases Glucosylation

    Directory of Open Access Journals (Sweden)

    Carolina Varela Chavez

    2016-03-01

    Full Text Available Clostridium sordellii lethal toxin (TcsL is a powerful virulence factor responsible for severe toxic shock in man and animals. TcsL belongs to the large clostridial glucosylating toxin (LCGT family which inactivates small GTPases by glucosylation with uridine-diphosphate (UDP-glucose as a cofactor. Notably, TcsL modifies Rac and Ras GTPases, leading to drastic alteration of the actin cytoskeleton and cell viability. TcsL enters cells via receptor-mediated endocytosis and delivers the N-terminal glucosylating domain (TcsL-cat into the cytosol. TcsL-cat was found to preferentially bind to phosphatidylserine (PS-containing membranes and to increase the glucosylation of Rac anchored to the lipid membrane. We have previously reported that the N-terminal four helical bundle structure (1–93 domain recognizes a broad range of lipids, but that TcsL-cat specifically binds to PS and phosphatidic acid. Here, we show using mutagenesis that the PS binding site is localized on the tip of the four-helix bundle which is rich in positively-charged amino acids. Residues Y14, V15, F17, and R18 on loop 1, between helices 1 and 2, in coordination with R68 from loop 3, between helices 3 and 4, form a pocket which accommodates L-serine. The functional PS-binding site is required for TcsL-cat binding to the plasma membrane and subsequent cytotoxicity. TcsL-cat binding to PS facilitates a high enzymatic activity towards membrane-anchored Ras by about three orders of magnitude as compared to Ras in solution. The PS-binding site is conserved in LCGTs, which likely retain a common mechanism of binding to the membrane for their full activity towards membrane-bound GTPases.

  8. The binding site for regulatory 14-3-3 protein in plant plasma membrane H+-ATPase: Involvement of a region promoting phosphorylation-independent interaction in addition to the phosphorylation-dependent C-terminal end

    DEFF Research Database (Denmark)

    Fuglsang, Anja T; Borch, Jonas; Bych, Katrine

    2003-01-01

    14-3-3 proteins constitute a family of well conserved proteins interacting with a large number of phosphorylated binding partners in eukaryotic cells. The plant plasma membrane H+-ATPase is an unusual target in that a unique phosphothreonine motif (946YpTV, where pT represents phosphothreonine...... of the Arabidopsis plasma membrane H+-ATPase isoform 2 (AHA2). Following site-directed mutagenesis within the 45 C-terminal residues of AHA2, we conclude that, in addition to the 946YpTV motif, a number of residues located further upstream are required for phosphorylation-independent binding of 14-3-3. Among these...

  9. Photoluminescence recovery by in-situ exposure of plasma-damaged n-GaN to atomic hydrogen at room temperature

    Directory of Open Access Journals (Sweden)

    Shang Chen

    2012-06-01

    Full Text Available The effect of in-situ exposure of n-GaN damaged by Cl2 plasma to atomic hydrogen (H radicals at room temperature was investigated. We found that the PL intensities of the band-edge emission, which had been drastically reduced by plasma-beam irradiation at a Cl ion dose of 5 × 1016 cm−2, recovered to values close to those of as-grown samples after H radical exposure at a dose of 3.8 × 1017 cm−2. XPS revealed the appearance of a peak at a binding energy of 18.3 eV, which is tentatively assigned to Ga-H, and confirmed the removal of Cl after H radical exposure.

  10. The formation of hexagonal-shaped InGaN-nanodisk on GaN-nanowire observed in plasma source molecular beam epitaxy

    KAUST Repository

    Ng, Tien Khee; Gasim, Anwar; Cha, Dong Kyu; Janjua, Bilal; Yang, Yang; Jahangir, Shafat; Zhao, Chao; Bhattacharya, Pallab; Ooi, Boon S.

    2014-01-01

    sensitive growth kinetics during plasma-assisted MBE of InGaN at low temperature, i.e. when the substrate temperature was reduced from 800 °C (GaN growth) to <600 °C (InGaN growth), during which sparsely populated metal-droplet formation prevails and further

  11. The pestivirus N terminal protease N(pro) redistributes to mitochondria and peroxisomes suggesting new sites for regulation of IRF3 by N(pro.).

    Science.gov (United States)

    Jefferson, Matthew; Whelband, Matthew; Mohorianu, Irina; Powell, Penny P

    2014-01-01

    The N-terminal protease of pestiviruses, N(pro) is a unique viral protein, both because it is a distinct autoprotease that cleaves itself from the following polyprotein chain, and also because it binds and inactivates IRF3, a central regulator of interferon production. An important question remains the role of N(pro) in the inhibition of apoptosis. In this study, apoptotic signals induced by staurosporine, interferon, double stranded RNA, sodium arsenate and hydrogen peroxide were inhibited by expression of wild type N(pro), but not by mutant protein N(pro) C112R, which we show is less efficient at promoting degradation of IRF3, and led to the conclusion that N(pro) inhibits the stress-induced intrinsic mitochondrial pathway through inhibition of IRF3-dependent Bax activation. Both expression of N(pro) and infection with Bovine Viral Diarrhea Virus (BVDV) prevented Bax redistribution and mitochondrial fragmentation. Given the role played by signaling platforms during IRF3 activation, we have studied the subcellular distribution of N(pro) and we show that, in common with many other viral proteins, N(pro) targets mitochondria to inhibit apoptosis in response to cell stress. N(pro) itself not only relocated to mitochondria but in addition, both N(pro) and IRF3 associated with peroxisomes, with over 85% of N(pro) puncta co-distributing with PMP70, a marker for peroxisomes. In addition, peroxisomes containing N(pro) and IRF3 associated with ubiquitin. IRF3 was degraded, whereas N(pro) accumulated in response to cell stress. These results implicate mitochondria and peroxisomes as new sites for IRF3 regulation by N(pro), and highlight the role of these organelles in the anti-viral pathway.

  12. Effects of fluorine-based plasma treatment and thermal annealing on high-Al content AlGaN Schottky contact

    International Nuclear Information System (INIS)

    Liu Fang; Qin Zhixin

    2016-01-01

    Fluorine plasma treatment was used prior to the Schottky metal deposition on the undoped Al 0.45 Ga 0.55 N, which aimed at the solar-blind wavelength. After fluorine plasma treatment and before depositing the Ni/Au Schottky, the samples were thermal annealed in the N 2 gas at 400 °C. The reverse leakage current density of Al 0.45 Ga 0.55 N Schottky diode was reduced by 2 orders of magnitude at −10 V. The reverse leakage current density was reduced by 3 orders of magnitude after thermal annealing. Further capacitance–frequency analysis revealed that the fluorine-based plasma treatment reduces the surface states of AlGaN by one order of magnitude at different surface state energies. The capacitance–frequency analysis also proved that the concentration of carriers in AlGaN top is reduced through fluorine plasma treatment. (paper)

  13. Sustained high βN plasmas on EAST tokamak

    Science.gov (United States)

    Gao, Xiang; the EAST team

    2018-05-01

    Sustained high normalized beta (βN ∼ 1.9) plasmas with an ITER-like tungsten divertor have been achieved on EAST tokamak recently. The high power NBI heating system of 4.8 MW and the 4.6 GHz lower hybrid wave of 1 MW were developed and applied to produce edge and internal transport barriers in high βN discharges. The central flat q profile with q (ρ) ∼ 1 at ρ safety factor q95 = 4.7 is identified by the multi-channel far-infrared laser polarimeter and the EFIT code. The fraction of non-inductive current is about 40%. The relation between fishbone activity and ITB formation is observed and discussed.

  14. Biochemical Characterization of Mycobacterium smegmatis RnhC (MSMEG_4305), a Bifunctional Enzyme Composed of Autonomous N-Terminal Type I RNase H and C-Terminal Acid Phosphatase Domains.

    Science.gov (United States)

    Jacewicz, Agata; Shuman, Stewart

    2015-08-01

    Mycobacterium smegmatis encodes several DNA repair polymerases that are adept at incorporating ribonucleotides, which raises questions about how ribonucleotides in DNA are sensed and removed. RNase H enzymes, of which M. smegmatis encodes four, are strong candidates for a surveillance role. Here, we interrogate the biochemical activity and nucleic acid substrate specificity of M. smegmatis RnhC, a bifunctional RNase H and acid phosphatase. We report that (i) the RnhC nuclease is stringently specific for RNA:DNA hybrid duplexes; (ii) RnhC does not selectively recognize and cleave DNA-RNA or RNA-DNA junctions in duplex nucleic acid; (iii) RnhC cannot incise an embedded monoribonucleotide or diribonucleotide in duplex DNA; (iv) RnhC can incise tracts of 4 or more ribonucleotides embedded in duplex DNA, leaving two or more residual ribonucleotides at the cleaved 3'-OH end and at least one or two ribonucleotides on the 5'-PO4 end; (v) the RNase H activity is inherent in an autonomous 140-amino-acid (aa) N-terminal domain of RnhC; and (vi) the C-terminal 211-aa domain of RnhC is an autonomous acid phosphatase. The cleavage specificity of RnhC is clearly distinct from that of Escherichia coli RNase H2, which selectively incises at an RNA-DNA junction. Thus, we classify RnhC as a type I RNase H. The properties of RnhC are consistent with a role in Okazaki fragment RNA primer removal or in surveillance of oligoribonucleotide tracts embedded in DNA but not in excision repair of single misincorporated ribonucleotides. RNase H enzymes help cleanse the genome of ribonucleotides that are present either as ribotracts (e.g., RNA primers) or as single ribonucleotides embedded in duplex DNA. Mycobacterium smegmatis encodes four RNase H proteins, including RnhC, which is characterized in this study. The nucleic acid substrate and cleavage site specificities of RnhC are consistent with a role in initiating the removal of ribotracts but not in single-ribonucleotide surveillance. Rnh

  15. Gel chromatography of immunoextracted plasma calcitonin in response to the calcium clamp in healthy males

    International Nuclear Information System (INIS)

    Bucht, E.; Toerring, O.; Sjoeberg, H.E.

    1985-01-01

    A radioimmunoassay (RIA) was developed for immunoreactive calcitonin (iCT) in human plasma. Antibodies against synthetic human calcitonin (hCT) coupled to bovine serum albumin (BSA) were raised in rabbits and were directed against the carboxy terminal part of CT. The detection limit of the assay was 8 pg/ml. In 7 males the iCT response to a calcium-clamp was studied. Blood was collected at 0,30 and 60 min after the start of the calcium infusion. iCT was measured directly in plasma and in extracts obtained after purification of plasma iCT by means of immobilized CT antiboides. There was a good correlation between iCT in plasma samples and extracts, r = 0.993, n = 14 (P< 0.001). Dilution curves of extracts and plasma were parallel with the hCT standard curves. Gel chromatography of the extracts on Sephadex G-50 and G-75 disclosed heterogeneity of iCT in normal plasma during basal conditions as well as during calcium stimulation. Thirty min after the start of the calcium clamp all molecular forms, most likely constituting monomeric and dimeric CT and larger forms, were increased, while after 60 min iCT seemed to constitute predominantly forms larger than monomeric TCY. Basal levels of unextracted iCT in healthy males (n = 44, 37 +/- 10 years) were 15 +/- 9 pg-equivalents/ml (mean +/- SD), which was higher than in females (n = 40, 32 +/- 9 years) 11 +/- 4 pg-equivalents/ml (P < 0.05). (author)

  16. Highly potent antimicrobial peptides from N-terminal membrane-binding region of E. coli MreB.

    Science.gov (United States)

    Saikia, Karabi; Sravani, Yalavarthi Durga; Ramakrishnan, Vibin; Chaudhary, Nitin

    2017-02-23

    Microbial pathogenesis is a serious health concern. The threat escalates as the existing conventional antimicrobials are losing their efficacy against the evolving pathogens. Peptides hold promise to be developed into next-generation antibiotics. Antimicrobial peptides adopt amphipathic structures that could selectively bind to and disrupt the microbial membranes. Interaction of proteins with membranes is central to all living systems and we reasoned that the membrane-binding domains in microbial proteins could be developed into efficient antimicrobials. This is an interesting approach as self-like sequences could elude the microbial strategies of degrading the antimicrobial peptides, one of the mechanisms of showing resistance to antimicrobials. We selected the 9-residue-long membrane-binding region of E. coli MreB protein. The 9-residue peptide (C-terminal amide) and its N-terminal acetylated analog displayed broad-spectrum activity, killing Gram-negative bacteria, Gram-positive bacteria, and fungi. Extension with a tryptophan residue at the N-terminus drastically improved the activity of the peptides with lethal concentrations ≤10 μM against all the organisms tested. The tryptophan-extended peptides caused complete killing of C. albicans as well as gentamicin and methicillin resistant S. aureus at 5 μM concentration. Lipid-binding studies and electron microscopic analyses of the peptide-treated microbes suggest membrane disruption as the mechanism of killing.

  17. The Lectin Domain of the Polypeptide GalNAc Transferase Family of Glycosyltransferases (ppGalNAc Ts) Acts as a Switch Directing Glycopeptide Substrate Glycosylation in an N- or C-terminal Direction, Further Controlling Mucin Type O-Glycosylation

    DEFF Research Database (Denmark)

    Gerken, Thomas A; Revoredo, Leslie; Thome, Joseph J C

    2013-01-01

    and specificity that differ between transferase isoforms. For example, ppGalNAc T1, T2, and T14 prefer C-terminally placed GalNAc-O-Thr, whereas ppGalNAc T3 and T6 prefer N-terminally placed GalNAc-O-Thr. Several transferase isoforms, ppGalNAc T5, T13, and T16, display equally enhanced N- or C-terminal activities...... relative to the nonglycosylated control peptides. This N- and/or C-terminal selectivity is presumably due to weak glycopeptide binding to the lectin domain, whose orientation relative to the catalytic domain is dynamic and isoform-dependent. Such N- or C-terminal glycopeptide selectivity provides...

  18. Diagnostics of N2-Ar plasma mixture excited in A 13.56 MHz hollow cathode discharge system: Application to remote plasma treatment of polyamide surface

    International Nuclear Information System (INIS)

    Saloum, S.; Naddaf, M.; Al-khaled, B.

