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Sample records for alanine aminotransaminase alt

  1. ALT (Alanine Aminotransferase) Test

    MedlinePlus

    ... to help recognize heart or muscle injury. ALT values are often compared to the results of other tests such as alkaline phosphatase (ALP) , total protein , and bilirubin to help determine which form of liver disease is present. ALT is often used to monitor the treatment ...

  2. 21 CFR 862.1030 - Alanine amino transferase (ALT/SGPT) test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alanine amino transferase (ALT/SGPT) test system. 862.1030 Section 862.1030 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  3. 21 CFR 862.1030 - Alanine amino transferase (ALT/SGPT) test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Alanine amino transferase (ALT/SGPT) test system. 862.1030 Section 862.1030 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  4. 21 CFR 862.1030 - Alanine amino transferase (ALT/SGPT) test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Alanine amino transferase (ALT/SGPT) test system. 862.1030 Section 862.1030 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  5. 21 CFR 862.1030 - Alanine amino transferase (ALT/SGPT) test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Alanine amino transferase (ALT/SGPT) test system. 862.1030 Section 862.1030 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  6. 21 CFR 862.1030 - Alanine amino transferase (ALT/SGPT) test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Alanine amino transferase (ALT/SGPT) test system. 862.1030 Section 862.1030 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  7. PPAR{alpha} regulates the hepatotoxic biomarker alanine aminotransferase (ALT1) gene expression in human hepatocytes

    SciTech Connect

    Thulin, Petra; Rafter, Ingalill; Stockling, Kenneth; Tomkiewicz, Celine; Norjavaara, Ensio; Aggerbeck, Martine; Hellmold, Heike; Ehrenborg, Ewa; Andersson, Ulf; Cotgreave, Ian; Glinghammar, Bjoern

    2008-08-15

    In this work, we investigated a potential mechanism behind the observation of increased aminotransferase levels in a phase I clinical trial using a lipid-lowering drug, the peroxisome proliferator-activated receptor (PPAR) {alpha} agonist, AZD4619. In healthy volunteers treated with AZD4619, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were elevated without an increase in other markers for liver injury. These increases in serum aminotransferases have previously been reported in some patients receiving another PPAR{alpha} agonist, fenofibrate. In subsequent in vitro studies, we observed increased expression of ALT1 protein and mRNA in human hepatocytes after treatment with fenofibric acid. The PPAR effect on ALT1 expression was shown to act through a direct transcriptional mechanism involving at least one PPAR response element (PPRE) in the proximal ALT1 promoter, while no effect of fenofibrate and AZD4619 was observed on the ALT2 promoter. Binding of PPARs to the PPRE located at - 574 bp from the transcriptional start site was confirmed on both synthetic oligonucleotides and DNA in hepatocytes. These data show that intracellular ALT expression is regulated by PPAR agonists and that this mechanism might contribute to increased ALT activity in serum.

  8. Aspartate Aminotransferase (AST/GOT) and Alanine Aminotransferase (ALT/GPT) Detection Techniques

    PubMed Central

    Huang, Xing-Jiu; Choi, Yang-Kyu; Im, Hyung-Soon; Yarimaga, Oktay; Yoon, Euisik; Kim, Hak-Sung

    2006-01-01

    The levels of aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT) in serum can help people diagnose body tissues especially the heart and the liver are injured or not. This article provides a comprehensive review of research activities that concentrate on AST/GOT and ALT/GPT detection techniques due to their clinical importance. The detection techniques include colorimetric, spectrophotometric, chemiluminescence, chromatography, fluorescence and UV absorbance, radiochemical, and electrochemical techniques. We devote the most attention on experimental principle. In some methods a few representative devices and important conclusions are presented.

  9. Prevalence of elevated alanine-aminotransferase (ALT) among US adolescents and associated factors: NHANES 1999-2004

    PubMed Central

    Fraser, Abigail; Longnecker, Matthew P.; Lawlor, Debbie A

    2007-01-01

    Background & aims Non-alcoholic fatty liver disease (NAFLD) is a common cause of liver disease in children and adolescents. The majority of studies of NAFLD in children have been in select populations of the clinically obese. Study aims were to estimate the prevalence of elevated alanine-aminotransferase (ALT, as a marker of NAFLD) in a general contemporary adolescent population and to identify leading risk factors for ALT elevation (> 30 U/L). Methods We analysed data of adolescent participants (age 12-19, N=5586) in NHANES 1999-2004, a representative sample of the civilian non-institutionalized U.S population. Results The prevalence of elevated ALT (>30 U/L) was 7∙4% among white adolescents, 11∙5%, among Mexican Americans, and 6∙0%, among black adolescents. It was prevalent in 12∙4% of males compared to 3∙5% of females. Multivariable associations with elevated ALT were found for sex (OR male versus female = 7∙7, 95%CI: 3∙9, 15∙1), ethnicity (OR black versus white=0∙6, 95%CI: 0∙3, 1∙3; OR Mexican American versus white=1∙6, 95%CI: 1∙0, 2∙6), waist circumference (OR per 1 SD=1∙4, 95%CI: 1∙0, 2∙0), and fasting insulin (OR per 1 SD=1∙ 6, 95%CI: 1∙ 2, 2∙ 1). Age, C-reactive protein and triglycerides were also positively, and socio-economic position inversely associated with elevated ALT. The magnitude of associations with ALT was similar across ethnic groups. Conclusions ALT is associated with waist circumference and insulin resistance even in a young population. These characteristics could be utilized to identify adolescents who may benefit from screening for NAFLD, offering an opportunity to prevent disease progression at an early age. PMID:18054554

  10. LIMITED ELEVATIONS IN ANTITUBERCULOSIS DRUG-INDUCED SERUM ALANINE AMINOTRANSFERASE (ALT) LEVELS IN A COHORT OF NIGERIANS ON TREATMENT FOR PULMONARY TUBERCULOSIS AND HIV INFECTION IN YENAGOA.

    PubMed

    Ikuabe, Peter Ogie; Ebuenyi, Ikenna Desmond; Harry, Tubonye Clement

    2015-01-01

    This study, undertaken in a major tertiary hospital in the Niger Delta region of Nigeria was designed to examine the incidence of elevation in serum alanine aminotransference (ALT) in our patients who were on treatment for HIV/AIDS with some of them on antituberculosis drugs. Between January and December 2014, all admission records which include HIV status, Acid fast bacilli Status, Chest radiograph, CD4 cell count, degree of hepatotoxicity during antituberculosis drugs treatment according to WHO definition using clinical findings and ALT levels at baseline (ALTI) and at 4 weeks into treatment with antituberculosis drugs (ALT2) of all the patients on HAART with some on antituberculosis drugs were retrieved and retrospectively analyzed. Of the total of 707 patients on HAART, 80 were on both HAART and anti-tuberculosis treatment.There was a statistically significant correlation between ALT I levels in the PTB negative and PTB positive cohort at baseline χ2 10.725,d.f4,P = 0.030. After 4 weeks of antituberculosis treatment and HAART ALT2 level in expectedly, generally showed downward trend with no statistically significant correlation between PTB status and ALT2 (χ2 = 0.789, d.f2.P = 0.674) CONCLUSION: Anti-tuberculosis drug induced elevation in alanine amino transference is unexpectedly low in our patients on treatment for pulmonary tuberculosis and HIV infection. This is a key finding that requires further studies.

  11. Determination of Alanine Aminotransferase with an Electrochemical Nano Ir-C Biosensor for the Screening of Liver Diseases

    PubMed Central

    Hsueh, Chang-Jung; Wang, Joanne H.; Dai, Liming; Liu, Chung-Chiun

    2011-01-01

    Alanine aminotransaminase (ALT), is an enzyme that normally resides in serum and body tissues, especially in the liver. It is released into the serum as a result of tissue injury; hence the concentration of ALT in the serum may be increased with acute damage to hepatic cells. A single use, disposable biosensor, comprising iridium nano-particle as catalyst dispersed on carbon paste, has been developed for the determination of ALT concentration. The biosensor is based on quantifying H2O2 concentration produced by a serial of ALT enzymatic reactions. It operates well at room temperature in different physiological fluids: phosphate buffer, calf serum and human serum for ALT concentration of 0–544 ng/mL. Experimental results in human serum are compared to those obtained by spectrophotometric assays with excellent agreement. Therefore, the Ir/C biosensor shows good relationship on the dilution of concentrated ALT clinical applications. PMID:25586923

  12. Alanine transaminase (ALT) blood test

    MedlinePlus

    ... liver damage. Normal Results The normal range is: Male: 10 to 40 U/L Female: 7 to 35 U/L Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or may test different samples. Talk to your ...

  13. Paralogous ALT1 and ALT2 Retention and Diversification Have Generated Catalytically Active and Inactive Aminotransferases in Saccharomyces cerevisiae

    PubMed Central

    Peñalosa-Ruiz, Georgina; Aranda, Cristina; Ongay-Larios, Laura; Colon, Maritrini; Quezada, Hector; Gonzalez, Alicia

    2012-01-01

    Background Gene duplication and the subsequent divergence of paralogous pairs play a central role in the evolution of novel gene functions. S. cerevisiae possesses two paralogous genes (ALT1/ALT2) which presumably encode alanine aminotransferases. It has been previously shown that Alt1 encodes an alanine aminotransferase, involved in alanine metabolism; however the physiological role of Alt2 is not known. Here we investigate whether ALT2 encodes an active alanine aminotransferase. Principal Findings Our results show that although ALT1 and ALT2 encode 65% identical proteins, only Alt1 displays alanine aminotransferase activity; in contrast ALT2 encodes a catalytically inert protein. ALT1 and ALT2 expression is modulated by Nrg1 and by the intracellular alanine pool. ALT1 is alanine-induced showing a regulatory profile of a gene encoding an enzyme involved in amino acid catabolism, in agreement with the fact that Alt1 is the sole pathway for alanine catabolism present in S. cerevisiae. Conversely, ALT2 expression is alanine-repressed, indicating a role in alanine biosynthesis, although the encoded-protein has no alanine aminotransferase enzymatic activity. In the ancestral-like yeast L. kluyveri, the alanine aminotransferase activity was higher in the presence of alanine than in the presence of ammonium, suggesting that as for ALT1, LkALT1 expression could be alanine-induced. ALT2 retention poses the questions of whether the encoded protein plays a particular function, and if this function was present in the ancestral gene. It could be hypotesized that ALT2 diverged after duplication, through neo-functionalization or that ALT2 function was present in the ancestral gene, with a yet undiscovered function. Conclusions ALT1 and ALT2 divergence has resulted in delegation of alanine aminotransferase activity to Alt1. These genes display opposed regulatory profiles: ALT1 is alanine-induced, while ALT2 is alanine repressed. Both genes are negatively regulated by the Nrg1

  14. Evolutionary Diversification of Alanine Transaminases in Yeast: Catabolic Specialization and Biosynthetic Redundancy

    PubMed Central

    Escalera-Fanjul, Ximena; Campero-Basaldua, Carlos; Colón, Maritrini; González, James; Márquez, Dariel; González, Alicia

    2017-01-01

    Gene duplication is one of the major evolutionary mechanisms providing raw material for the generation of genes with new or modified functions. The yeast Saccharomyces cerevisiae originated after an allopolyploidization event, which involved mating between two different ancestral yeast species. ScALT1 and ScALT2 codify proteins with 65% identity, which were proposed to be paralogous alanine transaminases. Further analysis of their physiological role showed that while ScALT1 encodes an alanine transaminase which constitutes the main pathway for alanine biosynthesis and the sole pathway for alanine catabolism, ScAlt2 does not display alanine transaminase activity and is not involved in alanine metabolism. Moreover, phylogenetic studies have suggested that ScALT1 and ScALT2 come from each one of the two parental strains which gave rise to the ancestral hybrid. The present work has been aimed to the understanding of the properties of the ancestral type Lacchancea kluyveri LkALT1 and Kluyveromyces lactis KlALT1, alanine transaminases in order to better understand the ScALT1 and ScALT2 evolutionary history. These ancestral -type species were chosen since they harbor ALT1 genes, which are related to ScALT2. Presented results show that, although LkALT1 and KlALT1 constitute ScALT1 orthologous genes, encoding alanine transaminases, both yeasts display LkAlt1 and KlAlt1 independent alanine transaminase activity and additional unidentified alanine biosynthetic and catabolic pathway(s). Furthermore, phenotypic analysis of null mutants uncovered the fact that KlAlt1 and LkAlt1 have an additional role, not related to alanine metabolism but is necessary to achieve wild type growth rate. Our study shows that the ancestral alanine transaminase function has been retained by the ScALT1 encoded enzyme, which has specialized its catabolic character, while losing the alanine independent role observed in the ancestral type enzymes. The fact that ScAlt2 conserves 64% identity with LkAlt1

  15. Evolutionary Diversification of Alanine Transaminases in Yeast: Catabolic Specialization and Biosynthetic Redundancy.

    PubMed

    Escalera-Fanjul, Ximena; Campero-Basaldua, Carlos; Colón, Maritrini; González, James; Márquez, Dariel; González, Alicia

    2017-01-01

    Gene duplication is one of the major evolutionary mechanisms providing raw material for the generation of genes with new or modified functions. The yeast Saccharomyces cerevisiae originated after an allopolyploidization event, which involved mating between two different ancestral yeast species. ScALT1 and ScALT2 codify proteins with 65% identity, which were proposed to be paralogous alanine transaminases. Further analysis of their physiological role showed that while ScALT1 encodes an alanine transaminase which constitutes the main pathway for alanine biosynthesis and the sole pathway for alanine catabolism, ScAlt2 does not display alanine transaminase activity and is not involved in alanine metabolism. Moreover, phylogenetic studies have suggested that ScALT1 and ScALT2 come from each one of the two parental strains which gave rise to the ancestral hybrid. The present work has been aimed to the understanding of the properties of the ancestral type Lacchancea kluyveri LkALT1 and Kluyveromyces lactis KlALT1, alanine transaminases in order to better understand the ScALT1 and ScALT2 evolutionary history. These ancestral -type species were chosen since they harbor ALT1 genes, which are related to ScALT2. Presented results show that, although LkALT1 and KlALT1 constitute ScALT1 orthologous genes, encoding alanine transaminases, both yeasts display LkAlt1 and KlAlt1 independent alanine transaminase activity and additional unidentified alanine biosynthetic and catabolic pathway(s). Furthermore, phenotypic analysis of null mutants uncovered the fact that KlAlt1 and LkAlt1 have an additional role, not related to alanine metabolism but is necessary to achieve wild type growth rate. Our study shows that the ancestral alanine transaminase function has been retained by the ScALT1 encoded enzyme, which has specialized its catabolic character, while losing the alanine independent role observed in the ancestral type enzymes. The fact that ScAlt2 conserves 64% identity with LkAlt1

  16. Relationship between alcohol drinking and aspartate aminotransferase:alanine aminotransferase (AST:ALT) ratio, mean corpuscular volume (MCV), gamma-glutamyl transpeptidase (GGT), and apolipoprotein A1 and B in the U.S. population.

    PubMed

    Liangpunsakul, Suthat; Qi, Rong; Crabb, David W; Witzmann, Frank

    2010-03-01

    The misuse of alcohol, even at levels just above two drinks per day, is a public health problem, but identifying patients with this potentially unhealthy drinking is hindered by the lack of tests. Several blood tests, such as those testing for gamma-glutamyl transpeptidase (GGT) or mean corpuscular volume (MCV), are among the commonly used markers to identify very heavy drinking, but combinations of these markers have rarely been tested in lighter drinkers. We examined the relationship between alcohol drinking and the levels of these markers in a national population-based study composed primarily of lighter drinkers. Data were analyzed from 8,708 adult participants in the third U.S. National Health and Nutrition Examination Survey after excluding subjects with iron overload; with hepatitis B and C; who were pregnant; and who were taking prescription drugs such as phenytoin (Dilantin), barbiturates, and hydroxyurea (Droxia and Hydrea). The relationship between the amount of alcohol drinking and GGT, aspartate aminotransferase:alanine aminotransferase ratio, MCV of erythrocytes, and apolipoprotein A1 and B were analyzed and adjusted for potential liver injury risk factors. The prevalence of unhealthy alcohol drinking (defined as consumption of more than two standard drinks per day) was 6.7%. Heavier drinkers tended to be younger and reported an average of 4.2 drinks per day. When tested alone or in combination, the sensitivity and positive predictive values for these blood tests were too low to be clinically useful in identifying the subjects in the heavier drinking category. In this large, national, population-based study, the markers of heavy drinking studied here, either alone or in combination, did not appear to be useful in identifying unhealthy drinking. More work is needed to find the novel marker(s) associated with risky alcohol drinking.

  17. ALT/Space

    ERIC Educational Resources Information Center

    Rosenfeld, Malke, Ed.; Conarro, Ryan; Upshaw, Allison; Makol, Suzanne; Kelin, Daniel A., II; Redman, Jeff

    2013-01-01

    Stories in the "ALT/Space" section of each issue of "Teaching Artist Journal" illustrate and document a wide variety of topics surrounding the work of teaching artists while simultaneously revealing some larger truths about what it means to be an artist who teaches. This particular section focuses on the process and realities…

  18. Hepatic ALT isoenzymes are elevated in gluconeogenic conditions including diabetes and suppressed by insulin at the protein level

    PubMed Central

    Qian, Kun; Zhong, Shao; Xie, Keming; Yu, Daozhan; Yang, Rongze; Gong, Da-Wei

    2015-01-01

    Alanine transaminase (ALT) plays an important role in gluconeogenesis by converting alanine into pyruvate for glucose production. Early studies have shown that ALT activities are upregulated in gluconeogenic conditions and may be implicated in the development of diabetes. Since ALT consists of two isoforms, ALT1 and ALT2, with distinctive subcellular and tissue distributions, whether and how they are regulated are largely unknown. In this study, we found that both ALT isoforms in the liver were increased in diabetic GK rats and during fasting. However in ob/ob mice, only ALT2, but not ALT1, protein levels were elevated and the increase of ALT2 is correlated with that of ALT activity. We further demonstrated that, in vitro, both ALT1 and ALT2 were induced by glucocorticoid dexamethasone but suppressed by insulin in Fao hepatoma cells. Finally, we showed that the over-expression of ALT1 and ALT2 in Fao cells directly increased glucose output. Correctively, we have revealed the similarity and difference in the regulation of ALT isoforms in gluconeogenic conditions at the protein level, supporting that ALT isoenzymes play an important role in glucose metabolism and may be implicated the development of insulin resistance and diabetes. PMID:25865565

  19. Aerodynamic challenges of ALT

    NASA Technical Reports Server (NTRS)

    Hooks, I.; Homan, D.; Romere, P. O.

    1985-01-01

    The approach and landing test (ALT) of the Space Shuttle Orbiter presented a number of unique challenges in the area of aerodynamics. The purpose of the ALT program was both to confirm the use of the Boeing 747 as a transport vehicle for ferrying the Orbiter across the country and to demonstrate the flight characteristics of the Orbiter in its approach and landing phase. Concerns for structural fatigue and performance dictated a tailcone be attached to the Orbiter for ferry and for the initial landing tests. The Orbiter with a tailcone attached presented additional challenges to the normal aft sting concept of wind tunnel testing. The landing tests required that the Orbiter be separated from the 747 at approximately 20,000 feet using aerodynamic forces to fly the vehicles apart. The concept required a complex test program to determine the relative effects of the two vehicles on each other. Also of concern, and tested, was the vortex wake created by the 747 and the means for the Orbiter to avoid it following separation.

  20. Association of ALT and the metabolic syndrome among Mexican children.

    PubMed

    Elizondo-Montemayor, Leticia; Ugalde-Casas, Patricia A; Lam-Franco, Lorena; Bustamante-Careaga, Humberto; Serrano-González, Mónica; Gutiérrez, Norma G; Martínez, Ubaldo

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is emerging as a component of the metabolic syndrome (MetS); Hispanics being particularly predisposed. Alanine aminotransferase (ALT) is considered a marker of NAFLD. The aim of this study was to determine the prevalence and associations between ALT elevations and MetS in normal-weight, overweight and obese Mexican children and adolescents, since data in Mexico is scarce. Body mass index (BMI), waist circumference (WC), percentage body fat, blood pressure, glucose, lipid profiles, ALT and aspartate aminotransferase (AST) were measured in 236, 6-12yo normal-weight, overweight and obese Mexicans from eight public schools. The results showed that elevated ALT (>40 IU/L) was found in 17.7% of the obese and overweight population, with no gender difference. The prevalence of elevated ALT increased linearly across BMI categories (p = 0.001), from 0.0% for the normal-weight group (95%CI 0.0-€“8.0) to 22.4% for the obese one (95%CI 16.2-€“30.2). AST/ALT ratio <1 also increased linearly, as did the prevalence of MetS (p = 0.001), from 0.0% for the normal-weight group to 40.3% for the obese one. The prevalence of MetS was strongly associated with elevated ALT (p = 0.002), 50% in the elevated ALT group (95%CI 34.1-€“65.9) and 24.1% in the normal ALT one (95%CI 18.1-€“31.3). There was also a strong association between MetS and an AST/ALT ratio <1. WC was the best predictor of elevated ALT (AOR = 7.13). Pearson correlation showed that MetS components were significantly correlated with elevated ALT. Therefore elevated ALT levels were highly prevalent and strongly associated with MetS in Mexican children, it should be screened in overweight and obese children.

  1. ASA (ALT) Design, Develop, Deliver, Dominate

    DTIC Science & Technology

    2010-01-01

    Technology (ASA(ALT)) and the Principal Military Deputy to the ASA(ALT) ASA(ALT) Credo ASA(ALT) Overview Deputy for Acquisition and Systems...the people we serve and the communities we depend upon for support. ASA(ALT) Credo Assistant Secretary of the Army (Acquisition, Logistics and

  2. A pre-marketing ALT signal predicts post-marketing liver safety.

    PubMed

    Moylan, Cynthia A; Suzuki, Ayako; Papay, Julie I; Yuen, Nancy A; Ames, Michael; Hunt, Christine M

    2012-08-01

    Drug induced liver injury during drug development is evidenced by a higher incidence of serum alanine aminotransferase (ALT) elevations in treated versus placebo populations and termed an "ALT signal". We sought to quantify whether an ALT signal in pre-marketing clinical trials predicted post-marketing hepatotoxicity. Incidence of ALT elevations (ALT ≥ 3 times upper limits normal [× ULN]) for drug and placebo of new chemical entities and approved drugs associated with hepatotoxicity was calculated using the Food and Drug Administration (FDA) website. Post-marketing liver safety events were identified using the FDA Adverse Event Reporting System (AERS). The association of FDA AERS signal score (EB05 ≥ 2) and excess risk of pre-marketing ALT elevation (difference in incidence of ALT ≥ 3× ULN in treated versus placebo) was examined. An ALT signal of ≥ 1.2% was significantly associated with a post-marketing liver safety signal (p ≤ 0.013) and a 71.4% positive predictive value. An absent ALT signal was associated with a high likelihood of post-marketing liver safety; negative predictive value of 89.7%. Daily drug dose information improved the prediction of post-marketing liver safety. A cut-off of 1.2% increase in ALT ≥ 3× ULN in treated versus placebo groups provides an easily calculated method for predicting post-marketing liver safety.

  3. ALT-114 and ALT-118 Alternative Approaches to NIST ...

    EPA Pesticide Factsheets

    In 2016, US EPA approved two separate alternatives (ALT 114 and ALT 118) for the preparation and certification of Hydrogen Chloride (HCl) and Mercury (Hg) cylinder reference gas standards that can serve as EPA Protocol gases where EPA Protocol are required, but unavailable. The alternatives were necessary due to the unavailability of NIST reference materials (SRM, NTRM, CRM or RGM) or VSL reference materials (VSL PRM or VSL CRM), reference materials identified in EPA’s Green Book as necessary to establish the traceability of EPA protocol gases. ALT 114 and ALT 118 provides a pathway for gas vendors to prepare and certify traceable gas cylinder standards for use in certifying Hg and HCl CEMS. In this presentation, EPA will describe the mechanics and requirements of the performance-based approach, provide an update on the availability of these gas standards and also discuss the potential for producing and certifying gas standards for other compounds using this approach. This presentation discusses the importance of NIST-traceable reference gases relative to regulatory source compliance emissions monitoring. Specifically this presentation discusses 2 new approaches for making necessary reference gases available in the absence of NIST reference materials. Moreover, these approaches provide an alternative approach to rapidly make available new reference gases for additional HAPS regulatory compliance emissions measurement and monitoring.

  4. Alanine water complexes.

    PubMed

    Vaquero, Vanesa; Sanz, M Eugenia; Peña, Isabel; Mata, Santiago; Cabezas, Carlos; López, Juan C; Alonso, José L

    2014-04-10

    Two complexes of alanine with water, alanine-(H2O)n (n = 1,2), have been generated by laser ablation of the amino acid in a supersonic jet containing water vapor and characterized using Fourier transform microwave spectroscopy. In the observed complexes, water molecules bind to the carboxylic group of alanine acting as both proton donors and acceptors. In alanine-H2O, the water molecule establishes two intermolecular hydrogen bonds forming a six-membered cycle, while in alanine-(H2O)2 the two water molecules establish three hydrogen bonds forming an eight-membered ring. In both complexes, the amino acid moiety is in its neutral form and shows the conformation observed to be the most stable for the bare molecule. The microsolvation study of alanine-(H2O)n (n = 1,2) can be taken as a first step toward understanding bulk properties at a microscopic level.

  5. Probing alanine transaminase catalysis with hyperpolarized 13CD3-pyruvate

    PubMed Central

    Barb, A.W.; Hekmatyar, S.K.; Glushka, J.N.; Prestegard, J.H.

    2013-01-01

    Hyperpolarized metabolites offer a tremendous sensitivity advantage (>104 fold) when measuring flux and enzyme activity in living tissues by magnetic resonance methods. These sensitivity gains can also be applied to mechanistic studies that impose time and metabolite concentration limitations. Here we explore the use of hyperpolarization by dissolution dynamic nuclear polarization (DNP) in mechanistic studies of alanine transaminase (ALT), a well-established biomarker of liver disease and cancer that converts pyruvate to alanine using glutamate as a nitrogen donor. A specific deuterated, 13C-enriched analog of pyruvic acid, 13C3D3-pyruvic acid, is demonstrated to have advantages in terms of detection by both direct 13C observation and indirect observation through methyl protons introduced by ALT-catalyzed H–D exchange. Exchange on injecting hyperpolarized 13C3D3-pyruvate into ALT dissolved in buffered 1H2O, combined with an experimental approach to measure proton incorporation, provided information on mechanistic details of transaminase action on a 1.5 s timescale. ALT introduced, on average, 0.8 new protons into the methyl group of the alanine produced, indicating the presence of an off-pathway enamine intermediate. The opportunities for exploiting mechanism-dependent molecular signatures as well as indirect detection of hyperpolarized 13C3-pyruvate and products in imaging applications are discussed. PMID:23357427

  6. Inhibition study of alanine aminotransferase enzyme using sequential online capillary electrophoresis analysis.

    PubMed

    Liu, Lina; Chen, Yuanfang; Yang, Li

    2014-12-15

    We report the study of several inhibitors on alanine aminotransferase (ALT) enzyme using sequential online capillary electrophoresis (CE) assay. Using metal ions (Na(+) and Mg(2+)) as example inhibitors, we show that evolution of the ALT inhibition reaction can be achieved by automatically and simultaneously monitoring the substrate consumption and product formation as a function of reaction time. The inhibition mechanism and kinetic constants of ALT inhibition with succinic acid and two traditional Chinese medicines were derived from the sequential online CE assay. Our study could provide valuable information about the inhibition reactions of ALT enzyme.

  7. Faraday diagnostics for ALT-3

    SciTech Connect

    Oro, David M; Tabaka, Leonard J

    2011-01-13

    ALT-3 and R-Damage are experiments to be executed in collaboration between LANL and VNIIEF personnel. They are planned to be fielded in Sarov, Russia at VNIIEF. Both experiments employ Russian explosively driven pulse-power systems to generate a pulse of electrical current that is used to drive the experiment. The current pulse will be measured with Faraday-rotation fiber-optic loops. Using this well known technique, the change in the current enclosed by the loops is determined by measuring the change in the magnetic field integrated along the fiber-optic loop by detecting the Faraday rotation of linearly polarized light traveling through the fiber. The amount of polarization rotation of the light is related to the integrated magnetic field and therefore the enclosed current (Ampere's law) through the Verdet constant which for the optical-fibers used in this experiment has been determined to within 1 %. The presentation describes how the technique will be employed in the ALT-3 experiment.

  8. Comparison of Histologic Characteristics of Chinese Chronic Hepatitis B Patients with Persistently Normal or Mildly Elevated ALT

    PubMed Central

    Wang, Hong; Xue, Li; Yan, Rong; Zhou, Yin; Wang, Ming-Shan; Cheng, Mei-Juan; Hai-Jun Huang

    2013-01-01

    Liver disease can develop in chronic hepatitis B (CHB) patients with normal or mildly elevated alanine aminotransferase (ALT) who seldom undergo liver biopsy. We aimed to determine histologic characteristics of a large cohort of Chinese CHB patients undergoing liver biopsy and to evaluate the utility of ALT and HBV DNA values at the time of biopsy in predicting liver disease in this population. This prospective study enrolled 230 treatment-naïve patients with persistently normal or mildly elevated ALT. All patients had a liver biopsy. ALT, aspartate aminotransferase (AST), and HBV DNA levels were some of the other parameters measured. Using Scheuer's classification, significant histology was defined as stage ≧2 fibrosis and/or stage 1 fibrosis plus≧ grade 2 inflammation. Liver disease was observed in 34.4% and 61.8% of patients with normal ALT and mildly elevated ALT, respectively. Patients with mildly elevated ALT levels had significantly more events, including liver disease, elevated AST, and moderate to severe inflammation and liver fibrosis, than patients with normal ALT (all P≤0.005). A total of 107 patients (46.5%) had liver disease and 123 (53.5%) did not. PLT and ALT were significantly associated with liver disease (both P<0.001). Patients with elevated ALT, lower platelet count and HBV DNA < 7 log10copies/mL may have histologically significant changes associated with liver disease. Multivariate analysis showed that PLT and HBV DNA levels were significantly associated with liver disease in patients with normal ALT while gender and HBV DNA levels were significantly associated with liver disease in patients with mildly elevated ALT. Assessing liver damage via biopsy in patients with normal or mildly elevated ALT may help to identify those who would benefit from antiviral therapy. PMID:24260428

  9. A Micro-Platinum Wire Biosensor for Fast and Selective Detection of Alanine Aminotransferase

    PubMed Central

    Thuy, Tran Nguyen Thanh; Tseng, Tina T.-C.

    2016-01-01

    In this study, a miniaturized biosensor based on permselective polymer layers (overoxidized polypyrrole (Ppy) and Nafion®) modified and enzyme (glutamate oxidase (GlutOx)) immobilized micro-platinum wire electrode for the detection of alanine aminotransferase (ALT) was fabricated. The proposed ALT biosensor was measured electrochemically by constant potential amperometry at +0.7 V vs. Ag/AgCl. The ALT biosensor provides fast response time (~5 s) and superior selectivity towards ALT against both negatively and positively charged species (e.g., ascorbic acid (AA) and dopamine (DA), respectively). The detection range of the ALT biosensor is found to be 10–900 U/L which covers the range of normal ALT levels presented in the serum and the detection limit and sensitivity are found to be 8.48 U/L and 0.059 nA/(U/L·mm2) (N = 10), respectively. We also found that one-day storage of the ALT biosensor at −20 °C right after the sensor being fabricated can enhance the sensor sensitivity (1.74 times higher than that of the sensor stored at 4 °C). The ALT biosensor is stable after eight weeks of storage at −20 °C. The sensor was tested in spiked ALT samples (ALT activities: 20, 200, 400, and 900 U/L) and reasonable recoveries (70%~107%) were obtained. PMID:27240366

  10. The 'donations for decreased ALT (D4D)' prosocial behavior incentive scheme for NAFLD patients.

    PubMed

    Sumida, Yoshio; Yoshikawa, Toshikazu; Tanaka, Saiyu; Taketani, Hiroyoshi; Kanemasa, Kazuyuki; Nishimura, Tekeshi; Yamaguchi, Kanji; Mitsuyoshi, Hironori; Yasui, Kohichiroh; Minami, Masahito; Naito, Yuji; Itoh, Yoshito

    2014-12-01

    Physicians often experience difficulties in motivating patients with non-alcoholic fatty liver disease (NAFLD) to undergo lifestyle changes. The aim of this study is to examine whether 'Donations for Decreased alanine aminotransferase (ALT)' (D4D) prosocial behavior incentive can serve as an effective intrinsic motivational factor in comparison with conventional dietary and exercise intervention alone for NAFLD patients. Twenty-five NAFLD patients with elevated ALT were randomly assigned to a control group that received conventional dietary and exercise intervention alone, or a donation group whereby, as an incentive, we would make a monetary donation to the United Nations World Food Programme (WFP) based on the decrease in their ALT levels achieved over 12 weeks, in addition to receiving control intervention. In a donation group, we would donate US$1 to the WFP for every 1 IU/l of decrease in their ALT levels. There were no differences of pre-treatment clinical characteristics between the two groups. Significant reductions of ALT levels were achieved only in a donation group, although post-treatment ALT levels were not different between the two groups. These patients raised a total of $316 for the WFP. Promoting patients' intrinsic motivation by incorporating 'D4D' prosocial behavior incentive into conventional dietary and exercise intervention may provide a means to improve NAFLD. © The Author 2013. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Abdominal obesity validates the association between elevated alanine aminotransferase and newly diagnosed diabetes mellitus.

    PubMed

    Yueh, Chen-Yu; Yang, Yao-Hsu; Sung, Yi-Ting; Lee, Li-Wen

    2014-01-01

    To examine how elevated alanine aminotransferase (ALT) could be associated with newly diagnosed diabetes mellitus. We conducted a cross-sectional analysis on a mass health examination. The odds ratios (ORs) for diabetes mellitus and newly diagnosed diabetes mellitus were compared between people with and without abdominal obesity, together with and without elevated ALT levels. 5499 people were included in this study. Two hundred fifty two (4.6%) fulfilled the diagnosis of diabetes mellitus with 178 (3.2%) undiagnosed before. Metabolic syndrome was vigorously associated with diabetes mellitus and newly diagnosed diabetes mellitus (12.4% vs. 1.4% and 9.0% vs. 0.9%), but elevated ALT alone was not. However, coexisting with obesity, elevated ALTs were robustly associated with diabetes mellitus and newly diagnosed diabetes mellitus. For the incidence of newly diagnosed diabetes mellitus, in comparison to non-obese people with normal ALT (1.7%, OR = 1), obese people especially with elevated ALT levels had significantly higher ORs (obese with ALT ≤ 40 U/L: 4.7%, OR 1.73, 95% CI 1.08-2.77, P 0.023; ALT 41-80 U/L: 6.8%, OR 2.06, 95% CI 1.20-3.55, P 0.009; ALT 81-120 U/L: 8.8%, OR 3.07, 95% CI 1.38-6.84, P 0.006; ALT > 120 U/L: 18.2%, OR 7.44, 95% CI 3.04-18.18, P < 0.001). Abdominal obesity validates the association between elevated alanine aminotransferase and diabetes mellitus and newly diagnosed diabetes mellitus. People with abdominal obesity, especially with coexisting elevated ALT levels should be screened for undiagnosed diabetes mellitus.

  12. An innovative alt-alt telescope for small observatories and amateur astronomers

    NASA Astrophysics Data System (ADS)

    Riva, M.; Basso, S.; Canestrari, R.; Conconi, P.; Fugazza, D.; Ghigo, M.; Landoni, M.; Pareschi, G.; Spanó, P.; Tomelleri, R.; Zerbi, F. M.

    2012-09-01

    This paper want to show an innovative amateur oriented telescope with an unconventional alt-alt conguration. The goal is to make a telescope with good optical quality reducing production costs by adopting a gimbal based mounting to develop an alt-alt conguration suitable for a telescope. Reduce costs while preserving the optical quality is a necessary condition to allow small groups of amateur astronomers, schools and cultural clubs, with reduced economic resources, to acquire an astronomical instrument that encourages learning and advancing astrophysical knowledge. This unconventional mechanism for the realization of a telescope alt-alt provides signicant advantages. The traditional rotary motors coupled with expensive precision bearings are replaced with two simple linear actuators coupled to a properly preloaded gimbal joint and the cell becomes the primary structure of the telescope. A second advantage would be secured by mechanical simplicity evident in the easy portability of the instrument. The frame alt-alt has some limitations on the horizon pointing but does not show the zenith blind spot of the alt-az mount. A dedicated alt-alt pointing and tracking model is under development to be compatible with commercial telescope softwares and with the proposed new mounting.

  13. Porcine alanine transaminase after liver allo-and xenotransplantation

    PubMed Central

    Ekser, Burcin; Gridelli, Bruno; Cooper, David K.C.

    2013-01-01

    Aspartate transaminase (AST) and alanine transaminase (ALT) are measured following liver transplantation as indicators of hepatocellular injury. During a series of orthotopic liver allo-and xenotransplants, we observed that there was an increase in AST in all cases. The anticipated concomitant rise in ALT did not occur when a wild-type (WT) pig was the source of the liver graft, but did occur when a baboon or a genetically engineered (α1,3-galactosyltransferase gene-knockout [GTKO]) pig was the source of the graft. We hypothesized that the cience of Galα1,3 Gal in GTKO pig livers may render pig hepatocytes similar to human and baboon hepatocytes in their response to hepatocellular injury. Reviewing the literature, after WT pig liver allotransplantation or xenotransplantation, in the majority of reports, although changes in AST were reported, no mention was made of changes in ALT, suggesting that there was no change in ALT. However, Ramirez et al. reported two cases of liver xenotransplants from hCD55 pigs, following which there were increases in both AST and ALT, suggesting that it is not simply the cience of expression of Galα1,3 Gal that is the cause. We acknowledge that our observation is based on a small number of experiments, but we believe it is worth recording. PMID:22360753

  14. Porcine alanine transaminase after liver allo-and xenotransplantation.

    PubMed

    Ekser, Burcin; Gridelli, Bruno; Cooper, David K C

    2012-01-01

    Aspartate transaminase (AST) and alanine transaminase (ALT) are measured following liver transplantation as indicators of hepatocellular injury. During a series of orthotopic liver allo-and xenotransplants, we observed that there was an increase in AST in all cases. The anticipated concomitant rise in ALT did not occur when a wild-type (WT) pig was the source of the liver graft, but did occur when a baboon or a genetically engineered (α1,3-galactosyltransferase gene-knockout [GTKO]) pig was the source of the graft. We hypothesized that the cience of Galα1,3Gal in GTKO pig livers may render pig hepatocytes similar to human and baboon hepatocytes in their response to hepatocellular injury. Reviewing the literature, after WT pig liver allotransplantation or xenotransplantation, in the majority of reports, although changes in AST were reported, no mention was made of changes in ALT, suggesting that there was no change in ALT. However, Ramirez et al. reported two cases of liver xenotransplants from hCD55 pigs, following which there were increases in both AST and ALT, suggesting that it is not simply the cience of expression of Galα1,3Gal that is the cause. We acknowledge that our observation is based on a small number of experiments, but we believe it is worth recording.

  15. An assessment of racial differences in the upper limits of normal ALT levels in children and the effect of obesity on elevated values.