    2009-01-01

    N 2 -x % Ar plasma gas mixture, generated in a hollow cathode RF discharge system, has been characterized by both optical emission spectroscopy (OES) and double langmuir probe, as a function of experimental parameters: Total pressure (5-33 Pa), and different fractions of argon (7≤ x ≤ 80), at a constant applied RF power of 300 W. N 2 dissociation degree has been investigated qualitatively by both actinometry method and the ratio of the atomic nitrogen line emission intensity at 672.3 nm to the vibrational band (0-0) of the N 2 second positive system at 337.1 nm. Both methods showed that the increase of argon fraction enhances the dissociation of N 2 , with a maximum at x=50 for the pressure of 5 Pa, although the two methods give two opposite trends as a function of total pressure. Spectroscopic measurements showed that the vibrational temperature of N 2 second positive system increases with both argon fraction and total pressure increase, it lies between 4900 K and 12300 K. Langmuir probe measurements showed that, in the remote zone, the electron temperature falls in the range 1.57-1.75 eV, the N 2 + density varies between 5.10 9 cm-3 and 1.4 10 10 cm -3 , and that both the plasma ionization degree and electron temperature increase towards the source. In addition, the process of plasma-polyamide surface interaction, in the remote plasma zone, has been studied through optical emission spectroscopy analysis during plasma treatment of polyamide to monitor the possible emissions due to the polymer etching. An increase of atomic nitrogen line (672.3 nm) intensity is obtained, atomic carbon line (833.52 nm) and the band emission (0-0) from CN (B 2 Σ + -X 2 Σ + ) violet system were observed. The polyamide surface modification has been confirmed through the improvement of its hydrophilic character as the water contact angle measured after the plasma treatment significantly decreased. (author)

  19. Expression, purification, crystallization and preliminary X-ray analysis of calmodulin in complex with the regulatory domain of the plasma-membrane Ca2+-ATPase ACA8

    International Nuclear Information System (INIS)

    Tidow, Henning; Hein, Kim L.; Baekgaard, Lone; Palmgren, Michael G.; Nissen, Poul

    2010-01-01

    Plant plasma-membrane Ca 2+ -ATPase is regulated via binding of calmodulin to its autoinhibitory N-terminal domain. In this study, the expression, purification, crystallization and preliminary X-ray diffraction analysis of this protein complex from A. thaliana are reported. Plasma-membrane Ca 2+ -ATPases (PMCAs) are calcium pumps that expel Ca 2+ from eukaryotic cells to maintain overall Ca 2+ homoeostasis and to provide local control of intracellular Ca 2+ signalling. They are of major physiological importance, with different isoforms being essential, for example, for presynaptic and postsynaptic Ca 2+ regulation in neurons, feedback signalling in the heart and sperm motility. In the resting state, PMCAs are autoinhibited by binding of their C-terminal (in mammals) or N-terminal (in plants) tail to two major intracellular loops. Activation requires the binding of calcium-bound calmodulin (Ca 2+ -CaM) to this tail and a conformational change that displaces the autoinhibitory tail from the catalytic domain. The complex between calmodulin and the regulatory domain of the plasma-membrane Ca 2+ -ATPase ACA8 from Arabidopsis thaliana has been crystallized. The crystals belonged to space group C2, with unit-cell parameters a = 176.8, b = 70.0, c = 69.8 Å, β = 113.2°. A complete data set was collected to 3.0 Å resolution and structure determination is in progress in order to elucidate the mechanism of PMCA activation by calmodulin

  20. The Performance Improvement of N2 Plasma Treatment on ZrO2 Gate Dielectric Thin-Film Transistors with Atmospheric Pressure Plasma-Enhanced Chemical Vapor Deposition IGZO Channel.

    Science.gov (United States)

    Wu, Chien-Hung; Huang, Bo-Wen; Chang, Kow-Ming; Wang, Shui-Jinn; Lin, Jian-Hong; Hsu, Jui-Mei

    2016-06-01

    The aim of this paper is to illustrate the N2 plasma treatment for high-κ ZrO2 gate dielectric stack (30 nm) with indium-gallium-zinc-oxide (IGZO) thin-film transistors (TFTs). Experimental results reveal that a suitable incorporation of nitrogen atoms could enhance the device performance by eliminating the oxygen vacancies and provide an amorphous surface with better surface roughness. With N2 plasma treated ZrO2 gate, IGZO channel is fabricated by atmospheric pressure plasma-enhanced chemical vapor deposition (AP-PECVD) technique. The best performance of the AP-PECVD IGZO TFTs are obtained with 20 W-90 sec N2 plasma treatment with field-effect mobility (μ(FET)) of 22.5 cm2/V-s, subthreshold swing (SS) of 155 mV/dec, and on/off current ratio (I(on)/I(off)) of 1.49 x 10(7).

  1. Structure of the EMMPRIN N-terminal domain 1: Dimerization via [beta]-strand swapping

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Jinquan; Teplyakov, Alexey; Obmolova, Galina; Malia, Thomas; Wu, Sheng-Jiun; Beil, Eric; Baker, Audrey; Swencki-Underwood, Bethany; Zhao, Yonghong; Sprenkle, Justin; Dixon, Ken; Sweet, Raymond; Gilliland, Gary L.; (Centocor)

    2010-09-27

    Extracellular matrix metalloproteinase inducer (EMMPRIN), also known as Hab18G, CD147, Basigin, M6, and neurothelin, is a membrane glycoprotein expressed on the surface of various cell types and many cancer cells. EMMPRIN stimulates adjacent fibroblasts and tumor cells to produce matrix metalloproteinases and plays an important role in tumor invasion and metastasis, angiogenesis, spermatogensis and fertilization, cell-cell adhesion and communication, and other biological processes (reviewed in Ref. 1 and references therein). It was demonstrated that the EMMPRIN extracellular domain (ECD), which structurally belongs to the IgG superfamily, can form homo-oligomers in a cis dependent manner and the N-terminal domain 1 (residues 22-101) was necessary and sufficient to mediate this interaction. The crystal structure of the ECD of recombinant human EMMPRIN (Hab18G/CD147) expressed in E. coli was reported at 2.8 {angstrom} resolution (Yu et al. 2008). The construct consists of residues 22-205 of the mature protein and has both an N-terminal IgC2 domain (ND1, residues 22-101) and a C-terminal IgC2 domain (ND2, residues 107-205). The two domains are joined by a five amino acid residue linker that constitutes a flexible hinge between the two domains. The crystal form has four copies of the molecule in the asymmetric unit, each of which has a different inter-domain angle that varies from 121{sup o} to 144{sup o}. The two domains each have a conserved disulfide bridge and both are comprised of two {beta}-sheets formed by strands EBA and GFCC, and DEBA and AGFCC for ND1 and ND2, respectively. Based on the crystal packing in this structure, the authors proposed that lateral packing between the two IgG domains of EMMPRIN ECD represents a potential mechanism for cell adhesion. Here we report the 2.0-{angstrom} crystal structure of the N-terminal domain of EMMPRIN ECD (ND1) expressed in mammalian cells. The overall structure of the domain is very similar to that in the full length

  2. Analysis of proteolytic processes and enzymatic activities in the generation of huntingtin n-terminal fragments in an HEK293 cell model.

    Directory of Open Access Journals (Sweden)

    Andrew T N Tebbenkamp

    Full Text Available N-terminal fragments of mutant huntingtin (htt that terminate between residues 90-115, termed cleavage product A or 1 (cp-A/1, form intracellular and intranuclear inclusion bodies in the brains of patients with Huntington's disease (HD. These fragments appear to be proteolytic products of the full-length protein. Here, we use an HEK293 cell culture model to investigate huntingtin proteolytic processing; previous studies of these cells have demonstrated cleavage of htt to cp-A/1 like htt fragments.Recombinant N-terminal htt fragments, terminating at residue 171 (also referred to as cp-B/2 like, were efficiently cleaved to produce cp-A/1 whereas fragments representing endogenous caspase, calpain, and metalloproteinase cleavage products, terminating between residues 400-600, were inefficiently cleaved. Using cysteine-labeling techniques and antibody binding mapping, we localized the C-terminus of the cp-A/1 fragments produced by HEK293 cells to sequences minimally limited by cysteine 105 and an antibody epitope composed of residues 115-124. A combination of genetic and pharmacologic approaches to inhibit potential proteases, including γ-secretase and calpain, proved ineffective in preventing production of cp-A/1.Our findings indicate that HEK293 cells express a protease that is capable of efficiently cleaving cp-B/2 like fragments of htt with normal or expanded glutamine repeats. For reasons that remain unclear, this protease cleaves longer htt fragments, with normal or expanded glutamine expansions, much less efficiently. The protease in HEK293 cells that is capable of generating a cp-A/1 like htt fragment may be a novel protease with a high preference for a cp-B/2-like htt fragment as substrate.

  3. Dispersion and absorption of longitudinal electro-kinetic wave in ion-implanted GaN semiconductor plasmas

    Energy Technology Data Exchange (ETDEWEB)

    Soni, Dilip [Government P G Madhav Science College, Ujjain (M P) (India); Sharma, Giriraj, E-mail: grsharma@gmail.com [SRJ Government Girls’ College, Neemuch (M P) (India); Saxena, Ajay [Government College, Garoth, Dist. Mandsaur (M P) (India); Jadhav, Akhilesh [Government J Yoganandam Chhattisgarh College, Raipur (C G) (India)

    2015-07-31

    An analytical study on propagation characteristics of longitudinal electro-kinetic (LEK) waves is presented. Based on multi-fluid model of plasma, we have derived a dispersion relation for LEK waves in colloid laden GaN semiconductor plasmas. It is assumed that ions are implanted to form colloids in the GaN sample. The colloids are continuously bombarded by the plasma particles and stick on them, but they acquire a net negative charge due to relatively higher mobility of electrons. It is found from the dispersion relation that the presence of charged colloids not only modifies the existing modes but also supports new novel modes of LEKWs. It is hoped that the study would enhance understanding on dispersion and absorption of LEKWs and help in singling out the appropriate configurations in which GaN crystal would be better suited for fabrication of microwave devices.

  4. Luminescent, water-soluble silicon quantum dots via micro-plasma surface treatment

    International Nuclear Information System (INIS)

    Wu, Jeslin J; Siva Santosh Kumar Kondeti, Vighneswara; Bruggeman, Peter J; Kortshagen, Uwe R

    2016-01-01

    Silicon quantum dots (SiQDs), with their broad absorption, narrow and size-tunable emission, and potential biocompatibility are highly attractive materials in biological imaging applications. The inherent hydrophobicity and instability of hydrogen-terminated SiQDs are obstacles to their widespread implementation. In this work, we successfully produced highly luminescent, hydrophilic SiQDs with long-term stability in water using non-thermal plasma techniques. Hydrogen-terminated SiQDs were produced in a low-pressure plasma and subsequently treated in water using an atmospheric-pressure plasma jet for surface modification. Preliminary assessments of the chemical mechanism(s) involved in the creation of water-soluble SiQDs were performed using Fenton’s reaction and various plasma chemistries, suggesting both OH and O species play a key role in the oxidation of the SiQDs. (letter)

  5. Urine albumin/creatinine ratio, high sensitivity C-reactive protein and N-terminal pro brain natriuretic peptide--three new cardiovascular risk markers--do they improve risk prediction and influence treatment?

    DEFF Research Database (Denmark)

    Olsen, Michael H; Sehestedt, Thomas; Lyngbaek, Stig

    2010-01-01

    -proBNP), related to hemodynamic cardiovascular risk factors, high sensitivity C-reactive protein (hsCRP), related to metabolic cardiovascular risk factors and urine albumin/creatinine ratio (UACR), related to hemodynamic as well as metabolic risk factors. In healthy subjects with a 10-year risk of cardiovascular...... death lower than 5% based on HeartScore and therefore not eligible for primary prevention, the actual 10-year risk of cardiovascular death exceeded 5% in a small subgroup of subjects with UACR higher than the 95-percentile of approximately 1.6 mg/mmol. Combined use of high UACR or high hsCRP identified...... a larger subgroup of 16% with high cardiovascular risk in which primary prevention may be advised despite low-moderate cardiovascular risk based on HeartScore. Furthermore, combined use of high UACR or high Nt-proBNP in subjects with known cardiovascular disease or diabetes identified a large subgroup...

  6. Plasma turbulence driven by transversely large-scale standing shear Alfvén waves

    International Nuclear Information System (INIS)

    Singh, Nagendra; Rao, Sathyanarayan

    2012-01-01

    Using two-dimensional particle-in-cell simulations, we study generation of turbulence consisting of transversely small-scale dispersive Alfvén and electrostatic waves when plasma is driven by a large-scale standing shear Alfvén wave (LS-SAW). The standing wave is set up by reflecting a propagating LS-SAW. The ponderomotive force of the standing wave generates transversely large-scale density modifications consisting of density cavities and enhancements. The drifts of the charged particles driven by the ponderomotive force and those directly caused by the fields of the standing LS-SAW generate non-thermal features in the plasma. Parametric instabilities driven by the inherent plasma nonlinearities associated with the LS-SAW in combination with the non-thermal features generate small-scale electromagnetic and electrostatic waves, yielding a broad frequency spectrum ranging from below the source frequency of the LS-SAW to ion cyclotron and lower hybrid frequencies and beyond. The power spectrum of the turbulence has peaks at distinct perpendicular wave numbers (k ⊥ ) lying in the range d e −1 -6d e −1 , d e being the electron inertial length, suggesting non-local parametric decay from small to large k ⊥ . The turbulence spectrum encompassing both electromagnetic and electrostatic fluctuations is also broadband in parallel wave number (k || ). In a standing-wave supported density cavity, the ratio of the perpendicular electric to magnetic field amplitude is R(k ⊥ ) = |E ⊥ (k ⊥ )/|B ⊥ (k ⊥ )| ≪ V A for k ⊥ d e A is the Alfvén velocity. The characteristic features of the broadband plasma turbulence are compared with those available from satellite observations in space plasmas.

  7. Selective enrichment of n-3 fatty acids in human plasma lipid motifs following intake of marine fish

    Science.gov (United States)

    Plasma levels of n-3 long chain polyunsaturated fatty acids (LCPUFA) are associated with a reduction in risk of cardiovascular disease and other chronic, age-related diseases like Alzheimer’s disease. In this work, we tested the hypothesis that n-3 LCPUFA fatty acids in human plasma are incorporated...

  8. Molecular determinants of interactions between the N-terminal domain and the transmembrane core that modulate hERG K+ channel gating.

    Directory of Open Access Journals (Sweden)

    Jorge Fernández-Trillo

    Full Text Available A conserved eag domain in the cytoplasmic amino terminus of the human ether-a-go-go-related gene (hERG potassium channel is critical for its slow deactivation gating. Introduction of gene fragments encoding the eag domain are able to restore normal deactivation properties of channels from which most of the amino terminus has been deleted, and also those lacking exclusively the eag domain or carrying a single point mutation in the initial residues of the N-terminus. Deactivation slowing in the presence of the recombinant domain is not observed with channels carrying a specific Y542C point mutation in the S4-S5 linker. On the other hand, mutations in some initial positions of the recombinant fragment also impair its ability to restore normal deactivation. Fluorescence resonance energy transfer (FRET analysis of fluorophore-tagged proteins under total internal reflection fluorescence (TIRF conditions revealed a substantial level of FRET between the introduced N-terminal eag fragments and the eag domain-deleted channels expressed at the membrane, but not between the recombinant eag domain and full-length channels with an intact amino terminus. The FRET signals were also minimized when the recombinant eag fragments carried single point mutations in the initial portion of their amino end, and when Y542C mutated channels were used. These data suggest that the restoration of normal deactivation gating by the N-terminal recombinant eag fragment is an intrinsic effect of this domain directed by the interaction of its N-terminal segment with the gating machinery, likely at the level of the S4-S5 linker.