    PubMed

    Kliethermes, S; Ma, M; Purtell, C; Balasubramanian, N; Gonzalez, B; Layden, T J; Cotler, S J

    2017-10-01

    Childhood obesity is a risk factor for non-alcoholic fatty liver disease and poses important public health issues for children. Racial differences in alanine aminotransferase (ALT) levels among children have not been described. This study aimed to identify racial differences in upper limit normal (ULN) ALT levels and evaluate the effect of obesity on elevated levels in children without other metabolic risk factors. National Health and Nutrition Examination Surveys and clinical data from the Loyola University Health System were used to determine ULN ALT by race and gender. Quantile regression was used to evaluate the impact of obesity on elevated ALT and to identify potential risk factors for ALT above the ULN. Upper limit normal (ULN) ALT was approximately 28.0 and 21.0-24.0 U/L for boys and girls, respectively. No significant difference in ULN ALT across race was observed. Obesity was significantly associated with elevated ALT; obese children with elevated ALT had values 10 U/L higher than normal-weight children. Racial differences in ALT levels among adults are not evident in children. Obesity, in the absence of metabolic risk factors and other causes of liver disease, is associated with elevated ALT, providing evidence against the concept of healthy obesity in children. © 2016 World Obesity Federation.

  16. Hepatocyte nuclear factor 4α transactivates the mitochondrial alanine aminotransferase gene in the kidney of Sparus aurata.

    PubMed

    Salgado, María C; Metón, Isidoro; Anemaet, Ida G; González, J Diego; Fernández, Felipe; Baanante, Isabel V

    2012-02-01

    Alanine aminotransferase (ALT) plays an important role in amino acid metabolism and gluconeogenesis. The preference of carnivorous fish for protein amino acids instead of carbohydrates as a source of energy lead us to study the transcriptional regulation of the mitochondrial ALT (mALT) gene and to characterize the enzyme kinetics and modulation of mALT expression in the kidney of gilthead sea bream (Sparus aurata) under different nutritional and hormonal conditions. 5'-Deletion analysis of mALT promoter in transiently transfected HEK293 cells, site-directed mutagenesis and electrophoretic mobility shift assays allowed us to identify HNF4α as a new factor involved in the transcriptional regulation of mALT expression. Quantitative RT-PCR assays showed that starvation and the administration of streptozotocin (STZ) decreased HNF4α levels in the kidney of S. aurata, leading to the downregulation of mALT transcription. Analysis of the tissue distribution showed that kidney, liver, and intestine were the tissues with higher mALT and HNF4α expression. Kinetic analysis indicates that mALT enzyme is more efficient in catalyzing the conversion of L: -alanine to pyruvate than the reverse reaction. From these results, we conclude that HNF4α transactivates the mALT promoter and that the low levels of mALT expression found in the kidney of starved and STZ-treated fish result from a decreased expression of HNF4α. Our findings suggest that the mALT isoenzyme plays a major role in oxidazing dietary amino acids, and points to ALT as a target for a biotechnological action to spare protein and optimize the use of dietary nutrients for fish culture.

  17. Markerless Mutagenesis in Methanococcus maripaludis Demonstrates Roles for Alanine Dehydrogenase, Alanine Racemase, and Alanine Permease

    PubMed Central

    Moore, Brian C.; Leigh, John A.

    2005-01-01

    Among the archaea, Methanococcus maripaludis has the unusual ability to use l- or d-alanine as a nitrogen source. To understand how this occurs, we tested the roles of three adjacent genes encoding homologs of alanine dehydrogenase, alanine racemase, and alanine permease. To produce mutations in these genes, we devised a method for markerless mutagenesis that builds on previously established genetic tools for M. maripaludis. The technique uses a negative selection strategy that takes advantage of the ability of the M. maripaludis hpt gene encoding hypoxanthine phosphoribosyltransferase to confer sensitivity to the base analog 8-azahypoxanthine. In addition, we developed a negative selection method to stably incorporate constructs into the genome at the site of the upt gene encoding uracil phosphoribosyltransferase. Mutants with in-frame deletion mutations in the genes for alanine dehydrogenase and alanine permease lost the ability to grow on either isomer of alanine, while a mutant with an in-frame deletion mutation in the gene for alanine racemase lost only the ability to grow on d-alanine. The wild-type gene for alanine dehydrogenase, incorporated into the upt site, complemented the alanine dehydrogenase mutation. Hence, the permease is required for the transport of either isomer, the dehydrogenase is specific for the l isomer, and the racemase converts the d isomer to the l isomer. Phylogenetic analysis indicated that all three genes had been acquired by lateral gene transfer from the low-moles-percent G+C gram-positive bacteria. PMID:15659675

  18. Diurnal variation in serum alanine aminotransferase activity in the US population.

    PubMed

    Ruhl, Constance E; Everhart, James E

    2013-02-01

    Serum alanine aminotransferase (ALT) activity has been reported to be greater in the afternoon than the early morning, but data are scarce. We examined diurnal variation of ALT in a national population-based sample. Participants in the 1999 to 2008 US National Health and Nutrition Examination Survey were randomly assigned to morning (AM; n = 4474 adolescents, 11,235 adults) or afternoon/evening (PM; n = 4887 adolescents, 11,735 adults) examinations. We examined ALT distributions graphically and compared both geometric mean ALT and the prevalence of elevated ALT, defined as >31 IU/L for adolescent boys, >24 IU/L for adolescent girls, >43 IU/L for adult men, and >30 IU/L for adult women, between AM and PM examination groups. The examination groups were similar with the exception in the AM group of a longer fasting time and slightly higher prevalence of diabetes among adolescents and viral hepatitis B among adult women. ALT distributions were similar between examination sessions among the 4 groups. Among adolescents and men, neither mean ALT nor prevalence of abnormal ALT differed by examination group. Among women, mean ALT was statistically significant, but minimally higher in the PM group (19.6 IU/L) than the AM group (19.1 IU/L; P = 0.009). Among 1 subgroup, women with chronic viral hepatitis, there was a higher prevalence of abnormal ALT in the PM group (P = 0.018 in unadjusted analysis). Adjusting for liver injury risk factors had little effect on the difference in mean ALT. In general, clinically significant diurnal variation in ALT activity was not found in the US population.

  19. Prevalence and predictors of alanine aminotransferase elevation among normal weight, overweight and obese youth in Mexico.

    PubMed

    Purcell, Maura; Flores, Yvonne N; Zhang, Zuo-Feng; Denova-Gutiérrez, Edgar; Salmeron, Jorge

    2013-09-01

    This study aimed to determine the prevalence of and risk factors associated with elevated alanine aminotransferase (ALT) levels among a sample of normal weight, overweight and obese youth from two urban populations in Central Mexico. Baseline data from 1262 youth aged 8-19 years who participated in the Mexican Health Worker Cohort Study from March 2004 to April 2006 were reviewed, including 680 girls and 582 boys, with a total of 83 participants with elevated ALT level (>40 U/L). Information was obtained from self-administered questionnaires, anthropometric results and clinical measurements. Associations of interest were examined using multivariate logistic regression models. A total of 3.8% of girls and 9.8% of boys had elevated ALT levels. Elevated ALT was observed in 28.9% of the obese and 14.2% of the overweight participants. Metabolic syndrome (MS) occurred in 6.1% of the study population and those with MS had a high percentage of elevated ALT (14.5% of girls and 40.0% of boys, respectively). Abdominal obesity and insulin resistance were also associated with a greater risk of elevated ALT. Obesity and certain metabolic risk factors are important predictors for elevated ALT. Screening for ALT levels in obese youth could help to identify those at risk and reduce the possibility of future liver diseases. © 2013 Wiley Publishing Asia Pty Ltd and Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine.

  20. Detection of TTV in peripheral blood cells from patients with altered ALT and AST levels.

    PubMed

    de Oliveira, Jaqueline Carvalho; Nasser, Thiago Franco; Oda, Julie Massayo Maeda; Aoki, Mateus Nóbrega; Carneiro, Juliana Laino do Val; Barbosa, Décio Sabbatini; Reiche, Edna Maria Vissoci; Watanabe, Maria Angelica Ehara

    2008-04-01

    This work analyzes the prevalence of TTV DNA in peripheral blood cells from patients with hepatic alterations and healthy blood donors and measures levels of sodium, potassium, urea, creatinine, phosphatase alkaline, total and direct bilirubin, gamma glutamyl transferase (GGT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in certain randomly selected patients. DNA samples from 111 individuals were evaluated. They were divided into two groups, "A" (study) and "B" (control), including 54 patients with liver enzyme alterations (ALT/AST) presenting non-B-non-C hepatitis and 57 blood donors, respectively. TTV DNA was determined by nested PCR. Certain products of the second-round PCR were sequenced. Serum biochemical assay was performed and disclosed TTV in 31.48% (17/54) of patients in group A and 5.26% (3/57) in the control group B. TTV prevalence was significantly higher in patients with liver disease than in healthy donors. In group A, sodium, potassium, urea, creatinine, phosphatase alkaline, total and direct bilirubin, gamma glutamyl transferase (GGT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were analyzed in certain randomly selected patients and no significant difference in biochemical levels (p>0.05) was found when TTV infected and noninfected individuals were compared. Knowledge related to TTV has rapidly increased, but many fundamental aspects remain unclear. This led us to question the role of TTV and doubt remains as to whether or not it is just a commensal virus. Further studies are necessary to confirm and extend these findings.

  1. ALT-114 and ALT-118 Alternative Approaches to NIST-Traceable Reference Gases

    EPA Science Inventory

    In 2016, US EPA approved two separate alternatives (ALT 114 and ALT 118) for the preparation and certification of Hydrogen Chloride (HCl) and Mercury (Hg) cylinder reference gas standards that can serve as EPA Protocol gases where EPA Protocol are required, but unavailable. The a...

  2. Alanine aminotransferase and mortality in patients with type 2 diabetes (ZODIAC-38).

    PubMed

    Deetman, Petronella E; Alkhalaf, Alaa; Landman, Gijs W D; Groenier, Klaas H; Kootstra-Ros, Jenny E; Navis, Gerjan; Bilo, Henk J G; Kleefstra, Nanne; Bakker, Stephan J L

    2015-08-01

    Combined data suggest a bimodal association of alanine aminotransferase (ALT) with mortality in the general population. Little is known about the association of ALT with mortality in patients with type 2 diabetes. We therefore investigated the association of ALT with all-cause, cardiovascular and noncardiovascular mortality in patients with type 2 diabetes. A prospective study was performed in patients with type 2 diabetes, treated in primary care, participating in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) study. Cox regression analyses were performed to determine the associations of log2 -transformed baseline ALT with all-cause, cardiovascular and noncardiovascular mortality. In 1187 patients with type 2 diabetes (67 ± 12 years, 45% female), ALT levels were 11 (8-16) U/L. During median follow-up for 11.1 (6.1-14.0) years, 553 (47%) patients died, with 238 (20%) attributable to cardiovascular causes. Overall, ALT was inversely associated with all-cause mortality (hazard ratio [HR] 0.81; 95% confidence interval [CI] 0.72-0.92), independently of potential confounders. This was less attributable to cardiovascular mortality (HR 0.87; 95% CI 0.72-1.05), than to noncardiovascular mortality (HR 0.77; 95% CI 0.65-0.90). Despite the overall inverse association of ALT with mortality, it appeared that a bimodal association with all-cause mortality was present with increasing risk for levels of ALT above normal (P = 0.003). In patients with type 2 diabetes, low levels of ALT are associated with an increased risk of all-cause mortality, in particular noncardiovascular mortality, compared to normal levels of ALT, while risk again starts to increase when levels are above normal. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

  3. The Association of Low Serum Alanine Aminotransferase Activity With Mortality in the US Population

    PubMed Central

    Ruhl, Constance E.; Everhart, James E.

    2013-01-01

    Elevated alanine aminotransferase (ALT) activity, an important marker of liver injury, has been associated inconsistently with higher mortality. We evaluated whether persons with nonelevated ALT levels are the most appropriate comparison group by examining the relationships of low ALT with mortality and body composition in the US National Health and Nutrition Examination Survey (NHANES). In NHANES 1988–1994, the mortality risk of persons in ALT deciles 1, 2, 3, and 10 was compared with that of persons in deciles 4–9 (mortality was relatively flat across these deciles) over an 18-year period (through 2006) among 14,950 viral-hepatitis-negative adults. In NHANES 1999–2006, low ALT was evaluated in association with dual-energy x-ray absorptiometry body composition measures among 15,028 adults. Multivariate-adjusted mortality was higher for decile 1 (hazard ratio (HR) = 1.42, 95% confidence interval (CI): 1.24, 1.63), decile 2 (HR = 1.27, 95% CI: 1.06, 1.53), and decile 3 (HR = 1.25, 95% CI: 1.04, 1.50) and nonsignificantly higher for decile 10 (HR = 1.21, 95% CI: 0.91, 1.61) than for deciles 4–9. Adjusted appendicular lean mass was decreased among the lowest ALT deciles. In the US population, low ALT was associated with higher mortality risk, possibly attributable to decreased appendicular lean mass. For mortality studies of elevated ALT levels, the most appropriate comparison group is persons in the middle range of ALT rather than all persons with nonelevated ALT. PMID:24071009

  4. Gender differences in healthy ranges for serum alanine aminotransferase levels in adolescence.

    PubMed

    Poustchi, Hossein; George, Jacob; Esmaili, Saeed; Esna-Ashari, Farzaneh; Ardalan, Gelayol; Sepanlou, Sadaf Ghajarieh; Alavian, Seyed Moayed

    2011-01-01

    There is a worldwide epidemic of obesity among adolescents who subsequently are at increased risk for the development of non alcoholic fatty liver disease (NAFLD). The serum alanine aminotransferase (ALT) is the most frequently used test for screening these individuals, but no age and gender-specific upper limits of normal (ULN) based on healthy population data in children are available. The objective of the present study was to define ULN for ALT in healthy children in order to use this as a tool for case finding. A total of 975 school children (aged 7-18 years) were included in the study cohort. Highly significant correlations (all p<0.001) were noted between ALT values and measures of BMI, systolic and diastolic blood pressure, insulin levels, HOMA-IR, total cholesterol and triglyceride concentrations. In order to define the population with no risk factors, we excluded subjects having abnormal values for factors that correlated with ALT. This population comprised 186 boys and 185 girls. In boys, median serum ALT levels were 16 IU/L and 9, 11, 18, and 30 IU/L for the 5th, 25th, 75th, and 95th percentiles. In girls, median serum ALT was 13, and 7, 9, 16, and 21 IU/L for the 5th, 25th, 75th, and 95th percentiles, respectively. The ULNs for ALT were 30 IU/L and 21 IU/L for boys and girls respectively. We found a linear relationship between age and ALT in females (p<0.001) but not in males. By multiple logistic regression, independent predictors of an elevated ALT included the BMI, waist hip ratio and levels of serum total cholesterol. In females, age was an additional inverse predictor. In children and adolescents, these normal limits for ALT should be applied. Those with persistent elevations should be investigated further.

  5. Association between Serum Uric Acid and Elevated Alanine Aminotransferase in the General Population

    PubMed Central

    Chen, Shuang; Guo, Xiaofan; Yu, Shasha; Sun, Guozhe; Yang, Hongmei; Li, Zhao; Sun, Yingxian

    2016-01-01

    Background: Both the serum uric acid (SUA) level and elevated alanine aminotransferase (ALT) are related to metabolic syndrome. However, the association between SUA and elevated ALT has not been elucidated in the general population. The objective of this study was to investigate the association between SUA and elevated ALT in the general population of China; Methods: A total of 11,572 adults (≥35 years of age) participated in this survey. Elevated ALT was defined as >40 U/L. SUA ≥ 7.0 mg/dL in males or ≥6.0 mg/dL in females was defined as hyperuricemia. SUA within the reference range was divided into quartiles, and its associations with elevated ALT were evaluated by logistic regressions; Results: A total of 7.4% participants had elevated ALT. The prevalence of hyperuricemia was 14.9% in males and 7.3% in females. There was a significantly positive dose-response association between SUA levels and the prevalence of elevated ALT. After adjusting for potential confounders, a positive relationship for elevated ALT was observed in subjects with hyperuricemia (odds ratio [OR]: 2.032, 95% confidence interval [CI]: 1.443–2.861 for men; OR: 2.045, 95% CI: 1.221–3.425 for women, both p < 0.05). Within the reference range, the association between SUA and elevated ALT persisted in the fourth quartile (OR: 1.467, 95% CI: 1.063–2.025 for men; OR: 1.721, 95% CI: 1.146–2.585 for women, both p < 0.05); Conclusions: Our results indicated that an increased SUA level, even within the reference range, was independently associated with elevated ALT in Chinese adults. PMID:27563918

  6. Serum alanine aminotransferase is correlated with hematocrit in healthy human subjects.

    PubMed

    Hu, Yun; Snitker, Soren; Ryan, Kathleen A; Yang, Rongze; Mitchell, Braxton D; Shuldiner, Alan R; Zhu, Dalong; Gong, Da-Wei

    2012-05-01

    Serum alanine aminotransferase (ALT) activity is a widely-used surrogate marker for liver injury. However, mild elevation of serum ALT is frequently observed in apparently healthy individuals, making it sometimes challenging to interpret whether this laboratory abnormality is medically benign or serious. To obtain a better understanding of the factors influencing ALT levels, we examined the relation between ALT and a number of anthropometric and biochemistry measurements in humans. We assessed the associations of ALT with hematocrit (HCT) in 1,200 apparently healthy adults from an Amish population. Multivariate analyses were carried out to determine whether observed associations were independent of other factors known to modulate ALT and HCT, including body mass index (BMI) and sex. The correlation detected in the Amish was then replicated in an independent population sample (N = 9,842) from the National Health and Nutrition Examination Survey (NHANES) III. ALT levels were positively correlated with HCT (r = 0.33, p < 0.0001) in both Amish and NHANES III. The magnitude of association was unchanged after adjustment for BMI, but was reduced by age/sex adjustment to r = 0.18 (p < 0.0001) and r = 0.17 (p < 0.0001) in the Amish and NHANES populations, respectively. HCT accounts for about 3% of the population variation in ALT, which is smaller than the contributions of gender and BMI, but larger than individual blood pressure and cholesterol components. We observed a correlation between ALT and HCT, suggesting that HCT may be a newly identified modulator of ALT in humans.

  7. Serum alanine aminotransferase levels decrease further with carbohydrate than fat restriction in insulin-resistant adults.

    PubMed

    Ryan, Marno Celeste; Abbasi, Fahim; Lamendola, Cindy; Carter, Susan; McLaughlin, Tracey Lynn

    2007-05-01

    Although weight loss interventions have been shown to reduce steatosis in nonalcoholic fatty liver disease (NAFLD), the impact of dietary macronutrient composition is unknown. We assessed the effect on serum alanine aminotransferase (ALT) concentrations of two hypocaloric diets varying in amounts of carbohydrate and fat in obese insulin-resistant individuals, a population at high risk for NAFLD. Post hoc analysis of ALT concentrations was performed in 52 obese subjects with normal baseline values and insulin resistance, as quantified by the steady-state plasma glucose (SSPG) test, who were randomized to hypocaloric diets containing either 60% carbohydrate/25% fat or 40% carbohydrate/45% fat (15% protein) for 16 weeks. The primary end point was change in ALT, which was evaluated according to diet, weight loss, SSPG, and daylong insulin concentrations. Although both diets resulted in significant decreases in weight and SSPG, daylong insulin, and serum ALT concentrations, the 40% carbohydrate diet resulted in greater decreases in SSPG (P < 0.04), circulating insulin (P < 0.01), and ALT (9.5 +/- 9.4 vs. 4.2 +/- 8.3 units/l; P < 0.04) concentrations. ALT changes correlated with improvement in insulin sensitivity (P = 0.04) and daylong insulin (P < 0.01). Individuals with ALT concentrations above the proposed upper limits experienced significant declines in ALT, unlike those with lower ALT levels. In a population at high risk for NAFLD, a hypocaloric diet moderately lower in carbohydrate decreased serum ALT concentrations to a greater degree than a higher-carbohydrate/low-fat diet, despite equal weight loss. This may result from a relatively greater decline in daylong insulin concentrations. Further research with histological end points is needed to further explore this finding.

  8. Clinical features of hepatitis C virus carriers with persistently normal alanine aminotransferase levels.

    PubMed

    Uto, Hirofumi; Mawatari, Seiich; Kumagai, Kotaro; Ido, Akio; Tsubouchi, Hirohito

    2012-02-01

    Hepatitis C virus (HCV) infection causes chronic hepatitis, which frequently leads to hepatic fibrosis and hepatocellular carcinoma (HCC). Alanine aminotransferase (ALT) is a biomarker of hepatocyte injury and is associated with the progression of hepatic fibrosis. Advanced hepatic fibrosis also predisposes HCV carriers to a risk of HCC. In contrast, some cases with persistent HCV infection have normal ALT levels that persist for a long time, and these HCV carriers have no or mild hepatitis and hepatic fibrosis. These HCV carriers are defined as persistent normal ALT (PNALT) cases and their risk of HCC is low compared to HCV carriers with abnormal ALT. However, there are various definitions of normal ALT and PNALT, and advanced hepatic fibrosis may be missed without a liver biopsy. In addition, there is also a risk of ALT elevation in HCV carriers with PNALT, which increases the risk of progression to hepatic fibrosis and HCC. Most HCV carriers with PNALT have asymptomatic or nonspecific symptoms. HCV carriers with PNALT are also considered to be responsive to interferon-based treatment. Thus, assessment of hepatic fibrosis is important in HCV carriers, and the eradication of HCV infection is more likely in HCV carriers with evidence of hepatic fibrosis, regardless of their ALT levels.

  9. [Association of metabolic syndrome markers with abnormal alanine aminotransferase levels in healthy children].

    PubMed

    Arancibia, Gabriel; García, Hernán; Jaime, Francisca; Bancalari, Rodrigo; Harris, Paul R

    2012-07-01

    There is a high prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) among pediatric patients. The identification of clinical predictors of these conditions would allow a timely treatment. To evaluate the relationship between serum alanine aminotransferase levels and parameters of metabolic syndrome in asymptomatic school students without hepatic illness. A randomized sample of 175 children aged between 9 and 14 years (54% females) was selected, from a database of 3010 students living in Santiago, Chile. Weight, height, abdominal circumference, systolic and diastolic blood pressure were measured. A fasting blood sample was obtained to measure glucose, total cholesterol, HDL, LDL-cholesterol, triglycerides, alanine aminotransferase (ALT) and insulin levels. Forty percent of participants were obese, 17% had metabolic syndrome and 13.1% had abnormal ALT levels. Compared with children with normal ALT levels, the latter had significantly higher waist obesity, body mass index, systolic and diastolic blood pressure and triglycerides. However on multivariate analysis, only waist obesity was independently associated with abnormal ALT levels (adjusted odds ratio 3.93, 95% confidence intervals 1.44-10.78, p = 0.008). Only waist obesity was independently associated with abnormal ALT levels in this sample of children.

  10. Elevated alanine aminotransferase levels in HIV-infected persons without hepatitis B or C virus coinfection.

    PubMed

    Alghamdi, Saad; Alrbiaan, Abdullah; Alaraj, Ali; Alhuraiji, Ahmad; Alghamdi, Mohammad; Alrajhi, Abdulrahman

    2016-01-01

    Mortality related to human immunodeficiency (HIV) has improved with the use of antiretroviral therapy; however, liver disease-related mortality remains a major concern for the HIV population. Elevation of alanine aminotransferase (ALT) has been noted in HIV-infected persons even without viral hepatitis infection. The objective of this study was to determine the incidence and prevalence of chronic alanine ALT elevation among patients infected with HIV who are negative for hepatitis B or C infection. Retrospective chart review. We reviewed the medical records of all patients infected with HIV who had been treated from November 2002 to December 2010. Patients with an unknown or positive HBV or HCV infection status were excluded. We identified patient demographics, route of transmission, peak viral load, and nadir CD4 count. We followed 440 patients for up to 2265 person-years. A total of 123 patients developed chronically elevated ALT levels, with an incidence of 5.8 cases per 100 person-years. Chronically elevated ALT levels were associated with high HIV viral load, mean body mass index, and diabetes mellitus. We found exposure to lamivudine in 58% of the patients, efavirenz in 41%, and zidovudine in 38%. Abdominal ultrasounds revealed fatty liver in 20 of 39 (51%) of the patients. Among patients without viral hepatitis coinfection, the prevalence and incidence of chronic elevated ALT levels were high and accompanied by high HIV RNA levels and increased BMI. The limitations of this report are its retrospective nature and lack of a control group.

  11. Factors underlying the association of body mass index with serum ALT in Chinese hypertensive adults without known hepatic diseases*

    PubMed Central

    Zhang, Yan; Qin, Xian-hui; Li, Jian-ping; Cui, Yi-min; Liu, Ze-yuan; Zhao, Zhi-gang; Ge, Jun-bo; Guan, De-ming; Hu, Jian; Wang, Yan-ni; Zhang, Fu-min; Xu, Xin; Xu, Xi-ping; Huo, Yong

    2013-01-01

    Objective: High body mass index (BMI) is considered as the most important risk factor for elevated serum alanine aminotransferase (ALT) concentration. This study examined an array of factors, including waist circumference (WC) and folate deficiency, which may mediate the association of BMI with serum ALT concentration in Chinese hypertensive adults without known hepatic diseases. Methods: A multicenter, cross-sectional study was carried out. A total of 378 patients with mild or moderate hypertension and without known hepatic diseases were recruited from five hospitals in Harbin, Shanghai, Beijing, Xi’an, and Nanjing. Results: Of the 360 hypertensive patients with complete data in our final analysis, 13.6% had high ALT concentrations (>40 IU/L). Factors including BMI, WC, triglyceride level, and folate concentration were associated with ALT concentration in univariate analysis. Consistently higher prevalence rates of elevated ALT were observed in subjects with lower folate concentrations (≥12 vs. <12 nmol/L, 9.9% vs. 17.8%, P=0.03), with higher BMI (≥28 vs. <28 kg/m2, 21.5% vs. 11.4%, P=0.02) or higher WC (≥90 vs. <90 cm, 18.5% vs. 10.0%, P=0.02). However, in multivariate analysis, the association between BMI and ALT concentration disappeared (P=0.802 in males and 0.369 in females), while WC in females (P<0.001) and folate concentration (P=0.036 in males and 0.044 in females) remained as significant predictors for ALT concentration. Conclusions: This multicenter study demonstrated that WC and low folate concentration were important factors underlying the association between BMI and ALT concentrations in Chinese hypertensive adults without known hepatic diseases. PMID:23897794

  12. Incremental Predictive Value of Serum AST-to-ALT Ratio for Incident Metabolic Syndrome: The ARIRANG Study

    PubMed Central

    Ahn, Song Vogue; Baik, Soon Koo; Cho, Youn zoo; Koh, Sang Baek; Huh, Ji Hye; Chang, Yoosoo; Sung, Ki-Chul; Kim, Jang Young

    2016-01-01

    Aims The ratio of aspartate aminotransferase (AST) to alanine aminotransferase (ALT) is of great interest as a possible novel marker of metabolic syndrome. However, longitudinal studies emphasizing the incremental predictive value of the AST-to-ALT ratio in diagnosing individuals at higher risk of developing metabolic syndrome are very scarce. Therefore, our study aimed to evaluate the AST-to-ALT ratio as an incremental predictor of new onset metabolic syndrome in a population-based cohort study. Material and Methods The population-based cohort study included 2276 adults (903 men and 1373 women) aged 40–70 years, who participated from 2005–2008 (baseline) without metabolic syndrome and were followed up from 2008–2011. Metabolic syndrome was defined according to the harmonized definition of metabolic syndrome. Serum concentrations of AST and ALT were determined by enzymatic methods. Results During an average follow-up period of 2.6-years, 395 individuals (17.4%) developed metabolic syndrome. In a multivariable adjusted model, the odds ratio (95% confidence interval) for new onset of metabolic syndrome, comparing the fourth quartile to the first quartile of the AST-to-ALT ratio, was 0.598 (0.422–0.853). The AST-to-ALT ratio also improved the area under the receiver operating characteristic curve (AUC) for predicting new cases of metabolic syndrome (0.715 vs. 0.732, P = 0.004). The net reclassification improvement of prediction models including the AST-to-ALT ratio was 0.23 (95% CI: 0.124–0.337, P<0.001), and the integrated discrimination improvement was 0.0094 (95% CI: 0.0046–0.0143, P<0.001). Conclusions The AST-to-ALT ratio independently predicted the future development of metabolic syndrome and had incremental predictive value for incident metabolic syndrome. PMID:27560931

  13. Low ALT blood levels predict long-term all-cause mortality among adults. A historical prospective cohort study.

    PubMed

    Ramaty, E; Maor, E; Peltz-Sinvani, N; Brom, A; Grinfeld, A; Kivity, S; Segev, S; Sidi, Y; Kessler, T; Sela, B A; Segal, G

    2014-12-01

    Increased blood levels of alanine amino transferase (ALT, also known as SGPT; serum glutamic pyruvic transaminase) serve as a marker of liver injury by various mechanisms. Less is known about the clinical implications associated with low-normal ALT levels. Previous studies showed low ALT levels to be associated with poor long-term outcomes among elderlies, serving as a biomarker for increased incidence of frailty and subsequent risk of mortality. However, it has not been determined yet whether low-normal ALT values might be predictive of frailty and mortality in younger, middle-aged adults. We conducted a historical prospective cohort analysis. A total of 23,506 adults with ALT levels within the normal range, at the mean age of 48 ± 11 years, participating in an annual screening program for preventive medicine, were followed-up for a median period of 8.5 years during which 638 died. Low-normal ALT values (serum ALT activity <17IU/L) were found to be predictive for increased risk of all-cause mortality (HR=1.6; 95% CI 1.34-1.92; p<0.001). Statistically significant correlation was demonstrated even after applying a multifactorial model correction for age, gender, eGFR, low albumin, arterial hypertension, diabetes mellitus and ischemic heart disease. We suggest that low-normal ALT values may serve as an independent predictive marker for increased long-term mortality in middle-aged adults. Copyright © 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  14. Incremental Predictive Value of Serum AST-to-ALT Ratio for Incident Metabolic Syndrome: The ARIRANG Study.

    PubMed

    Yadav, Dhananjay; Choi, Eunhee; Ahn, Song Vogue; Baik, Soon Koo; Cho, Youn Zoo; Koh, Sang Baek; Huh, Ji Hye; Chang, Yoosoo; Sung, Ki-Chul; Kim, Jang Young

    2016-01-01

    The ratio of aspartate aminotransferase (AST) to alanine aminotransferase (ALT) is of great interest as a possible novel marker of metabolic syndrome. However, longitudinal studies emphasizing the incremental predictive value of the AST-to-ALT ratio in diagnosing individuals at higher risk of developing metabolic syndrome are very scarce. Therefore, our study aimed to evaluate the AST-to-ALT ratio as an incremental predictor of new onset metabolic syndrome in a population-based cohort study. The population-based cohort study included 2276 adults (903 men and 1373 women) aged 40-70 years, who participated from 2005-2008 (baseline) without metabolic syndrome and were followed up from 2008-2011. Metabolic syndrome was defined according to the harmonized definition of metabolic syndrome. Serum concentrations of AST and ALT were determined by enzymatic methods. During an average follow-up period of 2.6-years, 395 individuals (17.4%) developed metabolic syndrome. In a multivariable adjusted model, the odds ratio (95% confidence interval) for new onset of metabolic syndrome, comparing the fourth quartile to the first quartile of the AST-to-ALT ratio, was 0.598 (0.422-0.853). The AST-to-ALT ratio also improved the area under the receiver operating characteristic curve (AUC) for predicting new cases of metabolic syndrome (0.715 vs. 0.732, P = 0.004). The net reclassification improvement of prediction models including the AST-to-ALT ratio was 0.23 (95% CI: 0.124-0.337, P<0.001), and the integrated discrimination improvement was 0.0094 (95% CI: 0.0046-0.0143, P<0.001). The AST-to-ALT ratio independently predicted the future development of metabolic syndrome and had incremental predictive value for incident metabolic syndrome.

  15. Serum gamma-glutamyltransferase, alanine aminotransferase, and aspartate aminotransferase activity in Iranian healthy blood donor men.

    PubMed

    Khedmat, Hossein; Fallahian, Farahnaz; Abolghasemi, Hassan; Hajibeigi, Bashir; Attarchi, Zohre; Alaeddini, Farshid; Holisaz, Mohammad Taghi; Pourali, Masoumeh; Sharifi, Shahin; Zarei, Nasrin

    2007-02-14

    To determine serum gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activity, and to assess their correlation with demographic and clinical findings in healthy blood donors. This cross-sectional study was performed in 934 male blood donors, aged 18 to 68 years, who consecutively attended Tehran blood transfusion service in 2006. All participants were seronegative for HBV or HCV infections, non alcohol users, and all underwent a standard interview and anthropometric tests. Clinical and biochemical parameters including AST, ALT, and GGT activities were determined. Patients taking drugs known to cause hepatic fat deposition were excluded. For AST, ALT, and GGT variables, we used 33.33 and 66.66 percentiles, so that each of them was divided into three tertiles. Mean AST, ALT, and GGT activities were 25.26 +/- 12.58 U/L (normal range 5-35 U/L), 33.13 +/- 22.98 (normal range 5-35 U/L), and 25.11 +/- 18.32 (normal range 6-37 U/L), respectively. By univariate analyses, there were significant associations between increasing AST, ALT, or GGT tertiles and age, body weight, body mass index, and waist and hip circumferences (P<0.05). By multiple linear regression analyses, ALT was found to be positively correlated with dyslipidemia (B=6.988, P=0.038), whereas ALT and AST were negatively correlated with age. AST, ALT, and GGT levels had positive correlation with family history of liver disease (B=15.763, P<0.001), (B=32.345, P<0.001), (B=24.415, P<0.001), respectively. Although we did not determine the cutoffs of the upper normal limits for AST, ALT, and GGT levels, we would suggest screening asymptomatic patients with dyslipidemia and also subjects with a family history of liver disease.

  16. ALT-3 target design and simulations

    SciTech Connect

    Peterson, Jeffrey H

    2011-01-12

    ALT-3 is an experiment being designed in collaboration between Russian VNIIEF scientists and LANL that aims to conduct high velocity material experiments to measure shock velocities and pressures near 1 TPa. The DEMG (Disck Explosive Magnetic Generator) is used to drive> 60MA currents to accelerate an aluminum liner to speeds in excess of 20 km/s. 1-D and 2-D simulations of the aluminum target are presented with information on the free surface velocity profile, the state of the target, and the shock velocity in the target. 2-D simulations are presented showing the different targets available as well as a scenario with a perturbed liner impacter.

  17. ALT-3 Target & CMU Version 4

    SciTech Connect

    Griego, Jeffrey R; Atchison, Walter L.; Holtkamp, David; Oro, David M.; Reinovsky, Robert E.; Rousculp, Christopher L.; Tabaka, Leonard J.

    2012-06-11

    The third Advance Liner Technology (ALT-3) experiment is the next in a long tradition of collaborations between LANL and RFNC/VNIIEF in high-explosive pulsed-power. Here a VNIIEF provided Disk Explosive Magnetic Generator (DEMG) will drive a LANL provided experimental load and diagnostic package. The objective of the experiment is to explore the use of a cylindrical liner-ontarget in tera-Pascal equation of state measurement. This presentation will discuss version 4 of the experimental target and central measuring unit (CMU) along with R & D already performed in fabrication of the target.

  18. Effect of Caffeine-Containing Beverage Consumption on Serum Alanine Aminotransferase Levels in Patients with Chronic Hepatitis C Virus Infection: A Hospital-Based Cohort Study

    PubMed Central

    Sasaki, Yachiyo; Ohfuji, Satoko; Fukushima, Wakaba; Tamori, Akihiro; Enomoto, Masaru; Habu, Daiki; Iwai, Shuji; Uchida-Kobayashi, Sawako; Fujii, Hideki; Shiomi, Susumu; Kawada, Norifumi; Hirota, Yoshio

    2013-01-01

    Introduction To date, there have been no prospective studies examining the effect of coffee consumption on serum alanine aminotransferase (ALT) level among individuals infected with the hepatitis C virus (HCV). We conducted a hospital-based cohort study among patients with chronic HCV infection to assess an association between baseline coffee consumption and subsequent ALT levels for 12 months. Materials and Methods From 1 August 2005 to 31 July 2006, total 376 HCV-RNA positive patients were recruited. A baseline questionnaire elicited information on the frequency of coffee consumption and other caffeine-containing beverages. ALT level as a study outcome was followed through the patients’ medical records during 12 months. The association between baseline beverage consumption and subsequent ALT levels was evaluated separately among patients with baseline ALT levels within normal range (≤45 IU/L) and among those with higher ALT levels (>45 IU/L). Results Among 229 patients with baseline ALT levels within normal range, 186 (81%) retained normal ALT levels at 12 months after recruitment. Daily drinkers of filtered coffee were three times more likely to preserve a normal ALT level than non-drinkers (OR=2.74; P=0.037). However, decaffeinated coffee drinkers had a somewhat inverse effect for sustained normal ALT levels, with marginal significance (OR=0.26; P=0.076). In addition, among 147 patients with higher baseline ALT levels, 39 patients (27%) had ALT reductions of ≥20 IU/L at 12 months after recruitment. Daily drinkers of filtered coffee had a significantly increased OR for ALT reduction (OR=3.79; P=0.034). However, in decaffeinated coffee drinkers, OR could not be calculated because no patients had ALT reduction. Conclusion Among patients with chronic HCV infection, daily consumption of filtered coffee may have a beneficial effect on the stabilization of ALT levels. PMID:24349501

  19. Effect of caffeine-containing beverage consumption on serum alanine aminotransferase levels in patients with chronic hepatitis C virus infection: a hospital-based cohort study.

    PubMed

    Sasaki, Yachiyo; Ohfuji, Satoko; Fukushima, Wakaba; Tamori, Akihiro; Enomoto, Masaru; Habu, Daiki; Iwai, Shuji; Uchida-Kobayashi, Sawako; Fujii, Hideki; Shiomi, Susumu; Kawada, Norifumi; Hirota, Yoshio

    2013-01-01

    To date, there have been no prospective studies examining the effect of coffee consumption on serum alanine aminotransferase (ALT) level among individuals infected with the hepatitis C virus (HCV). We conducted a hospital-based cohort study among patients with chronic HCV infection to assess an association between baseline coffee consumption and subsequent ALT levels for 12 months. From 1 August 2005 to 31 July 2006, total 376 HCV-RNA positive patients were recruited. A baseline questionnaire elicited information on the frequency of coffee consumption and other caffeine-containing beverages. ALT level as a study outcome was followed through the patients' medical records during 12 months. The association between baseline beverage consumption and subsequent ALT levels was evaluated separately among patients with baseline ALT levels within normal range (≤45 IU/L) and among those with higher ALT levels (>45 IU/L). Among 229 patients with baseline ALT levels within normal range, 186 (81%) retained normal ALT levels at 12 months after recruitment. Daily drinkers of filtered coffee were three times more likely to preserve a normal ALT level than non-drinkers (OR=2.74; P=0.037). However, decaffeinated coffee drinkers had a somewhat inverse effect for sustained normal ALT levels, with marginal significance (OR=0.26; P=0.076). In addition, among 147 patients with higher baseline ALT levels, 39 patients (27%) had ALT reductions of ≥20 IU/L at 12 months after recruitment. Daily drinkers of filtered coffee had a significantly increased OR for ALT reduction (OR=3.79; P=0.034). However, in decaffeinated coffee drinkers, OR could not be calculated because no patients had ALT reduction. Among patients with chronic HCV infection, daily consumption of filtered coffee may have a beneficial effect on the stabilization of ALT levels.