  9. Transformación en el tiempo: definiendo el sitio de Xuenkal, Yucatán, durante el periodo Clásico Terminal Transformation in time: Defining the nature of Xuenkal, Yucatan, during the Terminal Classic

    Directory of Open Access Journals (Sweden)

    T. Kam Manahan

    2010-01-01

    Full Text Available El antiguo centro maya de Xuenkal, ubicado en la región Cupul, aproximadamente a 45 km hacia el noreste de Chichén Itzá fue uno de los sitios tierra adentro que contaban con una ocupación Sotuta sustancial. La investigación del Proyecto Arqueológico Xuenkal (PAX se enfoca en el estudio de la cultura material Sotuta y su relación con la ocupación Cehpech del Clásico Tardío-Terminal con el propósito de entender la naturaleza de tal transición. Utilizando una metodología de excavación de pozos de sondeo en contextos domésticos sugerimos que la ocupación pre-Sotuta fue mucho más robusta de lo que originalmente pensábamos. Los resultados del estudio del patrón de asentamiento demuestran que existía un asentamiento Cehpech extensivo que se extendía hacia la periferia, y las excavaciones de las unidades domésticas revelan que durante el Clásico Tardío Xuenkal era un asentamiento mucho más próspero de lo que imaginábamos y que sus pobladores probablemente tenían un contacto estrecho y recíproco con sus vecinos de Ek' Balam, Kulubá y Cobá. En contraste, el asentamiento Sotuta se limita a grupos residenciales localizados dentro del núcleo del sitio. Estos datos en conjunto sugieren que el control que ejerció Sotuta sobre Xuenkal está probablemente ligado al resultado de un conflicto político regional, más que una transformación autóctona.The ancient Maya center of Xuenkal, located in the Cupul region about 45 km northeast of Chichén Itzá, is one of the few known interior sites that witnessed a substantial Sotuta occupation. Proyecto Arqueológico Xuenkal (PAX research is investigating the Sotuta material and its relationship to preceding Late-Terminal Classic Cehpech settlement in order to understand the nature of this transition. Drawing upon extensive test excavations and broad excavations of household groups, we suggest that the pre-Sotuta Xuenkal occupation was much more robust than previously hypothesized

  10. The relationship between N-terminal prosomatostatin, all-cause and cardiovascular mortality in patients with type 2 diabetes mellitus (ZODIAC-35)

    NARCIS (Netherlands)

    van Dijk, Peter R; Landman, Gijs W D; van Essen, Larissa; Struck, Joachim; Groenier, Klaas H; Bilo, Henk J G; Bakker, Stephan J L; Kleefstra, Nanne

    2015-01-01

    BACKGROUND: The hormone somatostatin inhibits growth hormone release from the pituitary gland and is theoretically linked to diabetes and diabetes related complications. This study aimed to investigate the relationship between levels of the stable somatostatin precursor, N-terminal prosomatostatin

  11. The relationship between N-terminal prosomatostatin, all-cause and cardiovascular mortality in patients with type 2 diabetes mellitus (ZODIAC-35)

    NARCIS (Netherlands)

    van Dijk, Peter R; Landman, Gijs W D; van Essen, Larissa; Struck, Joachim; Groenier, Klaas H; Bilo, Henk J G; Bakker, Stephan J L; Kleefstra, Nanne

    2015-01-01

    Background: The hormone somatostatin inhibits growth hormone release from the pituitary gland and is theoretically linked to diabetes and diabetes related complications. This study aimed to investigate the relationship between levels of the stable somatostatin precursor, N-terminal prosomatostatin

  12. Proliferación y diferenciación osteogénica de células madre mesenquimales en hidrogeles de plasma sanguíneo humano

    Directory of Open Access Journals (Sweden)

    Itali M. Linero

    2014-03-01

    Full Text Available Introducción. La utilización de las células madre mesenquimales en la práctica clínica ha aumentado considerablemente en la última década, ya que juegan un papel favorable en los procesos de reparación y regeneración tisular, siendo la principal herramienta de la terapia celular para el tratamiento de enfermedades que afectan funcionalmente el tejido óseo y cartilaginoso. Objetivo. Evaluar la proliferación y capacidad de diferenciación osteogénica in vitro de células madre mesenquimales derivadas de tejido adiposo humano en un hidrogel de plasma sanguíneo. Materiales y métodos. Se obtuvieron células madre mesenquimales a partir de explantes de tejido adiposo humano y se caracterizaron por citometría de flujo; se buscó demostrar su multipotencialidad por su capacidad de diferenciación osteogénica y adipogénica. Se evaluó la proliferación celular y la capacidad de diferenciación osteogénica de las células cultivadas en hidrogeles de plasma sanguíneo. Resultados. Las células madre mesenquimales derivadas de tejido adiposo cultivadas en el hidrogel de plasma sanguíneo humano mostraron un patrón de proliferación muy similar al de las células cultivadas en monocapa y, además, mantuvieron su capacidad de diferenciación hacia el linaje osteogénico. Conclusiones. El hidrogel de plasma sanguíneo humano es un soporte adecuado para que las células madre mesenquimales derivadas de tejido adiposo humano proliferen y se diferencien hacia el linaje osteogénico y constituye un vehículo adecuado para su administración en regeneración del tejido óseo.

  13. Antenna Correlation From Input Parameters for Arbitrary Topologies and Terminations

    DEFF Research Database (Denmark)

    Alrabadi, Osama; Andersen, Jørgen Bach; Pedersen, Gert Frølund

    2012-01-01

    The spatial correlation between pairs of antennas in a system comprised of N RF ports is found by extending the N × N scattering matrix to (N + 1)×(N + 1) spatial scattering matrix, where the extra space dimension accounts for the reference port patterns. The lossless property of the spatial...... scattering matrix in a 3D uniform field is employed for expressing the spatial correlation between the port patterns at arbitrary complex terminations merely from the reference scattering parameters and the complex terminations without any far-field calculation....

  14. Mutational analysis of the N-terminal topogenic signal of watermelon glyoxysomal malate dehydrogenase using the heterologous host Hansenula polymorpha

    NARCIS (Netherlands)

    Gietl, Christine; Faber, Klaas Nico; Klei, Ida J. van der; Veenhuis, Marten

    1994-01-01

    We have studied the significance of the N-terminal presequence of watermelon (Citrullus vulgaris) glyoxysomal malate dehydrogenase [gMDH; (S)-malate:NAD+ oxidoreductase; EC 1.1.1.37] in microbody targeting. The yeast Hansenula polymorpha was used as heterologous host for the in vivo expression of

  15. Investigation of the flatband voltage (V(FB)) shift of Al2O3 on N2 plasma treated Si substrate.

    Science.gov (United States)

    Kim, Hyungchul; Lee, Jaesang; Jeon, Heeyoung; Park, Jingyu; Jeon, Hyeongtag

    2013-09-01

    The relationships between the physical and electrical characteristics of films treated with N2 plasma followed by forming gas annealing (FGA) were investigated. The Si substrates were treated with various radio frequency (RF) power levels under a N2 ambient. Al2O3 films were then deposited on Si substrates via remote plasma atomic-layer deposition. The plasma characteristics, such as the radical and ion density, were investigated using optical emission spectroscopy. Through X-ray photoelectron spectroscopy, the chemical-bonding configurations of the samples treated with N2 plasma and FGA were examined. The quantity of Si-N bonds increased as the RF power was increased, and Si--O--N bonds were generated after FGA. The flatband voltage (VFB) was shifted in the negative direction with increasing RF power, but the VFB values of the samples after FGA shifted in the positive direction due to the formation of Si--O--N bonds. N2 plasma treatment with various RF power levels slightly increased the leakage current due to the generation of defect sites.

  16. Variation of betaine, N,N-dimethylglycine, choline, glycerophosphorylcholine, taurine and trimethylamine-N-oxide in the plasma and urine of overweight people with type 2 diabetes over a two-year period.

    Science.gov (United States)

    McEntyre, Christopher J; Lever, Michael; Chambers, Stephen T; George, Peter M; Slow, Sandy; Elmslie, Jane L; Florkowski, Christopher M; Lunt, Helen; Krebs, Jeremy D

    2015-05-01

    Plasma betaine concentrations and urinary betaine excretions have high test-retest reliability. Abnormal betaine excretion is common in diabetes. We aimed to confirm the individuality of plasma betaine and urinary betaine excretion in an overweight population with type 2 diabetes and compare this with the individuality of other osmolytes, one-carbon metabolites and trimethylamine-N-oxide (TMAO), thus assessing their potential usefulness as disease markers. Urine and plasma were collected from overweight subjects with type 2 diabetes at four time points over a two-year period. We measured the concentrations of the osmolytes: betaine, glycerophosphorylcholine (GPC) and taurine, as well as TMAO, and the one-carbon metabolites, N,N-dimethylglycine (DMG) and free choline. Samples were measured using tandem mass spectrometry (LC-MS/MS). Betaine showed a high degree of individuality (or test-retest reliability) in the plasma (index of individuality = 0.52) and urine (index of individuality = 0.45). Betaine in the plasma had positive and negative log-normal reference change values (RCVs) of 54% and -35%, respectively. The other osmolytes, taurine and GPC were more variable in the plasma of individuals compared to the urine. DMG and choline showed high individuality in the plasma and urine. TMAO was highly variable in the plasma and urine (log-normal RCVs ranging from 403% to -80% in plasma). Betaine is highly individual in overweight people with diabetes. Betaine, its metabolite DMG, and precursor choline showed more reliability than the osmolytes, GPC and taurine. The low reliability of TMAO suggests that a single TMAO measurement has low diagnostic value. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  17. Characterization, cell-surface expression and ligand-binding properties of different truncated N-terminal extracellular domains of the ionotropic glutamate receptor subunit GluR1.

    Science.gov (United States)

    McIlhinney, R A; Molnár, E

    1996-04-01

    To identify the location of the first transmembrane segment of the GluR1 glutamate receptor subunit artificial stop codons have been introduced into the N-terminal domain at amino acid positions 442, 510, and 563, namely just before and spanning the proposed first two transmembrane regions. The resultant truncated N-terminal fragments of GluR1, termed NT1, NT2, and NT3 respectively were expressed in Cos-7 cells and their cellular distribution and cell-surface expression analysed using an N-terminal antibody to GluR1. All of the fragments were fully glycosylated and were found to be associated with cell membranes but none was secreted. Differential extraction of the cell membranes indicated that both NT1 and NT2 behave as peripheral membrane proteins. In contrast NT3, like the full subunit, has integral membrane protein properties. Furthermore only NT3 is expressed at the cell surface as determined by immunofluorescence and cell-surface biotinylation. Protease protection assays indicated that only NT3 had a cytoplasmic tail. Binding studies using the selective ligand [(3)H]alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate ([(3)H]AMPA) demonstrated that NT3 does not bind ligand. Together these results indicate that the first transmembrane domain of the GluR1 subunit lies between residues 509 and 562, that the N-terminal domain alone cannot form a functional ligand-binding site and that this domain can be targeted to the cell surface provided that it has a transmembrane-spanning region.

  18. Inductively coupled plasma-induced defects in n-type GaN studied from Schottky diode characteristics

    International Nuclear Information System (INIS)

    Nakamura, W.; Tokuda, Y.; Ueda, H.; Kachi, T.

    2006-01-01

    Inductively coupled plasma-(ICP-)induced defects in n-type GaN have been studied from current-voltage (I-V) characteristics and deep-level transient spectroscopy (DLTS) for Schottky diodes fabricated on etched surfaces. The samples after ICP etching show the ohmic I-V characteristics. Schottky characteristics are obtained after annealing at 600 and 800 deg. C in N 2 , but are not restored to that of the control samples. DLTS shows that the effect of ICP etching is small on the region beyond 80 nm from the surface. These results suggest that there remain ICP-induced damage in the near-surface region after thermal annealing

  19. The pestivirus N terminal protease N(pro redistributes to mitochondria and peroxisomes suggesting new sites for regulation of IRF3 by N(pro..

    Directory of Open Access Journals (Sweden)

    Matthew Jefferson

    Full Text Available The N-terminal protease of pestiviruses, N(pro is a unique viral protein, both because it is a distinct autoprotease that cleaves itself from the following polyprotein chain, and also because it binds and inactivates IRF3, a central regulator of interferon production. An important question remains the role of N(pro in the inhibition of apoptosis. In this study, apoptotic signals induced by staurosporine, interferon, double stranded RNA, sodium arsenate and hydrogen peroxide were inhibited by expression of wild type N(pro, but not by mutant protein N(pro C112R, which we show is less efficient at promoting degradation of IRF3, and led to the conclusion that N(pro inhibits the stress-induced intrinsic mitochondrial pathway through inhibition of IRF3-dependent Bax activation. Both expression of N(pro and infection with Bovine Viral Diarrhea Virus (BVDV prevented Bax redistribution and mitochondrial fragmentation. Given the role played by signaling platforms during IRF3 activation, we have studied the subcellular distribution of N(pro and we show that, in common with many other viral proteins, N(pro targets mitochondria to inhibit apoptosis in response to cell stress. N(pro itself not only relocated to mitochondria but in addition, both N(pro and IRF3 associated with peroxisomes, with over 85% of N(pro puncta co-distributing with PMP70, a marker for peroxisomes. In addition, peroxisomes containing N(pro and IRF3 associated with ubiquitin. IRF3 was degraded, whereas N(pro accumulated in response to cell stress. These results implicate mitochondria and peroxisomes as new sites for IRF3 regulation by N(pro, and highlight the role of these organelles in the anti-viral pathway.

  20. Influence of dietary long-chain n-3 fatty acids from menhaden fish oil on plasma concentrations of alpha-tocopherol in geriatric beagles.

    Science.gov (United States)

    Hall, Jean A; Tooley, Katie A; Gradin, Joseph L; Jewell, Dennis E; Wander, Rosemary C

    2002-01-01

    To determine effects of dietary n-3 fatty acids from Menhaden fish oil on plasma alpha-tocopherol concentrations in Beagles. 32 female Beagles. For 82 days, dogs were fed diets that contained 1 of 2 ratios of n-6:n-3 fatty acids (40:1 [low n-3] and 1.4:1 [high n-3]) and 1 of 3 concentrations of all-rac-alpha-tocopheryl acetate (low, 17 mg/kg of diet; medium, 101 mg/kg; and high, 447 mg/kg) in a 2 X 3 factorial study. Diets high in n-3 fatty acids significantly increased total content of n-3 fatty acids in plasma (17.0 g/100 g of fatty acids), compared with low n-3 diets (2.02 g/100 g of fatty acids). Mean +/- SEM plasma concentration of cholesterol was significantly lower in dogs consuming high n-3 diets (4.59 +/- 0.48 mmol/L), compared with dogs consuming low n-3 diets (5.71 +/- 0.48 mmol/L). A significant interaction existed between the ratio for n-6 and n-3 fatty acids and amount of alpha-tocopheryl acetate in the diet (plasma alpha-tocopherol concentration expressed on a molar basis), because the plasma concentration of alpha-toco-pherol was higher in dogs consuming low n-3 diets, compared with those consuming high n-3 diets, at the 2 higher amounts of dietary alpha-tocopheryl acetate. Plasma alpha-tocopherol concentration expressed relative to total lipid content did not reveal effects of dietary n-3 fatty acids on concentration of alpha-tocopherol. Plasma alpha-tocopherol concentration is not dependent on dietary ratio of n-6 and n-3 fatty acids when alpha-tocopherol concentration is expressed relative to the total lipid content of plasma.