  20. Histological and Clinical Characteristics of Patients with Chronic Hepatitis C and Persistently Normal Alanine Aminotransferase Levels

    PubMed Central

    Guzman, Grace

    2014-01-01

    Patients with chronic hepatitis C virus (HCV) infection and persistently normal alanine aminotransferase (PNALT) are generally described to have mild liver disease. The aim of this study was to compare clinical and histological features in HCV-infected patients with PNALT and elevated ALT. Patients presenting to the University of Illinois Medical Center, Chicago, who had biopsy proven HCV, an ALT measurement at the time of liver biopsy, at least one additional ALT measurement over the next 12 months, and liver biopsy slides available for review were identified. PNALT was defined as ALT ≤ 30 on at least 2 different occasions over 12 months. Of 1200 patients with HCV, 243 met the study criteria. 13% (32/243) of patients had PNALT while 87% (211/243) had elevated ALT. Significantly more patients with PNALT had advanced fibrosis (F3 and F4) compared to those with elevated ALT (P = 0.007). There was no significant difference in the histology activity index score as well as mean inflammatory score between the two groups. In conclusion, in a well-characterized cohort of patients at a tertiary medical center, PNALT did not distinguish patients with mild liver disease. PMID:24891947

  1. ALT-I pump limiter experiments

    SciTech Connect

    Goebel, D.M.; Conn, R.W.; Campbell, G.A.; Leung, W.K.; Dippel, K.H.; Finken, K.H.; Wolf, G.H.; Thomas, G.J.; Pontau, A.E.; Hsu, W.

    1987-09-01

    Results from the ALT-I pump limiter experiments in TEXTOR are presented. ALT-I has demonstrated control of the plasma density in a high recycling tokamak by pumping up to 15% of the core efflux. The closed pump limiter designs with restricted entrance geometries to reduce the backflow of neutral gas to the plasma remove over 50% of the ion flux incident on the collection slot. Up to 80% of the entrance ion flux is removed when the edge electron temperature is less than 10 eV and plasma-neutral gas interactions are minimized inside the limiter. Results from a 3-D Monte Carlo neutral gas transport code agree closely with these experimental results. The compound curvature of the head is found to distribute the heat over the surface as predicted in the original designs. Impurity removal experiments demonstrate that significant helium exhaust can be achieved with a pump limiter. During ohmic heating in TEXTOR, the energy and particle confinement times are proportional to the line averaged core density. With ICRH auxiliary heating, tau/sub E/ follow L-mode scaling independent of particle removal by the pump limiter. Pump limiter operation does not directly modify the SOL plasma density and electron temperature, but controls the core plasma density by changing the global recycling at the boundary. The global particle confinement, the particle flux to the limiter, and the edge electron temperature follow the changes in the core density and auxiliary heating power. 25 refs.

  2. HIF3A DNA Methylation Is Associated with Childhood Obesity and ALT

    PubMed Central

    Wang, Shuo; Song, Jieyun; Yang, Yide; Zhang, Yining; Wang, Haijun; Ma, Jun

    2015-01-01

    Gene polymorphisms associated so far with body mass index (BMI) can explain only 1.18–1.45% of observed variation in BMI. Recent studies suggest that epigenetic modifications, especially DNA methylation, could contribute to explain part of the missing heritability, and two epigenetic genome-wide analysis studies (EWAS) have reported that Hypoxia Inducible Factor 3 Alpha Subunit (HIF3A) methylation was associated with BMI or BMI change. We therefore assessed whether the HIF3A methylation is associated with obesity and other obesity-related phenotypes in Chinese children. The subjects included 110 severe obese cases aged 7–17y and 110 normal-weight controls matched by age and gender for measurement of blood DNA methylation levels at the HIF3A gene locus using the Sequenom’s MassARRAY system. We observed significantly higher methylation levels in obese children than in controls at positions 46801642 and 46801699 in HIF3A gene (P<0.05), and found positive associations between methylation and alanine aminotransferase (ALT) levels adjusted by gender, age and BMI at the position 46801699 (r = 0.226, P = 0.007). These results suggest that HIF3A DNA methylation is associated with childhood obesity, and has a BMI-independent association with ALT. The results provide evidence for identifying epigenetic factors of elivated ALT and may be useful for risk assessment and personalized medicine of liver diseases such as non-alcoholic fatty liver disease (NAFLD). PMID:26717317

  3. HIF3A DNA Methylation Is Associated with Childhood Obesity and ALT.

    PubMed

    Wang, Shuo; Song, Jieyun; Yang, Yide; Zhang, Yining; Wang, Haijun; Ma, Jun

    2015-01-01

    Gene polymorphisms associated so far with body mass index (BMI) can explain only 1.18-1.45% of observed variation in BMI. Recent studies suggest that epigenetic modifications, especially DNA methylation, could contribute to explain part of the missing heritability, and two epigenetic genome-wide analysis studies (EWAS) have reported that Hypoxia Inducible Factor 3 Alpha Subunit (HIF3A) methylation was associated with BMI or BMI change. We therefore assessed whether the HIF3A methylation is associated with obesity and other obesity-related phenotypes in Chinese children. The subjects included 110 severe obese cases aged 7-17y and 110 normal-weight controls matched by age and gender for measurement of blood DNA methylation levels at the HIF3A gene locus using the Sequenom's MassARRAY system. We observed significantly higher methylation levels in obese children than in controls at positions 46801642 and 46801699 in HIF3A gene (P<0.05), and found positive associations between methylation and alanine aminotransferase (ALT) levels adjusted by gender, age and BMI at the position 46801699 (r = 0.226, P = 0.007). These results suggest that HIF3A DNA methylation is associated with childhood obesity, and has a BMI-independent association with ALT. The results provide evidence for identifying epigenetic factors of elivated ALT and may be useful for risk assessment and personalized medicine of liver diseases such as non-alcoholic fatty liver disease (NAFLD).

  4. Molecular and phenotypic characterization of transgenic wheat and sorghum events expressing the barley alanine aminotransferase.

    PubMed

    Peña, Pamela A; Quach, Truyen; Sato, Shirley; Ge, Zhengxiang; Nersesian, Natalya; Dweikat, Ismail M; Soundararajan, Madhavan; Clemente, Tom

    2017-08-11

    The expression of a barley alanine aminotransferase gene impacts agronomic outcomes in a C3 crop, wheat. The use of nitrogen-based fertilizers has become one of the major agronomic inputs in crop production systems. Strategies to enhance nitrogen assimilation and flux in planta are being pursued through the introduction of novel genetic alleles. Here an Agrobacterium-mediated approach was employed to introduce the alanine aminotransferase from barley (Hordeum vulgare), HvAlaAT, into wheat (Triticum aestivum) and sorghum (Sorghum bicolor), regulated by either constitutive or root preferred promoter elements. Plants harboring the transgenic HvAlaAT alleles displayed increased alanine aminotransferase (alt) activity. The enhanced alt activity impacted height, tillering and significantly boosted vegetative biomass relative to controls in wheat evaluated under hydroponic conditions, where the phenotypic outcome across these parameters varied relative to time of year study was conducted. Constitutive expression of HvAlaAT translated to elevation in wheat grain yield under field conditions. In sorghum, expression of HvAlaAT enhanced enzymatic activity, but no changes in phenotypic outcomes were observed. Taken together these results suggest that positive agronomic outcomes can be achieved through enhanced alt activity in a C3 crop, wheat. However, the variability observed across experiments under greenhouse conditions implies the phenotypic outcomes imparted by the HvAlaAT allele in wheat may be impacted by environment.

  5. Serum alanine aminotransferase elevation during 10 days of acetaminophen administration in non-drinkers

    PubMed Central

    Heard, Kennon J.; Green, Jody L.; Dart, Richard C.

    2011-01-01

    Asymptomatic alanine aminotransferase (ALT) elevations have been detected with acetaminophen use at the maximum daily dose of 4 grams/day (g/d) for more than 3 consecutive days in subjects with and without concurrent ethanol use. The purpose of this study is to describe the changes in serum ALT activity in non-drinkers treated with acetaminophen for 10 days. Methods Study Objective to describe the change in serum ALT in non-drinkers administered acetaminophen for 10 days. Study Design: Prospective, single arm trial. Setting: Outpatients. Interventions: Acetaminophen 4 g/day starting on day study day 1. Measurements: Serum ALT, total billirubin and international normalized ratio (INR) were measured on study day 0, 4, 7, 9, 11 and 14. Main Results Twenty four subjects completed the trial. Median ALT increased from 24 IU/L at day 0 to 39 IU/L by day 7, remained elevated through day 11 (38 IU/L) and began to trend down by day 14 (35 IU/L). The increase in ALT during the study was statistically significant (p= 0.0002). Sixty-six percent of subjects had an ALT above the upper limits of normal at day 11; the largest elevation was 3.8 the upper limits of normal. No subject developed symptoms of liver injury or had an elevation in INR or serum bilirubin. Conclusions Daily use of acetaminophen at the daily maximum dose of 4 g/day for 10 days causes asymptomatic ALT elevations in subjects who do not consume ethanol. PMID:20653358

  6. Endocannabinoid receptor blockade reduces alanine aminotransferase in polycystic ovary syndrome independent of weight loss.

    PubMed

    Dawson, Alison J; Kilpatrick, Eric S; Coady, Anne-Marie; Elshewehy, Abeer M M; Dakroury, Youssra; Ahmed, Lina; Atkin, Stephen L; Sathyapalan, Thozhukat

    2017-07-14

    Evidence suggests that endocannabinoid system activation through the cannabinoid receptor 1 (CB1) is associated with enhanced liver injury, and CB1 antagonism may be beneficial. The aim of this study was to determine the impact of rimonabant (CB1 antagonist) on alanine aminotransferase (ALT), a hepatocellular injury marker, and a hepatic inflammatory cytokine profile. Post hoc review of 2 studies involving 50 obese women with PCOS and well matched for weight, randomised to weight reducing therapy; rimonabant (20 mg od) or orlistat (120 mg tds), or to insulin sensitising therapy metformin, (500 mg tds), or pioglitazone (45 mg od). No subject had non-alcoholic fatty liver disease (NAFLD). Treatment with rimonabant for 12 weeks reduced both ALT and weight (p < 0.01), and there was a negative correlation between Δ ALT and Δ HOMA-IR (p < 0.001), but not between Δ ALT and Δ weight. There was a significant reduction of weight with orlistat (p < 0.01); however, orlistat, metformin and pioglitazone had no effect on ALT. The free androgen index fell in all groups (p < 0.05). The inflammatory marker hs-CRP was reduced by pioglitazone (p < 0.001) alone and did not correlate with changes in ALT. The inflammatory cytokine profile for IL-1β, IL-6, IL-7, IL-10, IL12, TNF-α, MCP-1 and INF-γ did not differ between groups. None of the interventions had an effect on biological variability of ALT. Rimonabant through CB1 receptor blockade decreased serum ALT that was independent of weight loss and hepatic inflammatory markers in obese women with PCOS without NAFLD. ISRCTN58369615 (February 2007; retrospectively registered) ISRCTN75758249 (October 2007; retrospectively registered).

  7. Trunk Fat is Associated with Increased Serum Levels of Alanine Aminotransferase in the US

    PubMed Central

    Ruhl, Constance E.; Everhart, James E.

    2010-01-01

    Background & Aims Liver injury is associated with obesity and related measures such as body mass index (BMI) and waist circumference. The relationship between liver injury and body composition has not been evaluated in a population-based study. Methods Using data from a US population-based survey, we examined the contributions of body composition, measured by dual-energy x-ray absorptiometry (DXA), to increased serum alanine aminotransferase (ALT) activity among 11,821 adults without viral hepatitis. Trunk fat, extremity fat, trunk lean, and extremity lean mass were divided by height squared and used to categorize subjects into quintiles; logistic regression odds ratios (OR) were calculated for increased ALT. Results Increased ALT was associated with higher measures of fat and lean mass (p<0.001) after adjustment for alcohol consumption and other liver injury risk factors in separate models for each DXA measure. Trunk fat was associated with increased ALT (p≤0.001) in models also including any 1 of the other 3 measures. Extremity fat was independently inversely associated among women (p<0.001). Trunk and extremity lean mass were not independently related to increased ALT. In models that contained all 4 DXA measures, the OR (95% confidence interval) for increased ALT for the highest, relative to lowest, quintile of trunk fat/height squared was 13.8 (5.4-35.3) for men and 7.8 (3.9-15.8) for women. When BMI, waist circumference, and trunk fat were considered together, only trunk fat remained independently associated with increased ALT. Conclusions Trunk fat is a major body composition determinant of increased ALT, supporting the hypothesis that liver injury can be induced by metabolically active intra-abdominal fat. PMID:20060831

  8. Association between Elevated Alanine Aminotransferase and Urosepsis in Children with Acute Pyelonephritis

    PubMed Central

    Kim, Dongwan; Lee, Sung Hyun; Ryoo, Eell; Cho, Hye Kyung; Kim, Yun Mi

    2016-01-01

    Purpose The aim of this study is to investigate the association between elevated alanine aminotransferase (ALT) and urosepsis in children with acute pyelonephritis (APN). Methods We retrospectively identified all children who were managed in our hospital with APN during a decade period. In our study a diagnosis of APN was defined as having a positive urine culture and a positive (99m)Tc-dimercaptosuccinic acid scintigraphy. We compared those with elevated ALT and those with normal ALT according to the following variables: age, gender, duration of fever prior to admission, presence of hypotension, C-reactive protein (CRP), creatinine, presence of anemia, white blood cells count, platelet count, blood culture result, and grades of vesicoureteral reflux. In addition, the correlation between elevated ALT and positive blood culture was analyzed in detail. Results A total of 996 children were diagnosed with APN, of which 883 were included in the study. ALT was elevated in 81 children (9.2%). In the analysis of demographic characteristics, the number of children with elevated ALT was higher in children between 0 to 3 months, boys, and in those with positive blood culture (p=0.002, 0.036, and 0.010, respectively). In multivariate analysis of variables associated with positive blood culture, age younger than 3 months, elevated ALT, elevated CRP, and elevated creatinine showed statistical significance (p=0.004, 0.030, 0.043, and 0.044, respectively). Conclusion Our study demonstrates the association between elevated ALT and increased prevalence of urosepsis in addition to elevated CRP, elevated creatinine, and age younger than 3 months in children with APN. PMID:27066449

  9. Frequency of hepatitis C viral RNA in anti-hepatitis C virus non- reactive blood donors with raised alanine aminotransferase.

    PubMed

    Ali, Nadir; Ahmed, Syed Azhar; Moinuddin; Hoch, Susan Fisher; Chotani, Rashid A

    2011-12-01

    The objective of this study was to find out the frequency of HCV RNA in anti-HCV non-reactive blood donors with raised alanine amino transferase (ALT). The study was conducted at Baqai Institute of Haematology, Baqai Medical University, Karachi, in collaboration with Combined Military Hospital, Malir Cantt, Karachi. The demographic data of blood donors was recorded, and anti-HCV, HBsAg and HIV were screened. Four hundred consecutive donors with raised ALT above the reference range were included in study. HCV RNA RT-PCR was performed on 5 sample minipools using Bio-Rad Real time PCR equipment. HCV RNA was detected in 1/400 (0.25%) blood donors. Finding of raised ALT in blood donors warrants further investigations. In case, if raised ALT is unexplained presence of HCV RNA may be suspected.

  10. Layout modification for library cell Alt-PSM composability

    NASA Astrophysics Data System (ADS)

    Cao, Ke; Hu, Jiang; Cheng, Mosong

    2004-05-01

    In sub-wavelength lithography, light field Alt-PSM (Alternating Phase Shifting Mask) is an essential technology for poly layer printability. In a standard cell based design, the problem of obtaining Alt-PSM compliance for an individual cell layout has been solved well [3]. However, placing Alt-PSM compliant cells together can not guarantee Alt-PSM compliance of the entire chip/block layout due to phase interactions among adjacent cells. A simple solution to this Alt-PSM composability problem is to wrap blank area around each cell, which is very inefficient on chip area usage. In this paper, we formulate the composability problem as a graph model and propose a polynomial time optimal algorithm to achieve Alt-PSM composability with the least impact on cell layout.

  11. Dose-Response Relationship between Alanine Aminotransferase Levels within the Reference Interval and Metabolic Syndrome in Chinese Adults

    PubMed Central

    Wu, Peipei; Chen, Qicai; Chen, Lili; Zhang, Pengpeng; Xiao, Juan; Chen, Xiaoxiao; Liu, Meng

    2017-01-01

    Purpose Elevation in serum alanine aminotransferase (ALT) levels is a biomarker for metabolic syndrome (MS); however, the relationship has not been fully investigated within the reference interval of ALT levels. Our objective was to explore the relationship between serum ALT levels within the reference interval and MS in Chinese adults. Materials and Methods This cross-sectional study included 16028 adults, who attended routine health check-ups at Shengli Oilfield Central Hospital from January 2006 to March 2012. The reference interval of serum ALT level was defined as less than 40 U/L. Logistic regression models and restricted cubic spline were used to evaluate the association of ALT with MS. Results The prevalence of MS in the total population was 13.7% (6.4% for females and 18.4% for males). Multiple logistic regression showed that ALT levels were positively associated with MS after adjustment for potential confounding factors. The odds ratio of MS in the top quartile was 4.830 [95% confidence interval (CI): 2.980–7.829] in females and 3.168 (95% CI: 2.649–3.790) in males, compared with the ALT levels in the bottom quartile. The restricted cubic spline models revealed a positive non-linear dose-response relationship between ALT levels and the risk of MS in women (p for nonlinearity was 0.0327), but a positive linear dose-response relationship in men (p for nonlinearity was 0.0659). Conclusion Serum ALT levels within the reference interval are positively associated with MS in a dose-response manner. Elevated ALT levels, even within the reference interval, may reflect early dysmetabolic changes. PMID:27873509

  12. Alanine aminotransferase normalization at week 8 predicts viral response during hepatitis C treatment.

    PubMed

    Dogan, Umit Bilge; Akin, Mustafa Salih; Yalaki, Serkan

    2013-12-14

    To investigate alanine aminotransferase (ALT) and sustained virological response (SVR) in chronic hepatitis C (CHC) during peginterferon-ribavirin treatment. One hundred and fifty-one genotype 1 CHC patients underwent treatment for 48 wk with peginterferon and ribavirin, and were retrospectively divided into two groups as having a rapid virological response (RVR) (Group 1, n = 52) and not having an RVR (Group 2, n = 99). We also subdivided each group into two according to the initial ALT level being high (Group 1h and Group 2h) or normal (Group 1n and Group 2n). HCV RNA and ALT levels were measured at baseline; at 4, 12, 24 and 48 wk during the treatment period; and at 24 wk follow-up. ALT levels were also obtained at 8 wk. According to the results of ALT, patients were enrolled in either the follow-up abnormal or follow-up normalized ALT groups at each interval. Patients with high and normal ALT levels were compared for each interval in terms of SVR. The SVR rates were 83% vs 40% (P = 0.000), 82% vs 84% (P = 0.830), and 37% vs 44% (P = 0.466) when comparing Group 1 with 2, 1h with 1n, and 2h with 2n, respectively. In Group 2h, the SVR rates were 34% vs 40% (P = 0.701), 11% vs 52% (P = 0.004), 12% vs 50% (P = 0.007), 7% vs 50% (P = 0.003), 6% vs 53% (P = 0.001), and 0% vs 64% (P = 0.000) when comparing patients with high and normalized ALT levels at week 4, 8, 12, 24, 48 and 72, respectively. The multiple logistic regression analysis revealed that RVR (OR = 7.05; 95%CI: 3.1-16.05, P = 0.000), complete early virological response (cEVR) (OR = 17.55; 95%CI: 6.32-48.76, P = 0.000), normalization of ALT at 8 wk (OR = 3.04; 95%CI: 1.31-7.06, P = 0.008), and at 12 wk (OR = 4.21; 95%CI: 1.65-10.76, P = 0.002) were identified as independent significant predictive factors for SVR. Normalization of ALT at 8 wk may predict viral response during peginterferon-ribavirin treatment in genotype-1 CHC patients especially without RVR.

  13. Inhibitors of alanine racemase enzyme: a review.

    PubMed

    Azam, Mohammed Afzal; Jayaram, Unni

    2016-08-01

    Alanine racemase is a fold type III PLP-dependent amino acid racemase enzyme catalysing the conversion of l-alanine to d-alanine utilised by bacterial cell wall for peptidoglycan synthesis. As there are no known homologs in humans, it is considered as an excellent antibacterial drug target. The standard inhibitors of this enzyme include O-carbamyl-d-serine, d-cycloserine, chlorovinyl glycine, alaphosphin, etc. d-Cycloserine is indicated for pulmonary and extra pulmonary tuberculosis but therapeutic use of drug is limited due to its severe toxic effects. Toxic effects due to off-target affinities of cycloserine and other substrate analogs have prompted new research efforts to identify alanine racemase inhibitors that are not substrate analogs. In this review, an updated status of known inhibitors of alanine racemase enzyme has been provided which will serve as a rich source of structural information and will be helpful in generating selective and potent inhibitor of alanine racemase.

  14. [Raman scattering study of DL-alanine].

    PubMed

    Gong, Yan; Wang, Wen-qing

    2006-01-01

    Studies of Raman vibration spectra are useful to obtaining information on biomolecular crystals. The cell dimensions of the L- and DL-alanine crystals are nearly identical, and both structures belong to the orthorhombic system, but the space group is P2(1) 2(1) 2(1) for the L-isomer, and Pna2(1) for the racemate crystal. The Raman spectrum of L-alanine has been measured by many authors. The present work is focusing on the Raman scattering study of DL-alanine powder. Based on the analysis of the differences between DL-alanine and L-alanine Raman spectra, the authors obtained indispensable information on hydrogen bond and the motion of the molecular conformation in alanine crystals.

  15. A systems biology approach to understanding elevated serum alanine transaminase levels in a clinical trial with ximelagatran.

    PubMed

    Andersson, Ulf; Lindberg, Johan; Wang, Shunghuang; Balasubramanian, Raji; Marcusson-Ståhl, Maritha; Hannula, Mira; Zeng, Chenhui; Juhasz, Peter J; Kolmert, Johan; Bäckström, Jonas; Nord, Lars; Nilsson, Kerstin; Martin, Steve; Glinghammar, Björn; Cederbrant, Karin; Schuppe-Koistinen, Ina

    2009-12-01

    Ximelagatran was developed for the prevention and treatment of thromboembolic conditions. However, in long-term clinical trials with ximelagatran, the liver injury marker, alanine aminotransferase (ALT) increased in some patients. Analysis of plasma samples from 134 patients was carried out using proteomic and metabolomic platforms, with the aim of finding predictive biomarkers to explain the ALT elevation. Analytes that were changed after ximelagatran treatment included 3-hydroxybutyrate, pyruvic acid, CSF1R, Gc-globulin, L-glutamine, protein S and alanine, etc. Two of these analytes (pyruvic acid and CSF1R) were studied further in human cell cultures in vitro with ximelagatran. A systems biology approach applied in this study proved to be successful in generating new hypotheses for an unknown mechanism of toxicity.

  16. Vibrational dynamics of crystalline L-alanine

    SciTech Connect

    Bordallo, H.N.; Eckert, J.; Barthes, M.

    1997-11-01

    The authors report a new, complete vibrational analysis of L-alanine and L-alanine-d{sub 4} which utilizes IINS intensities in addition to frequency information. The use of both isotopomers resulted in a self-consistent force field for and assignment of the molecular vibrations in L-alanine. Some details of the calculation as well as a comparison of calculated and observed IINS spectra are presented. The study clarifies a number of important issues on the vibrational dynamics of this molecule and presents a self-consistent force field for the molecular vibrations in crystalline L-alanine.

  17. The influence of magnesium on the activity of some enzymes (AST, ALT, ALP) and lead content in some tissues.

    PubMed

    Todorovic, Tatjana; Vujanovic, Dragana

    2002-12-01

    Many authors in different studies have reported the antagonism between Mg and Pb. Our previous results suggested that oral Mg treatment have better effect on investigation biochemical parameters (protoporphyrins, aminolevulinic acid--ALA and d-aminolevulinic dehydratase ALA-D) used in evaluating Pb intoxication, then CaNa2EDTA, chelation agents, currently used in therapy of Pb intoxication. The toxic effect of Pb induced considerably modifies the activity of many other enzymes. In this work we have examined the influence of Mg (as alternative therapy of Pb poisoning) on enzymes activity--biochemical markers for general health conditions--aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in condition of lead intoxication. Many studies showed disturbances of activity ALT, AST and ALP. The aim of this study was to confirm positive effects of Mg intake in condition of such intoxication at the level on activity of investigated enzymes. The experiment was performed on 45 male Wister rats, divided in three groups. I--control group; II--group treated daily for 30 days with 100 mg Pb, per kg body weight and next 60 without Pb treatment (spontaneous detoxication); III group--the same treatment as II group for the first 30 days, but next 60 days rats were treated orally with 40 mg Mg/kg body weight. Activity of AST and ALT was significant increased in condition of Pb poisoning, but ALP activity was significant reduced. Influence of excessive oral Mg treatment was positive: decrease of AST activity and ALT activity, which was probably in correlation with significant elimination of Pb from liver and increase of ALT enzyme activity at the normal level.

  18. New pediatric percentiles of liver enzyme serum levels (ALT, AST, GGT): Effects of age, sex, BMI and pubertal stage.

    PubMed

    Bussler, Sarah; Vogel, Mandy; Pietzner, Diana; Harms, Kristian; Buzek, Theresa; Penke, Melanie; Händel, Norman; Körner, Antje; Baumann, Ulrich; Kiess, Wieland; Flemming, Gunter

    2017-09-19

    The present study aims to clarify the effects of sex, age, BMI and puberty on transaminase serum levels in children and adolescents and to provide new age- and sex-related percentiles for alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyltransferase (GGT). Venous blood and anthropometric data were collected from 4,126 cases. Excluded were cases of participants with potential hepatotoxic medication, with evidence of potential illness at the time of blood sampling and non-normal BMI (BMI < 10(th) or > 90(th) ). The resulting data (N = 3,131 cases) were used for the calculations of ALT, AST, and GGT percentiles. Age- and sex-related reference intervals were established by using an LMSP-type method. Serum levels of transaminases follow age-specific patterns and relate to the onset of puberty. This observation is more pronounced in girls than in boys. The ALT percentiles showed similar shaped patterns in both sexes. Multivariate regression confirmed significant effects of puberty and BMI-SDS (β = 2.21) on ALT. Surprisingly, AST serum levels were negatively influenced by age (β = -1.42) and BMI-SDS (β = -0.15). The GGT percentiles revealed significant sex-specific differences, correlated positively with age (β = 0.37) and showed significant association with BMI-SDS (β = 1.16). Current reference values of ALT, AST and GGT serum levels were calculated for children between 11 months and 16.0 years, using modern analytical and statistical methods. This study extends the current knowledge about transaminases by revealing influences of age, sex, BMI, and puberty on the serum concentrations of all three parameters and has for these parameters one of the largest sample sizes published so far. This article is protected by copyright. All rights reserved. © 2017 by the American Association for the Study of Liver Diseases.

  19. Catalytic Stereoinversion of L-Alanine to Deuterated D-Alanine.

    PubMed

    Moozeh, Kimia; So, Soon Mog; Chin, Jik

    2015-08-03

    A combination of an achiral pyridoxal analogue and a chiral base has been developed for catalytic deuteration of L-alanine with inversion of stereochemistry to give deuterated D-alanine under mild conditions (neutral pD and 25 °C) without the use of any protecting groups. This system can also be used for catalytic deuteration of D-alanine with retention of stereochemistry to give deuterated D-alanine. Thus a racemic mixture of alanine can be catalytically deuterated to give an enantiomeric excess of deuterated D-alanine. While catalytic deracemization of alanine is forbidden by the second law of thermodynamics, this system can be used for catalytic deracemization of alanine with deuteration. Such green and biomimetic approach to catalytic stereocontrol provides insights into efficient amino acid transformations.

  20. Correlation of serum alanine aminotransferase and aspartate aminotransferase with coronary heart disease

    PubMed Central

    Shen, Jianying; Zhang, Jingying; Wen, Jing; Ming, Qiang; Zhang, Ji; Xu, Yawei

    2015-01-01

    Objective: This study aimed to explore the relationship between different risk factors (especially serum alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and coronary heart disease (CHD). Methods: A total of 610 inpatients were recruited. Initial coronary angiography (CAG) was performed to evaluate the severity of coronary lesions. On the basis of findings from CAG, patients were divided into control group (n=260) and CHD group (n=350). Logistic regression analysis was employed for the evaluation of clinical characteristics and biochemical parameters, aiming to explore the relationship between risk factors (including AST and ALT) and CHD. Results: Results showed type 2 diabetes, hypertension, dyslipidemia, smoking and family history of CHD were clinical risk factors of CHD. Laboratory examinations showed the serum levels of triglycerides, low-density lipoprotein, AST and ALT in CHD group were significantly higher than those in control group (P<0.05). Of these parameters, the AST was 50.98±8.12 U/L in CHD group and 20.14±3.94 U/L in control group (P<0.01); the ALT was 42.31±8.34 U/L in CHD group and 18.25±6.38 U/L in control group (P<0.01). Conclusion: The serum levels of AST and ALT in CHD patients are higher than those in controls. High serum AST and ALT are biochemical markers which can be used to predict the severity of CHD and are also independent risk factors of CHD. PMID:26064360

  1. Prevalence of elevated alanine transaminase in Australia and its relationship to metabolic risk factors: A cross-sectional study of 9,447 people.

    PubMed

    Mahady, Suzanne E; Gale, Joanne; Macaskill, Petra; Craig, Jonathan C; George, Jacob

    2017-01-01

    Elevated alanine transaminase (ALT) is a strong predictor of metabolic syndrome, but there are few data from the Australian population. We aimed to determine the prevalence of elevated ALT and association with metabolic risk factors. In this cross-sectional study including adult participants (N = 9,447) from a nationwide, population-based survey, we assessed the prevalence of elevated ALT [defined as ≥ 40 IU/L (men) and ≥ 30 IU/L (women) as baseline, and ALT as ≥ 30 IU/L (men) and ≥ 19 IU/L (women) as lower threshold], distribution of metabolic risk factors, and independent predictors of elevated ALT in logistic regression models. Analyses were weighted to the population with population weights. Elevated ALT levels were found in 11.2% of the Australian population. People with elevated ALT were younger (43 vs 46 yrs) with more truncal adiposity (100 vs 91 cm), higher pro-atherogenic lipids and glucose and exercised less (120 vs 160 min per week, P < 0.05 for all analyses). Regression analyses indicated that younger age, male sex, diabetes, triglycerides, apolipoprotein B, and waist circumference were independent predictors of elevated ALT. The population attributable fraction of elevated ALT due to truncal obesity was estimated at 47%. These data demonstrate a high prevalence of elevated ALT in the general population that is closely associated with metabolic risk factors. Individuals with elevated ALT should be evaluated for co-existent metabolic disorders. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  2. Histological features and HLA class II alleles in hepatitis C virus chronically infected patients with persistently normal alanine aminotransferase levels.

    PubMed

    Renou, C; Halfon, P; Pol, S; Cacoub, P; Jouve, E; Bronowicki, J P; Arpurt, J P; Rifflet, H; Picon, M; Causse, X; Canva, V; Denis, J; Tran, A; Bourliére, M; Ouzan, D; Pariente, A; Dantin, S; Alric, L; Cartier, V; Reville, M; Caillat-Zucman, S

    2002-10-01

    A significant proportion of individuals with chronic hepatitis C virus (HCV) infection have persistently normal alanine aminotransferase (ALT) levels. Although data are controversial, such patients usually have weaker histological damage and a lower progression rate of fibrosis. The aims of this study were: (1) to compare demographic, virological, and histological parameters of HCV patients with normal ALT values with those of HCV patients with elevated ALT levels; and (2) to determine whether HLA class II alleles contribute to the persistence of normal ALT levels in HCV patients. Eighty three patients with chronic HCV infection and persistently normal ALT values (group 1) and 233 patients with chronic HCV infection and elevated ALT levels (group 2) were studied. Histological features were expressed using Knodell and Metavir scores. HLA DRB1* and DQB1* genotyping was performed using hybridisation with sequence specific oligonucleotides after genomic amplification. The kappa2 and Fisher's exact tests were used to compare discrete variables and phenotype frequencies between the two groups, and Wilcoxon's test was used for continuous variables. A multivariate logistic regression model was used to determine which variables predicted normal ALT values. ALT levels were correlated with the severity of liver damage. In group 1, 93% of patients had an F0 or F1 Metavir index of fibrosis compared with 47% of patients in group 2 (p<0.001). A longer duration of infection (p<0.001) and increased DRB1*11 phenotype frequency (pc=0.03) were observed among patients with normal ALT. The two groups did not differ with regard to the mode of contamination or viral genotype. After logistic regression, young age (p=0.0008), female sex (p=0.01), long duration of infection (p=0.0001), and HLA DRB1*11 (p=0.050) were more strongly associated with persistence of normal ALT. Our study confirms that patients with chronic hepatitis C and normal ALT levels have less severe liver disease than those

  3. PNPLA3 I148M polymorphism is associated with elevated alanine transaminase levels in Mexican Indigenous and Mestizo populations.

    PubMed

    Larrieta-Carrasco, Elena; Acuña-Alonzo, Victor; Velázquez-Cruz, Rafael; Barquera-Lozano, Rodrigo; León-Mimila, Paola; Villamil-Ramírez, Hugo; Menjivar, Marta; Romero-Hidalgo, Sandra; Méndez-Sánchez, Nahúm; Cárdenas, Vanessa; Bañuelos-Moreno, Manuel; Flores, Yvonne N; Quiterio, Manuel; Salmerón, Jorge; Sánchez-Muñoz, Fausto; Villarreal-Molina, Teresa; Aguilar-Salinas, Carlos A; Canizales-Quinteros, Samuel

    2014-07-01

    The patatin like phospholipase domain-containing (PNPLA3) I148M variant is the strongest genetic factor associated with elevated alanine transaminase (ALT) levels in different populations, particularly in Hispanics who have the highest 148M risk allele frequency reported to date. It has been suggested that Indigenous ancestry is associated with higher ALT levels in Mexicans. The aim of the present study was to assess the frequency of the PNPLA3 148M risk allele in Mexican indigenous and Mestizo individuals, and to examine its association with serum ALT levels. The study included a total of 1624 Mexican individuals: 919 Indigenous subjects from five different native groups and 705 Mexican Mestizo individuals (141 cases with ALT levels ≥ 40 U/L and 564 controls with ALT <40 U/L). The I148M polymorphism was genotyped by TaqMan assays. The frequency of elevated ALT levels in Indigenous populations was 18.7%, and varied according to obesity status: 14.4% in normal weight, 19.9% in overweight and 24.5% in obese individuals. The Mexican indigenous populations showed the highest reported frequency of the PNPLA3 148M risk allele (mean 0.73). The M148M genotype was significantly associated with elevated ALT levels in indigenous individuals (OR = 3.15, 95 % CI 1.91-5.20; P = 7.1 × 10(-6)) and this association was confirmed in Mexican Mestizos (OR = 2.24, 95% CI 1.50-3.33; P = 8.1 × 10(-5)). This is the first study reporting the association between M148M genotype and elevated ALT levels in Indigenous Mexican populations. The 148M allele risk may be considered an important risk factor for liver damage in Mexican indigenous and Mestizo populations.

  4. Alanine increases blood pressure during hypotension

    NASA Technical Reports Server (NTRS)

    Conlay, L. A.; Maher, T. J.; Wurtman, R. J.

    1990-01-01

    The effect of L-alanine administration on blood pressure (BP) during haemorrhagic shock was investigated using anesthetized rats whose left carotid arteries were cannulated for BP measurement, blood removal, and drug administration. It was found that L-alanine, in doses of 10, 25, 50, 100, and 200 mg/kg, increased the systolic BP of hypotensive rats by 38 to 80 percent (while 100 mg/kg pyruvate increased BP by only 9.4 mmhg, not significantly different from saline). The results suggest that L-alanine might influence cardiovascular function.

  5. Alanine increases blood pressure during hypotension

    NASA Technical Reports Server (NTRS)

    Conlay, L. A.; Maher, T. J.; Wurtman, R. J.

    1990-01-01

    The effect of L-alanine administration on blood pressure (BP) during haemorrhagic shock was investigated using anesthetized rats whose left carotid arteries were cannulated for BP measurement, blood removal, and drug administration. It was found that L-alanine, in doses of 10, 25, 50, 100, and 200 mg/kg, increased the systolic BP of hypotensive rats by 38 to 80 percent (while 100 mg/kg pyruvate increased BP by only 9.4 mmhg, not significantly different from saline). The results suggest that L-alanine might influence cardiovascular function.

  6. Production of Alanine by Fusarium moniliforme

    PubMed Central

    Carito, Sebastian L.; Pisano, Michael A.

    1966-01-01

    Fusarium moniliforme grown in a chemically defined medium in submerged culture accumulated amino acids extracellularly. Alanine and glutamic acid were present in greatest amounts, with traces of glycine, lysine, threonine, and valine detectable. Increasing the glucose and urea concentrations of the medium increased yields of alanine. Further increases in alanine production occurred with elevated levels of mineral salts in the medium, whereas the addition of a vitamin mixture proved to be inhibitory. Chemical changes resulting from the growth of F. moniliforme in the final fermentation medium disclosed maximal alanine production, mycelial weight, and glucose consumption after 72 hr of incubation at 28.5 C. Total soluble nitrogen, by contrast, was minimal at the same time period. The pH remained in the alkaline range throughout the fermentation. PMID:5914495

  7. The alanine racemase of Mycobacterium smegmatis is essential for growth in the absence of D-alanine.

    PubMed

    Milligan, Daniel L; Tran, Sieu L; Strych, Ulrich; Cook, Gregory M; Krause, Kurt L

    2007-11-01

    Alanine racemase, encoded by the gene alr, is an important enzyme in the synthesis of d-alanine for peptidoglycan biosynthesis. Strains of Mycobacterium smegmatis with a deletion mutation of the alr gene were found to require d-alanine for growth in both rich and minimal media. This indicates that alanine racemase is the only source of d-alanine for cell wall biosynthesis in M. smegmatis and confirms alanine racemase as a viable target gene for antimycobacterial drug development.

  8. ALT-II armor tile design for upgraded TEXTOR operation

    SciTech Connect

    Newberry, B.L.; McGrath, R.T.; Watson, R.D.; Kohlhaas, W.; Finken, K.H.; Noda, N.