  1. Nuclear import of influenza B virus nucleoprotein: Involvement of an N-terminal nuclear localization signal and a cleavage-protection motif

    International Nuclear Information System (INIS)

    Wanitchang, Asawin; Narkpuk, Jaraspim; Jongkaewwattana, Anan

    2013-01-01

    The nucleoprotein of influenza B virus (BNP) shares several characteristics with its influenza A virus counterpart (ANP), including localization in the host's nucleus. However, while the nuclear localization signal(s) (NLS) of ANP are well characterized, little is known about those of BNP. In this study, we showed that the fusion protein bearing the BNP N-terminus fused with GFP (N70–GFP) is exclusively nuclear, and identified a highly conserved KRXR motif spanning residues 44–47 as a putative NLS. In addition, we demonstrated that residues 3–15 of BNP, though not an NLS, are also crucial for nuclear import. Results from mutational analyses of N70–GFP and the full-length BNP suggest that this region may be required for protection of the N-terminus from proteolytic cleavage. Altogether, we propose that the N-terminal region of BNP contains the NLS and cleavage-protection motif, which together drive its nuclear localization. - Highlights: • The N-terminal region of BNP is required for nuclear accumulation. • The conserved motif at position 44–47 is a putative nuclear localization signal. • The first 15 amino acids of BNP may function as a cleavage-protection motif. • BNP may get access to the nucleus via a mechanism distinct from ANP

  2. Nuclear import of influenza B virus nucleoprotein: Involvement of an N-terminal nuclear localization signal and a cleavage-protection motif

    Energy Technology Data Exchange (ETDEWEB)

    Wanitchang, Asawin; Narkpuk, Jaraspim; Jongkaewwattana, Anan, E-mail: anan.jon@biotec.or.th

    2013-08-15

    The nucleoprotein of influenza B virus (BNP) shares several characteristics with its influenza A virus counterpart (ANP), including localization in the host's nucleus. However, while the nuclear localization signal(s) (NLS) of ANP are well characterized, little is known about those of BNP. In this study, we showed that the fusion protein bearing the BNP N-terminus fused with GFP (N70–GFP) is exclusively nuclear, and identified a highly conserved KRXR motif spanning residues 44–47 as a putative NLS. In addition, we demonstrated that residues 3–15 of BNP, though not an NLS, are also crucial for nuclear import. Results from mutational analyses of N70–GFP and the full-length BNP suggest that this region may be required for protection of the N-terminus from proteolytic cleavage. Altogether, we propose that the N-terminal region of BNP contains the NLS and cleavage-protection motif, which together drive its nuclear localization. - Highlights: • The N-terminal region of BNP is required for nuclear accumulation. • The conserved motif at position 44–47 is a putative nuclear localization signal. • The first 15 amino acids of BNP may function as a cleavage-protection motif. • BNP may get access to the nucleus via a mechanism distinct from ANP.

  3. Effect of an Energy Reservoir on the Atmospheric Propagation of Laser-Plasma Filaments

    Science.gov (United States)

    Eisenmann, Shmuel; Peñano, Joseph; Sprangle, Phillip; Zigler, Arie

    2008-04-01

    The ability to select and stabilize a single filament during propagation of an ultrashort, high-intensity laser pulse in air makes it possible to examine the longitudinal structure of the plasma channel left in its wake. We present the first detailed measurements and numerical 3-D simulations of the longitudinal plasma density variation in a laser-plasma filament after it passes through an iris that blocks the surrounding energy reservoir. Since no compensation is available from the surrounding background energy, filament propagation is terminated after a few centimeters. For this experiment, simulations indicate that filament propagation is terminated by plasma defocusing and ionization loss, which reduces the pulse power below the effective self-focusing power. With no blockage, a plasma filament length of over a few meters was observed.

  4. Effect of an Energy Reservoir on the Atmospheric Propagation of Laser-Plasma Filaments

    International Nuclear Information System (INIS)

    Eisenmann, Shmuel; Penano, Joseph; Sprangle, Phillip; Zigler, Arie

    2008-01-01

    The ability to select and stabilize a single filament during propagation of an ultrashort, high-intensity laser pulse in air makes it possible to examine the longitudinal structure of the plasma channel left in its wake. We present the first detailed measurements and numerical 3-D simulations of the longitudinal plasma density variation in a laser-plasma filament after it passes through an iris that blocks the surrounding energy reservoir. Since no compensation is available from the surrounding background energy, filament propagation is terminated after a few centimeters. For this experiment, simulations indicate that filament propagation is terminated by plasma defocusing and ionization loss, which reduces the pulse power below the effective self-focusing power. With no blockage, a plasma filament length of over a few meters was observed

  5. Diagnostics of N{sub 2}-Ar plasma mixture excited in a 13.56 MHz hollow cathode discharge system: application to remote plasma treatment of polyamide surface

    Energy Technology Data Exchange (ETDEWEB)

    Saloum, S; Naddaf, M; Alkhaled, B [Atomic Energy Commission of Syria (AECS), Physics Department, PO Box 6091, Damascus (Syrian Arab Republic)], E-mail: scientific@aec.org.sy

    2008-02-21

    N{sub 2}-x% Ar plasma gas mixture, generated in a hollow cathode RF discharge system, has been characterized by both optical emission spectroscopy (OES) and double Langmuir probe, as a function of experimental parameters: total pressure (5-33 Pa), and different fractions of argon (7 {<=} x {<=} 80), at a constant applied RF power of 300 W. N{sub 2} dissociation degree has been investigated qualitatively by both the actinometry method and the ratio I{sub N}/I{sub N{sub 2}} of the atomic nitrogen line emission intensity at 672.3 nm to the vibrational band (0-0) of the N{sub 2} second positive system at 337.1 nm. Both methods showed that the increase in argon fraction enhances the dissociation of N{sub 2}, with a maximum at x = 50 for the pressure of 5 Pa, although the two methods give two opposite trends as a function of total pressure. Spectroscopic measurements showed that the vibrational temperature of the N{sub 2} second positive system increases with both argon fraction and total pressure increase, it lies between 4900 and 12 300 K. Langmuir probe measurements showed that, in the remote zone, the electron temperature falls in the range 1.57-1.75 eV, the N{sub 2}{sup +} density varies between 5 x 10{sup 9} and 1.4 x 10{sup 10} cm{sup -3} and that both the plasma ionization degree and electron temperature increase towards the source. In addition, the process of plasma-polyamide (PA) surface interaction, in the remote plasma zone, has been studied through OES analysis during plasma treatment of PA to monitor the possible emissions due to the polymer etching. An increase in atomic nitrogen line (672.3 nm) intensity is obtained, atomic carbon line (833.52 nm) and the band emission (0-0) from the CN (B {sup 2}{sigma}{sup +}-X {sup 2}{sigma}{sup +}) violet system were observed. The PA surface modification has been confirmed through the improvement of its hydrophilic character as the water contact angle measured after the plasma treatment significantly decreased.

  6. Properties of catalase-peroxidase lacking its C-terminal domain

    International Nuclear Information System (INIS)

    Baker, Ruletha D.; Cook, Carma O.; Goodwin, Douglas C.

    2004-01-01

    Catalase-peroxidases have a two-domain structure. The N-terminal domain contains the bifunctional active site, but the function of the C-terminal domain is unknown. We produced catalase-peroxidase containing only its N-terminal domain (KatG Nterm ). Removal of the C-terminal domain did not result in unexpected changes in secondary structure as evaluated by CD, but KatG Nterm had neither catalase nor peroxidase activity. Partial recovery of both activities was achieved by incubating KatG Nterm with the separately expressed and isolated KatG C-terminal domain. Spectroscopic measurements revealed a shift in heme environment from a mixture of high-spin species (wtKatG) to exclusively hexacoordinate, low-spin (KatG Nterm ). Moreover, a >1000-fold lower k on for CN - binding was observed for KatG Nterm . EPR spectra for KatG Nterm and the results of site-specific substitution of active site histidines suggested that the distal histidine was the sixth ligand. Thus, one important role for the C-terminal domain may be to support the architecture of the active site, preventing heme ligation by this catalytically essential residue

  7. Fine tuning of the catalytic activity of colicin E7 nuclease domain by systematic N-terminal mutations

    Czech Academy of Sciences Publication Activity Database

    Németh, E.; Körtvélyesi, T.; Thulstrup, P. W.; Christensen, H. E. M.; Kožíšek, Milan; Nagata, K.; Czene, A.; Gyurcsik, B.

    2014-01-01

    Roč. 23, č. 8 (2014), s. 1113-1122 ISSN 0961-8368 Grant - others:Seventh Framework Programme of the European Union(XE) FP7-312284; OPPC(CZ) CZ.2.16/3.1.00/24016 Institutional support: RVO:61388963 Keywords : DNA cleavage * flow linear dichroism * isothermal calorimetry * positively charged N-terminal residues * Zn2+ binding Subject RIV: CE - Biochemistry Impact factor: 2.854, year: 2014

  8. N-terminal-pro-B-type natriuretic peptide during pharmacological heart rate reduction in hyperthyroidism

    DEFF Research Database (Denmark)

    Schultz, M; Kistorp, C; Corell, P

    2009-01-01

    days. Before treatment, N-terminal-pro-B-type natriuretic peptide was independently associated with thyroid function (free triiodothyronine-index, r=0.64, p=0.001) and the hemoglobin concentration (r=-0.36, p=0.031). The verapamil treatment induced a decrease in parameters reflecting cardiac function......-index decreased from median 319 to 315 arbitrary units (p=0.039) and free triiodothyronine-index increased from 8.6 to 9.9 arbitrary units (p=0.010). No changes in echocardiographic parameters were observed. A decrease in resting heart rate in untreated hyperthyroidism due to verapamil treatment did not result...

  9. Plasma urocortin in human systolic heart failure.

    Science.gov (United States)

    Ng, Leong L; Loke, Ian W; O'Brien, Russell J; Squire, Iain B; Davies, Joan E

    2004-04-01

    Urocortin (UCN), a member of the corticotrophin-releasing factor family, is expressed in heart, brain and gut. UCN has potent cardiostimulatory, cardioprotective, vasodilator and diuretic/natriuretic effects, and cardiac UCN expression is increased in heart failure (HF). In the present study, we investigated plasma levels of UCN in 119 patients with HF and 212 age- and gender-matched controls to clarify its relationship with gender and disease severity. UCN was elevated in HF [normal males, 19.5 (3.9-68.8) pmol/l and HF males, 50.2 (6.9-108.2) pmol/l, P fall in UCN levels with increasing NYHA class was reinforced by a significant correlation between UCN and ejection fraction ( r(s) = 0.45, P < 0.0005) in HF patients. Although receiver operating characteristic (ROC) curves for diagnosis of all HF cases yielded an area under the curve (AUC) of 0.76, ROC AUCs for patients with early HF (NYHA class I and II) were better (0.91). ROC AUCs for logistic models incorporating N-terminal probrain natriuretic peptide (N-BNP) and UCN were better than either peptide alone. In conclusion, plasma UCN is elevated in HF, especially in its early stages. Its decline with increasing HF severity may expedite disease progression due to diminished cardioprotective/anti-inflammatory effects. UCN measurement may also complement N-BNP in the diagnosis of early HF.

  10. Atomic Layer Deposition of Silicon Nitride from Bis(tert-butylamino)silane and N2 Plasma.

    Science.gov (United States)

    Knoops, Harm C M; Braeken, Eline M J; de Peuter, Koen; Potts, Stephen E; Haukka, Suvi; Pore, Viljami; Kessels, Wilhelmus M M

    2015-09-09

    Atomic layer deposition (ALD) of silicon nitride (SiNx) is deemed essential for a variety of applications in nanoelectronics, such as gate spacer layers in transistors. In this work an ALD process using bis(tert-butylamino)silane (BTBAS) and N2 plasma was developed and studied. The process exhibited a wide temperature window starting from room temperature up to 500 °C. The material properties and wet-etch rates were investigated as a function of plasma exposure time, plasma pressure, and substrate table temperature. Table temperatures of 300-500 °C yielded a high material quality and a composition close to Si3N4 was obtained at 500 °C (N/Si=1.4±0.1, mass density=2.9±0.1 g/cm3, refractive index=1.96±0.03). Low wet-etch rates of ∼1 nm/min were obtained for films deposited at table temperatures of 400 °C and higher, similar to that achieved in the literature using low-pressure chemical vapor deposition of SiNx at >700 °C. For novel applications requiring significantly lower temperatures, the temperature window from room temperature to 200 °C can be a solution, where relatively high material quality was obtained when operating at low plasma pressures or long plasma exposure times.

  11. The effect of N-stearoylethanolamine on plasma lipid composition in rats with experimental insulin resistance

    Directory of Open Access Journals (Sweden)

    O. V. Onopchenko

    2015-02-01

    Full Text Available A model of insulin resistance (IR, induced by prolonged high fat diet with high content of saturated fats was used to investigate the effect of N-stearoylethanolamine (NSE on the composition of free fatty acids (FFA, plasma lipoprotein spectrum and content of proinflammatory cytokine TNFα in rats. The results of this work showed a rise in the content of monounsaturated fatty acids (18:1 n-9 and a reduction in the level of polyunsaturated fatty acids (20:4 n-6 in plasma of rats with experimental IR. These findings are accompanied by the increased TNFα production and significant changes in plasma lipoprotein profile of rats with the fat overload. Particularly, a decreased high-density lipoprotein (HDL cholesterol level and increased low-density (LDL and very low-density lipoprotein (VLDL cholesterol level were detected. The NSE administration to obese rats with IR restored the content of mono- and polyunsaturated FFA, increased HDL cholesterol content and reduced LDL cholesterol level. In addition, the IR rats treated with NSE showed normalization in the serum TNFα level. Our results showed the restoration of plasma lipid profile under NSE administration in rats with obesity-induced IR. Considering the fact that plasma lipid composition displays the lipid metabolism in general, the NSE actions may play a significant role in the prevention of IR-associated complications.

  12. Study of corrosion resistance properties of nitrided carbon steel using radiofrequency N{sub 2}/H{sub 2} cold plasma process

    Energy Technology Data Exchange (ETDEWEB)

    Bouanis, F.Z. [Unite Materiaux et Transformations (UMET), Ingenierie des Systemes Polymeres, CNRS UMR 8207, ENSCL, BP 90108, F-59652 Villeneuve d' Ascq Cedex (France); Jama, C., E-mail: charafeddine.jama@ensc-lille.f [Unite Materiaux et Transformations (UMET), Ingenierie des Systemes Polymeres, CNRS UMR 8207, ENSCL, BP 90108, F-59652 Villeneuve d' Ascq Cedex (France); Traisnel, M. [Unite Materiaux et Transformations (UMET), Ingenierie des Systemes Polymeres, CNRS UMR 8207, ENSCL, BP 90108, F-59652 Villeneuve d' Ascq Cedex (France); Bentiss, F. [Laboratoire de Chimie de Coordination et d' Analytique, Faculte des Sciences, Universite Chouaib Doukkali, B.P. 20, M-24000 El Jadida (Morocco)

    2010-10-15

    C38 carbon steel have been plasma-nitrided using a radiofrequency cold plasma discharge treatment in order to investigate the influence of gas composition on corrosion behaviour of nitrided substrates. The investigated C38 steel was nitrided by a RF plasma discharge treatment using two different gas mixtures (75% N{sub 2}/25% H{sub 2} and 25% N{sub 2}/75% H{sub 2}) at different times of plasma-treatment on non-heated substrates. Electron Probe Microanalysis (EPMA) showed that the nitrided layer formed using 75% N{sub 2}/25% H{sub 2} gas mixture was thicker compared to those formed in the case of 25% N{sub 2}/75% H{sub 2} or pure N{sub 2}. The modifications of the corrosion resistance characteristics of plasma-nitrided C38 steel in 1 M HCl solution were investigated by weight loss measurements and ac impedance technique. The results obtained from these two evaluation methods were in good agreement. It was shown that the nitriding treatment in both cases (75% N{sub 2}/25% H{sub 2} and 25% N{sub 2}/75% H{sub 2}) improves the corrosion resistance of investigated carbon steel, while the better performance is obtained for the 75% N{sub 2}/25% H{sub 2} gas mixture. X-ray photoelectron spectroscopy (XPS) was carried out before and after immersion in corrosive medium in order to establish the mechanism of corrosion inhibition using N{sub 2}/H{sub 2} cold plasma nitriding process.

  13. Differential functions of C- and N-terminal hepatitis B x protein in liver cells treated with doxorubicin in normoxic or hypoxic condition.