    1994-08-01

    The upgrade of the TEXTOR tokamak at KFA Juelich was recently completed. This upgrade extended the TEXTOR pulse length from 5 seconds to 10 seconds. The auxiliary heating was increased to a total of 8.0 MW through a combination of neutral beam injection and radio frequency heating. Originally, the inertially cooled armor tiles of the full toroidal belt Advanced Limiter Test -- II (ALT-II) were designed for a 5-second operation with total heating of 6.0 MW. The upgrade of TEXTOR will increase the energy deposited per pulse onto the ALT-II by about 300%. Consequently, the graphite armor tiles for the ALT-II had to be redesigned to avoid excessively high graphite armor surface temperatures that would lead to unacceptable contamination of the plasma. This redesign took the form of two major changes in the ALT-II armor tile geometry. The first design change was an increase of the armor tile thermal mass, primarily by increasing the radial thickness of each tile from 17 mm to 20 mm. This increase in the radial tile dimension reduces the overall pumping efficiency of the ALT-II pump limiter by about 30%. The reduction in exhaust efficiency is unfortunate, but could be avoided only by active cooling of the ALT-II armor tiles. The active cooling option was too complicated and expensive to be considered at this time. The second design change involved redefining the plasma facing surface of each armor tile in order to fully utilize the entire surface area. The incident charged particle heat flux was distributed uniformly over the armor tile surfaces by carefully matching the radial, poloidal and toroidal curvature of each tile to the plasma flow in the TEXTOR boundary layer. This geometry redefinition complicates the manufacturing of the armor tiles, but results in significant thermal performance gains. In addition to these geometry upgrades, several material options were analyzed and evaluated.

  9. ALT-II armor tile design for upgraded TEXTOR operation

    SciTech Connect

    Newberry, B.L.; McGrath, R.T.; Watson, R.D.

    1994-12-31

    The upgrade of the TEXTOR tokamak at KFA Julich will be completed in the spring of 1994. The upgrade will extend the TEXTOR pulse length from 5 seconds to 10 seconds. The auxiliary heating systems are also scheduled to be upgraded so that eventually a total of 8.0 MW auxiliary heating will be available through a combination of neutral beam injection and radio frequency heating. Originally, the inertially cooled armor tiles on the full toroidal belt Advanced Limiter Test - II (ALT-II) were designed for 5-second operation with a total heating power of 6.0 MW. The upgrade of TEXTOR will increase the energy deposited per pulse onto ALT-II by more than 300%. Consequently, the graphite armor tiles for ALT-II had to be redesigned in order to increase their thermal inertia and, thereby, avoid excessively high graphite armor surface temperatures that would lead to unacceptable contamination of the plasma. The armor tile thermal inertia had been increase primarily by expanding the radial thickness of the tiles from 17 mm to 20 mm. This increase in radial tile dimension will reduce the overall pumping efficiency of the ALT-II pump limiter by about 30%. The final armor tile design was a compromise between increasing the power handling capability and reducing the particle exhaust efficiency of ALT-II. The reduction in exhaust efficiency is unfortunate, but could only be avoided by active cooling of the ALT-II armor tiles. The active cooling option was too complicated and expensive to be considered at this time.

  10. β-Alanine supplementation and military performance.

    PubMed

    Hoffman, Jay R; Stout, Jeffrey R; Harris, Roger C; Moran, Daniel S

    2015-12-01

    During sustained high-intensity military training or simulated combat exercises, significant decreases in physical performance measures are often seen. The use of dietary supplements is becoming increasingly popular among military personnel, with more than half of the US soldiers deployed or garrisoned reported to using dietary supplements. β-Alanine is a popular supplement used primarily by strength and power athletes to enhance performance, as well as training aimed at improving muscle growth, strength and power. However, there is limited research examining the efficacy of β-alanine in soldiers conducting operationally relevant tasks. The gains brought about by β-alanine use by selected competitive athletes appears to be relevant also for certain physiological demands common to military personnel during part of their training program. Medical and health personnel within the military are expected to extrapolate and implement relevant knowledge and doctrine from research performed on other population groups. The evidence supporting the use of β-alanine in competitive and recreational athletic populations suggests that similar benefits would also be observed among tactical athletes. However, recent studies in military personnel have provided direct evidence supporting the use of β-alanine supplementation for enhancing combat-specific performance. This appears to be most relevant for high-intensity activities lasting 60-300 s. Further, limited evidence has recently been presented suggesting that β-alanine supplementation may enhance cognitive function and promote resiliency during highly stressful situations.

  11. Solved? The reductive radiation chemistry of alanine.

    PubMed

    Pauwels, Ewald; De Cooman, Hendrik; Waroquier, Michel; Hole, Eli O; Sagstuen, Einar

    2014-02-14

    The structural changes throughout the entire reductive radiation-induced pathway of l-α-alanine are solved on an atomistic level with the aid of periodic DFT and nudged elastic band (NEB) simulations. This yields unprecedented information on the conformational changes taking place, including the protonation state of the carboxyl group in the "unstable" and "stable" alanine radicals and the internal transformation converting these two radical variants at temperatures above 220 K. The structures of all stable radicals were verified by calculating EPR properties and comparing those with experimental data. The variation of the energy throughout the full radiochemical process provides crucial insight into the reason why these structural changes and rearrangements occur. Starting from electron capture, the excess electron quickly localizes on the carbon of a carboxyl group, which pyramidalizes and receives a proton from the amino group of a neighboring alanine molecule, forming a first stable radical species (up to 150 K). In the temperature interval 150-220 K, this radical deaminates and deprotonates at the carboxyl group, the detached amino group undergoes inversion and its methyl group sustains an internal rotation. This yields the so-called "unstable alanine radical". Above 220 K, triggered by the attachment of an additional proton on the detached amino group, the radical then undergoes an internal rotation in the reverse direction, giving rise to the "stable alanine radical", which is the final stage in the reductive radiation-induced decay of alanine.

  12. Orbiter 'Enterprise' turns and banks during second ALT

    NASA Technical Reports Server (NTRS)

    1977-01-01

    The Orbiter 101 'Enterprise' makes a turn and bank maneuver during the second free flight of the Shuttle Apporach and Landing Tests (ALTs) conducted on September 13, 1977 at Dryden Flight Research Center in Southern California. The 'Enterprise' separated form the NASA 747 carrier aircraft and after a five-minute, 28-second unpowered flight landed on a runway below. Astronauts Joe H. Engle, and Richard H. Truly were the crew of the 'Enterprise.' The ALT free flights are designed to verify Orbiter subsonic airworthiness, integrated systems operations and pilot-guided approach and landing capability and satisfying prerequisites to automatic flight control and navigation mode.

  13. β-Alanine Biosynthesis in Methanocaldococcus jannaschii

    PubMed Central

    Wang, Yu; Xu, Huimin

    2014-01-01

    One efficient approach to assigning function to unannotated genes is to establish the enzymes that are missing in known biosynthetic pathways. One group of such pathways is those involved in coenzyme biosynthesis. In the case of the methanogenic archaeon Methanocaldococcus jannaschii as well as most methanogens, none of the expected enzymes for the biosynthesis of the β-alanine and pantoic acid moieties required for coenzyme A are annotated. To identify the gene(s) for β-alanine biosynthesis, we have established the pathway for the formation of β-alanine in this organism after experimentally eliminating other known and proposed pathways to β-alanine from malonate semialdehyde, l-alanine, spermine, dihydrouracil, and acryloyl-coenzyme A (CoA). Our data showed that the decarboxylation of aspartate was the only source of β-alanine in cell extracts of M. jannaschii. Unlike other prokaryotes where the enzyme producing β-alanine from l-aspartate is a pyruvoyl-containing l-aspartate decarboxylase (PanD), the enzyme in M. jannaschii is a pyridoxal phosphate (PLP)-dependent l-aspartate decarboxylase encoded by MJ0050, the same enzyme that was found to decarboxylate tyrosine for methanofuran biosynthesis. A Km of ∼0.80 mM for l-aspartate with a specific activity of 0.09 μmol min−1 mg−1 at 70°C for the decarboxylation of l-aspartate was measured for the recombinant enzyme. The MJ0050 gene was also demonstrated to complement the Escherichia coli panD deletion mutant cells, in which panD encoding aspartate decarboxylase in E. coli had been knocked out, thus confirming the function of this gene in vivo. PMID:24891443

  14. Factors Associated With Persistent Increase in Level of Alanine Aminotransferase in Patients With Chronic Hepatitis B Receiving Oral Antiviral Therapy.

    PubMed

    Jacobson, Ira M; Washington, Mary K; Buti, Maria; Thompson, Alexander; Afdhal, Nezam; Flisiak, Robert; Akarca, Ulus Salih; Tchernev, Konstantin G; Flaherty, John F; Aguilar Schall, Raul; Myers, Robert P; Subramanian, G Mani; McHutchison, John G; Younossi, Zobair; Marcellin, Patrick; Patel, Keyur

    2017-07-01

    Despite complete suppression of viral DNA with antiviral agents, in some patients with chronic hepatitis B (CHB), serum levels of alanine aminotransferase (ALT) do not normalize. We investigated factors associated with persistent increases in ALT level in patients with CHB given long-term tenofovir disoproxil fumarate. We analyzed data from 471 hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with CHB participating in 2 phase 3 trials. We identified patients with an increased level of ALT (above the upper limit of normal range) after 5 years (240 weeks) of tenofovir disoproxil fumarate therapy. We analyzed findings from liver biopsy specimens collected from 467 patients (99%) at baseline and 339 patients (72%) at year 5 of treatment; biopsy specimens were evaluated by an independent pathologist. We performed stepwise, forward, multivariate regression analyses of specified baseline characteristics and on-treatment response parameters to identify factors associated with persistent increases in ALT level. Of the 471 patients, 87 (18%) still had an increased ALT level at year 5 of treatment. Factors associated significantly with a persistent increase in ALT level were a steatosis score of 5% or greater (grade 1 or more) at baseline (odds ratio [OR], 2.236; 95% confidence interval [CI], 1.031-4.852; P = .042) and at year 5 (OR, 3.392; 95% CI, 1.560 ≥ 7.375; P = .002), HBeAg seropositivity at baseline (OR, 3.297; 95% CI, 1.653-6.576; P < .001), and age 40 years or older (OR, 2.099; 95% CI, 1.014-4.342; P = .046). Of the 42 HBeAg-positive patients with steatosis at baseline, 21 (50%) had an increased ALT level at year 5 of treatment. Patients with persistent increases in ALT level were more likely to have an increase in steatosis at year 5 than those with a normal ALT level. HBeAg seropositivity and hepatic steatosis contribute to persistent increases in ALT level in patients with CHB receiving suppressive antiviral treatment. Clinical

  15. Interaction between obesity and the Hypoxia Inducible Factor 3 Alpha Subunit rs3826795 polymorphism in relation with plasma alanine aminotransferase.

    PubMed

    Wang, Shuo; Song, Jieyun; Yang, Yide; Zhang, Yining; Chawla, Nitesh V; Ma, Jun; Wang, Haijun

    2017-07-28

    Hypoxia Inducible Factor 3 Alpha Subunit (HIF3A) DNA has been demonstrated to be associated with obesity in the methylation level, and it also has a Body Mass Index (BMI)-independent association with plasma alanine aminotransferase (ALT). However, the relation among obesity, plasma ALT, HIF3A polymorphism and methylation remains unclear. This study aims to identify the association between HIF3A polymorphism and plasma ALT, and further to determine whether the effect of HIF3A polymorphism on ALT could be modified by obesity or mediated by DNA methylation. The HIF3A rs3826795 polymorphism was genotyped in a case-control study including 2030 Chinese children aged 7-18 years (705 obese cases and 1325 non-obese controls). Furthermore, the HIF3A DNA methylation of the peripheral blood was measured in 110 severely obese children and 110 age- and gender- matched normal-weight controls. There was no overall association between the HIF3A rs3826795 polymorphism and ALT. A significant interaction between obesity and rs3826795 in relation with ALT was found (P inter = 0.042), with rs3826795 G-allele number elevating ALT significantly only in obese children (β' = 0.075, P = 0.037), but not in non-obese children (β' = -0.009, P = 0.741). Additionally, a mediation effect of HIF3A methylation was found in the association between the HIF3A rs3826795 polymorphism and ALT among obese children (β' = 0.242, P = 0.014). This is the first study to report the interaction between obesity and HIF3A gene in relation with ALT, and also to reveal a mediation effect among the HIF3A polymorphism, methylation and ALT. This study provides new evidence to the function of HIF3A gene, which would be helpful for future risk assessment and personalized treatment of liver diseases.

  16. SAFETY study: Alanine aminotransferase cutoff values are set too high for reliable detection of pediatric chronic liver disease

    PubMed Central

    Schwimmer, Jeffrey B.; Dunn, Winston; Norman, Gregory J.; Pardee, Perrie E.; Middleton, Michael S.; Kerkar, Nanda; Sirlin, Claude B.

    2010-01-01

    Background & Aims The appropriate alanine aminotransferase (ALT) threshold value to use for diagnosis of chronic liver disease in children is unknown. We sought to develop sex-specific, biology-based, pediatric ALT thresholds. Methods The screening ALT for elevation in today’s youth (SAFETY) study collected observational data from acute care children’s hospitals, the national health and nutrition examination survey (NHANES, 1999–2006), overweight children with and without non-alcoholic fatty liver disease (NAFLD), and children with chronic Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infections. The study compared the sensitivity and specificity of ALT thresholds currently used by children’s hospitals versus study-derived, sex-specific, biology-based, ALT thresholds for detecting children with NAFLD, HCV, or HBV. Results The median upper limit of ALT at children’s hospitals was 53 U/L (range, 30–90). The 95th percentile levels for ALT in healthy weight, metabolically normal, liver disease-free, NHANES pediatric participants were 25.8 U/L (boys) and 22.1 U/L (girls). The concordance statistics of these NHANES-derived thresholds for liver disease detection were 0.85 (95% confidence interval [CI] 0.74–0.96) in boys and 0.91 (95% CI 0.83–0.99) in girls for NAFLD, 0.80 (95% CI 0.70–0.91) in boys and 0.79 (95% CI 0.69–0.89) in girls for HBV, and 0.86 (95% CI 0.77–0.95) in boys and 0.84 (95% CI 0.75–0.93) in girls for HCV. Using current children’s hospitals ALT thresholds, the median sensitivity for detection of NAFLD, HBV, and HCV ranged from 32% to 48%; median specificity was 92% (boys) and 96% (girls). Using NHANES-derived thresholds, the sensitivities were 72% (boys) and 82% (girls); specificities were 79% (boys) and 85% (girls). Conclusions The upper limit of ALT used in children’s hospitals varies widely and is set too high to reliably detect chronic liver disease. Biology-based thresholds provide higher sensitivity and only

  17. Yield of diagnostic tests in obese children with an elevated alanine aminotransferase.

    PubMed

    Rudolph, Bryan; Rivas, Yolanda; Kulak, Shulamit; Pan, Debra; Ewart, Michelle; Levin, Terry L; Thompson, John F; Scharbach, Kathryn

    2015-12-01

    Nonalcoholic fatty liver disease (NAFLD) is associated with obesity and affects roughly 10% of children. However, NAFLD is often diagnosed by exclusion - that is, obese children with an elevated alanine aminotransferase (ALT) are screened for other liver diseases in the absence of a biopsy. This testing is nonstandardized, and professional society recommendations differ. This study examines the yield of testing for disorders other than NAFLD in this patient population. A retrospective study was performed in 120 obese, asymptomatic, noncholestatic children with an ALT ≥40 U/L and additional diagnostic testing. No patients were found to have Wilson's, hepatitis A, hepatitis B, hepatitis C, cytomegalovirus, alpha-1 antitrypsin deficiency, autoimmune hepatitis, celiac disease or Epstein-Barr virus. Only one patient (1/120) was identified with definite disease other than NAFLD, which was muscular dystrophy. The positive predictive value of a screening test was 5%, and the specificity was 97%. Of 70 children with an abdominal ultrasound, no significant abnormalities were identified. Extensive testing in asymptomatic, noncholestatic, obese children with an elevated ALT may be of limited diagnostic value and false-positive tests are likely. Large, prospective studies are needed to help focus the work up in this patient population. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  18. Irritable Bowel Syndrome May Be Associated with Elevated Alanine Aminotransferase and Metabolic Syndrome

    PubMed Central

    Lee, Seung-Hwa; Kim, Kwang-Min; Joo, Nam-Seok

    2016-01-01

    Purpose Recent studies have revealed close relationships between hepatic injury, metabolic pathways, and gut microbiota. The microorganisms in the intestine also cause irritable bowel syndrome (IBS). The aim of this study was to examine whether IBS was associated with elevated hepatic enzyme [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)], gamma-glutamyl transferase (γ-GT) levels, and metabolic syndrome (MS). Materials and Methods This was a retrospective, cross-sectional, case-control study. The case and control groups comprised subjects who visited our health promotion center for general check-ups from June 2010 to December 2010. Of the 1127 initially screened subjects, 83 had IBS according to the Rome III criteria. The control group consisted of 260 age- and sex-matched subjects without IBS who visited our health promotion center during the same period. Results Compared to control subjects, patients with IBS showed significantly higher values of anthropometric parameters (body mass index, waist circumference), liver enzymes, γ-GT, and lipid levels. The prevalences of elevated ALT (16.9% vs. 7.7%; p=0.015) and γ-GT (24.1% vs. 11.5%; p=0.037) levels were significantly higher in patients with IBS than in control subjects. A statistically significant difference was observed in the prevalence of MS between controls and IBS patients (12.7% vs. 32.5%; p<0.001). The relationships between elevated ALT levels, MS, and IBS remained statistically significant after controlling for potential confounding factors. Conclusion On the basis of our study results, IBS may be an important condition in certain patients with elevated ALT levels and MS. PMID:26632395

  19. Irritable Bowel Syndrome May Be Associated with Elevated Alanine Aminotransferase and Metabolic Syndrome.

    PubMed

    Lee, Seung Hwa; Kim, Kyu Nam; Kim, Kwang Min; Joo, Nam Seok

    2016-01-01

    Recent studies have revealed close relationships between hepatic injury, metabolic pathways, and gut microbiota. The microorganisms in the intestine also cause irritable bowel syndrome (IBS). The aim of this study was to examine whether IBS was associated with elevated hepatic enzyme [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)], gamma-glutamyl transferase (γ-GT) levels, and metabolic syndrome (MS). This was a retrospective, cross-sectional, case-control study. The case and control groups comprised subjects who visited our health promotion center for general check-ups from June 2010 to December 2010. Of the 1127 initially screened subjects, 83 had IBS according to the Rome III criteria. The control group consisted of 260 age- and sex-matched subjects without IBS who visited our health promotion center during the same period. Compared to control subjects, patients with IBS showed significantly higher values of anthropometric parameters (body mass index, waist circumference), liver enzymes, γ-GT, and lipid levels. The prevalences of elevated ALT (16.9% vs. 7.7%; p=0.015) and γ-GT (24.1% vs. 11.5%; p=0.037) levels were significantly higher in patients with IBS than in control subjects. A statistically significant difference was observed in the prevalence of MS between controls and IBS patients (12.7% vs. 32.5%; p<0.001). The relationships between elevated ALT levels, MS, and IBS remained statistically significant after controlling for potential confounding factors. On the basis of our study results, IBS may be an important condition in certain patients with elevated ALT levels and MS.

  20. Ethanol reduces lifespan, body weight, and serum alanine aminotransferase level of aldehyde dehydrogenase 2 knockout mouse.

    PubMed

    Matsumoto, Akiko; Vasiliou, Vasilis; Kawamoto, Toshihiro; Tanaka, Keitaro; Ichiba, Masayoshi

    2014-07-01

    The aldehyde dehydrogenase 2 (Aldh2) knockout mouse is an animal model of a polymorphism at the human ALDH2 locus (ALDH2*2). To detect differences in the basic phenotype of this animal model, lifespan, body weight (BW), and serum alanine aminotransferase (ALT) level were evaluated. Aldh2(+/+) , Aldh2(+/-) , and Aldh2(-/-) mice were maintained, from 10 weeks of age, on standard solid food, with liquid supplied as ethanol (EtOH) solution at a concentration of 0 to 20% (forced EtOH consumption). For animals provided with water (without EtOH), mice of the distinct genotypes exhibited no difference in lifespan, with the mean values ranging from 90 to 96 weeks for female mice and 97 to 105 weeks for male mice. For animals provided with EtOH, there was a dose-dependent reduction of lifespan in Aldh2(-/-) mice with p for trend <0.001. For example, the mean lifespans of the Aldh2(-/-) females in the 0, 3, 10, and 20% groups were 95, 85, 70, and 29 weeks, respectively. No influence on lifespan was found for Aldh2(+/+) and Aldh2(+/-) mice. BW and ALT level of Aldh2(-/-) mice were significantly lower than those of Aldh2(+/+) mice when the mice were treated with EtOH. While multiple regression analysis suggested that the BW and ALT level in Aldh2(-/-) mice correlated with lifespan, adjustment for EtOH concentration revealed that this correlation was not significant (i.e., reflected EtOH dependence). Aldh2(-/-) mice were unchanged in terms of their basic phenotype under standard laboratory conditions. However, chronic EtOH administration (forced consumption) in these mice resulted in dose-dependent reductions in lifespan, BW, and serum ALT level. Copyright © 2014 by the Research Society on Alcoholism.

  1. Development of the alt Mutant of Pisum sativum L. 1

    PubMed Central

    Guo, Wei Wen; Proebsting, William M.; Potter, Sandra W.; Daley, Larry S.; Potter, John R.

    1987-01-01

    The alt (albina-terminalis) mutant of Pisum sativum L. germinates normally, produces several nodes, and then above a sharp transition produces 2 to 3 bleached nodes, ceases growth, and eventually dies. Green nodes have normal chlorophyll content, absorption spectra, photosynthetic rates, and ultrastructure. In bleaching tissues, the chloroplasts degenerate rapidly, followed by extensive disruption and loss of the remaining cytoplasm and organelles. Application of tissue extracts of normal genotypes of pea, corn, and bean stimulates apical development of alt. The resulting tissues have essentially normal structure and function. Application of thiamine, thiamine monophosphate, and thiamine pyrophosphate also stimulate normal apical development at concentrations of 1 micromolar and above. Partial characterization of the stimulus from pea seed extracts is consistent with thiamine as the active factor. Images Fig. 4 Fig. 6 Fig. 8 PMID:16665809

  2. Unequal hydrolysis of salicylic acid-D-alanine and salicylic acid-L-alanine conjugate in rabbit intestinal microorganisms.

    PubMed

    Nakamura, J; Tagami, C; Nishida, K; Sasaki, H

    1992-02-01

    The behavior of salicylic acid-D-alanine conjugate (salicyl-D-alanine) following intravenous, oral and intracecal administration was examined in rabbits, then compared with that of salicylic acid-L-alanine conjugate (salicyl-L-alanine) as reported previously. Following intravenous administration, salicyl-D-alanine eliminated rapidly from the blood, and its blood concentration was almost identical with that of salicyl-L-alanine. In both cases, salicylic acid could not be detected in the blood, indicating that systemic de-conjugation of D-alanine might not occur. Unchanged salicyl-D-alanine was found in the blood mainly following oral and intracecal administration of salicyl-D-alanine. On the other hand, salicylic acid formed extensively following oral and intracecal administration of salicyl-L-alanine, suggesting that the presystemic de-conjugation of D-alanine and L-alanine was unequal. Furthermore, in vitro incubation of salicyl-D-alanine with cecal content, in which the major source of salicyl-L-alanine hydrolysis is found, showed that the hydrolysis of salicyl-D-alanine was negligible in rabbit intestinal microorganisms.

  3. Understanding and Targeting the ALT Pathway in Human Breast Cancer

    DTIC Science & Technology

    2014-09-01

    by ectopic expression of ESCO2. PLoS One 4, e6936 (2009). 35. Leung, J. W. et al. Alpha thalassemia/ mental retardation syndrome X-linked gene...identified mutations and loss of ATRX protein as being hallmarks of ALT- immortalized cell lines and tumors. Our efforts to understand the mechanism...by which loss of ATRX facilitates telomere recombination have uncovered a novel role for this protein in promoting telomere cohesion. Furthermore

  4. Army AL&T, July-September 2008

    DTIC Science & Technology

    2008-09-01

    4. TITLE AND SUBTITLE Army AL&T, July - September 2008 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) 5d...PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES) Army Acquisition, Logistics & Technology (AT&L...9900 Belvoir Road Suite 101,Fort Belvoir,VA,22060-5567 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME( S ) AND ADDRESS

  5. 21 CFR 582.5118 - Alanine.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Alanine. 582.5118 Section 582.5118 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements...

  6. 21 CFR 582.5118 - Alanine.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Alanine. 582.5118 Section 582.5118 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1...

  7. 21 CFR 582.5118 - Alanine.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Alanine. 582.5118 Section 582.5118 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1...

  8. 21 CFR 582.5118 - Alanine.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Alanine. 582.5118 Section 582.5118 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1...

  9. 21 CFR 582.5118 - Alanine.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Alanine. 582.5118 Section 582.5118 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1...

  10. Serum γ-Glutamyltransferase, Alanine Aminotransferase and Aspartate Aminotransferase Activity in Healthy Blood Donor of Different Ethnic Groups in Gorgan.

    PubMed

    Marjani, Abdoljalal; Mehrpouya, Masoumeh; Pourhashem, Zeinab

    2016-07-01

    Measure of liver enzymes may help to increase safety of blood donation for both blood donor and recipient. Determination of liver enzymes may prepare valuable clinical information. To assess serum γ-Glutamyltransferase (GGT), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) activities in healthy blood donors in different ethnic groups in Gorgan. This study was performed in 450 healthy male blood donors, in three ethnic groups (Fars, Sistanee and Turkman) who attended Gorgan blood transfusion center. Liver enzymes (GGT, ALT and AST) were determined. Serum AST and ALT in three ethnic groups were significant except for serum GGT levels. There was significant correlation between family histories of liver disease and systolic blood pressure and AST in Fars, and GGT in Sistanee ethnic groups. Several factors, such as age, family history of diabetes mellitus, family history of liver disease and smoking habit had no effect on some liver enzymes in different ethnic groups in this area. Variation of AST, ALT, and GGT enzyme activities in healthy subjects was associated with some subjects in our study groups. According to our study, it suggests that screening of AST and GGT enzymes in subjects with family history of liver disease is necessary in different ethnic groups.

  11. Serum γ-Glutamyltransferase, Alanine Aminotransferase and Aspartate Aminotransferase Activity in Healthy Blood Donor of Different Ethnic Groups in Gorgan

    PubMed Central

    Mehrpouya, Masoumeh; Pourhashem, Zeinab

    2016-01-01

    Introduction Measure of liver enzymes may help to increase safety of blood donation for both blood donor and recipient. Determination of liver enzymes may prepare valuable clinical information. Aim To assess serum γ-Glutamyltransferase (GGT), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) activities in healthy blood donors in different ethnic groups in Gorgan. Materials and Methods This study was performed in 450 healthy male blood donors, in three ethnic groups (Fars, Sistanee and Turkman) who attended Gorgan blood transfusion center. Liver enzymes (GGT, ALT and AST) were determined. Results Serum AST and ALT in three ethnic groups were significant except for serum GGT levels. There was significant correlation between family histories of liver disease and systolic blood pressure and AST in Fars, and GGT in Sistanee ethnic groups. Conclusion Several factors, such as age, family history of diabetes mellitus, family history of liver disease and smoking habit had no effect on some liver enzymes in different ethnic groups in this area. Variation of AST, ALT, and GGT enzyme activities in healthy subjects was associated with some subjects in our study groups. According to our study, it suggests that screening of AST and GGT enzymes in subjects with family history of liver disease is necessary in different ethnic groups. PMID:27630834

  12. Alternative Liquid Fuels Simulation Model (AltSim).

    SciTech Connect

    Williams, Ryan; Baker, Arnold Barry; Drennen, Thomas E.

    2009-12-01

    The Alternative Liquid Fuels Simulation Model (AltSim) is a high-level dynamic simulation model which calculates and compares the production and end use costs, greenhouse gas emissions, and energy balances of several alternative liquid transportation fuels. These fuels include: corn ethanol, cellulosic ethanol from various feedstocks (switchgrass, corn stover, forest residue, and farmed trees), biodiesel, and diesels derived from natural gas (gas to liquid, or GTL), coal (coal to liquid, or CTL), and coal with biomass (CBTL). AltSim allows for comprehensive sensitivity analyses on capital costs, operation and maintenance costs, renewable and fossil fuel feedstock costs, feedstock conversion ratio, financial assumptions, tax credits, CO{sub 2} taxes, and plant capacity factor. This paper summarizes the structure and methodology of AltSim, presents results, and provides a detailed sensitivity analysis. The Energy Independence and Security Act (EISA) of 2007 sets a goal for the increased use of biofuels in the U.S., ultimately reaching 36 billion gallons by 2022. AltSim's base case assumes EPA projected feedstock costs in 2022 (EPA, 2009). For the base case assumptions, AltSim estimates per gallon production costs for the five ethanol feedstocks (corn, switchgrass, corn stover, forest residue, and farmed trees) of $1.86, $2.32, $2.45, $1.52, and $1.91, respectively. The projected production cost of biodiesel is $1.81/gallon. The estimates for CTL without biomass range from $1.36 to $2.22. With biomass, the estimated costs increase, ranging from $2.19 per gallon for the CTL option with 8% biomass to $2.79 per gallon for the CTL option with 30% biomass and carbon capture and sequestration. AltSim compares the greenhouse gas emissions (GHG) associated with both the production and consumption of the various fuels. EISA allows fuels emitting 20% less greenhouse gases (GHG) than conventional gasoline and diesels to qualify as renewable fuels. This allows several of the CBTL

  13. Predictive value of serum ALT and T-cell receptor beta variable chain for HBeAg seroconversion in chronic hepatitis B patients during tenofovir treatment

    PubMed Central

    Yang, Jiezuan; Yan, Dong; Guo, Renyong; Chen, Jiajia; Li, Yongtao; Fan, Jun; Fu, Xuyan; Yao, Xinsheng; Diao, Hongyan; Li, Lanjuan

    2017-01-01

    Abstract Effective antiviral therapy plays a key role in slowing the progression of chronic hepatitis B (CHB). Identification of serum indices, including hepatitis B e antigen (HBeAg) expression and seroconversion, will facilitate evaluation of the efficacy of antiviral therapy in HBeAg-positive CHB patients. The biochemical, serological, virological parameters, and the frequency of circulating CD4+CD25+ regulatory T cell (Treg) in 32 patients were measured at baseline and every 12 weeks during 96 weeks of tenofovir disoproxil fumarate (TDF) treatment. The relationship between the hepatitis B virus (HBV) deoxyribonucleic acid (DNA) and Treg and alanine aminotransferase (ALT) levels was analyzed, respectively. The molecular profiles of T-cell receptor beta variable chain (TRBV) were determined using gene melting spectral pattern. For the seroconverted 12 patients, ALT declined to normal levels by week 24 and remained at this level in subsequent treatment; moreover, the predictive cutoff value of ALT for HBeAg seroconversion (SC) was 41.5 U/L at week 24. The positive correlation between HBV DNA and Treg and ALT was significant in SC patients, but not in non-SC patients. Six TRBV families (BV3, BV11, BV12, BV14, BV20, and BV24) were predominantly expressed in SC patients at baseline. The decline of ALT could be used to predict HBeAg seroconversion for CHB patients during TDF treatment. In addition, the profile of Tregs and TRBVs may be associated with HBeAg seroconversion and could also be a potential indicator for predicting HBeAg SC and treatment outcome for CHB patients. PMID:28272219

  14. Predictive value of serum ALT and T-cell receptor beta variable chain for HBeAg seroconversion in chronic hepatitis B patients during tenofovir treatment.

    PubMed

    Yang, Jiezuan; Yan, Dong; Guo, Renyong; Chen, Jiajia; Li, Yongtao; Fan, Jun; Fu, Xuyan; Yao, Xinsheng; Diao, Hongyan; Li, Lanjuan

    2017-03-01

    Effective antiviral therapy plays a key role in slowing the progression of chronic hepatitis B (CHB). Identification of serum indices, including hepatitis B e antigen (HBeAg) expression and seroconversion, will facilitate evaluation of the efficacy of antiviral therapy in HBeAg-positive CHB patients. The biochemical, serological, virological parameters, and the frequency of circulating CD4CD25 regulatory T cell (Treg) in 32 patients were measured at baseline and every 12 weeks during 96 weeks of tenofovir disoproxil fumarate (TDF) treatment. The relationship between the hepatitis B virus (HBV) deoxyribonucleic acid (DNA) and Treg and alanine aminotransferase (ALT) levels was analyzed, respectively. The molecular profiles of T-cell receptor beta variable chain (TRBV) were determined using gene melting spectral pattern. For the seroconverted 12 patients, ALT declined to normal levels by week 24 and remained at this level in subsequent treatment; moreover, the predictive cutoff value of ALT for HBeAg seroconversion (SC) was 41.5 U/L at week 24. The positive correlation between HBV DNA and Treg and ALT was significant in SC patients, but not in non-SC patients. Six TRBV families (BV3, BV11, BV12, BV14, BV20, and BV24) were predominantly expressed in SC patients at baseline. The decline of ALT could be used to predict HBeAg seroconversion for CHB patients during TDF treatment. In addition, the profile of Tregs and TRBVs may be associated with HBeAg seroconversion and could also be a potential indicator for predicting HBeAg SC and treatment outcome for CHB patients.

  15. The association of liver fat content and serum alanine aminotransferase with bone mineral density in middle-aged and elderly Chinese men and postmenopausal women.

    PubMed

    Xia, Ming-Feng; Lin, Huan-Dong; Yan, Hong-Mei; Bian, Hua; Chang, Xin-Xia; Zhang, Lin-Shan; He, Wan-Yuan; Gao, Xin

    2016-01-13

    Recent studies have linked non-alcoholic fatty liver disease (NAFLD) to a reduced bone mineral density (BMD). We aimed to detect the quantitative association of liver fat content (LFC) and serum alanine aminotransferase (ALT) with BMD in a middle-aged and elderly Chinese population. The lumbar spine, hip and whole body BMDs were measured using dual-energy x-ray absorptiometry (Lunar iDXA, GE Healthcare) in 1659 Chinese (755 men and 1028 postmenopausal women) from Shanghai Changfeng community. Liver fat content was quantified via an ultrasound quantitative method. Multivariate linear regression analyses were carried out to determine the independent association of LFC and serum ALT with BMD and bone metabolic biomarkers. We also attempted to investigate the synergistic association between LFC and ALT as risk factors for bone mineral loss in Chinese. Subjects with higher LFC had significantly lower BMD at all skeletal sites. Univariate correlation analysis showed that both LFC and ALT were inversely associated with BMD at the spine (r = -0.116, P < 0.001 and r = -0.102, P = 0.005), hip (r = -0.095, P = 0.014 and r = -0.075, P = 0.041) and whole body sites (r = -0.134, P < 0.001 and r = -0.164, P < 0.001) in men. After confounders were controlled for, LFC and ALT remained associated with BMD and bone formation biomarkers in men, but not postmenopausal women. When both NAFLD and elevation of ALT were present, there was a significant synergistic worsening of the BMDs at all bone sites. Liver fat content and serum ALT were inversely correlated with BMD in middle-aged and elderly men. The underlying mechanism might relate to a reduction in osteoblast activity. Elevation of the hepatotoxic biomarker ALT may indicate high risk for osteoporosis in patients with NAFLD.

  16. Quick look analysis of an emergency separation for ALT captive-inert flight 1

    NASA Technical Reports Server (NTRS)

    Glenn, G. M.; Seale, R. H.

    1977-01-01

    Emergency separation capability for the landing configuration of ALT Captive Inert Flight Number One was investigated. The quick look analysis confirms emergency separation capability under nominal conditions for the ALT landing configuration. The recommended emergency separation procedure under those conditions is not applicable to all ALT configurations.

  17. Army AL&T, October-December 2007

    DTIC Science & Technology

    2007-12-01

    provides new knowledge and understanding to solve Army-unique problems as well as novel approaches to solve prob- lems with broad and, at times, un- foreseen...metric used to assess tech- nology maturity. The TRL approach was originally established by NASA and adopted by DOD to measure technology maturity...A_ALT_Oct-Dec 2007_V10_CC.qxp 9/25/2007 11:16 PM Page 18 biological mechanisms for the develop- ment of revolutionary approaches to ad- vanced

  18. High alanine aminotransferase is associated with decreased hepatic insulin sensitivity and predicts the development of type 2 diabetes.

    PubMed

    Vozarova, Barbora; Stefan, Norbert; Lindsay, Robert S; Saremi, Aramesh; Pratley, Richard E; Bogardus, Clifton; Tataranni, P Antonio

    2002-06-01

    It has been proposed that liver dysfunction may contribute to the development of type 2 diabetes. The aim of the present study was to examine whether elevated hepatic enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], or gamma -glutamyltranspeptidase [GGT]) are associated with prospective changes in liver or whole-body insulin sensitivity and/or insulin secretion and whether these elevated enzymes predict the development of type 2 diabetes in Pima Indians. We measured ALT, AST, and GGT in 451 nondiabetic (75-g oral glucose tolerance test) Pima Indians (aged 30 +/- 6 years, body fat 33 +/- 8%, ALT 45 +/- 29 units/l, AST 34 +/- 18 units/l, and GGT 56 +/- 40 units/l [mean +/- SD]) who were characterized for body composition (hydrodensitometry or dual-energy X-ray absorptiometry), whole-body insulin sensitivity (M), and hepatic insulin sensitivity (hepatic glucose output [HGO] during the low-dose insulin infusion of a hyperinsulinemic clamp) and acute insulin response (AIR) (25-g intravenous glucose challenge). Sixty-three subjects developed diabetes over an average follow-up of 6.9 +/- 4.9 years. In 224 subjects, who remained nondiabetic, follow-up measurements of M and AIR were available. At baseline, ALT, AST, and GGT were related to percent body fat (r = 0.16, 0.17, and 0.11, respectively), M (r = -0.32, - 0.28, and -0.24), and HGO (r = 0.27, 0.12, and 0.14; all P < 0.01). In a proportional hazard analysis with adjustment for age, sex, body fat, M, and AIR, higher ALT [relative hazard 90th vs. 10th centiles (95% CI): 1.9 (1.1-3.3), P = 0.02], but not AST or GGT, predicted diabetes. Elevated ALT at baseline was associated prospectively with an increase in HGO (r = 0.21, P = 0.001) but not with changes in M or AIR (both P = 0.1). Higher ALT concentrations were cross-sectionally associated with obesity and whole-body and hepatic insulin resistance and prospectively associated with a decline in hepatic insulin sensitivity and the development of

  19. Earthworms accumulate alanine in response to drought.

    PubMed

    Holmstrup, Martin; Slotsbo, Stine; Henriksen, Per G; Bayley, Mark

    2016-09-01

    Earthworms have ecologically significant functions in tropical and temperate ecosystems and it is therefore important to understand how these animals survive during drought. In order to explore the physiological responses to dry conditions, we simulated a natural drought incident in a laboratory trial exposing worms in slowly drying soil for about one month, and then analyzed the whole-body contents of free amino acids (FAAs). We investigated three species forming estivation chambers when soils dry out (Aporrectodea tuberculata, Aporrectodea icterica and Aporrectodea longa) and one species that does not estivate during drought (Lumbricus rubellus). Worms subjected to drought conditions (< -2MPa) substantially increased the concentration of FAAs and in particular alanine that was significantly upregulated in all tested species. Alanine was the most important FAA reaching 250-650μmolg(-1) dry weight in dehydrated Aporrectodea species and 300μmolg(-1) dry weight in L. rubellus. Proline was only weakly upregulated in some species as were a few other FAAs. Species forming estivation chambers (Aporrectodea spp.) did not show a better ability to conserve body water than the non-estivating species (L. rubellus) at the same drought level. These results suggest that the accumulation of alanine is an important adaptive trait in drought tolerance of earthworms in general. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. 21 CFR 172.540 - DL-Alanine.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true DL-Alanine. 172.540 Section 172.540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Agents and Related Substances § 172.540 DL-Alanine. DL-Alanine (a racemic mixture of D- and...

  1. On the existence of ‘L-alanine cadmium bromide'

    NASA Astrophysics Data System (ADS)

    Srinivasan, Bikshandarkoil R.

    2013-12-01

    It is argued that the recently reported nonlinear optical crystal L-alanine cadmium bromide, grown by slow solvent evaporation method at room temperature [P. Ilayabarathi, J. Chandrasekaran, Spectrochim. Acta 96A (2012) 684-689] is the well-known L-alanine crystal. The isolation of L-alanine crystal is explained due to fractional crystallization.

  2. On the existence of 'L-alanine cadmium bromide'.

    PubMed

    Srinivasan, Bikshandarkoil R

    2013-12-01

    It is argued that the recently reported nonlinear optical crystal L-alanine cadmium bromide, grown by slow solvent evaporation method at room temperature [P. Ilayabarathi, J. Chandrasekaran, Spectrochim. Acta 96A (2012) 684-689] is the well-known L-alanine crystal. The isolation of L-alanine crystal is explained due to fractional crystallization.

  3. Alternative Liquid Fuels Simulation Model (AltSim).

    SciTech Connect

    Baker, Arnold Barry; Williams, Ryan; Drennen, Thomas E.; Klotz, Richard

    2007-10-01

    The Alternative Liquid Fuels Simulation Model (AltSim) is a high-level dynamic simulation model which calculates and compares the production costs, carbon dioxide emissions, and energy balances of several alternative liquid transportation fuels. These fuels include: corn ethanol, cellulosic ethanol, biodiesel, and diesels derived from natural gas (gas to liquid, or GTL) and coal (coal to liquid, or CTL). AltSim allows for comprehensive sensitivity analyses on capital costs, operation and maintenance costs, renewable and fossil fuel feedstock costs, feedstock conversion efficiency, financial assumptions, tax credits, CO{sub 2} taxes, and plant capacity factor. This paper summarizes the preliminary results from the model. For the base cases, CTL and cellulosic ethanol are the least cost fuel options, at $1.60 and $1.71 per gallon, respectively. Base case assumptions do not include tax or other credits. This compares to a $2.35/gallon production cost of gasoline at September, 2007 crude oil prices ($80.57/barrel). On an energy content basis, the CTL is the low cost alternative, at $12.90/MMBtu, compared to $22.47/MMBtu for cellulosic ethanol. In terms of carbon dioxide emissions, a typical vehicle fueled with cellulosic ethanol will release 0.48 tons CO{sub 2} per year, compared to 13.23 tons per year for coal to liquid.

  4. Factors Predicting HBsAg Seroclearance and Alanine Transaminase Elevation in HBeAg-Negative Hepatitis B Virus-Infected Patients with Persistently Normal Liver Function

    PubMed Central

    Chien, Tai-Long; Wang, Jing-Houng; Kee, Kwong-Ming; Chen, Chien-Hung; Hung, Chao-Hung; Lu, Sheng-Nan

    2016-01-01

    Background A certain proportion of hepatitis B virus (HBV)-infected patients with persistently normal alanine transaminase (ALT) levels have significant fibrosis. Using liver stiffness measurements (Fibroscan®) and laboratory data, including serum ALT, quantitative HBsAg (qHBsAg), and HBV DNA, we attempted to predict the natural histories of these patients. Methods Non-cirrhotic HBeAg-negative chronic hepatitis B patients with persistently normal ALT were followed up prospectively with the end points of HBsAg seroclearance and ALT elevation above the upper limit of normal. The factors that were predictive of the end points were identified. Results A total of 235 patients with an average age of 48.1 +/- 10.7 years were followed up for 7 years. Eight patients (3.4%) lost HBsAg, and 15 patients (6.4%) experienced ALT elevation. The overall cumulative HBsAg seroclearances were 0.4%, 1.3% and 2.3% at years 1, 3 and 5, respectively. Regarding HBsAg seroclearance, the qHBsAg (< 30 IU/ml) cutoff resulted in a hazard ratio (HR) of 19.6 with a 95% confidence interval (CI) of 2.2–166.7 (P = 0.008). The baseline ALT level (odd ratio (OR) 1.075, 95% CI 1.020–1.132, P = 0.006) and a qHBsAg above 1000 IU/ml (3.7, 1.1–12.4, P = 0.032) were associated with ALT elevation. Limited to men, the baseline liver stiffness (1.6, 1.0–2.5, P = 0.031) and a qHBsAg above 1000 IU/ml (10.4, 2.1–52.4, P = 0.004) were factors that were independently associated with ALT elevation. Conclusion A low qHBsAg level predicted HBsAg clearance. Baseline ALT and a qHBsAg above 1000 IU/ml were independent predictive factors for ALT elevation. Among the men, the independent predictive factors for ALT elevation were qHBsAg and liver stiffness. PMID:27935953

  5. Complex Association between Alanine Aminotransferase Activity and Mortality in General Population: A Systematic Review and Meta-Analysis of Prospective Studies

    PubMed Central

    Que, Shuping; Wang, Linlin; Qin, Xue

    2014-01-01

    Objective Controversy exists in using alanine aminotransferase (ALT) activity for predicting long-term survival. Therefore, this research study investigated the association between ALT activity and mortality through a systematic review and meta-analysis of previous prospective studies. Methods Electronic literature databases, including PubMed, Embase, and the Institute for Scientific Information (ISI), were searched for relevant prospective observational studies (published before Dec 30, 2013) on the association between baseline ALT activity and ensuing all-cause/disease-specific mortality. Information on nationality, sample size, participant characteristics, follow-up duration, comparison, outcome assessment, hazard ratios (HRs) and adjusted covariates was extracted. Pooled HRs and corresponding 95% confidence intervals (CIs) were separately calculated for categorical risk estimates (highest vs. lowest ALT categories) and continuous risk estimates (per 5 U/l of ALT increment) in subgroups separated by age (<70/≥70 years). Results A total of twelve prospective cohort studies, totaling 206,678 participants and 16,249 deaths, were identified and analyzed. In the younger age group, the pooled HR for mortality related to liver-disease was about 1.24 (95% CI: 1.23–1.25) per 5 U/l of ALT increment. The dose-response HRs of all-cause mortality, cardiovascular (CV) disease-related mortality, and cancer-related mortality were 0.91 (0.88–0.94), 0.91 (0.85–0.96), 0.92 (0.86–0.98) respectively per 5 U/l of ALT elevation, with insignificant heterogeneity in the older population. There was an approximate decrease of 4‰ observed on HRs of all-cause, CV-related, and cancer-related mortality followed with one year's increment through meta-regression (all P<0.05). Conclusions The ALT-mortality association was inconsistent and seems particularly susceptible to age after synthesizing the previous prospective studies. In terms of the age, ALT activity was more valuable in

  6. Complex association between alanine aminotransferase activity and mortality in general population: a systematic review and meta-analysis of prospective studies.

    PubMed

    Liu, Zhengtao; Ning, Huaijun; Que, Shuping; Wang, Linlin; Qin, Xue; Peng, Tao

    2014-01-01

    Controversy exists in using alanine aminotransferase (ALT) activity for predicting long-term survival. Therefore, this research study investigated the association between ALT activity and mortality through a systematic review and meta-analysis of previous prospective studies. Electronic literature databases, including PubMed, Embase, and the Institute for Scientific Information (ISI), were searched for relevant prospective observational studies (published before Dec 30, 2013) on the association between baseline ALT activity and ensuing all-cause/disease-specific mortality. Information on nationality, sample size, participant characteristics, follow-up duration, comparison, outcome assessment, hazard ratios (HRs) and adjusted covariates was extracted. Pooled HRs and corresponding 95% confidence intervals (CIs) were separately calculated for categorical risk estimates (highest vs. lowest ALT categories) and continuous risk estimates (per 5 U/l of ALT increment) in subgroups separated by age (<70/≥ 70 years). A total of twelve prospective cohort studies, totaling 206,678 participants and 16,249 deaths, were identified and analyzed. In the younger age group, the pooled HR for mortality related to liver-disease was about 1.24 (95% CI: 1.23-1.25) per 5 U/l of ALT increment. The dose-response HRs of all-cause mortality, cardiovascular (CV) disease-related mortality, and cancer-related mortality were 0.91 (0.88-0.94), 0.91 (0.85-0.96), 0.92 (0.86-0.98) respectively per 5 U/l of ALT elevation, with insignificant heterogeneity in the older population. There was an approximate decrease of 4‰ observed on HRs of all-cause, CV-related, and cancer-related mortality followed with one year's increment through meta-regression (all P<0.05). The ALT-mortality association was inconsistent and seems particularly susceptible to age after synthesizing the previous prospective studies. In terms of the age, ALT activity was more valuable in predicting mortality in the older population

  7. Ceruloplasmin, a reliable marker of fibrosis in chronic hepatitis B virus patients with normal or minimally raised alanine aminotransferase

    PubMed Central

    Zeng, Da-Wu; Dong, Jing; Jiang, Jia-Ji; Zhu, Yue-Yong; Liu, Yu-Rui

    2016-01-01

    AIM To develop a non-invasive model to evaluate significant fibrosis and cirrhosis by investigating the association between serum ceruloplasmin (CP) levels and liver fibrosis in chronic hepatitis B (CHB) patients with normal or minimally raised alanine aminotransferase (ALT). METHODS Serum samples and liver biopsy were obtained from 193 CHB patients with minimally raised or normal ALT who were randomly divided into a training group (n = 97) and a validation group (n = 96). Liver histology was evaluated by the METAVIR scoring system. Receiver operator characteristic curves were applied to the diagnostic value of CP for measuring liver fibrosis in CHB patients. Spearman rank correlation analyzed the relationship between CP and liver fibrosis. A non-invasive model was set up through multivariate logistic regression analysis. RESULTS Serum CP levels individualized various fibrosis stages via area under the curve (AUC) values. Multivariate analysis revealed that CP levels were significantly related to liver cirrhosis. Combining CP with serum GGT levels, a CG model was set up to predict significant fibrosis and liver cirrhosis in CHB patients with normal or minimally raised ALT. The AUC, sensitivity, specificity, positive predictive value, and negative predictive value were 0.84, 83.1%, 78.6%, 39.6%, and 96.5% to predict liver cirrhosis, and 0.789, 80.26%, 68.38%, 62.25%, and 84.21% to predict significant fibrosis. This model expressed a higher AUC than FIB-4 (age, ALT, aspartate aminotransferase, platelets) and GP (globulin, platelets) models to predict significant fibrosis (P = 0.019 and 0.022 respectively) and revealed a dramatically greater AUC than FIB-4 (P = 0.033) to predict liver cirrhosis. CONCLUSION The present study showed that CP was independently and negatively associated with liver fibrosis. Furthermore, we developed a novel promising model (CG), based on routine serum markers, for predicting liver fibrosis in CHB patients with normal or minimally raised

  8. Elevated aspartate and alanine aminotransferase levels and natural death among patients with methamphetamine dependence.

    PubMed

    Kuo, Chian-Jue; Tsai, Shang-Ying; Liao, Ya-Tang; Conwell, Yeates; Lee, Wen-Chung; Huang, Ming-Chyi; Lin, Shih-Ku; Chen, Chiao-Chicy; Chen, Wei J

    2012-01-01

    Methamphetamine is one of the fastest growing illicit drugs worldwide, causing multiple organ damage and excessive natural deaths. The authors aimed to identify potential laboratory indices and clinical characteristics associated with natural death through a two-phase study. Methamphetamine-dependent patients (n = 1,254) admitted to a psychiatric center in Taiwan between 1990 and 2007 were linked with a national mortality database for causes of death. Forty-eight subjects died of natural causes, and were defined as the case subjects. A time-efficient sex- and age-matched nested case-control study derived from the cohort was conducted first to explore the potential factors associated with natural death through a time-consuming standardized review of medical records. Then the identified potential factors were evaluated in the whole cohort to validate the findings. In phase I, several potential factors associated with natural death were identified, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), comorbid alcohol use disorder, and the prescription of antipsychotic drugs. In phase II, these factors were confirmed in the whole cohort using survival analysis. For the characteristics at the latest hospital admission, Cox proportional hazards models showed that the adjusted hazard ratios for natural death were 6.75 (p<0.001) in the group with markedly elevated AST (>80 U/L) and 2.66 (p<0.05) in the group with mildly elevated AST (40-80 U/L), with reference to the control group (<40 U/L). As for ALT, the adjusted hazard ratios were 5.41 (p<0.001), and 1.44 (p>0.05). Comorbid alcohol use disorder was associated with an increased risk of natural death, whereas administration of antipsychotic drugs was not associated with lowered risk. This study highlights the necessity of intensive follow-up for those with elevated AST and ALT levels and comorbid alcohol use disorder for preventing excessive natural deaths.

  9. Elevation of alanine transaminase and gallbladder wall abnormalities as biomarkers of anaphylaxis in canine hypersensitivity patients.

    PubMed

    Quantz, Jonnie E; Miles, Macon S; Reed, Ann L; White, George A

    2009-12-01

    The purpose of the study was to evaluate alanine transaminase (ALT) and gallbladder wall abnormalities as possible biomarkers for anaphylaxis in dogs presented for acute hypersensitivity reactions. Pilot study. A private practice, small animal, 24-hour emergency and specialty hospital. Ninety-six dogs presenting 101 times on an emergency basis for hypersensitivity reactions from March 2007 through March 2009. Veterinarians acquired a history, physical exam, serum chemistry panel, blood pressure, and ultrasound image of the gallbladder. Dogs were then divided into 2 groups: dogs fulfilling the definition for anaphylaxis (moderate and severe systemic hypersensitivity) and dogs that did not fulfill the definition and were classified as allergic reactions (local hypersensitivity and mild systemic hypersensitivity). Elevated ALT was significantly associated with anaphylaxis (P<0.001). Increased gallbladder wall thickness and a striated wall pattern were significantly associated with anaphylaxis (P<0.001) and these changes were readily apparent to first-responder veterinarians. Decreased body temperature (P<0.001) and hypothermia (P=0.006) were significantly associated with anaphylaxis. There was no significant difference between groups regarding age, heart rate, or presence of respiratory signs. Lower blood pressure was significantly associated with anaphylaxis (P<0.001) but hypotension was not significantly different (P=0.09) between groups. Cutaneous signs were significantly associated with the allergic reactions group (P<0.001) and, when seen with anaphylaxis, were subtle. This study showed an elevated ALT and an abnormal gallbladder wall to be biomarkers significantly associated with anaphylaxis in dogs with acute hypersensitivity reactions.

  10. NQR in Alanine and Lysine Iodates

    NASA Astrophysics Data System (ADS)

    Petrosyan, A. M.; Burbelo, V. M.; Tamazyan, R. A.; Karapetyan, H. A.; Sukiasyan, R. P.

    2000-02-01

    The structure o f iodates of α- and β-alanine ( Ala) (2(β-Ala • HIO3) • H2O , β-Ala-2HIO3 , D L-Ala• HIO3 • 2H2O, L-Ala • HIO3) and L-lysine (L-Lys) (L-Lys • HIO3, L-Lys • 2HIO3,L-Lys • 3HIO3, L-Lys • 6HIO3) have been investigated by means of iodine-127 NQR, IR spectroscopy and X-ray diffraction

  11. Diorganosilacetylene-alt-diorganosilvinylene polymers and a process of preparation

    DOEpatents

    Barton, T.J.; Ijadi-Maghsoodi, S.; Pang, Y.

    1995-10-10

    The present invention provides linear organosilicon polymers including acetylene and vinylene moieties, and a process for their preparation. These diorganosilacetylene-alt-diorganosilvinylene linear polymers can be represented by the formula: --[--(R{sup 1})(R{sup 2})Si--C{triple_bond}C--(R{sup 3})(R{sup 4})Si--CH{double_bond}CH--]{sub n}--, wherein n{>=}2; and each R{sup 1}, R{sup 2}, R{sup 3}, and R{sup 4} is independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, aryl, and aralkyl radicals. The polymers are soluble in organic solvents, air stable, and can be pulled into fibers or cast into films. They can be thermally converted into silicon carbide ceramic materials.

  12. Diorganosilacetylene-alt-diorganosilvinylene polymers and a process of preparation

    DOEpatents

    Barton, Thomas J.; Ijadi-Maghsoodi, Sina; Pang, Yi

    1995-10-10

    The present invention provides linear organosilicon polymers including acetylene and vinylene moieties, and a process for their preparation. These diorganosilacetylene-alt-diorganosilvinylene linear polymers can be represented by the formula: --[--(R.sup.1)(R.sup.2)Si--C.tbd.C--(R.sup.3)(R.sup.4)Si--CH.dbd.CH--].sub .n --, wherein n.gtoreq.2; and each R.sup.1, R.sup.2, R.sup.3, and R.sup.4 is independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, aryl, and aralkyl radicals. The polymers are soluble in organic solvents, air stable, and can be pulled into fibers or cast into films. They can be thermally converted into silicon carbide ceramic materials.

  13. Diorganosilacetylene-alt-diorganosilvinylene polymers and a process of preparation

    DOEpatents

    Barton, T.J.; Ijadi-Maghsoodi, S.; Yi Pang.

    1993-08-31

    The present invention provides linear organosilicon polymers including acetylene and vinylene moieties, and a process for their preparation. These diorganosilacetylene-alt-diorganosilvinylene linear polymers can be represented by the formula: -[-(R[sup 1])(R[sup 2])Si-C[triple bond]C-(R[sup 3])(R[sup 4])Si-CH[double bond]CH-][sub n]-, wherein n[>=]2; each R[sup 1], R[sup 2], R[sup 3], and R[sup 4] is independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, aryl, and aralkyl radicals. The polymers are soluble in organic solvents, air stable, and can be pulled into fibers or cast into films. They can be thermally converted into silicon carbide ceramic materials.

  14. Studio delle popolazioni di blazar ad alte energie

    NASA Astrophysics Data System (ADS)

    Gasparrini, D.; Giommi, P.

    2008-10-01

    Utilizzando la grande quantita' di dati sui blazar disponibile ad oggi, e' possibile costruire una distribuzione spettrale di energia (SED) media per ciascuna classe di oggetti. Basandosi su un modello SSC, e' inoltre possibile stimare il comportamento di questi oggetti nella banda di energia dei raggi gamma partendo dalle informazioni ottenute da osservazioni in altre bande di energia quali il radio e l'X. Utilizzando le simulazioni sara` possibile prevedere un eventuale cambio di popolazione dominante ad alte energie(oltre 1GeV) rispetto a quanto avviene in banda radio dove domina la popolazione dei FSRQ rispetto ai BL Lac e cercare un'eventuale conferma dagli esperimenti AGILE e GLAST.

  15. Predictors of treatment efficacy and ALT non-normalization with sofosbuvir/ribavirin therapy for patients with hepatitis C virus genotype 2.

    PubMed

    Watanabe, Takao; Tokumoto, Yoshio; Joko, Kouji; Michitaka, Kojiro; Horiike, Norio; Tanaka, Yoshinori; Tada, Fujimasa; Kisaka, Yoshiyasu; Nakanishi, Seiji; Nonaka, Takashi; Yamauchi, Kazuhiko; Hirooka, Masashi; Abe, Masanori; Hiasa, Yoichi

    2017-09-01

    The tolerability and efficacy of sofosbuvir and ribavirin in patients infected with hepatitis C virus (HCV) genotype 2 were investigated under actual clinical conditions. A total of 208 patients with chronic HCV genotype 2 infection were treated with sofosbuvir 400 mg and ribavirin (weight-based dosing) for 12 weeks. Treatment discontinuation and sustained virological response 12 (SVR12) were evaluated. Moreover, factors associated with SVR12, hemoglobin decreasing to less than 10 g/dL during treatment, and alanine aminotransferase (ALT) non-normalization after treatment were evaluated. In all patients, SVR12 responses were 96.1% (200/208). About 6 of 8 patients (3.8%) who did not achieve SVR12 were re-treatment patients, and eight patients who did not achieve SVR all had liver cirrhosis. Multivariate analysis also identified body mass index (OR = 0.79; P < 0.001), platelet count (OR = 0.88; P = 0.003), and estimated glomerular filtration rate (eGFR) (OR = 0.96; P = 0.007) as independent contributing factors associated with hemoglobin decreasing to less than 10 g/dL during treatment, and only Mac-2 Binding Protein Glycosylation isomer (M2BpGi) (OR = 2.46; P = 0.017) as an independent contributing factor associated with ALT non-normalization after treatment. Cirrhotic patients may have a relatively high rate of treatment failure. In patients whose M2BpGi levels are elevated, their ALT tended to not normalize after treatment completion. These patients who did not achieve normalization of ALT after sofosbuvir plus RBV treatment need more careful observation for emergence of hepatocellular carcinoma even after achievement of SVR. © 2017 Wiley Periodicals, Inc.

  16. Green reduction of graphene oxide using alanine.

    PubMed

    Wang, Jiabin; Salihi, Elif Caliskan; Šiller, Lidija

    2017-03-01

    There remains a real need for the easy, eco-friendly and scalable preparation method of graphene due to various potential applications. Chemical reduction is the most versatile method for the large scale production of graphene. Here we report the operating conditions for a one-step, economical and green synthesis method for the reduction of graphene oxide using a biomolecule (alanine). Graphene oxide was produced by the oxidation and exfoliation of natural graphite flake with strong oxidants using Hummers method (Hummers and Offeman, 1958), but the method was revised in our laboratory to set up a safe and environmentally friendly route. The reduction of graphene oxide was investigated using alanine at various operating conditions in order to set up optimum conditions (treatment time, temperature and concentration of the reagent). Samples have been characterized by using UV-Visible spectroscopy, Fourier transform infrared spectroscopy, transmission electron microscopy, Raman spectroscopy and X-ray diffraction analysis. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Racemization of alanine by the alanine racemases from Salmonella typhimurium and Bacillus stearothermophilus: energetic reaction profiles

    SciTech Connect

    Faraci, W.S.; Walsh, C.T.

    1988-05-03

    Alanine racemases are bacterial pyridoxal 5'-phosphate (PLP) dependent enzymes providing D-alanine as an essential building block for biosynthesis of the peptidoglycan layer of the cell wall. Two isozymic alanine racemases, encoded by the dadB gene and the alr gene, from the Gram-negative mesophilic Salmonella typhimurium and one from the Gram-positive thermophilic Bacillus stearothermophilus have been examined for the racemization mechanism. Substrate deuterium isotope effects and solvent deuterium isotope effects have been measured in both L ..-->.. D and D..-->.. L directions for all three enzymes to assess the degree to which abstraction of the ..cap alpha..-proton or protonation of substrate PLP carbanion is limiting in catalysis. Additionally, experiments measuring internal return of ..cap alpha..-/sup 3/H from substrate to product and solvent exchange/substrate conversion experiments in /sup 3/H/sub 2/O have been used with each enzyme to examine the partitioning of substrate PLP carbanion intermediates and to obtain the relative heights of kinetically significant energy barriers in alanine racemase catalysis.

  18. Crystallization and preliminary crystallographic analysis of d-alanine-d-alanine ligase from Streptococcus mutans

    SciTech Connect

    Lu, Yong-Zhi; Sheng, Yu; Li, Lan-Fen; Tang, De-Wei; Liu, Xiang-Yu; Zhao, Xiaojun; Liang, Yu-He Su, Xiao-Dong

    2007-09-01

    A potential target for antibiotic drug design, d-alanine-d-alanine ligase from S. mutans, was expressed in E. coli, purified and crystallized. Diffraction data were collected to 2.4 Å resolution. d-Alanine-d-alanine ligase is encoded by the gene ddl (SMU-599) in Streptococcus mutans. This ligase plays a very important role in cell-wall biosynthesis and may be a potential target for drug design. To study the structure and function of this ligase, the gene ddl was amplified from S. mutans genomic DNA and cloned into the expression vector pET28a. The protein was expressed in soluble form in Escherichia coli strain BL21 (DE3). Homogeneous protein was obtained using a two-step procedure consisting of Ni{sup 2+}-chelating and size-exclusion chromatography. Purified protein was crystallized and the cube-shaped crystal diffracted to 2.4 Å. The crystal belongs to space group P3{sub 1}21 or P3{sub 2}21, with unit-cell parameters a = b = 79.50, c = 108.97 Å. There is one molecule per asymmetric unit.

  19. Maximization of orbiter altitude at ALT interface airspeed, mission planning, mission analysis and software

    NASA Technical Reports Server (NTRS)

    Glenn, G. M.

    1976-01-01

    The determination of the separation initial conditions (i.e. incidence angle) that maximize orbiter altitude at the ALT interface airspeed is considered. Optimum altitude airspeed profiles are generated for each orbiter incidence angle and tailcone configuration. Results show that the highest separation altitude does not result in the highest altitude at ALT interface airspeed. The altitude attainable at ALT interface airspeed should therefore be considered in the selection of the initial conditions (i.e. incidence angle). Without violating any known constraints, the incidence angles that maximize orbiter altitude at the ALT interface airspeeds are 7.0 deg for ALT free flight 1 and 5.5 deg for ALT free flight 6.

  20. Detailed design specification for the ALT Shuttle Information Extraction Subsystem (SIES)

    NASA Technical Reports Server (NTRS)

    Clouette, G. L.; Fitzpatrick, W. N.

    1976-01-01

    The approach and landing test (ALT) shuttle information extraction system (SIES) is described in terms of general requirements and system characteristics output products and processing options, output products and data sources, and system data flow. The ALT SIES is a data reduction system designed to satisfy certain data processing requirements for the ALT phase of the space shuttle program. The specific ALT SIES data processing requirements are stated in the data reduction complex approach and landing test data processing requirements. In general, ALT SIES must produce time correlated data products as a result of standardized data reduction or special purpose analytical processes. The main characteristics of ALT SIES are: (1) the system operates in a batch (non-interactive) mode; (2) the processing is table driven; (3) it is data base oriented; (4) it has simple operating procedures; and (5) it requires a minimum of run time information.

  1. ALT-711 decreases cardiovascular stiffness and has potential in diabetes, hypertension and heart failure.

    PubMed

    Doggrell, S A

    2001-05-01

    Vascular and/or myocardial stiffness is a major problem in ageing, diabetes, hypertension and heart failure. The development of the stiffness is partly due to the formation of glucose-dependent cross-links in the collagen. ALT-711 cleaves these cross-links. In aged-rhesus monkeys, ALT-711 decreases vascular stiffness and this effect is reversible. ALT-711 also decreases myocardial stiffness in the monkeys but this effect is not reversible in 39 weeks. ALT-711 has potential in the treatment of the stiffness associated with diabetes, hypertension and heart failure.

  2. Fine Particle Pollution, Alanine Transaminase, and Liver Cancer: A Taiwanese Prospective Cohort Study (REVEAL-HBV).

    PubMed

    Pan, Wen-Chi; Wu, Chih-Da; Chen, Mu-Jean; Huang, Yen-Tsung; Chen, Chien-Jen; Su, Huey-Jen; Yang, Hwai-I

    2016-03-01

    Exposure to fine particulate matter (PM2.5) may promote hepatic tumorgenesis through low-grade inflammation. Therefore, we assessed the association of long-term exposure levels of PM2.5 and subsequent risk of hepatocellular carcinoma (HCC) and investigated the mediation effect of inflammation as represented by alanine aminotransferase (ALT) on this association. Between 1991 and 1992, we recruited 23 820 participants in Taiwan with no history of HCC. Case patients of HCC were ascertained through computerized data linkage with the National Cancer Registry and death certification systems. Participants' exposures to PM2.5 were based on a four-year average retrieved from stationary monitoring sites. Cox proportional hazards models were used to assess the association between PM2.5 exposure and HCC incidence. Mediation effects of ALT on PM2.5-associated HCC incidence were estimated. A total of 464 HCC cases were newly diagnosed with a median follow-up of 16.9 years. Statistically significantly increasing trends between PM2.5 exposures and ALT were observed on the Main Island and Penghu Islets. The adjusted hazard ratio (HR) for HCC on the Penghu Islets was 1.22 (95% confidence interval [CI] = 1.02 to 1.47) per PM2.5 interquartile range (IQR) increment (0.73 µg/m(3)) exposure. We also found a positive association between PM2.5 exposure (per IQR increment, 13.1 µg/m(3)) and HCC incidence on the Main Island. Furthermore, ALT had a statistically significant mediation effect on PM2.5-associated HCC incidence (HR = 1.17, 95% CI = 1.02 to1.52 on the Main Island; HR = 1.04, 95% CI = 1.03 to 1.07 on the Penghu Islets) per PM2.5 IQR increment. Long-term PM2.5 exposure increased the risk for liver cancer, and chronic inflammation of the liver may underlie the pathogenesis. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. International society of sports nutrition position stand: Beta-Alanine.

    PubMed

    Trexler, Eric T; Smith-Ryan, Abbie E; Stout, Jeffrey R; Hoffman, Jay R; Wilborn, Colin D; Sale, Craig; Kreider, Richard B; Jäger, Ralf; Earnest, Conrad P; Bannock, Laurent; Campbell, Bill; Kalman, Douglas; Ziegenfuss, Tim N; Antonio, Jose

    2015-01-01

    The International Society of Sports Nutrition (ISSN) provides an objective and critical review of the mechanisms and use of beta-alanine supplementation. Based on the current available literature, the conclusions of the ISSN are as follows: 1) Four weeks of beta-alanine supplementation (4-6 g daily) significantly augments muscle carnosine concentrations, thereby acting as an intracellular pH buffer; 2) Beta-alanine supplementation currently appears to be safe in healthy populations at recommended doses; 3) The only reported side effect is paraesthesia (tingling), but studies indicate this can be attenuated by using divided lower doses (1.6 g) or using a sustained-release formula; 4) Daily supplementation with 4 to 6 g of beta-alanine for at least 2 to 4 weeks has been shown to improve exercise performance, with more pronounced effects in open end-point tasks/time trials lasting 1 to 4 min in duration; 5) Beta-alanine attenuates neuromuscular fatigue, particularly in older subjects, and preliminary evidence indicates that beta-alanine may improve tactical performance; 6) Combining beta-alanine with other single or multi-ingredient supplements may be advantageous when supplementation of beta-alanine is high enough (4-6 g daily) and long enough (minimum 4 weeks); 7) More research is needed to determine the effects of beta-alanine on strength, endurance performance beyond 25 min in duration, and other health-related benefits associated with carnosine.

  4. Alanine aminotransferase controls seed dormancy in barley

    PubMed Central

    Sato, Kazuhiro; Yamane, Miki; Yamaji, Nami; Kanamori, Hiroyuki; Tagiri, Akemi; Schwerdt, Julian G.; Fincher, Geoffrey B.; Matsumoto, Takashi; Takeda, Kazuyoshi; Komatsuda, Takao

    2016-01-01

    Dormancy allows wild barley grains to survive dry summers in the Near East. After domestication, barley was selected for shorter dormancy periods. Here we isolate the major seed dormancy gene qsd1 from wild barley, which encodes an alanine aminotransferase (AlaAT). The seed dormancy gene is expressed specifically in the embryo. The AlaAT isoenzymes encoded by the long and short dormancy alleles differ in a single amino acid residue. The reduced dormancy allele Qsd1 evolved from barleys that were first domesticated in the southern Levant and had the long dormancy qsd1 allele that can be traced back to wild barleys. The reduced dormancy mutation likely contributed to the enhanced performance of barley in industrial applications such as beer and whisky production, which involve controlled germination. In contrast, the long dormancy allele might be used to control pre-harvest sprouting in higher rainfall areas to enhance global adaptation of barley. PMID:27188711

  5. Neutral transport in the ALT-I limiter

    SciTech Connect

    Boley, C.D.; Heifetz, D.B.; Post, D.E.; Malinowski, M.E.

    1983-10-01

    The behavior of neutral atoms and molecules in the TEXTOR pump limiter ALT-I has been investigated with the aid of the 2-D Monte Carlo neutral transport code DEGAS. The code incorporates the full set of relevant collision processes (atomic and molecular), and it has a standard wall model which includes fast-neutral reflection and molecular desorption. The limiter was modeled with a 2-D geometry, which included corrections for 3-D effects. Among the quantities predicted by the code which are directly relevant to experiment include the neutral pressure within the plenum and along the duct leading into the plenum, the gettering rates, and the heat flux to the walls of the duct. These have been calculated for a variety of plasma parameters in the inlet, and the behavior with respect to variations of the duct widths has been studied. Because of the presence of the long duct separating the entrance chamber from the plenum, a high probability of ionization generally results, suggesting that a calculation allowing the plasma to adjust to the neutral sources might show a large amount of recycling.

  6. Crystal structure of the Apo form of D-Alanine:D-Alanine ligase (DDl) from Streptococcus mutans.

    PubMed

    Lu, Yongzhi; Xu, Hongyan; Zhao, Xiaojun

    2010-08-01

    D-Alanine:D-Alanine ligase (DDl) catalyzes the formation of D-Alanine:D-Alanine dipeptide and is an essential enzyme in bacterial cell wall biosynthesis.. This enzyme does not have a human ortholog, making it an attractive target for developing new antibiotic drugs. We determined the crystal structure at 2.23 A resolution of DDl from Streptococcus mutans (SmDDl), the principal aetiological agent of human dental caries. This structure reveals that SmDDl is a dimer and has a disordered omega-loop region.

  7. Insulin resistance is associated with elevated transaminases and low aspartate aminotransferase/alanine aminotransferase ratio in young adults with normal weight.

    PubMed

    Simental-Mendía, Luis E; Rodríguez-Morán, Martha; Gómez-Díaz, Rita; Wacher, Niels H; Rodríguez-Hernández, Heriberto; Guerrero-Romero, Fernando

    2017-04-01

    The aim of this study is to determine whether insulin resistance is associated with elevation of transaminases levels and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio in normal-weight healthy young adults. Apparently healthy nonpregnant women and men, aged 18-23 years, were enrolled in a cross-sectional study. According to the homeostasis model assessment of insulin resistance, the participants were allocated into groups of patients with (>2.5) and without (≤2.5) insulin resistance. Normal weight was defined by BMI of at least 18.5 and less than 25.0 kg/m. A multiple logistic regression analysis was carried out to determine the association between insulin resistance and elevated transaminases and AST/ALT ratio of 1 or less. A total of 1732 young adults were enrolled and allocated into groups with (n=287) and without (n=1445) insulin resistance. The prevalence of insulin resistance was 16.6% in the overall population. The multivariate logistic regression analysis adjusted by age, sex, waist circumference, and BMI indicated that the odds ratio (OR) between insulin resistance and elevated ALT concentrations is 1.65 [95% confidence interval (CI): 1.04-2.62, P=0.03], for AST/ALT ratio lower than 1 OR is 1.69 (95% CI: 1.27-2.26, P<0.001), and for elevated AST levels OR is 1.31 (95% CI: 0.71-2.43, P=0.377). The results of the present study suggest that insulin resistance is significantly associated with elevated ALT levels and AST/ALT ratio of lower than 1, but not with elevated AST levels.

  8. Trihalomethane exposure and biomonitoring for the liver injury indicator, alanine aminotransferase, in the United States population (NHANES 1999–2006)

    PubMed Central

    Burch, James B.; Everson, Todd M.; Seth, Ratanesh K.; Wirth, Michael D.; Chatterjee, Saurabh

    2015-01-01

    Exposure to trihalomethanes (or THMs: chloroform, bromoform, bromodichloromethane, and dibromochloromethane [DBCM]) formed via drinking water disinfection has been associated with adverse reproductive outcomes and cancers of the digestive or genitourinary organs. However, few studies have examined potential associations between THMs and liver injury in humans, even though experimental studies suggest that these agents exert hepatotoxic effects, particularly among obese individuals. This study examined participants in the National Health and Nutrition Examination Survey (1999–2006, N = 2781) to test the hypothesis that THMs are associated with liver injury as assessed by alanine aminotransferase (ALT) activity in circulation. Effect modification by body mass index (BMI) or alcohol consumption also was examined. Associations between blood THM concentrations and ALT activity were assessed using unconditional multiple logistic regression to calculate prevalence odds ratios (ORs) with 95% confidence intervals (CIs) for exposure among cases with elevated ALT activity (men: >40 IU/L, women: >30 IU/L) relative to those with normal ALT, after adjustment for variables that may confound the relationship between ALT and THMs. Compared to controls, cases were 1.35 times more likely (95% CI: 1.02, 1.79) to have circulating DBCM concentrations exceeding median values in the population. There was little evidence for effect modification by BMI, although the association varied by alcohol consumption. Among non-drinkers, cases were more likely than controls to be exposed to DBCM (OR: 3.30, 95% CI: 1.37–7.90), bromoform (OR: 2.88, 95% CI: 1.21–6.81), or brominated THMs (OR: 4.00, 95% CI: 1.31–12.1), but no association was observed among participants with low, or moderate to heavy alcohol consumption. Total THM levels exceeding benchmark exposure limits continue to be reported both in the United States and globally. Results from this study suggest a need for further

  9. Alanine repeats influence protein localization in splicing speckles and paraspeckles.

    PubMed

    Chang, Shuo-Hsiu; Chang, Wei-Lun; Lu, Chia-Chen; Tarn, Woan-Yuh

    2014-12-16

    Mammalian splicing regulatory protein RNA-binding motif protein 4 (RBM4) has an alanine repeat-containing C-terminal domain (CAD) that confers both nuclear- and splicing speckle-targeting activities. Alanine-repeat expansion has pathological potential. Here we show that the alanine-repeat tracts influence the subnuclear targeting properties of the RBM4 CAD in cultured human cells. Notably, truncation of the alanine tracts redistributed a portion of RBM4 to paraspeckles. The alanine-deficient CAD was sufficient for paraspeckle targeting. On the other hand, alanine-repeat expansion reduced the mobility of RBM4 and impaired its splicing activity. We further took advantage of the putative coactivator activator (CoAA)-RBM4 conjoined splicing factor, CoAZ, to investigate the function of the CAD in subnuclear targeting. Transiently expressed CoAZ formed discrete nuclear foci that emerged and subsequently separated-fully or partially-from paraspeckles. Alanine-repeat expansion appeared to prevent CoAZ separation from paraspeckles, resulting in their complete colocalization. CoAZ foci were dynamic but, unlike paraspeckles, were resistant to RNase treatment. Our results indicate that the alanine-rich CAD, in conjunction with its conjoined RNA-binding domain(s), differentially influences the subnuclear localization and biogenesis of RBM4 and CoAZ.