    Directory of Open Access Journals (Sweden)

    Davor Kin-Fan Chau

    Full Text Available Hepatitis viral B x protein (HBx, a hepatocarcinogen, is frequently mutated. Hypoxia influences the growth of HCC and also the sensitivity of tumor cells to treatments. We aimed to test the role of HBx and acute hypoxia in the efficacy of chemotherapy. In this study, we established 4 Chang liver cell lines with the full-length HBx (HBx, the first 50 amino acids of N-terminal HBx (HBx/50, the last 104 amino acids of C-terminal HBx (HBx/51 and empty vector (CL, respectively. MTT and TNUEL assays were used to assess cell viability and apoptosis respectively. Western blot was used to determine the expression of relevant proteins. Results showed that among 4 cell lines, doxorubicin was most effective in decreasing the viability and enhancing apoptosis in HBx/51 cells, while HBx/50 cells were most resistant to the treatment. Cells in hypoxia were more susceptible to doxorubicin than cells in normoxia. Hypoxia facilitated the Bid cleavage especially in HBx/51 cells via phosphorylating p38 MAPK. p38 MAPK inhibitor significantly reduced the tBid level and increased cell viability. In conclusion, N-terminal HBx and C-terminal HBx function differentially in their ability to regulate cell growth, with the former being promotive but the latter being inhibitory. The acute hypoxia may overcome the HBx-induced resistance and facilitate the chemotherapy.

  14. IMPLEMENTACIÓN DE UNA METODOLOGÍA PARA LA SEPARACIÓN DE PROTEOMAS DE PLASMA HUMANO MEDIANTE ELECTROFORESIS BIDIMENSIONAL

    Directory of Open Access Journals (Sweden)

    Ruth Andrea Rodríguez

    2015-09-01

    Full Text Available El análisis proteómico en derivados sanguíneos es una importante herramienta en el descubrimiento de biomarcadores para el diagnóstico de enfermedades, aunque su caracterización exhibe desafíos relacionados con el amplio rango dinámico de las proteínas. En este trabajo se implementaron las condiciones para la separación de proteomas de plasma sanguíneo por electroforesis bidimensional. En muestras de plasma de infante y adulto se evaluaron dos sistemas de pretratamiento de la muestra para reducir el rango dinámico de las proteínas: inmunodepleción de proteínas abundantes y enriquecimiento de proteínas de baja abundancia. Los proteomas se separaron por electroforesis bidimensional y las imágenes se analizaron con el programa Melanie 7.0. Se encontró que ambos métodos de pretratamiento fueron reproducibles y permitieron ver las diferencias en los proteomas de infante y adulto, como muestran los análisis de componentes principales y de clasificación jerárquica tipo heatmap. El porcentaje de recuperación de proteínas fue mayor con la inmunodepleción en comparación con el enriquecimiento proteico. Estos resultados permitieron concluir que con la inmunodepleción, se tiene mayor control de las proteínas eliminadas y por tanto menor pérdida de información, lo que permite su aplicación en estudios exploratorios para la identificación de potenciales biomarcadores de enfermedad.

  15. Determination of 5-hydroxy-N-methyl-2-pyrrolidone and 2-hydroxy-N-methylsuccinimide in human plasma and urine using liquid chromatography-electrospray tandem mass spectrometry.

    Science.gov (United States)

    Carnerup, M A; Akesson, B; Jönsson, B A

    2001-09-15

    A method for simultaneous determination of 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) and 2-hydroxy-N-methylsuccinimide (2-HMSI) was developed. These compounds are metabolites from N-methyl-2-pyrrolidone (NMP), a powerful and widely used organic solvent. 5-HNMP and 2-HMSI were purified from plasma and urine by solid-phase extraction using Isolute ENV+ columns, and analysed by liquid chromatography coupled to a mass spectrometer fitted with an atmospheric pressure turbo ion spray ionisation interface in the positive ion mode. The method was validated for plasma and urine concentrations from 0.12 to 25 microg/ml. The recoveries for 5-HNMP and 2-HMSI in plasma were 99 and 98%, respectively, and in urine 111 and 106%, respectively. For 5-HNMP and 2-HMSI, the within-day precision in plasma was 1-4 and 3-6%, respectively, and in urine 2-12 and 3-10%, respectively. The corresponding data for the between-day precision was 5 and 3-6%, respectively, and 4-6 and 7-8%, respectively. The detection limit for 5-HNMP was 4 ng/ml in plasma and 120 ng/ml in urine. For 2-HMSI, it was 5 ng/ml in plasma and 85 ng/ml in urine. The method is applicable for analysis of plasma and urine samples from workers exposed to NMP.

  16. The scavenger receptor SSc5D physically interacts with bacteria through the SRCR-containing N-terminal domain

    Directory of Open Access Journals (Sweden)

    Catarina Bessa-Pereira

    2016-10-01

    Full Text Available The scavenger receptor cysteine-rich (SRCR family comprises a group of membrane-attached or secreted proteins that contain one or more modules/domains structurally similar to the membrane distal domain of type I macrophage scavenger receptor. Although no all-inclusive biological function has been ascribed to the SRCR family, some of these receptors have been shown to recognize pathogen-associated molecular patterns (PAMP of bacteria, fungi or other microbes. SSc5D is a recently described soluble SRCR receptor produced by monocytes/macrophages and T lymphocytes, consisting of an N-terminal portion which contains five SRCR modules, and a large C-terminal mucin-like domain. Towards establishing a global common role for SRCR domains, we interrogated whether the set of five SRCR domains of SSc5D displayed pattern recognition receptor (PRR properties. For that purpose, we have expressed in a mammalian expression system the N-terminal SRCR-containing moiety of SSC5D (N-SSc5D, thus excluding the mucin-like domain likely by nature to bind microorganisms, and tested the capacity of the SRCR functional groups to physically interact with bacteria. Using conventional protein-bacteria binding assays, we showed that N-SSc5D had a superior capacity to bind to E. coli strains RS218 and IHE3034 compared with that of the extracellular domains of the SRCR proteins CD5 and CD6 (sCD5 and sCD6, respectively, and similar E. coli-binding properties as Spα, a proven PRR of the SRCR family. We have further designed a more sensitive, real-time and label-free surface plasmon resonance (SPR-based assay, and examined the capacity of N-SSc5D, Spα, sCD5 and sCD6 to bind to different bacteria. We demonstrated that the N-SSc5D compares with Spα in the capacity to bind to E. coli and L. monocytogenes, and further that it can distinguish between pathogenic E. coli RS218 and IHE3034 strains and the non-pathogenic laboratory E. coli strain BL21(DE3. Our work thus advocates the

  17. Synthesis of nanocrystalline magnesium nitride (Mg3N2) powder using thermal plasma

    International Nuclear Information System (INIS)

    Kim, Dong-Wook; Kim, Tae-Hee; Park, Hyun-Woo; Park, Dong-Wha

    2011-01-01

    Nanocrystalline magnesium nitride (Mg 3 N 2 ) powder was synthesized from bulk magnesium by thermal plasma at atmospheric pressure. Magnesium vapor was generated through heating the bulk magnesium by DC plasma jet and reacted with ammonia gas. Injecting position and flow rates of ammonia gas were controlled to investigate an ideal condition for Mg 3 N 2 synthesis. The synthesized Mg 3 N 2 was cooled and collected on the chamber wall. Characteristics of the synthesized powders for each experimental condition were analyzed by X-ray diffractometer (XRD), scanning electron microscopy (SEM) and thermogravity analysis (TGA). In absence of NH 3 , magnesium metal powder was formed. The synthesis with NH 3 injection in low temperature region resulted in a formation of crystalline magnesium nitride with trigonal morphology, whereas the mixture of magnesium metal and amorphous Mg 3 N 2 was formed when NH 3 was injected in high temperature region. Also, vaporization process of magnesium was discussed.

  18. INFLUENCIA DE LA NITRURACIÓN POR PLASMA SOBRE EL COMPORTAMIENTO A LA CORROSIÓN Y LA ADHESIÓN DE RECUBRIMIENTOS DLC SOBRE ACERO INOXIDABLE AISI 420

    Directory of Open Access Journals (Sweden)

    Jorge N. Pecina

    2016-01-01

    Full Text Available En este trabajo se estudió el comportamiento a la corrosió n y la adhesión de dos rec ubrimientos DLC (“Diamond Like Carbon ” , “Soft” y “Hard”, depositados por PACVD (“Plasma Assisted Chemical Vapour Deposition” sobre acero AISI 420, templado y revenido y /o nitrurado por plasma . Se analizaron por espectroscopía Raman y midió dureza en superficie. Se observó la microestructura por OM y SEM. Se realizaron pruebas de adhesión con indentación Rockwell C . S e practicaron ensayos de Niebla Salina e inmersión en HCl . Los DLC “ Soft ” presentaron una dureza de 5 00 HV y un espesor de 2 0 μm , mientras que los “ Hard ” tuvieron 1400 HV y 2 ,5 μm. Ambos recubrimientos presentaron bajo coeficiente de fricción y buena adhesión sobre el sustrato nitrurado . También presentaron buena resistencia a la corrosión atmosférica. En HCl el DLC retardó la degradación que se presentó rápidamente en las muestras sin recubrir.

  19. The mechanism of vault opening from the high resolution structure of the N-terminal repeats of MVP.

    Science.gov (United States)

    Querol-Audí, Jordi; Casañas, Arnau; Usón, Isabel; Luque, Daniel; Castón, José R; Fita, Ignasi; Verdaguer, Nuria

    2009-11-04

    Vaults are ubiquitous ribonucleoprotein complexes involved in a diversity of cellular processes, including multidrug resistance, transport mechanisms and signal transmission. The vault particle shows a barrel-shaped structure organized in two identical moieties, each consisting of 39 copies of the major vault protein MVP. Earlier data indicated that vault halves can dissociate at acidic pH. The crystal structure of the vault particle solved at 8 A resolution, together with the 2.1-A structure of the seven N-terminal domains (R1-R7) of MVP, reveal the interactions governing vault association and provide an explanation for a reversible dissociation induced by low pH. The structural comparison with the recently published 3.5 A model shows major discrepancies, both in the main chain tracing and in the side chain assignment of the two terminal domains R1 and R2.

  20. Age-dependent values of N-terminal pro-B-type natriuretic peptide are superior to a single cut-point for ruling out suspected systolic dysfunction in primary care

    DEFF Research Database (Denmark)

    Hildebrandt, Per; Collinson, Paul O; Doughty, Robert N

    2010-01-01

    The study evaluated the use of age-related decision limits for N-terminal pro-B-type natriuretic peptide (NT-proBNP), for ruling out suspected systolic dysfunction in symptomatic patients in primary care, compared with the present standards.......The study evaluated the use of age-related decision limits for N-terminal pro-B-type natriuretic peptide (NT-proBNP), for ruling out suspected systolic dysfunction in symptomatic patients in primary care, compared with the present standards....

  1. Influenza A H3N2 subtype virus NS1 protein targets into the nucleus and binds primarily via its C-terminal NLS2/NoLS to nucleolin and fibrillarin

    Science.gov (United States)

    2012-01-01

    Background Influenza A virus non-structural protein 1 (NS1) is a virulence factor, which is targeted into the cell cytoplasm, nucleus and nucleolus. NS1 is a multi-functional protein that inhibits host cell pre-mRNA processing and counteracts host cell antiviral responses. Previously, we have shown that the NS1 protein of the H3N2 subtype influenza viruses possesses a C-terminal nuclear localization signal (NLS) that also functions as a nucleolar localization signal (NoLS) and targets the protein into the nucleolus. Results Here, we show that the NS1 protein of the human H3N2 virus subtype interacts in vitro primarily via its C-terminal NLS2/NoLS and to a minor extent via its N-terminal NLS1 with the nucleolar proteins, nucleolin and fibrillarin. Using chimeric green fluorescence protein (GFP)-NS1 fusion constructs, we show that the nucleolar retention of the NS1 protein is determined by its C-terminal NLS2/NoLS in vivo. Confocal laser microscopy analysis shows that the NS1 protein colocalizes with nucleolin in nucleoplasm and nucleolus and with B23 and fibrillarin in the nucleolus of influenza A/Udorn/72 virus-infected A549 cells. Since some viral proteins contain NoLSs, it is likely that viruses have evolved specific nucleolar functions. Conclusion NS1 protein of the human H3N2 virus interacts primarily via the C-terminal NLS2/NoLS and to a minor extent via the N-terminal NLS1 with the main nucleolar proteins, nucleolin, B23 and fibrillarin. PMID:22909121

  2. Mortality and preoperative cardiac function in vascular amputees : an N-terminal pro-brain natriuretic peptide (NT-proBNP) pilot study

    NARCIS (Netherlands)

    Riemersma, Marcel; Dijkstra, Pieter U.; van Veldhuisen, Dirk Jan; Muskiet, Frits A. J.; van den Dungen, Jan A. M. M.; Geertzen, Jan H. B.

    Objective: To determine preoperative ventricular function in vascular amputees by measuring N-terminal pro-brain natriuretic peptide (NT-proBNP) and to analyse the relationship between NT-proBNP levels and 30-day postoperative mortality. Design: Prospective pilot study. Subjects and methods: In 19

  3. Simulation of impurity transport in the peripheral plasma due to the emission of dust in long pulse discharges on the Large Helical Device

    Directory of Open Access Journals (Sweden)

    M. Shoji

    2017-08-01

    Full Text Available Two different plasma termination processes by dust emission were observed in long pulse discharges in the Large Helical Device. One is a plasma termination caused by large amounts of carbon dust released from a lower divertor region. The other is termination caused by stainless steel (iron dust emission from the surface of a helical coil can. The effect of the dust emission on the sustainment of the long pulse discharges are investigated using a three-dimensional edge plasma transport code (EMC3-EIRENE coupled with a dust transport code (DUSTT. The simulation shows that the plasma is more influenced by the iron dust emission from the helical coil can than by the carbon dust emission from the divertor region. The simulation revealed that the plasma flow in divertor legs is quite effective for preventing dust from terminating the long pulse discharges.

  4. Surface Modification of Polypropylene Microporous Membrane by Atmospheric-Pressure Plasma Immobilization of N,N-dimethylamino Ethyl Methacrylate

    International Nuclear Information System (INIS)

    Zhong Shaofeng

    2010-01-01

    Surface modification of polypropylene microporous membrane (PPMM) was performed by atmospheric pressure dielectric barrier discharge plasma immobilization of N,N-dimethylamino ethyl methacrylate (DMAEMA). Structural and morphological changes on the membrane surface were characterized by attenuated total reflection-Fourier transform infrared spectroscopy (FT-IR/ATR), X-ray photoelectron spectroscope (XPS) and field emission scanning electron microscopy (FE-SEM). Water contact angles of the membrane surfaces were also measured by the sessile drop method. Results reveal that both the plasma-treating conditions and the adsorbed DMAEMA amount have remarkable effects on the immobilization degree of DMAEMA. Peroxide determination by 1,1-diphenyl-2-picrvlhydrazyl (DPPH) method verifies the exsistence of radicals induced by plasma, which activize the immobilization reaction. Pure water contact angle on the membrane surface decreased with the increase of DMAEMA immobilization degree, which indicates an enhanced hydrophilicity for the modified membranes. The effects of immobilization degrees on pure water fluxes were also measured. It is shown that pure water fluxes first increased with immobilization degree and then decreased. Finally, permeation of bovine serum albumin (BSA) and lysozyme solution were measured to evaluate the antifouling property of the DMAEMA-modified membranes, from which it is shown that both hydrophilicity and electrostatic repulsion are beneficial for membrane antifouling.

  5. High-quality InN grown on KOH wet etched N-polar InN template by RF-MBE

    International Nuclear Information System (INIS)

    Muto, D.; Araki, T.; Kitagawa, S.; Kurouchi, M.; Nanishi, Y.; Naoi, H.; Na, H.

    2006-01-01

    We have succeeded in dramatically decreasing the density of dislocations in InN by regrowing InN films on micro-facetted N-polar InN templates. The micro-facetted N-polar InN templates were formed by wet etching in a 10 mol/l KOH solution. InN films were regrown on the micro-facetted N-polar InN templates and on flat surface N-polar InN templates for comparison by radio-frequency plasma-assisted molecular beam epitaxy. InN regrown on micro-facetted InN had considerably smaller twist distribution than that grown on the flat InN templates. From transmission electron microscopy observation, it was confirmed that the InN grown on the micro-facetted InN template had much lower density of dislocations than that grown on the flat InN template, and moreover the propagation of edge dislocations was almost completely terminated at the interface between the regrown InN and the micro-facetted InN template. Based on the results, we propose that regrowth of InN on micro-facetted InN templates is an effective way to obtain high-quality InN films. (copyright 2006 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  6. Neurospora tryptophan synthase: N-terminal analysis and the sequence of the pyridoxal phosphate active site peptide

    International Nuclear Information System (INIS)

    Pratt, M.L.; Hsu, P.Y.; DeMoss, J.A.

    1986-01-01

    Tryptophan synthase (TS), which catalyzes the final step of tryptophan biosynthesis, is a multifunctional protein requiring pyridoxal phosphate (B6P) for two of its three distinct enzyme activities. TS from Neurospora has a blocked N-terminal, is a homodimer of 150 KDa and binds one mole of B6P per mole of subunit. The authors shown the N-terminal residue to be acyl-serine. The B6P-active site of holoenzyme was labelled by reduction of the B6P-Schiff base with [ 3 H]-NaBH 4 , and resulted in a proportionate loss of activity in the two B6P-requiring reactions. SDS-polyacrylamide gel electrophoresis of CNBr-generated peptides showed the labelled, active site peptide to be 6 KDa. The sequence of this peptide, purified to apparent homogeneity by a combination of C-18 reversed phase and TSK gel filtration HPLC is: gly-arg-pro-gly-gln-leu-his-lys-ala-glu-arg-leu-thr-glu-tyr-ala-gly-gly-ala-gln-ile-xxx-leu-lys-arg-glu-asp-leu-asn-his-xxx-gly-xxx-his-/sub ***/-ile-asn-asn-ala-leu. Although four residues (xxx, /sub ***/) are unidentified, this peptide is minimally 78% homologous with the corresponding peptide from yeast TS, in which residue (/sub ***/) is the lysine that binds B6P

  7. The subfamily-specific interaction between Kv2.1 and Kv6.4 subunits is determined by interactions between the N- and C-termini.

    Directory of Open Access Journals (Sweden)

    Elke Bocksteins

    Full Text Available The "silent" voltage-gated potassium (KvS channel subunit Kv6.4 does not form electrically functional homotetramers at the plasma membrane but assembles with Kv2.1 subunits, generating functional Kv2.1/Kv6.4 heterotetramers. The N-terminal T1 domain determines the subfamily-specific assembly of Kv1-4 subunits by preventing interactions between subunits that belong to different subfamilies. For Kv6.4, yeast-two-hybrid experiments showed an interaction of the Kv6.4 N-terminus with the Kv2.1 N-terminus, but unexpectedly also with the Kv3.1 N-terminus. We confirmed this interaction by Fluorescence Resonance Energy Transfer (FRET and co-immunoprecipitation (co-IP using N-terminal Kv3.1 and Kv6.4 fragments. However, full-length Kv3.1 and Kv6.4 subunits do not form heterotetramers at the plasma membrane. Therefore, additional interactions between the Kv6.4 and Kv2.1 subunits should be important in the Kv2.1/Kv6.4 subfamily-specificity. Using FRET and co-IP approaches with N- and C-terminal fragments we observed that the Kv6.4 C-terminus physically interacts with the Kv2.1 N-terminus but not with the Kv3.1 N-terminus. The N-terminal amino acid sequence CDD which is conserved between Kv2 and KvS subunits appeared to be a key determinant since charge reversals with arginine substitutions abolished the interaction between the N-terminus of Kv2.1 and the C-terminus of both Kv2.1 and Kv6.4. In addition, the Kv6.4(CKv3.1 chimera in which the C-terminus of Kv6.4 was replaced by the corresponding domain of Kv3.1, disrupted the assembly with Kv2.1. These results indicate that the subfamily-specific Kv2.1/Kv6.4 heterotetramerization is determined by interactions between Kv2.1 and Kv6.4 that involve both the N- and C-termini in which the conserved N-terminal CDD sequence plays a key role.

  8. Nonlinear coherent structures of Alfvén wave in a collisional plasma

    International Nuclear Information System (INIS)

    Jana, Sayanee; Chakrabarti, Nikhil; Ghosh, Samiran

    2016-01-01

    The Alfvén wave dynamics is investigated in the framework of two-fluid approach in a compressible collisional magnetized plasma. In the finite amplitude limit, the dynamics of the nonlinear Alfvén wave is found to be governed by a modified Korteweg-de Vries Burgers equation (mKdVB). In this mKdVB equation, the electron inertia is found to act as a source of dispersion, and the electron-ion collision serves as a dissipation. The collisional dissipation is eventually responsible for the Burgers term in mKdVB equation. In the long wavelength limit, this weakly nonlinear Alfvén wave is shown to be governed by a damped nonlinear Schrödinger equation. Furthermore, these nonlinear equations are analyzed by means of analytical calculation and numerical simulation to elucidate the various aspects of the phase-space dynamics of the nonlinear wave. Results reveal that nonlinear Alfvén wave exhibits the dissipation mediated shock, envelope, and breather like structures. Numerical simulations also predict the formation of dissipative Alfvénic rogue wave, giant breathers, and rogue wave holes. These results are discussed in the context of the space plasma.

  9. Nonlinear coherent structures of Alfvén wave in a collisional plasma

    Energy Technology Data Exchange (ETDEWEB)

    Jana, Sayanee; Chakrabarti, Nikhil [Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700 064 (India); Ghosh, Samiran [Department of Applied Mathematics, University of Calcutta, 92, Acharya Prafulla Chandra Road, Kolkata 700 009 (India)

    2016-07-15

    The Alfvén wave dynamics is investigated in the framework of two-fluid approach in a compressible collisional magnetized plasma. In the finite amplitude limit, the dynamics of the nonlinear Alfvén wave is found to be governed by a modified Korteweg-de Vries Burgers equation (mKdVB). In this mKdVB equation, the electron inertia is found to act as a source of dispersion, and the electron-ion collision serves as a dissipation. The collisional dissipation is eventually responsible for the Burgers term in mKdVB equation. In the long wavelength limit, this weakly nonlinear Alfvén wave is shown to be governed by a damped nonlinear Schrödinger equation. Furthermore, these nonlinear equations are analyzed by means of analytical calculation and numerical simulation to elucidate the various aspects of the phase-space dynamics of the nonlinear wave. Results reveal that nonlinear Alfvén wave exhibits the dissipation mediated shock, envelope, and breather like structures. Numerical simulations also predict the formation of dissipative Alfvénic rogue wave, giant breathers, and rogue wave holes. These results are discussed in the context of the space plasma.

  10. Importance of the content and localization of tyrosine residues for thyroxine formation within the N-terminal part of human thyroglobulin

    NARCIS (Netherlands)

    den Hartog, M. T.; Sijmons, C. C.; Bakker, O.; Ris-Stalpers, C.; de Vijlder, J. J.

    1995-01-01

    Thyroxine (T4) is formed by coupling of iodinated tyrosine residues within thyroglobulin (TG). In mature TG, some iodinated tyrosine residues are involved preferentially in T4 formation. In order to investigate the specific role of various tyrosine residues in T4 formation, N-terminal TG fragments

  11. Head-to-head comparison of BNP and IL-6 as markers of clinical and experimental heart failure: Superiority of BNP.

    Science.gov (United States)

    Birner, Christoph M; Ulucan, Coskun; Fredersdorf, Sabine; Rihm, Munhie; Löwel, Hannelore; Stritzke, Jan; Schunkert, Heribert; Hengstenberg, Christian; Holmer, Stephan; Riegger, Günter; Luchner, Andreas

    2007-11-01

    Activation of BNP and IL-6 are hallmarks of left ventricular (LV) dysfunction and congestive heart failure (CHF). To assess the relative activation of BNP and IL-6 in clinical and experimental heart failure, we performed a human study in which plasma N-terminal proBNP (NT-proBNP) and IL-6 were measured in a large group of patients in the chronic phase after myocardial infarction (MI) and an animal study in which LV gene expression of BNP and IL-6 was assessed in rapid ventricular pacing-induced heart failure. In the human study, NT-proBNP and IL-6 were measured by non-extracted, enzyme-linked immunoassay in 845 subjects (n=468 outpatients after MI, MONICA MI register Augsburg; and 377 siblings without MI, control). NT-proBNP (295+/-23pg/mL vs. CTRL 84+/-8, PNT-proBNP was significantly correlated with several cardiac structural and functional parameters (EF, LVMI, history of MI, CHF symptoms; all PNT-proBNP with a greater sensitivity, specificity, and ROC-area (85%, 88%, and 0.87, respectively) as compared to IL-6 (69%, 53%, and 0.67, respectively). In the animal study, IL-6 and BNP expression were both significantly elevated in CHF (both PBNP. In addition, BNP mRNA expression displayed a stronger inverse correlation with LV function (r=-0.74; Pheart failure but to a significantly lesser degree than that of BNP. Both the stronger expression of BNP and the better correlation with LV function provide the molecular basis for a diagnostic superiority of NT-proBNP in clinical LV dysfunction and heart failure.

  12. Detection of left ventricular enlargement and impaired systolic function with plasma N-terminal pro brain natriuretic peptide concentrations

    DEFF Research Database (Denmark)

    Grønning, Bjørn Aaris; Nilsson, Jens C.; Søndergaard, Lars

    2002-01-01

    overlap in the range of plasma levels between healthy subjects and subjects with heart failure. We hypothesized that imprecision of the reference method (ie, the echocardiographic evaluation of left ventricular [LV] function) may have affected results from those earlier studies. We therefore wanted...... to investigate the diagnostic potential of NT-proBNP with magnetic resonance imaging as the reference method for the cardiac measurements. METHODS: Forty-eight patients with stable symptomatic heart failure in New York Heart Association functional classifications II to IV were examined once with blood samples...

  13. The interaction between fishbone modes and shear Alfvén waves in tokamak plasmas

    Science.gov (United States)

    He, Hongda; Liu, Yueqiang; Dong, J. Q.; Hao, G. Z.; Wu, Tingting; He, Zhixiong; Zhao, K.

    2016-05-01

    The resonant interaction between the energetic particle triggered fishbone mode and the shear Alfvén waves is computationally investigated and firmly demonstrated based on a tokamak plasma equilibrium, using the self-consistent MHD-kinetic hybrid code MARS-K (Liu et al 2008 Phys. Plasmas 15 112503). This type of continuum resonance, occurring critically due to the mode’s toroidal rotation in the plasma frame, significantly modifies the eigenmode structure of the fishbone instability, by introducing two large peaks of the perturbed parallel current density near but offside the q  =  1 rational surface (q is the safety factor). The self-consistently computed radial plasma displacement substantially differs from that being assumed in the conventional fishbone theory.

  14. Plasma proteomic changes during hypothermic and normothermic cardiopulmonary bypass in aortic surgeries.

    Science.gov (United States)

    Oda, Teiji; Yamaguchi, Akane; Yokoyama, Masao; Shimizu, Koji; Toyota, Kosaku; Nikai, Tetsuro; Matsumoto, Ken-Ichi

    2014-10-01

    Deep hypothermic circulatory arrest (DHCA) is a protective method against brain ischemia in aortic surgery. However, the possible effects of DHCA on the plasma proteins remain to be determined. In the present study, we used novel high‑throughput technology to compare the plasma proteomes during DHCA (22˚C) with selective cerebral perfusion (SCP, n=7) to those during normothermic cardiopulmonary bypass (CPB, n=7). Three plasma samples per patient were obtained during CPB: T1, prior to cooling; T2, during hypothermia; T3, after rewarming for the DHCA group and three corresponding points for the normothermic group. A proteomic analysis was performed using isobaric tag for relative and absolute quantification (iTRAQ) labeling tandem mass spectrometry to assess quantitative protein changes. In total, the analysis identified 262 proteins. The bioinformatics analysis revealed a significant upregulation of complement activation at T2 in normothermic CPB, which was suppressed in DHCA. These findings were confirmed by the changes of the terminal complement complex (SC5b‑9) levels. At T3, however, the level of SC5b‑9 showed a greater increase in DHCA compared to normothermic CPB, while 48 proteins were significantly downregulated in DHCA. The results demonstrated that DHCA and rewarming potentially exert a significant effect on the plasma proteome in patients undergoing aortic surgery.

  15. Characterization of cDNA for human tripeptidyl peptidase II: The N-terminal part of the enzyme is similar to subtilisin

    International Nuclear Information System (INIS)

    Tomkinson, B.; Jonsson, A-K

    1991-01-01

    Tripeptidyl peptidase II is a high molecular weight serine exopeptidase, which has been purified from rat liver and human erythrocytes. Four clones, representing 4453 bp, or 90% of the mRNA of the human enzyme, have been isolated from two different cDNA libraries. One clone, designated A2, was obtained after screening a human B-lymphocyte cDNA library with a degenerated oligonucleotide mixture. The B-lymphocyte cDNA library, obtained from human fibroblasts, were rescreened with a 147 bp fragment from the 5' part of the A2 clone, whereby three different overlapping cDNA clones could be isolated. The deduced amino acid sequence, 1196 amino acid residues, corresponding to the longest open rading frame of the assembled nucleotide sequence, was compared to sequences of current databases. This revealed a 56% similarity between the bacterial enzyme subtilisin and the N-terminal part of tripeptidyl peptidase II. The enzyme was found to be represented by two different mRNAs of 4.2 and 5.0 kilobases, respectively, which probably result from the utilziation of two different polyadenylation sites. Futhermore, cDNA corresponding to both the N-terminal and C-terminal part of tripeptidyl peptidase II hybridized with genomic DNA from mouse, horse, calf, and hen, even under fairly high stringency conditions, indicating that tripeptidyl peptidase II is highly conserved

  16. Aspectos éticos de la fase terminal Ethical aspects of terminal phase care

    Directory of Open Access Journals (Sweden)

    Oscar Velásquez

    1993-02-01

    Full Text Available

    Partiendo de una definición de la ética en general, de la ética médica y de la bioética, el autor discute estos conceptos en cuanto se relacionan con la atención del paciente en fase terminal, así como los temas de la muerte, el sufrimiento y los sentimientos que despierta el saberse moribundo. Hace énfasis en las relaciones médico-paciente y médico-familla y en los valores éticos de la igualdad y la reciprocidad. Plantea cómo a menudo el médico carece de una actitud correcta frente al paciente terminal y propone guías para el trabajo médico en tales circunstancias. Destaca la necesidad de respetar en todo momento la autonomía y la dignidad del enfermo y de saber usar con sabiduría los recursos tecnológicos disponibles.

     

    The author starts with definitions of ethics, medical ethics and bioethics and discusses their relationship with terminal patient care; also discussed are the subjects of death, suffering and the feelings that appear with the selfawareness of being near-death. Emphasis Is given on both patient-physician and family-physician relationships and on the values of equality and reciprocity. Guidelines are proposed for the approach and medical care of terminal patients and their families; they deal mainly with the need to respect autonomy and dignity and with the wise use of technological advances presently available.