  10. Production of the Allergenic Protein Alt a 1 by Alternaria Isolates from Working Environments

    PubMed Central

    Skóra, Justyna; Otlewska, Anna; Gutarowska, Beata; Leszczyńska, Joanna; Majak, Iwona; Stępień, Łukasz

    2015-01-01

    The aim of the study was to evaluate the ability of Alternaria isolates from workplaces to produce Alt a 1 allergenic protein, and to analyze whether technical materials (cellulose, compost, leather) present within the working environment stimulate or inhibit Alt a 1 production (ELISA test). Studies included identification of the isolated molds by nucleotide sequences analyzing of the ITS1/ITS2 regions, actin, calmodulin and Alt a 1 genes. It has been shown that Alternaria molds are significant part of microbiocenosis in the archive, museum, library, composting plant and tannery (14%–16% frequency in the air). The presence of the gene encoding the Alt a 1 protein has been detected for the strains: Alternaria alternata, A. lini, A. limoniasperae A. nobilis and A. tenuissima. Environmental strains produced Alt a 1 at higher concentrations (1.103–6.528 ng/mL) than a ATCC strain (0.551–0.975 ng/mL). It has been shown that the homogenization of the mycelium and the use of ultrafiltration allow a considerable increase of Alt a 1 concentration. Variations in the production of Alt a 1 protein, depend on the strain and extraction methods. These studies revealed no impact of the technical material from the workplaces on the production of Alt a 1 protein. PMID:25689994

  11. Production of the allergenic protein Alt a 1 by Alternaria isolates from working environments.

    PubMed

    Skóra, Justyna; Otlewska, Anna; Gutarowska, Beata; Leszczyńska, Joanna; Majak, Iwona; Stępień, Łukasz

    2015-02-16

    The aim of the study was to evaluate the ability of Alternaria isolates from workplaces to produce Alt a 1 allergenic protein, and to analyze whether technical materials (cellulose, compost, leather) present within the working environment stimulate or inhibit Alt a 1 production (ELISA test). Studies included identification of the isolated molds by nucleotide sequences analyzing of the ITS1/ITS2 regions, actin, calmodulin and Alt a 1 genes. It has been shown that Alternaria molds are significant part of microbiocenosis in the archive, museum, library, composting plant and tannery (14%-16% frequency in the air). The presence of the gene encoding the Alt a 1 protein has been detected for the strains: Alternaria alternata, A. lini, A. limoniasperae A. nobilis and A. tenuissima. Environmental strains produced Alt a 1 at higher concentrations (1.103-6.528 ng/mL) than a ATCC strain (0.551-0.975 ng/mL). It has been shown that the homogenization of the mycelium and the use of ultrafiltration allow a considerable increase of Alt a 1 concentration. Variations in the production of Alt a 1 protein, depend on the strain and extraction methods. These studies revealed no impact of the technical material from the workplaces on the production of Alt a 1 protein.

  12. Switch telomerase to ALT mechanism by inducing telomeric DNA damages and dysfunction of ATRX and DAXX.

    PubMed

    Hu, Yang; Shi, Guang; Zhang, Laichen; Li, Feng; Jiang, Yuanling; Jiang, Shuai; Ma, Wenbin; Zhao, Yong; Songyang, Zhou; Huang, Junjiu

    2016-08-31

    Activation of telomerase or alternative lengthening of telomeres (ALT) is necessary for tumours to escape from dysfunctional telomere-mediated senescence. Anti-telomerase drugs might be effective in suppressing tumour growth in approximately 85-90% of telomerase-positive cancer cells. However, there are still chances for these cells to bypass drug treatment after switching to the ALT mechanism to maintain their telomere integrity. But the mechanism underlying this switch is unknown. In this study, we used telomerase-positive cancer cells (HTC75) to discover the mechanism of the telomerase-ALT switch by inducing telomere-specific DNA damage, alpha-thalassemia X-linked syndrome protein (ATRX) knockdown and deletion of death associated protein (DAXX). Surprisingly, two important ALT hallmarks in the ALT-like HTC75 cells were observed after treatments: ALT-associated promyelocytic leukaemia bodies (APBs) and extrachromosomal circular DNA of telomeric repeats. Moreover, knocking out hTERT by utilizing the CRISPR/Cas9 technique led to telomere elongation in a telomerase-independent manner in ALT-like HTC75 cells. In summary, this is the first report to show that inducing telomeric DNA damage, disrupting the ATRX/DAXX complex and inhibiting telomerase activity in telomerase-positive cancer cells lead to the ALT switch.

  13. Preliminary design analysis of the ALT-II limiter for TEXTOR

    SciTech Connect

    Koski, J.A.; Boyd, R.D.; Kempka, S.M.; Romig, A.D. Jr.; Smith, M.F.; Watson, R.D.; Whitley, J.B.; Conn, R.W.; Grotz, S.P.

    1983-01-01

    Installation of a large toroidal belt pump limiter, Advanced Limiter Test II (ALT-II), on the TEXTOR tokamak at Juelich, FRG is anticipated for early 1986. This paper discusses the preliminary mechanical design and materials considerations undertaken as part of the feasibility study phase for ALT-II.

  14. Some Features of "Alt" Texts Associated with Images in Web Pages

    ERIC Educational Resources Information Center

    Craven, Timothy C.

    2006-01-01

    Introduction: This paper extends a series on summaries of Web objects, in this case, the alt attribute of image files. Method: Data were logged from 1894 pages from Yahoo!'s random page service and 4703 pages from the Google directory; an img tag was extracted randomly from each where present; its alt attribute, if any, was recorded; and the…

  15. Production of D-Alanine by Corynebacterium fascians

    PubMed Central

    Yamada, Shigeki; Maeshima, Haruko; Wada, Mitsuru; Chibata, Ichiro

    1973-01-01

    A strain identified as Corynebacterium fascians was found to accumulate extracellular D-alanine from glycerol. Cultural conditions for the accumulation of D-alanine were investigated and, as a result, a yield of 7 g of D-alanine per liter was obtained after a 96-h incubation in a medium containing 5% glycerol, 4% (NH4)2HPO4, and 0.3% corn steep liquor. Optical purity of D-alanine was dependent upon the concentration of corn steep liquor. At the optimal condition, almost optically pure D-alanine was formed and readily isolated (5 g/liter) from the fermentation broth. The product was not contaminated with any detectable amount of other amino acids, except for glycine which was present at a concentration of less than 1 percent. PMID:4699220

  16. Mechanisms of itch evoked by β-alanine.

    PubMed

    Liu, Qin; Sikand, Parul; Ma, Chao; Tang, Zongxiang; Han, Liang; Li, Zhe; Sun, Shuohao; LaMotte, Robert H; Dong, Xinzhong

    2012-10-17

    β-Alanine, a popular supplement for muscle building, induces itch and tingling after consumption, but the underlying molecular and neural mechanisms are obscure. Here we show that, in mice, β-alanine elicited itch-associated behavior that requires MrgprD, a G-protein-coupled receptor expressed by a subpopulation of primary sensory neurons. These neurons exclusively innervate the skin, respond to β-alanine, heat, and mechanical noxious stimuli but do not respond to histamine. In humans, intradermally injected β-alanine induced itch but neither wheal nor flare, suggesting that the itch was not mediated by histamine. Thus, the primary sensory neurons responsive to β-alanine are likely part of a histamine-independent itch neural circuit and a target for treating clinical itch that is unrelieved by anti-histamines.

  17. Mechanisms of itch evoked by β-alanine

    PubMed Central

    Liu, Qin; Sikand, Parul; Ma, Chao; Tang, Zongxiang; Han, Liang; Li, Zhe; Sun, Shuohao; LaMotte, Robert H.; Dong, Xinzhong

    2012-01-01

    β-alanine, a popular supplement for muscle building, induces itch and tingling after consumption, but the underlying molecular and neural mechanisms are obscure. Here we show that, in mice, β-alanine elicited itch-associated behavior that requires MrgprD, a G protein-coupled receptor expressed by a subpopulation of primary sensory neurons. These neurons exclusively innervate the skin, respond to β-alanine, heat and mechanical noxious stimuli but do not respond to histamine. In humans, intradermally injected β-alanine induced itch but neither wheal nor flare suggesting that the itch was not mediated by histamine. Thus, the primary sensory neurons responsive to β-alanine are likely part of a histamine-independent itch neural circuit and a target for treating clinical itch that is unrelieved by anti-histamines. PMID:23077038

  18. The structure of alanine racemase from Acinetobacter baumannii.

    PubMed

    Davis, Emily; Scaletti-Hutchinson, Emma; Opel-Reading, Helen; Nakatani, Yoshio; Krause, Kurt L

    2014-09-01

    Acinetobacter baumannii is an opportunistic Gram-negative bacterium which is a common cause of hospital-acquired infections. Numerous antibiotic-resistant strains exist, emphasizing the need for the development of new antimicrobials. Alanine racemase (Alr) is a pyridoxal 5'-phosphate dependent enzyme that is responsible for racemization between enantiomers of alanine. As D-alanine is an essential component of the bacterial cell wall, its inhibition is lethal to prokaryotes, making it an excellent antibiotic drug target. The crystal structure of A. baumannii alanine racemase (AlrAba) from the highly antibiotic-resistant NCTC13302 strain has been solved to 1.9 Å resolution. Comparison of AlrAba with alanine racemases from closely related bacteria demonstrates a conserved overall fold. The substrate entryway and active site of the enzymes were shown to be highly conserved. The structure of AlrAba will provide the template required for future structure-based drug-design studies.

  19. Evaluation of Preoperative Aspartate Transaminase/Alanine Transaminase Ratio as an Independent Predictive Biomarker in Patients With Metastatic Renal Cell Carcinoma Undergoing Cytoreductive Nephrectomy: A Propensity Score Matching Study.

    PubMed

    Ishihara, Hiroki; Kondo, Tsunenori; Yoshida, Kazuhiko; Omae, Kenji; Takagi, Toshio; Iizuka, Junpei; Tanabe, Kazunari

    2017-10-01

    The usefulness of the aspartate transaminase (AST)/alanine transaminase (ALT) ratio (De Ritis ratio) as a predictive biomarker for patients with metastatic renal cell carcinoma (mRCC) undergoing cytoreductive nephrectomy (CN) remains unclear. The data from 118 patients were retrospectively evaluated. The endpoints were cancer-specific survival (CSS) and overall survival (OS) after CN. We compared these according to the AST/ALT ratio before and after 1:1 propensity score matching. The independent predictors for CSS and OS were also analyzed. The area under the receiver operating characteristic curve was 0.603. The maximum Youden index indicated that the cutoff value for the AST/ALT ratio was 1.24. Before matching, a high AST/ALT ratio was significantly associated with inferior CSS and OS (P < .05 for all). After matching, 34 patients each were allocated to the high and low AST/ALT ratio groups. In the matched cohort, CSS and OS tended to be lower in the high AST/ALT ratio group, although the results were not statistically significant (median CSS, 18.4 months vs. not reached, P = .121; OS, 18.4 months vs. not reached, P = .0957). Furthermore, multivariate analyses revealed that the AST/ALT ratio was an independent predictor for CSS and OS (CSS hazard ratio, 2.17, P = .0472; OS hazard ratio, 2.30, P = .0258). The preoperative AST/ALT ratio can be an effective predictive biomarker for CSS and OS in patients with mRCC. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Comparison of EPR response of alanine and Gd₂O₃-alanine dosimeters exposed to TRIGA Mainz reactor.

    PubMed

    Marrale, M; Schmitz, T; Gallo, S; Hampel, G; Longo, A; Panzeca, S; Tranchina, L

    2015-12-01

    In this work we report some preliminary results regarding the analysis of electron paramagnetic resonance (EPR) response of alanine pellets and alanine pellets added with gadolinium used for dosimetry at the TRIGA research reactor in Mainz, Germany. Two set-ups were evaluated: irradiation inside PMMA phantom and irradiation inside boric acid phantom. We observed that the presence of Gd2O3 inside alanine pellets increases the EPR signal by a factor of 3.45 and 1.24 in case of PMMA and boric acid phantoms, respectively. We can conclude that in the case of neutron beam with a predominant thermal neutron component the addition of gadolinium oxide can significantly improve neutron sensitivity of alanine pellets. Monte Carlo (MC) simulations of both response of alanine and Gd-added alanine pellets with FLUKA code were performed and a good agreement was achieved for pure alanine dosimeters. For Gd2O3-alanine deviations between MC simulations and experimental data were observed and discussed.

  1. New use of an old drug: chloroquine reduces viral and ALT levels in HCV non-responders (a randomized, triple-blind, placebo-controlled pilot trial).

    PubMed

    Peymani, Payam; Yeganeh, Behzad; Sabour, Siamak; Geramizadeh, Bita; Fattahi, Mohammad Reza; Keyvani, Hossein; Azarpira, Negar; Coombs, Kevin M; Ghavami, Saied; Lankarani, Kamran B

    2016-06-01

    Hepatitis C virus (HCV) infection induces autophagy, but the virus assimilates the autophagic response into its own life cycle. Chloroquine (CQ) is an autophagy inhibitor that is clinically used to treat malaria. The aims of this pilot clinical trial were to evaluate the therapeutic potential and short-term safety of CQ in patients with chronic HCV genotype 1, who were unresponsive to a combination of pegylated interferon alpha and ribavirin. Ten non-responders to previous antiviral treatment(s) were randomized to receive either CQ (150 mg daily for 8 weeks) or placebo, and were followed for 4 weeks after CQ therapy. HCV RNA load and plasma alanine transaminase (ALT) levels were measured at baseline, week 4 (initial response), week 8 (end-of-treatment response), and at the end of 12 weeks. A significant decrease in HCV RNA after the treatments (week 8) was observed in all patients in the CQ group (P = 0.04). However, HCV RNA levels increased within 4 weeks after discontinuation of CQ treatment although they were still lower than baseline. In addition, the ALT normalized during treatment in the CQ group. However, this response was also lost after treatment cessation. This study provides preliminary evidence that CQ is possibly a safe treatment option for HCV non-responders.

  2. β-Alanine supplementation for athletic performance: an update.

    PubMed

    Bellinger, Phillip M

    2014-06-01

    β-alanine supplementation has become a common practice among competitive athletes participating in a range of different sports. Although the mechanism by which chronic β-alanine supplementation could have an ergogenic effect is widely debated, the popular view is that β-alanine supplementation augments intramuscular carnosine content, leading to an increase in muscle buffer capacity, a delay in the onset of muscular fatigue, and a facilitated recovery during repeated bouts of high-intensity exercise. β-alanine supplementation appears to be most effective for exercise tasks that rely heavily on ATP synthesis from anaerobic glycolysis. However, research investigating its efficacy as an ergogenic aid remains equivocal, making it difficult to draw conclusions as to its effectiveness for training and competition. The aim of this review was to update, summarize, and critically evaluate the findings associated with β-alanine supplementation and exercise performance with the most recent research available to allow the development of practical recommendations for coaches and athletes. A critical review of the literature reveals that when significant ergogenic effects have been found, they have been generally shown in untrained individuals performing exercise bouts under laboratory conditions. The body of scientific data available concerning highly trained athletes performing single competition-like exercise tasks indicates that this type of population receives modest but potentially worthwhile performance benefits from β-alanine supplementation. Recent data indicate that athletes may not only be using β-alanine supplementation to enhance sports performance but also as a training aid to augment bouts of high-intensity training. β-alanine supplementation has also been shown to increase resistance training performance and training volume in team-sport athletes, which may allow for greater overload and superior adaptations compared with training alone. The ergogenic

  3. Characterisation of a flavonoid ligand of the fungal protein Alt a 1

    PubMed Central

    Garrido-Arandia, María; Silva-Navas, Javier; Ramírez-Castillejo, Carmen; Cubells-Baeza, Nuria; Gómez-Casado, Cristina; Barber, Domingo; Pozo, Juan C.; Melendi, Pablo G.; Pacios, Luis F.; Díaz-Perales, Araceli

    2016-01-01

    Spores of pathogenic fungi are virtually ubiquitous and cause human disease and severe losses in crops. The endophytic fungi Alternaria species produce host-selective phytotoxins. Alt a 1 is a strongly allergenic protein found in A. alternata that causes severe asthma. Despite the well-established pathogenicity of Alt a 1, the molecular mechanisms underlying its action and physiological function remain largely unknown. To gain insight into the role played by this protein in the pathogenicity of the fungus, we studied production of Alt a 1 and its activity in spores. We found that Alt a 1 accumulates inside spores and that its release with a ligand is pH-dependent, with optimum production in the 5.0–6.5 interval. The Alt a 1 ligand was identified as a methylated flavonoid that inhibits plant root growth and detoxifies reactive oxygen species. We also found that Alt a 1 changes its oligomerization state depending on the pH of the surrounding medium and that these changes facilitate the release of the ligand. Based on these results, we propose that release of Alt a 1 should be a pathogenic target in approaches used to block plant defenses and consequently to favor fungal entry into the plant. PMID:27633190

  4. Variant repeats are interspersed throughout the telomeres and recruit nuclear receptors in ALT cells

    PubMed Central

    Conomos, Dimitri; Stutz, Michael D.; Hills, Mark; Neumann, Axel A.; Bryan, Tracy M.

    2012-01-01

    Telomeres in cells that use the recombination-mediated alternative lengthening of telomeres (ALT) pathway elicit a DNA damage response that is partly independent of telomere length. We therefore investigated whether ALT telomeres contain structural abnormalities that contribute to ALT activity. Here we used next generation sequencing to analyze the DNA content of ALT telomeres. We discovered that variant repeats were interspersed throughout the telomeres of ALT cells. We found that the C-type (TCAGGG) variant repeat predominated and created a high-affinity binding site for the nuclear receptors COUP-TF2 and TR4. Nuclear receptors were directly recruited to telomeres and ALT-associated characteristics were induced after incorporation of the C-type variant repeat by a mutant telomerase. We propose that the presence of variant repeats throughout ALT telomeres results from recombination-mediated telomere replication and spreading of variant repeats from the proximal regions of the telomeres and that the consequent binding of nuclear receptors alters the architecture of telomeres to facilitate further recombination. PMID:23229897

  5. Association of the I148M/PNPLA3 variant with elevated alanine transaminase levels in normal-weight and overweight/obese Mexican children.

    PubMed

    Larrieta-Carrasco, Elena; León-Mimila, Paola; Villarreal-Molina, Teresa; Villamil-Ramírez, Hugo; Romero-Hidalgo, Sandra; Jacobo-Albavera, Leonor; Gutiérrez-Vidal, Roxana; López-Contreras, Blanca E; Guillén-Pineda, Luz E; Sánchez-Muñoz, Fausto; Bojalil, Rafael; Mejía-Domínguez, Ana M; Méndez-Sánchez, Nahúm; Domínguez-López, Aaron; Aguilar-Salinas, Carlos A; Canizales-Quinteros, Samuel

    2013-05-15

    Non-alcoholic fatty liver disease (NAFLD) and elevated alanine transaminase (ALT) levels are common in obese Hispanic adults and children. Recently, a PNPLA3 gene variant (I148M) was strongly associated with NAFLD and higher ALT levels in obese adults, including Hispanics. The aims of this study were to estimate the frequency of elevated ALT levels, and to address the influence of obesity and PNPLA3/I148M on ALT levels in a general population sample of Mexican school-aged children. A total of 1037 non-related Mexican children aged 6 to 12 years were genotyped for the I148M variant. Anthropometric, clinical and metabolic parameters were collected from all participants. Elevated ALT levels (>35 U/L) were more frequent in obese (26.9%) and overweight (9.3%) than in normal weight children (2.2%). The M148M genotype was significantly associated with elevated ALT levels in this population (OR=3.7, 95% CI 2.3-5.9; P=3.7×10(-8)), and children carrying the M148M genotype showed significantly lower HDL cholesterol levels and BMI z-core (P=0.036 and 0.015, respectively). On stratifying by BMI percentile, this genotype conferred a much greater risk of elevated ALT levels in normal weight (OR=19.9, 95% CI 2.5-157.7; P=0.005) than overweight and obese children (OR=3.4, 95% CI 1.3-8.9; P=0.014 and OR=3.1, 95% CI 1.7-5.5; P=1.4 x10(-4), respectively). The I148M PNPLA3 variant is strongly associated with elevated ALT levels in normal weight and overweight/obese Mexican children. Thus, the M148M genotype may be considered as an important risk factor for liver damage in this population. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Post-test navigation data analysis techniques for the shuttle ALT

    NASA Technical Reports Server (NTRS)

    1975-01-01

    Postflight test analysis data processing techniques for shuttle approach and landing tests (ALT) navigation data are defined. Postfight test processor requirements are described along with operational and design requirements, data input requirements, and software test requirements. The postflight test data processing is described based on the natural test sequence: quick-look analysis, postflight navigation processing, and error isolation processing. Emphasis is placed on the tradeoffs that must remain open and subject to analysis until final definition is achieved in the shuttle data processing system and the overall ALT plan. A development plan for the implementation of the ALT postflight test navigation data processing system is presented. Conclusions are presented.

  7. Elevated Aspartate and Alanine Aminotransferase Levels and Natural Death among Patients with Methamphetamine Dependence

    PubMed Central

    Kuo, Chian-Jue; Tsai, Shang-Ying; Liao, Ya-Tang; Conwell, Yeates; Lee, Wen-Chung; Huang, Ming-Chyi; Lin, Shih-Ku; Chen, Chiao-Chicy; Chen, Wei J.

    2012-01-01

    Background Methamphetamine is one of the fastest growing illicit drugs worldwide, causing multiple organ damage and excessive natural deaths. The authors aimed to identify potential laboratory indices and clinical characteristics associated with natural death through a two-phase study. Methods Methamphetamine-dependent patients (n = 1,254) admitted to a psychiatric center in Taiwan between 1990 and 2007 were linked with a national mortality database for causes of death. Forty-eight subjects died of natural causes, and were defined as the case subjects. A time-efficient sex- and age-matched nested case-control study derived from the cohort was conducted first to explore the potential factors associated with natural death through a time-consuming standardized review of medical records. Then the identified potential factors were evaluated in the whole cohort to validate the findings. Results In phase I, several potential factors associated with natural death were identified, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), comorbid alcohol use disorder, and the prescription of antipsychotic drugs. In phase II, these factors were confirmed in the whole cohort using survival analysis. For the characteristics at the latest hospital admission, Cox proportional hazards models showed that the adjusted hazard ratios for natural death were 6.75 (p<0.001) in the group with markedly elevated AST (>80 U/L) and 2.66 (p<0.05) in the group with mildly elevated AST (40–80 U/L), with reference to the control group (<40 U/L). As for ALT, the adjusted hazard ratios were 5.41 (p<0.001), and 1.44 (p>0.05). Comorbid alcohol use disorder was associated with an increased risk of natural death, whereas administration of antipsychotic drugs was not associated with lowered risk. Conclusions This study highlights the necessity of intensive follow-up for those with elevated AST and ALT levels and comorbid alcohol use disorder for preventing excessive natural

  8. The effectiveness of fermented turmeric powder in subjects with elevated alanine transaminase levels: a randomised controlled study

    PubMed Central

    2013-01-01

    Background Previous animal studies have shown that Curcuma longa (turmeric) improves liver function. Turmeric may thus be a promising ingredient in functional foods aimed at improving liver function. The purpose of the study is to investigate the hepatoprotective effect of fermented turmeric powder (FTP) on liver function in subjects with elevated alanine transaminase (ALT) levels. Methods A randomised, double-blind, placebo-controlled trial was conducted between November 2010 and April 2012 at the clinical trial center for functional foods of the Chonbuk National University Hospital. The trial included 60 subjects, 20 years old and above, who were diagnosed mild to moderate elevated ALT levels between 40 IU/L and 200 IU/L. Sixty subjects were randomised to receive FTP 3.0 g per day or placebo 3.0 g per day for 12 weeks. The treatment group received two capsules of FTP three times a day after meals, for 12 weeks. The primary efficacy endpoint was change in the ALT levels in the two groups. The secondary efficacy endpoints included its effect on aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TB), and lipid profiles. Safety was assessed throughout the study using ongoing laboratory tests. Adverse events (AEs) were also recorded. Results Sixty subjects were randomised in the study (30 into the FTP group, 30 into the placebo group), and among them, twelve subjects were excluded from the analysis for protocol violation, adverse events or consent withdrawal. The two groups did not differ in baseline characteristics. After 12 weeks of treatment, 48 subjects were evaluated. Of the 48 subjects, 26 randomly received FTP capsules and 22 received placebo. The FTP group showed a significant reduction in ALT levels after 12 weeks of treatment compared with the placebo group (p = 0.019). There was also observed that the serum AST levels were significantly reduce in the FTP group than placebo group (p = 0.02). The GGT levels

  9. Plasma sphingolipids as potential indicators of hepatic necroinflammation in patients with chronic hepatitis C and normal alanine aminotransferase level.

    PubMed

    Li, Jun-Feng; Qu, Feng; Zheng, Su-Jun; Ren, Jin-Yu; Wu, Hui-Li; Liu, Mei; Liu, Hui; Ren, Feng; Chen, Yu; Zhang, Jin-Lan; Duan, Zhong-Ping

    2014-01-01

    Accurate estimation of hepatic necroinflammation caused by chronic hepatitis C (CHC) is crucial for prediction of prognosis and design of therapeutic strategy, which is particularly true for CHC patients with normal alanine aminotransferase (ALT) level. Recent studies have shown that sphingolipids have a close relationship with hepatitis C virus infection. The present study aimed to identify plasma sphingolipids related to hepatic necroinflammation. We included 120 treatment-naïve CHC patients and 64/120 had normal ALT levels (<40 U/L). CHC patients who underwent liver biopsies were subjected to Scheuer scoring analysis for scope of hepatic inflammation. Plasma sphingolipids were detected by high-performance liquid chromatography tandem mass spectrometry. Our results showed 44 plasma sphingolipids were detected altogether. Of all detected sphingolipids, hexosylceramide (HexCer) (d18∶1/22∶0) and HexCer (d18∶1/24∶0) showed a significant difference among G0/G1, G2, and G3/G4 (P<0.05). For identifying hepatic necroinflammation (G≥2), after adjusting other factors, the odds ratio (OR) of HexCer (d18∶1/22∶0) reached 1.01 (95% confidence interval [CI]: 1.00-1.02). Furthermore, the area under the curve (AUC) of HexCer (d18∶1/22∶0) was 0.7 (P = 0.01) and approached that of ALT (AUC = 0.78). However, in CHC patients with normal ALT, HexCer (d18∶1/22∶0) was an independent factor (OR: 1.02, 95% CI: 1.01-1.03) to identify the hepatic necroinflammation (G≥2). HexCer (d18∶1/22∶0) not only showed the largest AUC (0.78, P = 0.001), but also exhibited the highest specificity of all indicators. These results indicate that plasma HexCer (d18∶1/22∶0) is a potential indicator to distinguish hepatic necroinflammation in CHC patients. For CHC with normal ALT, the ability of HexCer (d18∶1/22∶0) to distinguish hepatic necroinflammation might be superior to conventional serum indicators.

  10. Plasma Sphingolipids as Potential Indicators of Hepatic Necroinflammation in Patients with Chronic Hepatitis C and Normal Alanine Aminotransferase Level

    PubMed Central

    Ren, Jin-Yu; Wu, Hui-Li; Liu, Mei; Liu, Hui; Ren, Feng; Chen, Yu; Zhang, Jin-Lan; Duan, Zhong-Ping

    2014-01-01

    Accurate estimation of hepatic necroinflammation caused by chronic hepatitis C (CHC) is crucial for prediction of prognosis and design of therapeutic strategy, which is particularly true for CHC patients with normal alanine aminotransferase (ALT) level. Recent studies have shown that sphingolipids have a close relationship with hepatitis C virus infection. The present study aimed to identify plasma sphingolipids related to hepatic necroinflammation. We included 120 treatment-naïve CHC patients and 64/120 had normal ALT levels (<40 U/L). CHC patients who underwent liver biopsies were subjected to Scheuer scoring analysis for scope of hepatic inflammation. Plasma sphingolipids were detected by high-performance liquid chromatography tandem mass spectrometry. Our results showed 44 plasma sphingolipids were detected altogether. Of all detected sphingolipids, hexosylceramide (HexCer) (d18∶1/22∶0) and HexCer (d18∶1/24∶0) showed a significant difference among G0/G1, G2, and G3/G4 (P<0.05). For identifying hepatic necroinflammation (G≥2), after adjusting other factors, the odds ratio (OR) of HexCer (d18∶1/22∶0) reached 1.01 (95% confidence interval [CI]: 1.00–1.02). Furthermore, the area under the curve (AUC) of HexCer (d18∶1/22∶0) was 0.7 (P = 0.01) and approached that of ALT (AUC = 0.78). However, in CHC patients with normal ALT, HexCer (d18∶1/22∶0) was an independent factor (OR: 1.02, 95% CI: 1.01–1.03) to identify the hepatic necroinflammation (G≥2). HexCer (d18∶1/22∶0) not only showed the largest AUC (0.78, P = 0.001), but also exhibited the highest specificity of all indicators. These results indicate that plasma HexCer (d18∶1/22∶0) is a potential indicator to distinguish hepatic necroinflammation in CHC patients. For CHC with normal ALT, the ability of HexCer (d18∶1/22∶0) to distinguish hepatic necroinflammation might be superior to conventional serum indicators. PMID:24736528

  11. Function of the D-alanine:D-alanine ligase lid loop: a molecular modeling and bioactivity study.

    PubMed

    Hrast, Martina; Vehar, Blaž; Turk, Samo; Konc, Janez; Gobec, Stanislav; Janežič, Dušanka

    2012-08-09

    D-Alanine:D-alanine ligase (Ddl) is an essential ATP-dependent bacterial enzyme involved in peptidoglycan biosynthesis. Discovery of Ddl inhibitors not competitive with ATP has proven to be difficult because the Ddl bimolecular d-alanine binding pocket is very restricted, as is accessibility to the active site for larger molecules in the catalytically active closed conformation of Ddl. A molecular dynamics study of the opening and closing of the Ddl lid loop informs future structure-based design efforts that allow for the flexibility of Ddl. A virtual screen on generated enzyme conformations yielded some hit inhibitors whose bioactivity was determined.

  12. The Role of ATRX in the Alternative Lengthening of Telomeres (ALT) Phenotype

    PubMed Central

    Amorim, João P.; Santos, Gustavo; Vinagre, João; Soares, Paula

    2016-01-01

    Telomeres are responsible for protecting chromosome ends in order to prevent the loss of coding DNA. Their maintenance is required for achieving immortality by neoplastic cells and can occur by upregulation of the telomerase enzyme or through a homologous recombination-associated process, the alternative lengthening of telomeres (ALT). The precise mechanisms that govern the activation of ALT or telomerase in tumor cells are not fully understood, although cellular origin may favor one of the other mechanisms that have been found thus far in mutual exclusivity. Specific mutational events influence ALT activation and maintenance: a unifying frequent feature of tumors that acquire this phenotype are the recurrent mutations of the Alpha Thalassemia/Mental Retardation Syndrome X-Linked (ATRX) or Death-Domain Associated Protein (DAXX) genes. This review summarizes the established criteria about this phenotype: its prevalence, theoretical molecular mechanisms and relation with ATRX, DAXX and other proteins (directly or indirectly interacting and resulting in the ALT phenotype). PMID:27657132

  13. The Role of ATRX in the Alternative Lengthening of Telomeres (ALT) Phenotype.

    PubMed

    Amorim, João P; Santos, Gustavo; Vinagre, João; Soares, Paula

    2016-09-19

    Telomeres are responsible for protecting chromosome ends in order to prevent the loss of coding DNA. Their maintenance is required for achieving immortality by neoplastic cells and can occur by upregulation of the telomerase enzyme or through a homologous recombination-associated process, the alternative lengthening of telomeres (ALT). The precise mechanisms that govern the activation of ALT or telomerase in tumor cells are not fully understood, although cellular origin may favor one of the other mechanisms that have been found thus far in mutual exclusivity. Specific mutational events influence ALT activation and maintenance: a unifying frequent feature of tumors that acquire this phenotype are the recurrent mutations of the Alpha Thalassemia/Mental Retardation Syndrome X-Linked (ATRX) or Death-Domain Associated Protein (DAXX) genes. This review summarizes the established criteria about this phenotype: its prevalence, theoretical molecular mechanisms and relation with ATRX, DAXX and other proteins (directly or indirectly interacting and resulting in the ALT phenotype).

  14. Differential Evolutionary Selection and Natural Evolvability Observed in ALT Proteins of Human Filarial Parasites.

    PubMed

    Devoe, Neil C; Corbett, Ian J; Barker, Linsey; Chang, Robert; Gudis, Polyxeni; Mullen, Nathan; Perez, Kailey; Raposo, Hugo; Scholz, John; May, Meghan

    2016-01-01

    The abundant larval transcript (ALT-2) protein is present in all members of the Filarioidea, and has been reported as a potential candidate antigen for a subunit vaccine against lymphatic filariasis. To assess the potential for vaccine escape or heterologous protection, we examined the evolutionary selection acting on ALT-2. The ratios of nonsynonymous (K(a)) to synonymous (K(s)) mutation frequencies (ω) were calculated for the alt-2 genes of the lymphatic filariasis agents Brugia malayi and Wuchereria bancrofti and the agents of river blindness and African eyeworm disease Onchocerca volvulus and Loa loa. Two distinct Bayesian models of sequence evolution showed that ALT-2 of W. bancrofti and L. loa were under significant (P<0.05; P < 0.001) diversifying selection, while ALT-2 of B. malayi and O. volvulus were under neutral to stabilizing selection. Diversifying selection as measured by ω values was notably strongest on the region of ALT-2 encoding the signal peptide of L. loa and was elevated in the variable acidic domain of L. loa and W. bancrofti. Phylogenetic analysis indicated that the ALT-2 consensus sequences formed three clades: the first consisting of B. malayi, the second consisting of W. bancrofti, and the third containing both O. volvulus and L. loa. ALT-2 selection was therefore not predictable by phylogeny or pathology, as the two species parasitizing the eye were selected differently, as were the two species parasitizing the lymphatic system. The most immunogenic regions of L. loa and W. bancrofti ALT-2 sequence as modeled by antigenicity prediction analysis did not correspond with elevated levels of diversifying selection, and were not selected differently than predicted antigenic epitopes in B. malayi and O. volvulus. Measurements of ALT-2 evolvability made by χ2 analysis between alleles that were stable (O. volvulus and B. malayi) and those that were under diversifying selection (W. bancrofti and L. loa) indicated significant (P<0

  15. Differential Evolutionary Selection and Natural Evolvability Observed in ALT Proteins of Human Filarial Parasites

    PubMed Central

    Devoe, Neil C.; Corbett, Ian J.; Barker, Linsey; Chang, Robert; Gudis, Polyxeni; Mullen, Nathan; Perez, Kailey; Raposo, Hugo; Scholz, John; May, Meghan

    2016-01-01

    The abundant larval transcript (ALT-2) protein is present in all members of the Filarioidea, and has been reported as a potential candidate antigen for a subunit vaccine against lymphatic filariasis. To assess the potential for vaccine escape or heterologous protection, we examined the evolutionary selection acting on ALT-2. The ratios of nonsynonymous (K(a)) to synonymous (K(s)) mutation frequencies (ω) were calculated for the alt-2 genes of the lymphatic filariasis agents Brugia malayi and Wuchereria bancrofti and the agents of river blindness and African eyeworm disease Onchocerca volvulus and Loa loa. Two distinct Bayesian models of sequence evolution showed that ALT-2 of W. bancrofti and L. loa were under significant (P<0.05; P < 0.001) diversifying selection, while ALT-2 of B. malayi and O. volvulus were under neutral to stabilizing selection. Diversifying selection as measured by ω values was notably strongest on the region of ALT-2 encoding the signal peptide of L. loa and was elevated in the variable acidic domain of L. loa and W. bancrofti. Phylogenetic analysis indicated that the ALT-2 consensus sequences formed three clades: the first consisting of B. malayi, the second consisting of W. bancrofti, and the third containing both O. volvulus and L. loa. ALT-2 selection was therefore not predictable by phylogeny or pathology, as the two species parasitizing the eye were selected differently, as were the two species parasitizing the lymphatic system. The most immunogenic regions of L. loa and W. bancrofti ALT-2 sequence as modeled by antigenicity prediction analysis did not correspond with elevated levels of diversifying selection, and were not selected differently than predicted antigenic epitopes in B. malayi and O. volvulus. Measurements of ALT-2 evolvability made by χ2 analysis between alleles that were stable (O. volvulus and B. malayi) and those that were under diversifying selection (W. bancrofti and L. loa) indicated significant (P<0

  16. The ASCUS/LSIL Triage Study for Cervical Cancer (ALTS) | Division of Cancer Prevention

    Cancer.gov

    ALTS was a clinical trial to find the best way to help women and their doctors decide what to do about the mildly abnormal and very common Pap test results known as ASCUS and LSIL. | ALTS was a clinical trial to find the best way to help women and their doctors decide what to do about the mildly abnormal and very common Pap test results known as ASCUS and LSIL.

  17. AltTrans: transcript pattern variants annotated for both alternative splicing and alternative polyadenylation.

    PubMed

    Le Texier, Vincent; Riethoven, Jean-Jack; Kumanduri, Vasudev; Gopalakrishnan, Chellappa; Lopez, Fabrice; Gautheret, Daniel; Thanaraj, Thangavel Alphonse

    2006-03-23

    The three major mechanisms that regulate transcript formation involve the selection of alternative sites for transcription start (TS), splicing, and polyadenylation. Currently there are efforts that collect data & annotation individually for each of these variants. It is important to take an integrated view of these data sets and to derive a data set of alternate transcripts along with consolidated annotation. We have been developing in the past computational pipelines that generate value-added data at genome-scale on individual variant types; these include AltSplice on splicing and AltPAS on polyadenylation. We now extend these pipelines and integrate the resultant data sets to facilitate an integrated view of the contributions from splicing and polyadenylation in the formation of transcript variants. The AltSplice pipeline examines gene-transcript alignments and delineates alternative splice events and splice patterns; this pipeline is extended as AltTrans to delineate isoform transcript patterns for each of which both introns/exons and 'terminating' polyA site are delineated; EST/mRNA sequences that qualify the transcript pattern confirm both the underlying splicing and polyadenylation. The AltPAS pipeline examines gene-transcript alignments and delineates all potential polyA sites irrespective of underlying splicing patterns. Resultant polyA sites from both AltTrans and AltPAS are merged. The generated database reports data on alternative splicing, alternative polyadenylation and the resultant alternate transcript patterns; the basal data is annotated for various biological features. The data (named as integrated AltTrans data) generated for both the organisms of human and mouse is made available through the Alternate Transcript Diversity web site at http://www.ebi.ac.uk/atd/. The reported data set presents alternate transcript patterns that are annotated for both alternative splicing and alternative polyadenylation. Results based on current transcriptome data

  18. AltTrans: Transcript pattern variants annotated for both alternative splicing and alternative polyadenylation

    PubMed Central

    Le Texier, Vincent; Riethoven, Jean-Jack; Kumanduri, Vasudev; Gopalakrishnan, Chellappa; Lopez, Fabrice; Gautheret, Daniel; Thanaraj, Thangavel Alphonse

    2006-01-01

    Background The three major mechanisms that regulate transcript formation involve the selection of alternative sites for transcription start (TS), splicing, and polyadenylation. Currently there are efforts that collect data & annotation individually for each of these variants. It is important to take an integrated view of these data sets and to derive a data set of alternate transcripts along with consolidated annotation. We have been developing in the past computational pipelines that generate value-added data at genome-scale on individual variant types; these include AltSplice on splicing and AltPAS on polyadenylation. We now extend these pipelines and integrate the resultant data sets to facilitate an integrated view of the contributions from splicing and polyadenylation in the formation of transcript variants. Description The AltSplice pipeline examines gene-transcript alignments and delineates alternative splice events and splice patterns; this pipeline is extended as AltTrans to delineate isoform transcript patterns for each of which both introns/exons and 'terminating' polyA site are delineated; EST/mRNA sequences that qualify the transcript pattern confirm both the underlying splicing and polyadenylation. The AltPAS pipeline examines gene-transcript alignments and delineates all potential polyA sites irrespective of underlying splicing patterns. Resultant polyA sites from both AltTrans and AltPAS are merged. The generated database reports data on alternative splicing, alternative polyadenylation and the resultant alternate transcript patterns; the basal data is annotated for various biological features. The data (named as integrated AltTrans data) generated for both the organisms of human and mouse is made available through the Alternate Transcript Diversity web site at . Conclusion The reported data set presents alternate transcript patterns that are annotated for both alternative splicing and alternative polyadenylation. Results based on current

  19. D-Amino acid dipeptide production utilizing D-alanine-D-alanine ligases with novel substrate specificity.

    PubMed

    Sato, Masaru; Kirimura, Kohtaro; Kino, Kuniki

    2005-06-01

    D-Alanine-D-alanine ligase (Ddl) is an important enzyme in the synthesis of bacterial peptidoglycan. The genes encoding Ddls from Escherichia coli K12 (EcDdlB), Oceanobacillus iheyensis JCM 11309 (OiDdl), Synechocystis sp. PCC 6803 (SsDdl) and Thermotoga maritima ATCC 43589 (TmDdl), the genomic DNA sequences of which have been determined, were cloned and the substrate specificities of these recombinant Ddls were investigated. Although OiDdl had a high substrate specificity for D-alanine; EcDdlB, SsDdl and TmDdl showed broad substrate specificities for D-serine, D-threonine, D-cysteine and glycine, in addition to D-alanine. Four D-amino acid dipeptides were produced using EcDdlB, and D-amino acid homo-dipeptides were successfully produced at high yields except for D-threonyl-D-threonine.