     

  17. 33 CFR 334.450 - Cape Fear River and tributaries at Sunny Point Army Terminal, Brunswick County, N.C.; restricted...

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Cape Fear River and tributaries... AND RESTRICTED AREA REGULATIONS § 334.450 Cape Fear River and tributaries at Sunny Point Army Terminal, Brunswick County, N.C.; restricted area. (a) The area. That portion of Cape Fear River due west of the main...

  18. Plasma-assisted Molecular Beam Epitaxy of N-polar InAlN-barrier High-electron-mobility Transistors.

    Science.gov (United States)

    Hardy, Matthew T; Storm, David F; Katzer, D Scott; Downey, Brian P; Nepal, Neeraj; Meyer, David J

    2016-11-24

    Plasma-assisted molecular beam epitaxy is well suited for the epitaxial growth of III-nitride thin films and heterostructures with smooth, abrupt interfaces required for high-quality high-electron-mobility transistors (HEMTs). A procedure is presented for the growth of N-polar InAlN HEMTs, including wafer preparation and growth of buffer layers, the InAlN barrier layer, AlN and GaN interlayers and the GaN channel. Critical issues at each step of the process are identified, such as avoiding Ga accumulation in the GaN buffer, the role of temperature on InAlN compositional homogeneity, and the use of Ga flux during the AlN interlayer and the interrupt prior to GaN channel growth. Compositionally homogeneous N-polar InAlN thin films are demonstrated with surface root-mean-squared roughness as low as 0.19 nm and InAlN-based HEMT structures are reported having mobility as high as 1,750 cm 2 /V∙sec for devices with a sheet charge density of 1.7 x 10 13 cm -2 .

  19. Real time ellipsometry for monitoring plasma-assisted epitaxial growth of GaN

    Energy Technology Data Exchange (ETDEWEB)

    Bruno, Giovanni [Institute of Inorganic Methodologies and of Plasmas, IMIP-CNR and INSTM UdR Bari, via Orabona, 4, 70126 Bari (Italy); Losurdo, Maria [Institute of Inorganic Methodologies and of Plasmas, IMIP-CNR and INSTM UdR Bari, via Orabona, 4, 70126 Bari (Italy)]. E-mail: maria.losurdo@ba.imip.cnr.it; Giangregorio, Maria M. [Institute of Inorganic Methodologies and of Plasmas, IMIP-CNR and INSTM UdR Bari, via Orabona, 4, 70126 Bari (Italy); Capezzuto, Pio [Institute of Inorganic Methodologies and of Plasmas, IMIP-CNR and INSTM UdR Bari, via Orabona, 4, 70126 Bari (Italy); Brown, April S. [Department of Electrical and Computer Engineering, Duke University, 128 Hudson Hall, Durham, NC (United States); Kim, Tong-Ho [Department of Electrical and Computer Engineering, Duke University, 128 Hudson Hall, Durham, NC (United States); Choi, Soojeong [Department of Electrical and Computer Engineering, Duke University, 128 Hudson Hall, Durham, NC (United States)

    2006-10-31

    GaN is grown on Si-face 4H-SiC(0 0 0 1) substrates using remote plasma-assisted methods including metalorganic chemical vapour deposition (RP-MOCVD) and molecular beam epitaxy (MBE). Real time spectroscopic ellipsometry is used for monitoring all the steps of substrate pre-treatments and the heteroepitaxial growth of GaN on SiC. Our characterization emphasis is on understanding the nucleation mechanism and the GaN growth mode, which depend on the SiC surface preparation.

  20. Investigating the DNA-binding ability of GATA-1-N-terminal zinc finger

    International Nuclear Information System (INIS)

    Wong, R.; Newton, A.; Crossley, M.; Mackay, J.

    2001-01-01

    Erythroid transcription factor GATA-1 interacts with both DNA and other proteins through its zinc finger domains (ZnFs). While it has been known for me time that the C-terminal ZnF binds DNA at GATA sites, only recently has it been observed that the N-terminal finger (NF) is capable of interacting with GATC sites. Further, a number of naturally occurring mutations in NF (V205M, G208S, R216Q, D218G) that lead to anaemia and thrombocytopenia have been identified. We are interested in characterising the NF-DNA interaction and determining the effects of mutation upon this interaction. Using nuclear magnetic resonance (NMR) spectroscopy, we have observed an interaction between recombinant NF and a 16-mer DNA duplex containing a core GATC sequence. This result forms the basis from which residues in NF involved in DNA binding can be identified, and work is being carried out to improve the quality of the NMR data with the aim of determining the solution structure of the NF-DNA complex. The DNA-binding affinity of both wild-type and mutant NFs mentioned above is also being investigated using isothermal titration calorimetry. These data suggest that the strength of the interaction between NF and the 16-mer DNA duplex is in the sub-micromolar range, and comparisons between the DNA-binding affinities of the NF mutants are being made. Together, these studies will help us to understand how GATA-1 acts as a transcriptional regulator and how mutations in NF domain of GATA-1 may lead to blood disorders

  1. Basic amino acid residues located in the N-terminal region of BEND3 are essential for its nuclear localization

    Energy Technology Data Exchange (ETDEWEB)

    Shiheido, Hirokazu, E-mail: shiheido@ak.med.kyoto-u.ac.jp; Shimizu, Jun

    2015-02-20

    BEN domain-containing protein 3 (BEND3) has recently been reported to function as a heterochromatin-associated protein in transcriptional repression in the nucleus. BEND3 should have nuclear localization signals (NLSs) to localize to the nucleus in light of its molecular weight, which is higher than that allowed to pass through nuclear pore complexes. We here analyzed the subcellular localization of deletion/site-directed mutants of human BEND3 by an immunofluorescence assay in an attempt to identify the amino acids essential for its nuclear localization. We found that three basic amino acid residues located in the N-terminal region of BEND3 (BEND3{sub 56–58}, KRK) are essential, suggesting that these residues play a role as a functional NLS. These results provide valuable information for progressing research on BEND3. - Highlights: • BEND3 localizes to the nucleus. • The N-terminal 60 amino acids region of BEND3 contains NLS. • Amino acids located between 56 and 58 of BEND3 (KRK) are part of NLS. • KRK motif is highly conserved among BEND3 homologs.

  2. The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing

    Science.gov (United States)

    Fang, Qing; Indzhykulian, Artur A; Mustapha, Mirna; Riordan, Gavin P; Dolan, David F; Friedman, Thomas B; Belyantseva, Inna A; Frolenkov, Gregory I; Camper, Sally A; Bird, Jonathan E

    2015-01-01

    The precise assembly of inner ear hair cell stereocilia into rows of increasing height is critical for mechanotransduction and the sense of hearing. Yet, how the lengths of actin-based stereocilia are regulated remains poorly understood. Mutations of the molecular motor myosin 15 stunt stereocilia growth and cause deafness. We found that hair cells express two isoforms of myosin 15 that differ by inclusion of an 133-kDa N-terminal domain, and that these isoforms can selectively traffic to different stereocilia rows. Using an isoform-specific knockout mouse, we show that hair cells expressing only the small isoform remarkably develop normal stereocilia bundles. However, a critical subset of stereocilia with active mechanotransducer channels subsequently retracts. The larger isoform with the 133-kDa N-terminal domain traffics to these specialized stereocilia and prevents disassembly of their actin core. Our results show that myosin 15 isoforms can navigate between functionally distinct classes of stereocilia, and are independently required to assemble and then maintain the intricate hair bundle architecture. DOI: http://dx.doi.org/10.7554/eLife.08627.001 PMID:26302205

  3. Involvement of the N-terminal part of cyclophilin B in the interaction with specific Jurkat T-cell binding sites.

    Science.gov (United States)

    Mariller, C; Haendler, B; Allain, F; Denys, A; Spik, G

    1996-07-15

    Cyclophilin B (CyPB) is secreted in biological fluids such as blood or milk and binds to a specific receptor present on the human lymphoblastic cell line Jurkat and on human peripheral blood lymphocytes. This study was intended to specify the areas of CyPB that are involved in the interaction with the receptor. A synthetic peptide corresponding to the first 24 N-terminal amino acid residues of CyPB was shown to specifically recognize the receptor. Moreover, modification of Arg18 of CyPB by p-hydroxyphenlglyoxal led to a dramatic loss of affinity for the receptor. However, when this residue was replaced by an alanine residue using site-directed mutagenesis, no modification of the binding properties was found, suggesting that Arg18 is not directly involved but is sufficiently close to the interaction site to interfere with the binding when modified. Competitive binding experiments using a chimaeric protein made up of the 24 N-terminal amino acid residues of CyPB fused to the cyclophilin A core sequence confirmed the involvement of this region of CyPB in receptor binding.

  4. Power absorption and confinement studies of ICRF-heated plasma in JIPP T-IIU tokamak

    International Nuclear Information System (INIS)

    Ida, K.; Ogawa, Y.; Toi, K.

    1988-08-01

    The energy confinement characteristics of ICRF-heated tokamak plasmas are studied at high input power density ∼ 2 MWm -3 volume averaged, on the JIPP T-IIU device(R = 0.91 m/a = 0.23 m). High electron and ion temperatures (T e ∼ 2.5 keV, T i ∼ 2.0 keV, at each maximum) have been achieved by the operation at a plasma current I P of 280 kA, plasma line-averaged electron density n-bar e of 7 x 10 13 cm -3 and input power of 2 MW, with a suppression of total radiation loss (30 to 40 % of the total input power) by a carbon coating on the vacuum vessel. The fraction of ICRF power absorbed by the plasma, α, is determined experimentally from the decay of the stored plasma energy just after the ICRF pulse is terminated. The value of α increases slightly with increasing electron density and decreases from 90 to 70 % as the ICRF power is increased from 1 MWm -3 to 2 MWm -3 volume averaged. The global energy confinement time τ E , defined by W P /(P OH + αP rf ), decreases by a factor of 2 ∼ 3 from that in ohmic plasmas as the heating power increases up to 2 MW. It is found that the energy confinement time has a strong line-averaged electron density dependence as τ E ∝n-bar e 0.6 , which is obtained by the use of the measured absorbed power, while the Kaye-Goldston scaling predicts τ E ∝n-bar e 0.26 . (author)

  5. Plasma cleaning and analysis of archeological artefacts from Sipán

    Science.gov (United States)

    Saettone, E. A. O.; da Matta, J. A. S.; Alva, W.; Chubaci, J. F. O.; Fantini, M. C. A.; Galvão, R. M. O.; Kiyohara, P.; Tabacniks, M. H.

    2003-04-01

    A novel procedure using plasma sputtering in an electron-cyclotron-resonance device has been applied to clean archeological MOCHE artefacts, unearthed at the Royal Tombs of Sipán. After successful cleaning, the pieces were analysed by a variety of complementary techniques, namely proton-induced x-ray emission, Rutherford backscattering spectroscopy, x-ray diffraction, electron microscopy, and inductively coupled plasma mass spectroscopy. With these techniques, it has been possible to not only determine the profiles of the gold and silver surface layers, but also to detect elements that may be relevant to explain the gilding techniques skillfully developed by the metal smiths of the MOCHE culture.

  6. Mortalité néonatale précoce et ses déterminants dans une maternité ...

    African Journals Online (AJOL)

    Introduction: Le but de ce travail était de déterminer les facteurs de risque de la mortalité néonatale dans une maternité de niveau I. Méthodes: Il s'agissait d'une étude de cohorte rétrospective qui s'est déroulée d'Août 2007 à Janvier 2008 au Centre d'Animation Sociale et Sanitaire (CASS) de Nkoldongo à Yaoundé.

  7. Plasma Discharge Process in a Pulsed Diaphragm Discharge System

    Science.gov (United States)

    Duan, Jianjin; Hu, Jue; Zhang, Chao; Wen, Yuanbin; Meng, Yuedong; Zhang, Chengxu

    2014-12-01

    As one of the most important steps in wastewater treatment, limited study on plasma discharge process is a key challenge in the development of plasma applications. In this study, we focus on the plasma discharge process of a pulsed diaphragm discharge system. According to the analysis, the pulsed diaphragm discharge proceeds in seven stages: (1) Joule heating and heat exchange stage; (2) nucleated site formation; (3) plasma generation (initiation of the breakdown stage); (4) avalanche growth and plasma expansion; (5) plasma contraction; (6) termination of the plasma discharge; and (7) heat exchange stage. From this analysis, a critical voltage criterion for breakdown is obtained. We anticipate this finding will provide guidance for a better application of plasma discharges, especially diaphragm plasma discharges.

  8. Crystal Structure of the N-Terminal Half of the Traffic Controller UL37 from Herpes Simplex Virus 1

    Energy Technology Data Exchange (ETDEWEB)

    Koenigsberg, Andrea L.; Heldwein, Ekaterina E.; Sandri-Goldin, Rozanne M.

    2017-08-02

    Inner tegument protein UL37 is conserved among all three subfamilies of herpesviruses. Studies of UL37 homologs from two alphaherpesviruses, herpes simplex virus 1 (HSV-1) and pseudorabies virus (PRV), have suggested that UL37 plays an essential albeit poorly defined role in intracellular capsid trafficking. At the same time, HSV and PRV homologs cannot be swapped, which suggests that in addition to a conserved function, UL37 homologs also have divergent virus-specific functions. Accurate dissection of UL37 functions requires detailed maps in the form of atomic-resolution structures. Previously, we reported the crystal structure of the N-terminal half of UL37 (UL37N) from PRV. Here, we report the crystal structure of HSV-1 UL37N. Comparison of the two structures reveals that UL37 homologs differ in their overall shapes, distributions of surface charges, and locations of projecting loops. In contrast, the previously identified R2 surface region is structurally conserved. We propose that within the N-terminal half of UL37, functional conservation is centered within the R2 surface region, whereas divergent structural elements pinpoint regions mediating virus-specific functions and may engage different binding partners. Together, the two structures can now serve as templates for a structure-guided exploration of both conserved and virus-specific functions of UL37.

    IMPORTANCEThe ability to move efficiently within host cell cytoplasm is essential for replication in all viruses. It is especially important in the neuroinvasive alphaherpesviruses, such as human herpes simplex virus 1 (HSV-1), HSV-2, and veterinarian pseudorabies virus (PRV), that infect the peripheral nervous system and have to travel long distances along axons. Capsid movement in these viruses is controlled by capsid-associated tegument proteins, yet their specific roles have not yet been defined. Systematic exploration of the roles of tegument proteins in capsid trafficking requires

  9. Farelo da vagem de algaroba associado a níveis de ureia na alimentação de ovinos: balanço de nitrogênio, N-ureico no plasma e parâmetros ruminais=Mesquite pod meal associated with levels of urea on feeding sheep: nitrogen balance, plasma urea-N and ruminal parameters

    Directory of Open Access Journals (Sweden)

    João Gonsalves Neto

    2012-07-01

    Full Text Available Objetivou-se neste trabalho avaliar os efeitos da inclusão de ureia em dietas contendo farelo da vagem de algaroba sobre o balanço de nitrogênio, N-ureico no plasma e parâmetros ruminais em ovinos. Foram utilizados oito animais, machos castrados, com peso médio de 33,5 kg, distribuídos em dois quadrados latinos 4 x 4. Os tratamentos constituíram da inclusão de níveis de ureia na dieta, sendo: 0; 0,5; 1,0 e 1,5% da MS total. A dieta foi fornecida como dieta total na relação volumoso:concentrado de 40:60 com base na MS total da dieta. Foi realizada a coleta total de urina e fezes e determinada a excreção de nitrogênio. Foi coletado sangue, seguido com a extração do plasma e determinação do N-ureico. Para avaliação do pH e N-amoniacal no líquido ruminal foram utilizados quatro animais fistulados no rúmen. A ingestão de N (31,68 g dia-1 e perdas vias fecal (7,94 g dia-1 e urinária (9,95 g dia-1 não sofreram alterações. As concentrações de N-amoniacal e N-ureico no plasma aumentaram de forma linear. O pH ruminal foi semelhante entre os tratamentos. A inclusão de ureia não influencia o balanço de nitrogênio, porém eleva as concentrações de N-amoniacal no rúmen e N-ureico no plasma podendo influenciar o gasto de energia no organismo.The goal of this study was to evaluate the effects of including urea in diets containing mesquite pod meal on nitrogen balance, plasma urea-N and ruminal parameters. Eight gelded males, with mean weight of 33.5 kg, were divided into two 4 x 4 Latin squares. Treatments consisted of following urea levels in diet: 0, 0.5, 1.0 and 1.5% of total dry matter. The diet was provided as total diet a 40:60 forage: concentrate ratio based on total diet DM. Total urine and feces were collected and nitrogen excretion was determined. Blood was collected, followed by plasma extraction and quantification of urea nitrogen. To evaluate pH and ammonia-N in rumen fluid, four rumen fistulated animals were

  10. Improving the secretion of a methyl parathion hydrolase in Pichia pastoris by modifying its N-terminal sequence.

    Directory of Open Access Journals (Sweden)

    Ping Wang

    Full Text Available Pichia pastoris is commonly used to express and secrete target proteins, although not all recombinant proteins can be successfully produced. In this study, we used methyl parathion hydrolase (MPH from Ochrobactrum sp. M231 as a model to study the importance of the N-terminus of the protein for its secretion. While MPH can be efficiently expressed intracellularly in P. pastoris, it is not secreted into the extracellular environment. Three MPH mutants (N66-MPH, D10-MPH, and N9-MPH were constructed through modification of its N-terminus, and the secretion of each by P. pastoris was improved when compared to wild-type MPH. The level of secreted D10-MPH was increased to 0.21 U/mL, while that of N9-MPH was enhanced to 0.16 U/mL. Although N66-MPH was not enzymatically active, it was secreted efficiently, and was identified by SDS-PAGE. These results demonstrate that the secretion of heterologous proteins in P. pastoris may be improved by modifying their N-terminal structures.

  11. Inhibition and labeling of the plant plasma membrane H+-ATPase with N-ethylmaleimide

    International Nuclear Information System (INIS)

    Katz, D.B.; Sussman, M.R.

    1987-01-01

    H + -ATPase activity in plasma membranes isolated from Avena sativa root cells is inhibited by N-ethylmaleimide, a covalent modifier of protein sulfhydryl groups. The rate of inhibition is reduced by ADP, MgADP, and MgATP, but even at 40 millimolar ADP the enzyme is only partially protected against inactivation. When plasma membranes are treated with N-[2- 3 H]ethylmaleimide and analyzed by sodium dodecyl sulfate polyaerylamide gel electrophoresis, prominent radioactive bands appear at M/sub r/ = 100,000 and several other positions. However, only radioactivity in the M/sub r/ = 100,000 protein is reduced by the presence of MgADP. These results provide independent evidence that the M/sub r/ = 100,000 polypeptide which is observed in purified preparations of the enzyme is the catalytic subunit of the H + -ATPase. When tryptic peptides are produced from N-[2- 3 H]ethylmaleimide labeled M/sub r/ = 100,000 protein and separated by reverse phase high performance liquid chromatography, two radioactive peaks are observed for which N-[2- 3 H]ethylmaleimide incorporation is reduced in the presence of MgADP

  12. Calidad del plasma rico en plaquetas: estudio de la activación plaquetaria Platelet-rich plasma quality: a study on platelet activation

    Directory of Open Access Journals (Sweden)

    C. Sáez-Torres Barroso

    2007-08-01

    Full Text Available Objetivo. El plasma rico en plaquetas (PRP es utilizado de forma cada vez más frecuente en técnicas quirúrgicas de regeneración tisular. No obstante, el procesamiento de la sangre hasta obtener PRP puede desencadenar la activación prematura de las plaquetas y la pérdida de los factores bioactivos. En este trabajo estudiamos la calidad de los concentrados de plaquetas obtenidos siguiendo la técnica de doble centrifugación en tubo. Método. Se someten 50 ml de sangre a una primera centrifugación a 200g 10 minutos, se recoge el sobrenadante y se centrifuga a 700g 15 minutos. Posteriormente, tras eliminar las 2/3 partes del plasma, se resuspenden las plaquetas y se analiza el grado de enriquecimiento, el estado de activación y la reserva funcional de las plaquetas. Resultados. El enriquecimiento en plaquetas del PRP fue de 364±177% (n=45 respecto de los niveles presentes en sangre total. Mediante el estudio de la expresión de CD62 por citometría de flujo se determinó el porcentaje de plaquetas activadas en las muestras de 8 donantes. Mientras que en la sangre no procesada se detectó un 2,7% de plaquetas activadas, tras la preparación del PRP éste era sólo de 3,6%, aumentando hasta el 16% en el concentrado almacenado toda la noche a 22º C. Tras la estimulación con trombina el porcentaje de plaquetas activadas fue de 96,2%. Conclusión. Este protocolo de preparación de PRP no produce una activación significativa de las plaquetas. La respuesta a la estimulación con trombina de los concentrados indica un buen estado de reserva plaquetaria.Objective. Platelet Rich Plasma (PRP is an autologous preparation currently used in oral and maxillofacial reconstructive surgery. Blood collection and preparation of platelet concentrates may lead to platelet activation and the premature loss of their granular load. In this study, we have analyzed the quality of the PRP obtained from a small volume of whole blood through a double centrifugation

  13. The N-terminal tropomyosin- and actin-binding sites are important for leiomodin 2's function.

    Science.gov (United States)

    Ly, Thu; Moroz, Natalia; Pappas, Christopher T; Novak, Stefanie M; Tolkatchev, Dmitri; Wooldridge, Dayton; Mayfield, Rachel M; Helms, Gregory; Gregorio, Carol C; Kostyukova, Alla S

    2016-08-15

    Leiomodin is a potent actin nucleator related to tropomodulin, a capping protein localized at the pointed end of the thin filaments. Mutations in leiomodin-3 are associated with lethal nemaline myopathy in humans, and leiomodin-2-knockout mice present with dilated cardiomyopathy. The arrangement of the N-terminal actin- and tropomyosin-binding sites in leiomodin is contradictory and functionally not well understood. Using one-dimensional nuclear magnetic resonance and the pointed-end actin polymerization assay, we find that leiomodin-2, a major cardiac isoform, has an N-terminal actin-binding site located within residues 43-90. Moreover, for the first time, we obtain evidence that there are additional interactions with actin within residues 124-201. Here we establish that leiomodin interacts with only one tropomyosin molecule, and this is the only site of interaction between leiomodin and tropomyosin. Introduction of mutations in both actin- and tropomyosin-binding sites of leiomodin affected its localization at the pointed ends of the thin filaments in cardiomyocytes. On the basis of our new findings, we propose a model in which leiomodin regulates actin poly-merization dynamics in myocytes by acting as a leaky cap at thin filament pointed ends. © 2016 Ly, Moroz, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  14. The conserved residue Arg46 in the N-terminal heptad repeat domain of HIV-1 gp41 is critical for viral fusion and entry.

    Directory of Open Access Journals (Sweden)

    Xiaoyi Wang

    Full Text Available During the process of HIV-1 fusion with the target cell, the N-terminal heptad repeat (NHR of gp41 interacts with the C-terminal heptad repeat (CHR to form fusogenic six-helix bundle (6-HB core. We previously identified a crucial residue for 6-HB formation and virus entry--Lys63 (K63 in the C-terminal region of NHR (aa 54-70, which forms a hydrophobic cavity. It can form an important salt bridge with Asp121 (D121 in gp41 CHR. Here, we found another important conserved residue for virus fusion and entry, Arg46 (R46, in the N-terminal region of NHR (aa 35-53, which forms a hydrogen bond with a polar residue, Asn43 (N43, in NHR, as a part of the hydrogen-bond network. R46 can also form a salt bridge with a negatively charged residue, Glu137 (E137, in gp41 CHR. Substitution of R46 with the hydrophobic residue Ala (R46A or the negatively charged residue Glu (R46E resulted in disruption of the hydrogen bond network, breakage of the salt bridge and reduction of 6-HB's stability, leading to impairment of viral fusion and decreased inhibition of N36, an NHR peptide. Similarly, CHR peptide C34 with substitution of E137 for Ala (E137A or Arg (E137R also exhibited reduced inhibitory activity against HIV-1 infection and HIV-1-mediated cell-to-cell fusion. These results suggest that the positively charged residue R46 and its hydrogen bond network, together with the salt bridge between R46 and E137, are important for viral fusion and entry and may therefore serve as a target for designing novel HIV fusion/entry inhibitors.

  15. Immunological and protective effects of Bordetella bronchiseptica subunit vaccines based on the recombinant N-terminal domain of dermonecrotic toxin.

    Science.gov (United States)

    Wang, Chuanwen; Liu, Liping; Zhang, Zhen; Yan, Zhengui; Yu, Cuilian; Shao, Mingxu; Jiang, Xiaodong; Chi, Shanshan; Wei, Kai; Zhu, Ruiliang

    2015-10-01

    Dermonecrotic toxin (DNT) produced by Bordetella bronchiseptica (B. bronchiseptica) can cause clinical turbinate atrophy in swine and induce dermonecrotic lesions in model mice. We know that the N-terminal of DNT molecule contains the receptor-binding domain, which facilitates binding to the target cells. However, we do not know whether this domain has sufficient immunogenicity to resist B. bronchiseptica damage and thereby to develop a subunit vaccine for the swine industry. In this study, we prokaryotically expressed the recombinant N-terminal of DNT from B. bronchiseptica (named DNT-N) and prepared it for the subunit vaccine to evaluate its immunogenicity. Taishan Pinus massoniana pollen polysaccharide (TPPPS), a known immunomodulator, was used as the adjuvant to examine its immune-conditioning effects. At 49 d after inoculation, 10 mice from each group were challenged with B. bronchiseptica, and another 10 mice were intradermally challenged with native DNT, to examine the protection imparted by the vaccines. The immune parameters (T-lymphocyte counts, cytokine secretions, serum antibody titers, and survival rates) and skin lesions were determined. The results showed that pure DNT-N vaccine significantly induced immune responses and had limited ability to resist the B. bronchiseptica and DNT challenge, whereas the mice administered with TPPPS or Freund's incomplete adjuvant vaccine could induce higher levels of the above immune parameters. Remarkably, the DNT-N vaccine combined with TPPPS adjuvant protected the mice effectively to prevent B. bronchiseptica infection. Our findings indicated that DNT-N has potential for development as an effective subunit vaccine to counteract the damage of B. bronchiseptica infection, especially when used conjointly with TPPPS. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. 78 FR 69991 - Advisory Committee; Veterinary Medicine Advisory Committee; Termination

    Science.gov (United States)

    2013-11-22

    .... FDA-2013-N-1380] Advisory Committee; Veterinary Medicine Advisory Committee; Termination AGENCY: Food... announcing the termination of the Veterinary Medicine Advisory Committee. This document removes the Veterinary Advisory Committee from the Agency's list of standing advisory committees. DATES: This rule is...

  17. Reduction of buffer layer conduction near plasma-assisted molecular-beam epitaxy grown GaN/AlN interfaces by beryllium doping

    International Nuclear Information System (INIS)

    Storm, D.F.; Katzer, D.S.; Binari, S.C.; Glaser, E.R.; Shanabrook, B.V.; Roussos, J.A.

    2002-01-01

    Beryllium doping of epitaxial GaN layers is used to reduce leakage currents through interfacial or buffer conducting layers grown by plasma-assisted molecular-beam epitaxy on SiC. Capacitance-voltage measurements of Schottky barrier test structures and dc pinch-off characteristics of unintentionally doped GaN high-electron-mobility transistors indicate that these leakage currents are localized near the GaN/AlN interface of our AlGaN/GaN/AlN device structures. Insertion of a 2000 Aa Be:GaN layer at the interface reduces these currents by three orders of magnitude

  18. Recubrimientos protectores para componentes de turbinas de aviación y de generación de energía depositados por proyección por plasma

    Directory of Open Access Journals (Sweden)

    Agüero Bruna, A.

    2000-08-01

    Full Text Available Coatings produced by aluminium diffusion, called aluminide are employed to increase the oxidation and corrosion resistance, increasing the life of Ni and Co base superalloys components at temperatures comprised between 900 and 1050ºC. Consequently these coatings are frequently employed in aeronautic and power generation turbines as well as in the chemical industry. Aluminides are industrially produced by pack cementation or CVD and recently it has been demonstrated that its resistance significantly increases when Cr is added (chrome-aluminides. During this work, a feasibility study has been carried out in order to determine if plasma spray can be employed for depositing this type of coatings on turbine blades. Therefore, aluminium and aluminium/chromium layers were deposited on Ni base IN100 superalloy specimens that were subsequently subjected to a diffusion heat treatment under Ar flow. Characterisation and analysis of the coatings were carried out by metallography , SEM and EDS. Cyclic oxidation tests were carried out at 1050º C while molten sulphate hot corrosion was performed at 900º C. The results of this preliminary study are promising and indicate that plasma spray can be developed as an industrial process for production of aluminide and chrome-aluminide coatings.

    Los recubrimientos producidos por difusión de aluminio, llamados aluminuros, se emplean para aumentar la resistencia a la oxidación y a la corrosión, incrementando la vida de componentes fabricados con superaleaciones de níquel y cobalto a temperaturas comprendidas entre 900 y 1050º C. Por ello se emplean muy frecuentemente en turbinas aeronaúticas y de producción de energía y en la industria química. Los aluminuros se obtienen industrialmente mediante cementación o CVD y recientemente se ha demostrado que su resistencia aumenta significativamente cuando se añade cromo (cromoaluminuros. Durante el presente trabajo, se ha realizado un estudio de viabilidad

  19. A massagem terapêutica em idosos não comunicantes com doença terminal

    OpenAIRE

    Marques, Cândida Nunes Casimiro, 1957-

    2010-01-01

    Tese de mestrado, Cuidados Paliativos, Faculdade de Medicina, Universidade de Lisboa, 2011 Contexto: A dor é um sintoma comum nos idosos, principalmente nos acamados com doença terminal. Estes doentes estão geralmente polimedicados, pelo que a utilização de meios não farmacológicos como terapêutica complementar da dor poderá ser uma mais-valia no alívio desta sintomatologia. A massagem terapêutica é utilizada desde há milénios no alívio da dor, e é uma das técnicas aplicadas nestes doentes...

  20. Protección catódica en estructuras sumergidas. Aplicación al proyecto de boyas y tuberías de un terminal portuario de descarga de crudo.

    OpenAIRE

    Orell Regis, Aina Isabel

    2014-01-01

    Este proyecto tiene por objeto el diseño de la protección catódica contra la corrosión de las boyas y las tuberías sumergidas en agua de mar de un terminal portuario de descarga de crudo. La protección catódica consiste en la igualación de los potenciales de las áreas anódicas y catódicas del material por el flujo de electrones suministrado. En el proyecto se han empleado los métodos de ánodos de sacrificio y de corriente impresa para analizar la protección catódica más adecuada de cada compo...