  20. A role for monoubiquitinated FANCD2 at telomeres in ALT cells.

    PubMed

    Fan, Qiang; Zhang, Fan; Barrett, Briana; Ren, Keqin; Andreassen, Paul R

    2009-04-01

    Both Fanconi anemia (FA) and telomere dysfunction are associated with chromosome instability and an increased risk of cancer. Because of these similarities, we have investigated whether there is a relationship between the FA protein, FANCD2 and telomeres. We find that FANCD2 nuclear foci colocalize with telomeres and PML bodies in immortalized telomerase-negative cells. These cells maintain telomeres by alternative lengthening of telomeres (ALT). In contrast, FANCD2 does not colocalize with telomeres or PML bodies in cells which express telomerase. Using a siRNA approach we find that FANCA and FANCL, which are components of the FA nuclear core complex, regulate FANCD2 monoubiquitination and the telomeric localization of FANCD2 in ALT cells. Transient depletion of FANCD2, or FANCA, results in a dramatic loss of detectable telomeres in ALT cells but not in telomerase-expressing cells. Furthermore, telomere loss following depletion of these proteins in ALT cells is associated with decreased homologous recombination between telomeres (T-SCE). Thus, the FA pathway has a novel function in ALT telomere maintenance related to DNA repair. ALT telomere maintenance is therefore one mechanism by which monoubiquitinated FANCD2 may promote genetic stability.

  1. Determination of Alt a 1 (Alternaria alternata) in poultry farms and a sawmill using ELISA.

    PubMed

    Prester, Ljerka; Macan, Jelena

    2010-03-01

    Farm and sawmill workers are exposed to high levels of allergenic fungi, such as Alternaria alternata, which are associated with respiratory diseases and asthma. The aim of this study was to measure the concentration of Alt a 1, a major allergen of A. alternata, in indoor dust samples collected in poultry farms and a sawmill using a monoclonal antibody-based enzyme immunoassay. A total of 45 dust samples were collected in poultry farms (30) and the sawmill (15) in Zagreb County (Croatia). The Alt a 1 allergen was detected in all dust samples (100%) collected in three poultry farms. The levels of Alt a 1 were in the range of 0.1-14 microg/g, and the median value was 0.37 microg/g. About 86% of dust samples contained Alt a 1 in the range of 0.1-1.0 microg/g. In the sawmill, no detectable level of Alt a 1 was found (limit of detection =0.12 microg/g). This study has shown that occupational exposure to Alt a 1 allergen in poultry farms deserves monitoring.

  2. Noncovalent and covalent functionalization of a (5, 0) single-walled carbon nanotube with alanine and alanine radicals.

    PubMed

    Rajarajeswari, Muthusivarajan; Iyakutti, Kombiah; Kawazoe, Yoshiyuki

    2012-02-01

    We have systematically investigated the noncovalent and covalent adsorption of alanine and alanine radicals, respectively, onto a (5, 0) single-walled carbon nanotube using first-principles calculation. It was found that XH···π (X = N, O, C) interactions play a crucial role in the non-ovalent adsorption and that the functional group close to the carbon nanotube exhibits a significant influence on the binding strength. Noncovalent functionalization of the carbon nanotube with alanine enhances the conductivity of the metallic (5, 0) nanotube. In the covalent adsorption of each alanine radical onto a carbon nanotube, the binding energy depends on the adsorption site on CNT and the electronegative atom that binds with the CNT. The strongest complex is formed when the alanine radical interacts with a (5, 0) carbon nanotube through the amine group. In some cases, the covalent interaction of the alanine radical introduces a half-filled band at the Fermi level due to the local sp (3) hybridization, which modifies the conductivity of the tube.

  3. Structure of D-alanine-D-alanine ligase from Yersinia pestis: nucleotide phosphate recognition by the serine loop.

    PubMed

    Tran, Huyen Thi; Hong, Myoung Ki; Ngo, Ho Phuong Thuy; Huynh, Kim Hung; Ahn, Yeh Jin; Wang, Zhong; Kang, Lin Woo

    2016-01-01

    D-Alanyl-D-alanine is an essential precursor of bacterial peptidoglycan and is synthesized by D-alanine-D-alanine ligase (DDL) with hydrolysis of ATP; this reaction makes DDL an important drug target for the development of antibacterial agents. Five crystal structures of DDL from Yersinia pestis (YpDDL) were determined at 1.7-2.5 Å resolution: apo, AMP-bound, ADP-bound, adenosine 5'-(β,γ-imido)triphosphate-bound, and D-alanyl-D-alanine- and ADP-bound structures. YpDDL consists of three domains, in which four loops, loop 1, loop 2 (the serine loop), loop 3 (the ω-loop) and loop 4, constitute the binding sites for two D-alanine molecules and one ATP molecule. Some of them, especially the serine loop and the ω-loop, show flexible conformations, and the serine loop is mainly responsible for the conformational change in substrate nucleotide phosphates. Enzyme-kinetics assays were carried out for both the D-alanine and ATP substrates and a substrate-binding mechanism was proposed for YpDDL involving conformational changes of the loops.

  4. The polyproline II conformation in short alanine peptides is noncooperative.

    PubMed

    Chen, Kang; Liu, Zhigang; Kallenbach, Neville R

    2004-10-26

    The finding that short alanine peptides possess a high fraction of polyproline II (PII) structure (Phi=-75 degrees, Psi=+145 degrees ) at low temperature has broad implications for unfolded states of proteins. An important question concerns whether or not this structure is locally determined or cooperative. We have monitored the conformation of alanine in a series of model peptides AcGGAnGGNH2 (n=1-3) over a temperature range from -10 degrees C to +80 degrees C. Use of 15N-labeled alanine substitutions makes it possible to measure 3JalphaN coupling constants accurately over the full temperature range. Based on a 1D next-neighbor model, the cooperative parameter sigma of PII nucleation is evaluated from the coupling constant data. The finding that sigma is close to unity (1 +/- 0.2) indicates a noncooperative role for alanine in PII structure formation, consistent with statistical surveys of the Protein Data Bank that suggest that most PII structure occurs in isolated residues. Lack of cooperativity in these models implies that hydration effects that influence PII conformation in water are highly localized. Using a nuclear Overhauser effect ratio strategy to define the alanine Psi angle, we estimate that, at 40 degrees C, the time-averaged alanine conformation (Phi=-80 degrees, Psi=+170 degrees ) deviates from canonical PII structure, indicating that PII melts at high temperature. Thus, the high-temperature state of short alanine peptides seems to be an unfolded ensemble with higher distribution in the extended beta structure basin, but not a coil.

  5. EPR/alanine dosimetry for two therapeutic proton beams

    NASA Astrophysics Data System (ADS)

    Marrale, Maurizio; Carlino, Antonio; Gallo, Salvatore; Longo, Anna; Panzeca, Salvatore; Bolsi, Alessandra; Hrbacek, Jan; Lomax, Tony

    2016-02-01

    In this work the analysis of the electron paramagnetic resonance (EPR) response of alanine pellets exposed to two different clinical proton beams employed for radiotherapy is performed. One beam is characterized by a passive delivery technique and is dedicated to the eyes treatment (OPTIS2 beam line). Alanine pellets were irradiated with a 70 MeV proton beam corresponding to 35 mm range in eye tissue. We investigated how collimators with different sizes and shape used to conform the dose to the planned target volume influence the delivered dose. For this purpose we performed measurements with varying the collimator size (Output Factor) and the results were compared with those obtained with other dosimetric techniques (such as Markus chamber and diode detector). This analysis showed that the dosimeter response is independent of collimator diameter if this is larger than or equal to 10 mm. The other beam is characterized by an active spot-scanning technique, the Gantry1 beam line (maximum energy 230 MeV), and is used to treat deep-seated tumors. The dose linearity of alanine response in the clinical dose range was tested and the alanine dose response at selected locations in depth was measured and compared with the TPS planned dose in a quasi-clinical scenario. The alanine response was found to be linear in the dose in the clinical explored range (from 10 to 70 Gy). Furthermore, a depth dose profile in a quasi-clinical scenario was measured and compared to the dose computed by the Treatment Planning System PSIPLAN. The comparison of calibrated proton alanine measurements and TPS dose shows a difference under 1% in the SOBP and a "quenching" effect up to 4% in the distal part of SOBP. The positive dosimetric characteristics of the alanine pellets confirm the feasibility to use these detectors for "in vivo" dosimetry in clinical proton beams.

  6. The effect of 1g of acetaminophen twice daily for 12 weeks on alanine transaminase levels--A randomized placebo-controlled trial.

    PubMed

    Ioannides, Sally J; Siebers, Robert; Perrin, Kyle; Weatherall, Mark; Crane, Julian; Travers, Justin; Shirtcliffe, Philippa; Beasley, Richard

    2015-07-01

    Acetaminophen is often used on a regular, daily basis for the treatment of chronic pain; however, the safety of regular acetaminophen is still debated. This study determined whether 12 weeks of treatment with acetaminophen at half the maximum recommended daily dose causes an increase in alanine transaminase (ALT) in healthy adults participating in a clinical trial of the effect of acetaminophen on asthma control and severity. 94 healthy adults aged 18-65 years with mild to moderate asthma and with no history of previous liver dysfunction and an ALT within 1.5 times the upper limit of normal at baseline participated in a randomized, double-blind, placebo-controlled, parallel-group, clinical trial of 1g of acetaminophen twice daily or placebo twice daily for 12 weeks. Liver function monitoring was undertaken at baseline, weeks 2, 4, 6 and 12. The primary outcome variable was mean ALT levels at week 12 compared to baseline in the acetaminophen group versus placebo group. 94 participants were randomized and commenced study treatment. One participant in each treatment group was withdrawn due to an increase in ALT to greater than three times the upper limit of normal. Mean ALT at week 12 was 25.4I U/L (SD 9.7) in the acetaminophen group (N=31) and 19.0 IU/L (SD 6.0) in the placebo group (N=54). After controlling for baseline this represented a statistically significant difference of 3.6 IU/L (95% CI 1.3 to 6.0, P=0.003). There was no progressive increase in ALT demonstrated throughout the trial. Regular, daily use of acetaminophen at half the maximum recommended daily dose for 12 weeks in a healthy adult population is associated with a small elevation in mean ALT of no probable clinical significance. Further assessment of the effects on liver function of the maximum recommended dose of acetaminophen is required. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  7. Risk factors associated with hepatitis B or C markers or elevated alanine aminotransferase level among blood donors on a tropical island: the Guadeloupe experience.

    PubMed

    Fest, T; Viel, J F; Agis, F; Coffe, C; Dupond, J L; Hervé, P

    1992-10-01

    Donated blood is currently screened for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), antibody to hepatitis C virus (anti-HCV), and alanine aminotransferase (ALT) levels to prevent posttransfusion hepatitis. A prospective study of 2368 blood donors was carried out in Guadeloupe (French West Indies) with a view to determining the risk factors associated with serologic abnormalities. Blood donors included in the study had to complete a questionnaire. Statistical analysis was performed on the data thus obtained: 571 donations (24%) were positive for at least one of the four analyzed markers. The results were that 3.2 percent were positive for HBsAg, 22 percent for anti-HBc, and 0.8 percent for anti-HCV, and 1.4 percent had ALT > or = 45 IU per L. A good correlation was found between anti-HCV and elevated ALT. Transfusion history and two socioeconomic categories (working class, military personnel) were found to be risk factors. Other risk factors were lifelong residence in Guadeloupe (with risk increasing with the number of years), birthplace and current residence in the southern part of the island, and the existence of gastrointestinal discomfort unrelated to viral hepatitis (odds ratio = 2.98). The results of this study illustrate the difficulty of implementing a preventive policy against posttransfusion hepatitis in a tropical area. The unique epidemiologic situation of Guadeloupe as regards hepatitis B virus has led to more restrictive criteria for the acceptance of blood donors.

  8. Effect of low-zinc status and essential fatty acids deficiency on the activities of aspartate aminotransferase and alanine aminotransferase in liver and serum of albino rats.

    PubMed

    Ajayi, Olubunmi Bolanle; Odutuga, Adewale

    2004-04-01

    The effects of dietary deficiencies of zinc and essential fatty acids (EFAs) or both on aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were investigated in young growing rats. Four groups of albino rats were fed diets deficient in either EFA (4% hydrogenated coconut oil) or zinc (6 ppm) or both. The control diet was adequate in EFA (4% soybean oil) and zinc (100 ppm). The feeding trial lasted eight weeks and the activities of AST and ALT were determined in the liver and serum. EFA deficiency had no significant (p > 0.05) effect on liver AST. However, zinc and the double deficiencies depressed AST activity in the organ. Deficiencies of EFA, zinc and their combination depressed ALT activity in the liver significantly (p < 0.05) with a concomitant increase recorded in the serum. The data suggested alteration in endothelial permeability of the plasma membrane and thus leakage of membrane constituents in the tissue studied. It is therefore considered that these deficient diets may affect liver tissue negatively in view of the role of these enzymes in amino acid metabolism.

  9. Folate Deficiency Was Associated with Increased Alanine Aminotransferase and Glutamyl Transpeptidase Concentrations in a Chinese Hypertensive Population: A Cross-Sectional Study.

    PubMed

    Li, Wen-Xing; Li, Wei; Cao, Jia-Qian; Yan, Haiyue; Sun, Yuanyuan; Zhang, Hong; Zhang, Qiang; Tang, Ling; Wang, Manman; Huang, Jing-Fei; Liu, Dahai

    2016-01-01

    Alanine aminotransferase (ALT), aspartate transaminase (AST), and glutamyl transpeptidase (GGT) were three key enzymes in the hepatic metabolism. This study aimed to investigate the effect of homocysteine (Hcy) metabolism gene polymorphisms and serum Hcy and folate level on the hepatic functions in a Chinese hypertensive population. A representative sample with 480 subjects aged 28-75 was enrolled in 2005.9-2005.12 from six hospitals in different Chinese regions. Serum ALT, AST and GGT were measured by using an automatic biochemistry analyzer. Serum Hcy was measured by high-performance liquid chromatography, and serum folate was measured by chemiluminescent immunoassay. Known genotypes were detected by PCR-RFLP methods. The results showed that the MTHFR C677T mutation was related a decreased serum AST level (r=-0.11, p=0.026), whereas the MTHFR A1298C mutation elevated serum AST level (r=0.11, p=0.032). Furthermore, multiple regression analysis showed that folate deficiency was associated with higher serum ALT (β (SE): 0.13 (0.06), p=0.031) and GGT level (β (SE): 0.18 (0.07), p=0.011). However, serum Hcy level may not affect the hepatic functions. Our data suggested that hepatic functions were affected by MTHFR gene polymorphisms and serum folate level. Further studies are needed to confirm these correlations in a larger population.

  10. Caramelization of maltose solution in presence of alanine.

    PubMed

    Fadel, H H M; Farouk, A

    2002-01-01

    Two solutions of maltose in water were used to prepare caramels. Alanine as a catalyst was added to one of these solutions. The caramelization was conducted at 130 degrees C for total time period 90 minutes. Convenient samples were taken of each caramel solution every 30 min and subjected to sensory analysis and isolation of volatile components. The odour and colour sensory tests were evaluated according to the international standard methods (ISO). The results showed that, the presence of alanine gave rise to a high significant (P < 0.01) decrease in acid attributes and remarkable increase in the sweet and caramel attributes, which are the most important caramel notes. On the other hand the increase in heating time in presence of alanine as a catalyst resulted in a high significant (P < 0.01) increase in the browning rate of caramel solution. The new technique Solid Phase Micro Extraction (SPME) was used for trapping the volatile components in the headspace of each caramel samples followed by thermal desorption and GC and GC - MS analysis. The 5-hydroxymethyl-2-furfural (HMF), the main characteristic caramel product, showed its highest value in sample containing alanine after heating for 60 minutes. The best sensory results of the sample contains alanine were confirmed by the presence of high concentrations of the most potent odorants of caramel besides to the formation of some volatile compounds have caramel like flavours such as 2-acetyl pyrrole, 2-furanones and 1-(2-furanyl)1,2-propandione.

  11. Tailcone on orbiter altitude attainable at the maximum ALT interface airspeed

    NASA Technical Reports Server (NTRS)

    Glenn, G. M.

    1977-01-01

    A preflight analysis performed for verification of the ALT mated vehicle incidence angle which maximizes the post separation altitude attainment by the orbiter at the maximum approach and landing test (ALT) interface airspeed (300 KEAS) is discussed. In the analysis, altitude versus airspeed profiles are generated for each of the three incidence angles that include and bound the recommended incidence angle for both the forward and the aft cg tailcone on orbiter configurations. Results show that the recommended incidence angles maximize the orbiter post separation altitude attainable within an acceptable tradeoff between separation clearance capability and orbiter structural constraints. Within constraints, the incidence angle that maximizes the orbiter altitude at the maximum ALT interface airspeed for both the forward and aft cg orbiter tailcone on configurations is 6.0 deg. The requirement for a parametric analysis of orbiter altitude attainable at the maximum ALT interface airspeed is stated along with the specifications, assumptions, and analytical approach used to determine orbiter altitude attainable at the maximum ALT interface airspeed.

  12. Analysis of the survivability of the shuttle (ALT) fault-tolerant avionics system

    NASA Technical Reports Server (NTRS)

    1976-01-01

    An extension of the Complementary-Analytic-Simulative Technique (CAST) is presented which is applicable to the Shuttle Data Processing Subsystem (DPS). A two step process was used. The first step provides models, both analytic and simulative, for analysis of the Approach-Landing Test (ALT) configuration. The ALT modeling and analysis are presented. Since CAST had already been shown to be multicomputer systems, the emphasis was placed on extending the CAST concept so it is applicable to computer systems including the multiplicity of input and output devices found in a real-time control system application. The DPS mission-critical survivability for a six-hour mission was determined to be 0.999863 for the Shuttle ALT baseline configuration. Thus it can be said that for ALT, the survivability is adequate. However, the fact that orbiting missions of up to 30 days are planned illustrates the necessity of extending the ALT work to be applicable to OFT and actual mission scenarios. The above analysis led to the evaluation of three selected options which identified two areas of possible improvement. These improvements would result from use of a recovery technique which combines roll ahead with memory copy, and increased TACAN fault detectability.

  13. Post-Irradiation Study of the Alanine Dosimeter

    PubMed Central

    Desrosiers, Marc F.

    2014-01-01

    Post-irradiation stability of high-dose dosimeters has traditionally been an important measurement influence quantity. Though the exceptional stability of the alanine dosimeter response with time has rendered this factor a non-issue for routine work, the archival quality of the alanine dosimeter has not been characterized. Here the alanine pellet dosimeter response is measured up to seven years post-irradiation for a range of absorbed doses. This long-term study is accompanied by an examination of the environmental influence quantities (e.g., ambient light) on the relatively short-term (3–4 month) stability of both pellet and film commercial dosimeters. Both dosimeter types demonstrated exceptional stability in the short term and proved to be relatively insensitive to common influence quantities. The long-term data revealed a complex dose-dependent response trend. PMID:26601033

  14. [Effects of ß-alanine supplementation on athletic performance].

    PubMed

    Domínguez, Raúl; Hernández Lougedo, Juan; Maté-Muñoz, José Luis; Garnacho-Castaño, Manuel Vicente

    2014-10-06

    Carnosine, dipeptide formed by amino acids ß-alanine and L-histidine, has important physiological functions among which its antioxidant and related memory and learning. However, in connection with the exercise, the most important functions would be associated with muscle contractility, improving calcium sensitivity in muscle fibers, and the regulatory function of pH. Thus, it is proposed that carnosine is the major intracellular buffer, but could contribute to 7-10% in buffer or buffer capacity. Since carnosine synthesis seems to be limited by the availability of ß-alanine supplementation with this compound has been gaining increasing popularity among the athlete population. Therefore, the objective of this study literature review was to examine all those research works have shown the effect of ß-alanine supplementation on athletic performance. Moreover, it also has attempted to establish a specific dosage that maximizing the potential benefits, minimize paresthesia, the main side effect presented in response to supplementation.

  15. First-principles studies of pure and fluorine substituted alanines

    NASA Astrophysics Data System (ADS)

    Ahmad, Sardar; Vaizie, Hamide; Rahnamaye Aliabad, H. A.; Ahmad, Rashid; Khan, Imad; Ali, Zahid; Jalali-Asadabadi, S.; Ahmad, Iftikhar; Khan, Amir Abdullah

    2016-05-01

    This paper communicates the structural, electronic and optical properties of L-alanine, monofluoro and difluoro substituted alanines using density functional calculations. These compounds exist in orthorhombic crystal structure and the calculated structural parameters such as lattice constants, bond angles and bond lengths are in agreement with the experimental results. L-alanine is an indirect band gap insulator, while its fluorine substituted compounds (monofluoroalanine and difluoroalanine) are direct band gap insulators. The substitution causes reduction in the band gap and hence these optically tailored direct wide band gap materials have enhanced optical properties in the ultraviolet (UV) region of electromagnetic spectrum. Therefore, optical properties like dielectric function, refractive index, reflectivity and energy loss function are also investigated. These compounds have almost isotropic nature in the lower frequency range while at higher energies, they have a significant anisotropic nature.

  16. On the existence of ``l-threonine formate'', ``l-alanine lithium chloride'' and ``bis l-alanine lithium chloride'' crystals

    NASA Astrophysics Data System (ADS)

    Petrosyan, A. M.; Ghazaryan, V. V.; Fleck, M.

    2013-03-01

    We argue that the recently reported crystals "L-threonine formate" as well as "L-alanine lithium chloride" and "bis L-alanine lithium chloride" actually are the well-known crystals L-threonine and L-alanine, respectively.

  17. Atomic Layer Deposition of L-Alanine Polypeptide

    SciTech Connect

    Fu, Yaqin; Li, Binsong; Jiang, Ying-Bing; Dunphy, Darren R.; Tsai, Andy; Tam, Siu-Yue; Fan, Hongyou Y.; Zhang, Hongxia; Rogers, David; Rempe, Susan; Atanassov, Plamen; Cecchi, Joseph L.; Brinker, C. Jeffrey

    2014-10-30

    L-Alanine polypeptide thin films were synthesized via atomic layer deposition (ALD). Rather, instead of using an amino acid monomer as the precursor, an L-alanine amino acid derivatized with a protecting group was used to prevent self-polymerization, increase the vapor pressure, and allow linear cycle-by-cycle growth emblematic of ALD. Moreover, the successful deposition of a conformal polypeptide film has been confirmed by FTIR, TEM, and Mass Spectrometry, and the ALD process has been extended to polyvaline.

  18. Environmental Stress Induces Trinucleotide Repeat Mutagenesis in Human Cells by Alt-Nonhomologous End Joining Repair.

    PubMed

    Chatterjee, Nimrat; Lin, Yunfu; Yotnda, Patricia; Wilson, John H

    2016-07-31

    Multiple pathways modulate the dynamic mutability of trinucleotide repeats (TNRs), which are implicated in neurodegenerative disease and evolution. Recently, we reported that environmental stresses induce TNR mutagenesis via stress responses and rereplication, with more than 50% of mutants carrying deletions or insertions-molecular signatures of DNA double-strand break repair. We now show that knockdown of alt-nonhomologous end joining (alt-NHEJ) components-XRCC1, LIG3, and PARP1-suppresses stress-induced TNR mutagenesis, in contrast to the components of homologous recombination and NHEJ, which have no effect. Thus, alt-NHEJ, which contributes to genetic mutability in cancer cells, also plays a novel role in environmental stress-induced TNR mutagenesis. Published by Elsevier Ltd.

  19. Space shuttle engineering and operations support. Separation operational limits for ALT free flights 1 through 5

    NASA Technical Reports Server (NTRS)

    Seale, R. H.

    1977-01-01

    The orbiter/SCA separation operational limits for the current target conditions of ALT free flights 1 through 5 are analyzed. The separation operational limits are used to verify that no separation design constraints are violated. The operational limits represent the acceptable dispersions in attainment of separation target conditions which assure safe separation. Safe separation is based on satisfying all specified separation design criteria except orbiter altitude at ALT interface airspeed. Separation operational limits are defined for each of the five orbiter tailcones on ALT free flight missions based upon preflight aerodynamics. The effect of carrier pilot steering compensation due to off-nominal flight conditions is determined to be within the separation operational limits.

  20. Alt a 1 from Alternaria interacts with PR5 thaumatin-like proteins.

    PubMed

    Gómez-Casado, Cristina; Murua-García, Amaya; Garrido-Arandia, María; González-Melendi, Pablo; Sánchez-Monge, Rosa; Barber, Domingo; Pacios, Luis F; Díaz-Perales, Araceli

    2014-05-02

    Alt a 1 is a protein found in Alternaria alternata spores related to virulence and pathogenicity and considered to be responsible for chronic asthma in children. We found that spores of Alternaria inoculated on the outer surface of kiwifruits did not develop hyphae. Nevertheless, the expression of Alt a 1 gene was upregulated, and the protein was detected in the pulp where it co-localized with kiwi PR5. Pull-down assays demonstrated experimentally that the two proteins interact in such a way that Alt a 1 inhibits the enzymatic activity of PR5. These results are relevant not only for plant defense, but also for human health as patients with chronic asthma could suffer from an allergic reaction when they eat fruit contaminated with Alternaria. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  1. Optimization of Alt-PSM structure for 45nm node ArF immersion lithography

    NASA Astrophysics Data System (ADS)

    Adachi, Takashi; Mesuda, Kei; Toyama, Nobuhito; Morikawa, Yasutaka; Mohri, Hiroshi; Hayashi, Naoya

    2005-11-01

    Alternating Aperture Phase Shifting Mask (Alt-APSM) has been expected as one of the practical techniques for 45nm node ArF lithography. We have already discussed and proposed the Single trench with undercut (UC) and bias structure is the primary candidate for 65nm node Alt-APSM structure. In fact, we have selected this structure as a standard in production for 65nm node Alt-PSM. For the 45nm node, according to the design shrinkage, mask rule such as MRC which specify minimum chrome CD between 0 and pi degree apertures and etc. is getting tighter. So, we need to consider about single trench with no undercut and bias structure. Such two types of structure are the candidates for 45nm node Alt-APSM. Exposure conditions will be considered as 0.9 or higher NA and the immersion technology as well. In this work, we will discuss about 45nm node Alt-PSM structure in terms of lithographic performance by using 3D rigorous optical simulation software. Two types of structure, single trench with UC and bias, and single trench with No UC and bias are compared. We examined the following items to find optimum Alt-PSM structure, 0/pi space bias to minimize CD difference at the wafer, quartz depth to optimize effective phase and optical proximity correction (OPC) to adjust printed line CD in through pitch condition. Wafer printing performance will be evaluated by the stability of line CD and 0-pi CD difference, contrast, NILS, phase angles, MEEF, ED-window and gate position shift.

  2. Stereoselective aminoacylation of a dinucleoside monophosphate by the imidazolides of DL-alanine and N-(tert-butoxycarbonyl)-DL-alanine

    NASA Technical Reports Server (NTRS)

    Profy, A. T.; Usher, D. A.

    1984-01-01

    The aminoacylation of diinosine monophosphate was studied experimentally. When the acylating agent was the imidazolide of N-(tert-butoxycarbonyl)-DL-alanine, a 40 percent enantiomeric excess of the isomer was incorporated at the 2' site and the positions of equilibrium for the reversible 2'-3' migration reaction differed for the D and L enantiomers. The reactivity of the nucleoside hydroxyl groups was found to decrease on the order 2'(3') less than internal 2' and less than 5', and the extent of the reaction was affected by the concentration of the imidazole buffer. Reaction of IpI with imidazolide of unprotected DL-alanine, by contrast, led to an excess of the D isomer at the internal 2' site. Finally, reaction with the N-carboxy anhydride of DL-alanine occurred without stereoselection. These results are found to be relevant to the study of the evolution of optical chemical activity and the origin of genetically directed protein synthesis.

  3. Stereoselective aminoacylation of a dinucleoside monophosphate by the imidazolides of DL-alanine and N-(tert-butoxycarbonyl)-DL-alanine

    NASA Technical Reports Server (NTRS)

    Profy, A. T.; Usher, D. A.

    1984-01-01

    The aminoacylation of diinosine monophosphate was studied experimentally. When the acylating agent was the imidazolide of N-(tert-butoxycarbonyl)-DL-alanine, a 40 percent enantiomeric excess of the isomer was incorporated at the 2' site and the positions of equilibrium for the reversible 2'-3' migration reaction differed for the D and L enantiomers. The reactivity of the nucleoside hydroxyl groups was found to decrease on the order 2'(3') less than internal 2' and less than 5', and the extent of the reaction was affected by the concentration of the imidazole buffer. Reaction of IpI with imidazolide of unprotected DL-alanine, by contrast, led to an excess of the D isomer at the internal 2' site. Finally, reaction with the N-carboxy anhydride of DL-alanine occurred without stereoselection. These results are found to be relevant to the study of the evolution of optical chemical activity and the origin of genetically directed protein synthesis.

  4. AltText: A Showcase of User Centred Design in the Netherlands

    NASA Astrophysics Data System (ADS)

    Asjes, Kathleen

    In the information processing chain many documents are produced that are inaccessible to the reading impaired. The altText project aims to increase the accessibility of this content by: a) raising awareness among content providers about content adaption; b) allowing content providers to deliver content in a way that suits the needs of the information receiver; c) developing an online service that converts written text into several accessible formats (Braille, synthetic speech, large print or DaisyXML). The name of this service is the altText conversion portal. The paper argues that user centred innovation will be crucial to the success of this project.

  5. Approach & Landing Test (ALT) - Shuttle Free-Flight (FF)-2 - New Release - DFRC, CA

    NASA Image and Video Library

    1977-09-13

    S77-28137 (13 Sept 1977) --- The Orbiter 101 "Enterprise" soars above the NASA 747 carrier aircraft during the second free flight of the Shuttle Approach and Landing Tests (ALTs) conducted on September 13, 1977 at Dryden Flight Research Center in Southern California. Astronauts Joe H. Engle, and Richard H. Truly were the crew of the "Enterprise." The ALT free flights are designed to verify Orbiter subsonic airworthiness, integrated systems operations and pilot-guided approach and landing capability and satisfying prerequisites to automatic flight control and navigation mode.

  6. High serum carotenoids are associated with lower risk for developing elevated serum alanine aminotransferase among Japanese subjects: the Mikkabi cohort study.

    PubMed

    Sugiura, Minoru; Nakamura, Mieko; Ogawa, Kazunori; Ikoma, Yoshinori; Yano, Masamichi

    2016-04-01

    Many recent studies have shown that antioxidant vitamins and/or carotenoids may reduce liver disease, but this association has not been well established with thorough longitudinal cohort studies. The objective of this study was to longitudinally investigate whether serum carotenoids at baseline are associated with the risk of developing elevated serum alanine aminotransferase (ALT) among Japanese subjects. We conducted a follow-up study of 1073 males and females aged between 30 and 79 years at baseline from the Mikkabi prospective cohort study. Those who participated in the baseline study and completed follow-up surveys were examined longitudinally. Exclusions included excessive alcohol consumption (≥60 g alcohol/d), hepatitis B and C and having a history of medication use for liver disease. A cohort of 213 males and 574 females free of elevated serum ALT (>30 IU/ml) at baseline was studied. Over a mean follow-up period of 7·4 (sd 3·1) years, thirty-one males and forty-nine females developed new elevated serum ALT. After adjustments for confounders, the hazard ratios for elevated serum ALT in the highest tertiles of basal serum β-carotene, β-cryptoxanthin and total provitamin A carotenoids against the lowest tertiles were 0·43 (95 % CI 0·22, 0·81), 0·51 (CI 0·27, 0·94) and 0·52 (CI 0·28, 0·97), respectively. For α-carotene and lycopene, borderline reduced risks were also observed; however, these were not significant. Our results further support the hypothesis that antioxidant carotenoids, especially provitamin A carotenoids, might help prevent earlier pathogenesis of non-alcoholic liver disease in Japanese subjects.

  7. The association between the genetic polymorphism of HLA-DQA1, DQB1, and DRB1 and serum alanine aminotransferase levels in chronic hepatitis C in the Chinese population.

    PubMed

    Yu, Rong-Bin; Hong, Xin; Ding, Wei-Liang; Tan, Yong-Fei; Zhang, Yong-Xiang; Sun, Nan-Xiong; Wu, Guan-Ling; Zhan, Sheng-Wei; Ge, Da-Fang

    2008-09-01

    To investigate a possible association between HLA genes with serum alanine aminotransferase (ALT) levels and evaluate whether the HLA-DQA1, DQB1, and DRB1 genes could influence the development of liver damage in chronic hepatitis C. A total of 145 patients with chronic hepatitis C virus (HCV) infection (36 patients with persistently normal ALT values; 109 patients with elevated ALT levels) and 160 uninfected healthy controls were examined for HLA-DQA1, DQB1, and DRB1 molecules by using polymerase chain reaction-sequencing based typing (PCR-SBT). Among the patients chronically infected with HCV, the frequencies of DQA1*0501, DQB1*0301, and DRB1*0401 alleles were significantly increased in the normal ALT group compared with those with abnormal ALT levels, whereas that of DQB1*0201 was significantly lower. As compared to uninfected healthy controls, DQA1*0501, DQB1*0301, and DRB1*0401 allele frequencies were also statistically higher in the normal ALT group, whereas that of DQB1*0201 was the inverse. The haplotype frequencies of DQA1*0301-DQB1*0301, DQA1*0501-DQB1*0301, and DRB1*1101-DQB1*0301 were found to be significantly higher in the normal ALT group. Multivariate logistic regression indicated that female sex, and the DQB1*0301 allele and DRB1*0401 allele were independently associated with normal ALT values, whereas DQB1*0201 allele was the inverse. These results suggest that particular HLA alleles may have an influence on the serum ALT level of chronic HCV infection as a host genetic factor in the Chinese population. The DQA1*0501, DQB1*0301, and DRB1*0401 alleles, and the DQA1*0301-DQB1*0301, DQA1*0501-DQB1*0301, and DRB1*1101-DQB1*0301 haplotypes seem to be associated with low hepatitis activity; whereas DQB1*0201 allele is closely correlated with the progression of liver injury in chronic HCV infection.

  8. [Regulation of key enzymes of L-alanine biosynthesis by Brevibacterium flavum producer strains].

    PubMed

    Melkonian, L O; Avetisova, G E; Ambartsumian, A A; Chakhalian, A Kh; Sagian, A S

    2013-01-01

    The mechanisms of L-alanine overproduction by Brevibacterium flavum producer strains were studied. It was shown that beta-CI-L-alanine is an inhibitor of some key enzymes involved in the synthesis of L-alanine, including alanine transaminase and valine-pyruvate transaminase. Two highly active B. flavum GL1 and GL1 8 producer strains, which are resistant to the inhibitory effect of beta-Cl-L-alanine, were obtained using a parental B. flavum AA5 producer strain, characterized by a reduced activity of alanine racemase (>or=98%). It was demonstrated that the increased L-alanine synthesis efficiency observed in the producer strains developed in this work is associated with the absence of inhibition of alanine transaminase by the end product of the biosynthesis reaction, as well as with the effect of derepression of both alanine transaminase and valine-pyruvate transaminase synthesis by the studied compound.

  9. Eating a healthy lunch improves serum alanine aminotransferase activity.

    PubMed

    Iwamoto, Masako; Yagi, Kaori; Yazumi, Kayoko; Komine, Airi; Shirouchi, Bungo; Sato, Masao

    2013-09-14

    Nutritional guidance and diet control play important roles in the treatment of obesity and non-alcoholic fatty liver. However, in Japan, nutritional guidance is difficult to provide in practice. Therefore, we evaluated the effects of providing the 'once-a-day' intervention of a healthy lunch on various metabolic parameters. For a 1-month preparatory period, 10 subjects generally consumed the lunches that were provided by the worksite cafeteria. This was followed by a 1-week washout period, after which, the subjects consumed healthy, low-calorie, well-balanced lunches for a 1-month test period. After the preparatory and test periods, blood samples were obtained from all subjects. The serum levels of indices relevant to metabolic syndrome and fatty liver were measured. Serum alanine aminotransferase activity significantly decreased by 20.3% after the healthy intervention. However, the indices of metabolic syndrome did not significantly change. Analysis of the relationship between serum alanine aminotransferase activity and nutrient content indicated that the improvement of serum alanine aminotransferase status was due to the higher vegetable content and lower animal-source protein of the meals provided. In summary, the 'once-a-day' intervention of providing a healthy lunch improved serum alanine aminotransferase status. A diet high in vegetables and low in animal-based protein is important in maintaining a healthy condition.

  10. Eating a healthy lunch improves serum alanine aminotransferase activity

    PubMed Central

    2013-01-01

    Background Nutritional guidance and diet control play important roles in the treatment of obesity and non-alcoholic fatty liver. However, in Japan, nutritional guidance is difficult to provide in practice. Therefore, we evaluated the effects of providing the ‘once-a-day’ intervention of a healthy lunch on various metabolic parameters. Methods For a 1-month preparatory period, 10 subjects generally consumed the lunches that were provided by the worksite cafeteria. This was followed by a 1-week washout period, after which, the subjects consumed healthy, low-calorie, well-balanced lunches for a 1-month test period. After the preparatory and test periods, blood samples were obtained from all subjects. The serum levels of indices relevant to metabolic syndrome and fatty liver were measured. Results Serum alanine aminotransferase activity significantly decreased by 20.3% after the healthy intervention. However, the indices of metabolic syndrome did not significantly change. Analysis of the relationship between serum alanine aminotransferase activity and nutrient content indicated that the improvement of serum alanine aminotransferase status was due to the higher vegetable content and lower animal-source protein of the meals provided. Conclusions In summary, the ‘once-a-day’ intervention of providing a healthy lunch improved serum alanine aminotransferase status. A diet high in vegetables and low in animal-based protein is important in maintaining a healthy condition. PMID:24034595

  11. A theoretical study of alanine dipeptide and analogs

    SciTech Connect

    Head-Gordon, T.; Head-Gordon, M.; Brooks, C. III; Pople, J. ); Frisch, M.J. )

    1989-01-01

    We Present a preliminary report on the conformational and energetic analysis of the molecule (S)-2-acetylamino-N-methylpropanamide (alanine dipeptide) and an analog molecule, (S)-{alpha}-formylaminopropanamide, using high-quality ab initio methods. Alanine dipeptide and its analogs are of interest since they incorporate many of the structural features found in proteins, such as intramolecular hydrogen bonds, conformational flexibility, and a variety of chemical functionality. One purpose of this study is to provide a useful benchmark calculation, MP2/6-31+G{sup **}//HF/6-31+G{sup *}, for a number of conformations of the alanine system. Based on the comparison of these benchmark calculations with lower-level basis sets, HF/3-21G was chosen to generate a fully relaxed {phi}, {psi} dihedral map. These calculations are the first of their kind on systems of this size. Features of the {phi},{psi} alanine dipeptide map that are discussed include the energetically accessible conformations and possible pathways for their interconversion. In addition, we illustrate the importance of fully optimized geometries and the proper evaluation of correlation energies,

  12. Formation of {gamma}-alumina nanorods in presence of alanine

    SciTech Connect

    Dabbagh, Hossein A.; Rasti, Elham; Yalfani, Mohammad S.; Medina, Francesc

    2011-02-15

    Graphical abstract: Nanorod aluminas with a possible hexagonal symmetry, high surface area and relatively narrow pore size distribution were obtained. Research highlights: {yields} Research highlights {yields} Boehmite was prepared using a green sol-gel process in the presence of alanine. {yields} Nanorod aluminas with a high surface area were obtained. {yields} Addition of alanine would shape the size of the holes and crevices. {yields} The morphologies of the nanorods were revealed by transmission electron microscope. -- Abstract: Boehmite and alumina nanostructures were prepared using a simple green sol-gel process in the presence of alanine in water medium at room temperature. The uncalcined (dried at 200 {sup o}C) and the calcined materials (at 500, 600 and 700 {sup o}C for 4 h) were characterized using XRD, TEM, SEM, N{sub 2} physisorption and TGA. Nanorod aluminas with a possible hexagonal symmetry, high surface area and relatively narrow pore size distribution were obtained. The surface area was enhanced and crystallization was retarded as the alanine content increased. The morphologies of the nanoparticles and nanorods were revealed by a transmission electron microscope (TEM).

  13. Spectrophotometric readout for an alanine dosimeter for food irradiation applications

    NASA Astrophysics Data System (ADS)

    Ebraheem, S.; Beshir, W. B.; Eid, S.; Sobhy, R.; Kovács, A.

    2003-06-01

    The alanine-electron spin resonance (EPR) readout system is well known as a reference and transfer dosimetry system for the evaluation of high doses in radiation processing. The high cost of an EPR/alanine dosimetry system is a serious handicap for large-scale routine application in irradiation facilities. In this study, the use of a complex produced by dissolving irradiated L-alanine in 1,4-phenyl diammonium dichloride solution was investigated for dosimetry purposes. This complex—having a purple colour—has an increasing absorbance with increasing dose in the range of 1-20 kGy. The applicability of spectrophotometric evaluation was studied by measuring the absorbance intensity of this complex at 360 and 505 nm, respectively. Fluorimetric evaluation was also investigated by measuring the emission of the complex at 435 nm as a function of dose. The present method is easy for routine application. The effect of the dye concentration as well as the suitable amount of irradiated alanine has been studied. With respect to routine application, the stability of the product complex after its formation was also investigated.

  14. Beta-alanine supplementation, muscle carnosine and exercise performance.

    PubMed

    Blancquaert, Laura; Everaert, Inge; Derave, Wim

    2015-01-01

    The use of dietary supplements in sports is widespread as athletes are continuously searching for strategies to increase performance at the highest level. Beta-alanine is such a supplement that became increasingly popular during the past years. This review examines the available evidence regarding the optimization of supplementation, the link between beta-alanine and exercise performance and the underlying ergogenic mechanism. It has been repeatedly demonstrated that chronic beta-alanine supplementation can augment intramuscular carnosine content. Yet, the factors that determine the loading process, as well as the mechanism by which this has an ergogenic effect, are still debated. On the basis of its biochemical properties, several functions are ascribed to carnosine, of which intramuscular pH buffer and calcium regulator are the most cited ones. In addition, carnosine has antiglycation and antioxidant properties, suggesting it could have a therapeutic potential. On the basis of the millimolar presence of carnosine in mammalian muscles, it must play a critical role in skeletal muscle physiology. The recent number of studies shows that this is related to an improved exercise homeostasis and excitation-contraction coupling. Recent developments have led to the optimization of the beta-alanine supplementation strategies to elevate muscle carnosine content, which are helpful in its application in sports and to potential future therapeutic applications.

  15. Computational alanine scanning with linear scaling semiempirical quantum mechanical methods.

    PubMed

    Diller, David J; Humblet, Christine; Zhang, Xiaohua; Westerhoff, Lance M

    2010-08-01

    Alanine scanning is a powerful experimental tool for understanding the key interactions in protein-protein interfaces. Linear scaling semiempirical quantum mechanical calculations are now sufficiently fast and robust to allow meaningful calculations on large systems such as proteins, RNA and DNA. In particular, they have proven useful in understanding protein-ligand interactions. Here we ask the question: can these linear scaling quantum mechanical methods developed for protein-ligand scoring be useful for computational alanine scanning? To answer this question, we assembled 15 protein-protein complexes with available crystal structures and sufficient alanine scanning data. In all, the data set contains Delta Delta Gs for 400 single point alanine mutations of these 15 complexes. We show that with only one adjusted parameter the quantum mechanics-based methods outperform both buried accessible surface area and a potential of mean force and compare favorably to a variety of published empirical methods. Finally, we closely examined the outliers in the data set and discuss some of the challenges that arise from this examination.

  16. Alanine flux in obese and healthy humans as evaluated by /sup 15/N- and /sup 2/H/sub 3/-labeled alanines

    SciTech Connect

    Hoffer, L.J.; Yang, R.D.; Matthews, D.E.; Bistrian, B.R.; Bier, D.M.; Young, V.R.

    1988-10-01

    Estimates of plasma alanine flux as measured in humans using L-(/sup 15/N)-alanine or L-(3,3,3-/sup 2/H/sub 3/)alanine were compared by simultaneous intravenous infusion of both tracers. Plasma isotope enrichments were measured by chemical ionization gas chromatography-mass spectrometry. In 16 obese women before and during a hypocaloric diet and in 4 normal men in the postabsorptive and fed states, the fluxes were highly correlated (r2 = 0.93) although plasma alanine flux with the /sup 2/H tracer was two to three times greater than that obtained with (/sup 15/N)alanine. The fluxes decreased with the hypocaloric diet in obese subjects and increased during the fed state in healthy adults. Thus, although the estimates of alanine flux differed according to the tracer used, both appear to give equivalent information about changes in alanine kinetics induced by the nutritional conditions examined.

  17. Prevalence of elevated ALT values, HBsAg, and anti-HCV in the primary care setting and evaluation of guideline defined hepatitis risk scenarios.

    PubMed

    Wolffram, Ingmar; Petroff, David; Bätz, Olaf; Jedrysiak, Katrin; Kramer, Jan; Tenckhoff, Hannelore; Berg, Thomas; Wiegand, Johannes

    2015-06-01

    Prevalence data for hepatitis B and C and an evaluation of a guideline based screening in the primary care setting are not yet available. We therefore implemented a hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus (HCV) screening and developed guideline based screening strategies. HBsAg, anti-HCV, and alanine aminotransferase (ALT) were included in a routine check-up together with a questionnaire covering 16 guideline adapted risk scenarios. Significant risk factors were identified by stepwise logistic regression. 51 private practices screened 21,008 patients. The HBsAg, anti-HCV, and HCV-RNA prevalence was 0.52%, 0.95%, and 0.43%, respectively. Infections were previously unknown in 85% and 65% of HBsAg and anti-HCV positive individuals, respectively. Sexual risk factors were under-reported, while the following scenarios were significantly associated with viral infections (Odds ratio [95% confidence interval]). HBV: Immigration (4.4 [2.9, 6.7]), infection in household (2.5 [1.2, 4.5]), male gender (1.6 [1.1, 2.4]). Male immigrants had a 2.1% HBsAg prevalence and 80% were unaware of the infection. HCV: IV drug use (384 [233, 644]), blood transfusion before 1992 (5.3 [3.5, 7.9]), immigration (2.4 [1.5, 3.6]). Presence of either one of the HBV related guideline defined risk scenarios or elevated ALT identified 82% of previously undiagnosed patients. Presence of one of the three significant HCV risk factors or elevated ALT levels diagnosed 83% of unknown HCV-RNA positive cases by screening only 26% of the population. Undiagnosed hepatitis B and C infections frequently exist in the primary care setting. Easy to apply guideline defined risk scenarios help to diagnose previously unknown infections. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  18. The unresolved puzzle why alanine extensions cause disease.

    PubMed

    Winter, Reno; Liebold, Jens; Schwarz, Elisabeth

    2013-08-01

    The prospective increase in life expectancy will be accompanied by a rise in the number of elderly people who suffer from ill health caused by old age. Many diseases caused by aging are protein misfolding diseases. The molecular mechanisms underlying these disorders receive constant scientific interest. In addition to old age, mutations also cause congenital protein misfolding disorders. Chorea Huntington, one of the most well-known examples, is caused by triplet extensions that can lead to more than 100 glutamines in the N-terminal region of huntingtin, accompanied by huntingtin aggregation. So far, nine disease-associated triplet extensions have also been described for alanine codons. The extensions lead primarily to skeletal malformations. Eight of these proteins represent transcription factors, while the nuclear poly-adenylate binding protein 1, PABPN1, is an RNA binding protein. Additional alanines in PABPN1 lead to the disease oculopharyngeal muscular dystrophy (OPMD). The alanine extension affects the N-terminal domain of the protein, which has been shown to lack tertiary contacts. Biochemical analyses of the N-terminal domain revealed an alanine-dependent fibril formation. However, fibril formation of full-length protein did not recapitulate the findings of the N-terminal domain. Fibril formation of intact PABPN1 was independent of the alanine segment, and the fibrils displayed biochemical properties that were completely different from those of the N-terminal domain. Although intranuclear inclusions have been shown to represent the histochemical hallmark of OPMD, their role in pathogenesis is currently unclear. Several cell culture and animal models have been generated to study the molecular processes involved in OPMD. These studies revealed a number of promising future therapeutic strategies that could one day improve the quality of life for the patients.

  19. [Reconstruction of soft tissue defect of the sole using an ALT flap].

    PubMed

    Kovács, István; Lóderer, Zoltán; Bognár, Gábor; Jánó, Zoltán; Németh, Róbert; Bognár, Gábor; Nagy, Attila

    2010-12-01

    Soft tissue defect of the sole is usually a quite challenging problem. In this case report the most frequently used reconstructive options of this problem are reviewed paying particular attention for the well applicable and reliable types. An ALT graft as a free flap to the sole offers a good possibility for coverage, which is resistant enough to mechanic strains.

  20. The Basis of Aluminum Tolerance Encoded by the Alt3 Locus of Rye

    USDA-ARS?s Scientific Manuscript database

    Aluminium (Al) toxicity, affecting around half of the world’s arable land, severely hinders the ability of crop plants to cope with drought and nutrient stresses by restricting root growth and function. Among the cultivated cereals, rye is the most Al tolerant. At the Alt3 Al tolerance locus on rye ...

  1. On the Trajectories of the Predetermined ALT Model: What Are We Really Modeling?

    ERIC Educational Resources Information Center

    Jongerling, Joran; Hamaker, Ellen L.

    2011-01-01

    This article shows that the mean and covariance structure of the predetermined autoregressive latent trajectory (ALT) model are very flexible. As a result, the shape of the modeled growth curve can be quite different from what one might expect at first glance. This is illustrated with several numerical examples that show that, for example, a…

  2. Crystal structures of d-alanine-d-alanine ligase from Xanthomonas oryzae pv. oryzae alone and in complex with nucleotides.

    PubMed

    Doan, Thanh Thi Ngoc; Kim, Jin-Kwang; Ngo, Ho-Phuong-Thuy; Tran, Huyen-Thi; Cha, Sun-Shin; Min Chung, Kyung; Huynh, Kim-Hung; Ahn, Yeh-Jin; Kang, Lin-Woo

    2014-03-01

    D-Alanine-D-alanine ligase (DDL) catalyzes the biosynthesis of d-alanyl-d-alanine, an essential bacterial peptidoglycan precursor, and is an important drug target for the development of antibacterials. We determined four different crystal structures of DDL from Xanthomonas oryzae pv. oryzae (Xoo) causing Bacteria Blight (BB), which include apo, ADP-bound, ATP-bound, and AMPPNP-bound structures at the resolution between 2.3 and 2.0 Å. Similarly with other DDLs, the active site of XoDDL is formed by three loops from three domains at the center of enzyme. Compared with d-alanyl-d-alanine and ATP-bound TtDDL structure, the γ-phosphate of ATP in XoDDL structure was shifted outside toward solution. We swapped the ω-loop (loop3) of XoDDL with those of Escherichia coli and Helicobacter pylori DDLs, and measured the enzymatic kinetics of wild-type XoDDL and two mutant XoDDLs with the swapped ω-loops. Results showed that the direct interactions between ω-loop and other two loops are essential for the active ATP conformation for D-ala-phosphate formation.

  3. An approximation of the Cioslowski-Mixon bond order indexes using the AlteQ approach

    NASA Astrophysics Data System (ADS)

    Salmina, Elena; Grishina, Maria A.; Potemkin, Vladimir A.

    2013-09-01

    Fast and reliable prediction of bond orders in organic systems based upon experimentally measured quantities can be performed using electron density features at bond critical points (J Am Chem Soc 105:5061-5068, 1983; J Phys Org Chem 16:133-141, 2003; Acta Cryst B 61:418-428, 2005; Acta Cryst B 63:142-150, 2007). These features are outcomes of low-temperature high-resolution X-ray diffraction experiments. However, a time-consuming procedure of gaining these quantities makes the prediction limited. In the present work we have employed an empirical approach AlteQ (J Comput Aided Mol Des 22:489-505, 2008) for evaluation of electron density properties. This approach uses a simple exponential function derived from comparison of electron density, gained from high-resolution X-ray crystallography, and distance to atomic nucleus what allows calculating density distribution in time-saving manner and gives results which are very close to experimental ones. As input data AlteQ accepts atomic coordinates of isolated molecules or molecular ensembles (for instance, protein-protein complexes or complexes of small molecules with proteins, etc.). Using AlteQ characteristics we have developed regression models predicting Cioslowski-Mixon bond order (CMBO) indexes (J Am Chem Soc 113(42):4142-4145, 1991). The models are characterized by high correlation coefficients lying in the range from 0.844 to 0.988 dependently on the type of covalent bond, thereby providing a bonding quantification that is in reasonable agreement with that obtained by orbital theory. Comparative analysis of CMBOs approximated using topological properties of AlteQ and experimental electron densities has shown that the models can be used for fast determination of bond orders directly from X-ray crystallography data and confirmed that AlteQ characteristics can replace experimental ones with satisfactory extent of accuracy.

  4. Formation of simple biomolecules from alanine in ocean by impacts

    NASA Astrophysics Data System (ADS)

    Umeda, Y.; Sekine, T.; Furukawa, Y.; Kakegawa, T.; Kobayashi, T.

    2013-12-01

    The biomolecules on the Earth are thought either to have originated from the extraterrestrial parts carried with flying meteorites or to have been formed from the inorganic materials on the Earth through given energy. From the standpoint to address the importance of impact energy, it is required to simulate experimentally the chemical reactions during impacts, because violent impacts may have occurred 3.8-4.0 Gyr ago to create biomolecules initially. It has been demonstrated that shock reactions among ocean (H2O), atmospheric nitrogen, and meteoritic constitution (Fe) can induce locally reduction environment to form simple bioorganic molecules such as ammonia and amino acid (Nakazawa et al., 2005; Furukawa et al., 2009). We need to know possible processes for alanine how chemical reactions proceed during repeated impacts and how complicated biomolecules are formed. Alanine can be formed from glycine (Umeda et al., in preparation). In this study, we carried out shock recovery experiments at pressures of 4.4-5.7 GPa to investigate the chemical reactions of alanine. Experiments were carried out with a propellant gun. Stainless steel containers (30 mm in diameter, 30 mm long) with 13C-labeled alanine aqueous solution immersed in olivine or hematite powders were used as targets. Air gap was present in the sample room (18 mm in diameter, 2 mm thick) behind the sample. The powder, solution, and air represent meteorite, ocean, and atmosphere on early Earth, respectively. Two powders of olivine and hematite help to keep the oxygen fugacity low and high during experiments, respectively in order to investigate the effect of oxygen fugacity on chemical processes of alanine. The recovered containers, after cleaned completely, were immersed into liquid nitrogen to freeze sample solution and then we drilled on the impact surface to extract water-soluble run products using pure water. Thus obtained products were analyzed by LC/MS for four amino acids (glycine, alanine, valine, and

  5. Structure of the Mycobacterium tuberculosis D-Alanine:D-Alanine Ligase, a Target of the Antituberculosis Drug D-Cycloserine

    SciTech Connect

    Bruning, John B.; Murillo, Ana C.; Chacon, Ofelia; Barletta, Raúl G.; Sacchettini, James C.

    2011-09-28

    D-Alanine:D-alanine ligase (EC 6.3.2.4; Ddl) catalyzes the ATP-driven ligation of two D-alanine (D-Ala) molecules to form the D-alanyl:D-alanine dipeptide. This molecule is a key building block in peptidoglycan biosynthesis, making Ddl an attractive target for drug development. D-Cycloserine (DCS), an analog of D-Ala and a prototype Ddl inhibitor, has shown promise for the treatment of tuberculosis. Here, we report the crystal structure of Mycobacterium tuberculosis Ddl at a resolution of 2.1 {angstrom}. This structure indicates that Ddl is a dimer and consists of three discrete domains; the ligand binding cavity is at the intersection of all three domains and conjoined by several loop regions. The M. tuberculosis apo Ddl structure shows a novel conformation that has not yet been observed in Ddl enzymes from other species. The nucleotide and D-alanine binding pockets are flexible, requiring significant structural rearrangement of the bordering regions for entry and binding of both ATP and D-Ala molecules. Solution affinity and kinetic studies showed that DCS interacts with Ddl in a manner similar to that observed for D-Ala. Each ligand binds to two binding sites that have significant differences in affinity, with the first binding site exhibiting high affinity. DCS inhibits the enzyme, with a 50% inhibitory concentration (IC{sub 50}) of 0.37 mM under standard assay conditions, implicating a preferential and weak inhibition at the second, lower-affinity binding site. Moreover, DCS binding is tighter at higher ATP concentrations. The crystal structure illustrates potential drugable sites that may result in the development of more-effective Ddl inhibitors.

  6. Kinetic mechanism and inhibition of Mycobacterium tuberculosis D-alanine:D-alanine ligase by the antibiotic D-cycloserine.

    PubMed

    Prosser, Gareth A; de Carvalho, Luiz Pedro S

    2013-02-01

    D-cycloserine (DCS) is an antibiotic that is currently used in second-line treatment of tuberculosis. DCS is a structural analogue of D-alanine, and targets two enzymes involved in the cytosolic stages of peptidoglycan synthesis: alanine racemase (Alr) and D-alanine:D-alanine ligase (Ddl). The mechanisms of inhibition of DCS have been well-assessed using Alr and Ddl enzymes from various bacterial species, but little is known regarding the interactions of DCS with the mycobacterial orthologues of these enzymes. We have over-expressed and purified recombinant Mycobacterium tuberculosis Ddl (MtDdl; Rv2981c), and report a kinetic examination of the enzyme with both its native substrate and DCS. MtDdl is activated by K(+), follows an ordered ter ter mechanism and displays distinct affinities for D-Ala at each D-Ala binding site (K(m,D-Ala1) = 0.075 mm, K(m,D-Ala2) = 3.6 mm). ATP is the first substrate to bind and is necessary for subsequent binding of D-alanine or DCS. The pH dependence of MtDdl kinetic parameters indicate that general base chemistry is involved in the catalytic step. DCS was found to competitively inhibit D-Ala binding at both MtDdl D-Ala sites with equal affinity (K(i,DCS1) = 14 μm, K(i,DCS2) = 25 μm); however, each enzyme active site can only accommodate a single DCS molecule at a given time. The pH dependence of K(i,DCS2) revealed a loss of DCS binding affinity at high pH (pK(a) = 7.5), suggesting that DCS binds optimally in the zwitterionic form. The results of this study may assist in the design and development of novel Ddl-specific inhibitors for use as anti-mycobacterial agents.

  7. Clinical applications of alanine/electron spin resonance dosimetry.

    PubMed

    Baffa, Oswaldo; Kinoshita, Angela

    2014-05-01

    This paper discusses the clinical applications of electron spin resonance (ESR) dosimetry focusing on the ESR/alanine system. A review of few past studies in this area is presented offering a critical overview of the challenges and opportunities for extending this system into clinical applications. Alanine/ESR dosimetry fulfills many of the required properties for several clinical applications such as water-equivalent composition, independence of the sensitivity for the energy range used in therapy and high precision. Improvements in sensitivity and the development of minidosimeters coupled with the use of a spectrometer of higher microwave frequency expanded the possibilities for clinical applications to the new modalities of radiotherapy (intensity-modulated radiation therapy and radiosurgery) and to the detection of low doses such as those present in some radiological image procedures.

  8. Degradation of glycine and alanine on irradiated quartz.

    PubMed

    Pawlikowski, Maciej; Benko, Aleksandra; Wróbel, Tomasz P

    2013-04-01

    Recent researches suggest participation of minerals in the formation of life under primordial conditions. Among all of the minerals, quartz seems to be one of the most probable to take part in such processes. However, an external source of energy is needed, e.g. electric discharge. A device simulating the proposed conditions was designed and was used to simulate prebiotic conditions. Investigation of processes occurring during the stimulation of quartz with electric discharge was studied by means of Ultraviolet-visible (UV-VIS) spectroscopy, in order to monitor the generation kinetics of free radicals. Additionally, infrared spectroscopy was applied to identify chemical reaction products created in a solution of alanine or glycine, in the presence of quartz treated with electric discharge. Formation of increased amounts of free radicals, compared to experiments performed without quartz and/or amino acid, is reported, along with identification of possible degradation products of alanine. No synthetic reactions were observed.

  9. First principles investigation of L-alanine in terahertz region.

    PubMed

    Zheng, Zhuan-Ping; Fan, Wen-Hui

    2012-06-01

    Terahertz absorption spectrum (0.5-4.0 THz) of L-alanine in the solid phase was measured by terahertz time-domain spectroscopy at room temperature. Simulations utilizing gaseous-state and solid-state theory were performed to determine the origins of the observed vibrational features. Our calculations showed that the measured features in solid-state materials could be well understood by considering the crystal packing interactions in a solid-state density functional theory calculation. Furthermore, intermolecular vibrations of L-alanine are found to be the dominating contributions to these measured spectral features in the range of 0.5-4.0 THz, except that located at 3.11 THz.

  10. How to manage HBeAg-negative chronic HBV infection with normal alanine aminotransferase levels in clinical practice?

    PubMed

    Puoti, Claudio

    2013-03-01

    Many HBsAg-positive/HBeAg-negative patients show normal alanine aminotransferase levels. However, in this group of patients two different virological and clinical subsets do exist: inactive HBV carriers and patients with chronic hepatitis B with transient virological and biochemical remission. Natural history and outcome, severity of liver damage and need for liver biopsy and antiviral treatment differ significantly between these groups of patients. It is not always easy to distinguish between inactive HBV carriers and patients suffering from HBeAg-negative chronic hepatitis with transient disease remission, as they share similar biochemical (normal serum ALT values) and virological (HBeAg negativity and low HBV DNA levels) features. In clinical practice, it is very important to differentiate inactive carriers from patients with chronic hepatitis B with spontaneous transient remission, as the former have a good prognosis with a very low risk of complications, while the latter have active liver disease with a high risk of progression to advanced hepatic fibrosis, cirrhosis and hepatocellular carcinoma. Thus, a careful assessment and adequate follow-up periods are needed. The aim of this review, written in the form of a dialog between a hepatologist and a newly diagnosed patient with HBV infection and normal alanine aminotransferase levels, is to give evidence-based suggestions for the management in clinical practice of HBsAg patients, on the basis of more recent international guidelines, covering many aspects of the condition, including advice on lifestyle and vaccination, indications for liver biopsy and treatment, the types and side effects of treatment and treatment endpoints. Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  11. Physiological hypercortisolemia increases proteolysis, glutamine, and alanine production

    SciTech Connect

    Darmaun, D.; Matthews, D.E.; Bier, D.M. Cornell Univ. Medical College, New York, NY )

    1988-09-01

    Physiological elevations of plasma cortisol levels, as are encountered in stress and severe trauma, were produced in six normal subjects by infusing them with hydrocortisone for 64 h. Amino acid kinetics were measured in the postabsorptive state using three 4-h infusions of L-(1-{sup 13}C)leucine, L-phenyl({sup 2}H{sub 5})phenylalanine, L-(2-{sup 15}N)glutamine, and L-(1-{sup 13}C)alanine tracers (1) before, (2) at 12 h, and (3) at 60 h of cortisol infusion. Before and throughout the study, the subjects ate a normal diet of adequate protein and energy intake. The cortisol infusion raised plasma cortisol levels significantly from 10 {plus minus} 1 to 32 {plus minus} 4 {mu}g/dl, leucine flux from 83 {plus minus} 3 to 97 {plus minus} 3 {mu}mol{center dot}kg{sup {minus}1}{center dot}h{sup {minus}1}, and phenylalanine flux from 34 {plus minus} 1 to 39 {plus minus} 1 (SE) {mu}mol{center dot}kg{sup {minus}1}{center dot}h{sup {minus}1} after 12 h of cortisol infusion. These increases were maintained until the cortisol infusion was terminated. These nearly identical 15% increases in two different essential amino acid appearance rates are reflective of increased whole body protein breakdown. Glutamine flux rose by 12 h of cortisol infusion and remained elevated at the same level at 64 h. The increase in flux was primarily due to a 55% increase in glutamine de novo synthesis. Alanine flux increased with acute hypercortisolemia and increased further at 60 h of cortisol infusion, a result primarily of increased alanine de novo synthesis. Insulin, alanine, and lactate plasma levels responded similarly with significant rises between the acute and chronic periods of cortisol infusion. Thus hypercortisolemia increases both protein breakdown and the turnover of important nonessential amino acids for periods of up to 64 h.

  12. Alanine, glutamate, and ammonia exchanges in acutely ischemic swine myocardium.

    PubMed

    Hacker, T A; Hall, J L; Stone, C K; Stanley, W C

    1992-01-01

    Coronary artery disease causes an increase in glutamate uptake and alanine output by the heart. We assessed the effects of acute myocardial ischemia on alanine and glutamate exchange and ammonia production in 10 anesthetized open-chest domestic swine (46.9 +/- 0.7 kg). Coronary blood flow was controlled through an extracorporal perfusion circuit. After a nonischemic control period (aerobic) the blood flow in the left anterior descending coronary artery was reduced by 60%. Arterial and anterior interventricular venous samples where drawn before and during 35 min of ischemia. Subendocardial blood flow, measured using radiolabeled microspheres, decreased from 1.27 +/- 0.16 to 0.25 +/- 0.09 (ml/g)/min, and left-ventricular wall-thickening fell to 47% of aerobic values. Ischemia resulted in a significant increase in the rate of glucose uptake (p less than 0.05) and a switch to net lactate production (p less than 0.01). Ischemia did not affect the rates of alanine output (-0.9 +/- 1.0 vs. -0.3 +/- 0.3 mumol/min) or glutamate uptake (-0.4 +/- 1.1 vs. 0.3 +/- 0.6 mumol/min), but did increase the venous-arterial difference for ammonia (-4.1 +/- 4.1 to 52.7 +/- 5.5 microM, p less than 0.0001) and the ammonia output (-0.33 +/- 0.24 to 1.34 +/- 0.14 mumol/min, p less than 0.0001). In conclusion, acute ischemia did not stimulate greater alanine output or glutamate uptake. However, acute ischemia did cause an increase in anaerobic glycolysis rate and ammonia output, which reflects a profound disruption in myocardial energy metabolism.

  13. Crystal structures of Aedes aegypti alanine glyoxylate aminotransferase.

    PubMed

    Han, Qian; Robinson, Howard; Gao, Yi Gui; Vogelaar, Nancy; Wilson, Scott R; Rizzi, Menico; Li, Jianyong

    2006-12-01

    Mosquitoes are unique in having evolved two alanine glyoxylate aminotransferases (AGTs). One is 3-hydroxykynurenine transaminase (HKT), which is primarily responsible for catalyzing the transamination of 3-hydroxykynurenine (3-HK) to xanthurenic acid (XA). Interestingly, XA is used by malaria parasites as a chemical trigger for their development within the mosquito. This 3-HK to XA conversion is considered the major mechanism mosquitoes use to detoxify the chemically reactive and potentially toxic 3-HK. The other AGT is a typical dipteran insect AGT and is specific for converting glyoxylic acid to glycine. Here we report the 1.75A high-resolution three-dimensional crystal structure of AGT from the mosquito Aedes aegypti (AeAGT) and structures of its complexes with reactants glyoxylic acid and alanine at 1.75 and 2.1A resolution, respectively. This is the first time that the three-dimensional crystal structures of an AGT with its amino acceptor, glyoxylic acid, and amino donor, alanine, have been determined. The protein is dimeric and adopts the type I-fold of pyridoxal 5-phosphate (PLP)-dependent aminotransferases. The PLP co-factor is covalently bound to the active site in the crystal structure, and its binding site is similar to those of other AGTs. The comparison of the AeAGT-glyoxylic acid structure with other AGT structures revealed that these glyoxylic acid binding residues are conserved in most AGTs. Comparison of the AeAGT-alanine structure with that of the Anopheles HKT-inhibitor complex suggests that a Ser-Asn-Phe motif in the latter may be responsible for the substrate specificity of HKT enzymes for 3-HK.

  14. Crystal Structures of Aedes Aegypt Alanine Glyoxylate Aminotransferase

    SciTech Connect

    Han,Q.; Robinson, H.; Gao, Y.; Vogelaar, N.; Wilson, S.; Rizzi, M.; Li, J.

    2006-01-01

    Mosquitoes are unique in having evolved two alanine glyoxylate aminotransferases (AGTs). One is 3-hydroxykynurenine transaminase (HKT), which is primarily responsible for catalyzing the transamination of 3-hydroxykynurenine (3-HK) to xanthurenic acid (XA). Interestingly, XA is used by malaria parasites as a chemical trigger for their development within the mosquito. This 3-HK to XA conversion is considered the major mechanism mosquitoes use to detoxify the chemically reactive and potentially toxic 3-HK. The other AGT is a typical dipteran insect AGT and is specific for converting glyoxylic acid to glycine. Here we report the 1.75{angstrom} high-resolution three-dimensional crystal structure of AGT from the mosquito Aedes aegypti (AeAGT) and structures of its complexes with reactants glyoxylic acid and alanine at 1.75 and 2.1{angstrom} resolution, respectively. This is the first time that the three-dimensional crystal structures of an AGT with its amino acceptor, glyoxylic acid, and amino donor, alanine, have been determined. The protein is dimeric and adopts the type I-fold of pyridoxal 5-phosphate (PLP)-dependent aminotransferases. The PLP co-factor is covalently bound to the active site in the crystal structure, and its binding site is similar to those of other AGTs. The comparison of the AeAGT-glyoxylic acid structure with other AGT structures revealed that these glyoxylic acid binding residues are conserved in most AGTs. Comparison of the AeAGT-alanine structure with that of the Anopheles HKT-inhibitor complex suggests that a Ser-Asn-Phe motif in the latter may be responsible for the substrate specificity of HKT enzymes for 3-HK.

  15. Characterization of psychrophilic alanine racemase from Bacillus psychrosaccharolyticus.

    PubMed

    Okubo, Y; Yokoigawa, K; Esaki, N; Soda, K; Kawai, H

    1999-03-16

    A psychrophilic alanine racemase gene from Bacillus psychrosaccharolyticus was cloned and expressed in Escherichia coli SOLR with a plasmid pYOK3. The gene starting with the unusual initiation codon GTG showed higher preference for codons ending in A or T. The enzyme purified to homogeneity showed the high catalytic activity even at 0 degrees C and was extremely labile over 35 degrees C. The enzyme was found to have a markedly large Km value (5.0 microM) for the pyridoxal 5'-phosphate (PLP) cofactor in comparison with other reported alanine racemases, and was stabilized up to 50 degrees C in the presence of excess amounts of PLP. The low affinity of the enzyme for PLP may be related to the thermolability, and may be related to the high catalytic activity, initiated by the transaldimination reaction, at low temperature. The enzyme has a distinguishing hydrophilic region around the residue no. 150 in the deduced amino acid sequence (383 residues), whereas the corresponding regions of other Bacillus alanine racemases are hydrophobic. The position of the region in the three dimensional structure of C atoms of the enzyme was predicted to be in a surface loop surrounding the active site. The region may interact with solvent and reduce the compactness of the active site.

  16. Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion.

    PubMed

    Sousa, Cristovão M; Biancur, Douglas E; Wang, Xiaoxu; Halbrook, Christopher J; Sherman, Mara H; Zhang, Li; Kremer, Daniel; Hwang, Rosa F; Witkiewicz, Agnes K; Ying, Haoqiang; Asara, John M; Evans, Ronald M; Cantley, Lewis C; Lyssiotis, Costas A; Kimmelman, Alec C

    2016-08-25

    Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by an intense fibrotic stromal response and deregulated metabolism. The role of the stroma in PDAC biology is complex and it has been shown to play critical roles that differ depending on the biological context. The stromal reaction also impairs the vasculature, leading to a highly hypoxic, nutrient-poor environment. As such, these tumours must alter how they capture and use nutrients to support their metabolic needs. Here we show that stroma-associated pancreatic stellate cells (PSCs) are critical for PDAC metabolism through the secretion of non-essential amino acids (NEAA). Specifically, we uncover a previously undescribed role for alanine, which outcompetes glucose and glutamine-derived carbon in PDAC to fuel the tricarboxylic acid (TCA) cycle, and thus NEAA and lipid biosynthesis. This shift in fuel source decreases the tumour’s dependence on glucose and serum-derived nutrients, which are limited in the pancreatic tumour microenvironment. Moreover, we demonstrate that alanine secretion by PSCs is dependent on PSC autophagy, a process that is stimulated by cancer cells. Thus, our results demonstrate a novel metabolic interaction between PSCs and cancer cells, in which PSC-derived alanine acts as an alternative carbon source. This finding highlights a previously unappreciated metabolic network within pancreatic tumours in which diverse fuel sources are used to promote growth in an austere tumour microenvironment.

  17. Pressure-induced phase transitions in L-alanine, revisited.

    PubMed

    Tumanov, N A; Boldyreva, E V; Kolesov, B A; Kurnosov, A V; Quesada Cabrera, R

    2010-08-01

    The effect of pressure on L-alanine has been studied by X-ray powder diffraction (up to 12.3 GPa), single-crystal X-ray diffraction, Raman spectroscopy and optical microscopy (up to approximately 6 GPa). No structural phase transitions have been observed. At approximately 2 GPa the cell parameters a and b become accidentally equal to each other, but without a change in space-group symmetry. Neither of two transitions reported by others (to a tetragonal phase at approximately 2 GPa and to a monoclinic phase at approximately 9 GPa) was observed. The changes in cell parameters were continuous up to the highest measured pressures and the cells remained orthorhombic. Some important changes in the intermolecular interactions occur, which also manifest themselves in the Raman spectra. Two new orthorhombic phases could be crystallized from a MeOH/EtOH/H(2)O pressure-transmitting mixture in the pressure range 0.8-4.7 GPa, but only if the sample was kept at these pressures for at least 1-2 d. The new phases converted back to L-alanine on decompression. Judging from the Raman spectra and cell parameters, the new phases are most probably not L-alanine but its solvates.

  18. Life and cancer without telomerase: ALT and other strategies for making sure ends (don't) meet.

    PubMed

    Apte, Manasi S; Cooper, Julia Promisel

    2017-02-01

    While most cancer cells rely on telomerase expression/re-activation for linear chromosome maintenance and sustained proliferation, a significant population of cancers (10-15%) employs telomerase-independent strategies, collectively dubbed Alternative Lengthening of Telomeres (ALT). Most ALT cells relax the usual role of telomeres as inhibitors of local homologous recombination while maintaining the ability of telomeres to prohibit local non-homologous end joining reactions. Here we review current concepts surrounding how ALT telomeres achieve this new balance via alterations in chromatin landscape, DNA damage repair processes and handling of telomeric transcription. We also discuss telomerase independent end maintenance strategies utilized by other organisms, including fruitflies and yeasts, to draw parallels and contrasts and highlight additional modes, beyond ALT, that may be available to telomerase-minus cancers. We conclude by commenting on promises and challenges in the development of effective anti-ALT cancer therapies.

  19. Alanine metabolism in isolated human kidney tubules--Use of a mathematical model.

    PubMed

    Fouque, D; Dugelay, S; Martin, G; Combet, J; Baverel, G

    1996-02-15

    To gain insight into the fate of alanine nitrogen and carbon taken up by the human kidney under certain conditions, isolated human kidney cortex tubules were incubated in Krebs-Henseleit medium with L-alanine as substrate. The tubules metabolized alanine at high rates and in a dose-dependent manner. Most of the alanine nitrogen removed was recovered as ammonia and to a lesser extent as glutamate. Glucose, lactate and glutamate were also found to be significant products of alanine carbon metabolism. A simple mathematical model allowing one to calculate flux of alanine carbon through the various metabolic steps involved is proposed and applied to data obtained in experiments in which 5 mM [U-14C]-,[1-14C]-, [2-14C]- and [3-14C]alanine were used as substrates in parallel. About 40% of the alanine carbon removed was recovered as CO2 and oxidation of C1 of alanine accounted for most of the CO2 released from alanine. Calculations reveal that the ATP produced exceeded 3.2-fold the ATP consumed in relation to alanine metabolism. It is concluded that, in human kidney, alanine may serve as an energy supplier and as a precursor of glucose and ammonia.

  20. l-Alanine Auxotrophy of Lactobacillus johnsonii as Demonstrated by Physiological, Genomic, and Gene Complementation Approaches

    PubMed Central

    van der Kaaij, Hengameh; Desiere, Frank; Mollet, Beat; Germond, Jacques-Edouard

    2004-01-01

    Using a chemically defined medium without l-alanine, Lactobacillus johnsonii was demonstrated to be strictly auxotrophic for that amino acid. A comparative genetic analysis showed that all known genes involved in l-alanine biosynthesis are absent from the genome of L. johnsonii. This auxotrophy was complemented by heterologous expression of the Bacillus subtilis l-alanine dehydrogenase. PMID:15006820

  1. 40 CFR 721.520 - Alanine, N-(2-carboxyethyl)-N-alkyl-, salt.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alanine, N-(2-carboxyethyl)-N-alkyl... Specific Chemical Substances § 721.520 Alanine, N-(2-carboxyethyl)-N-alkyl-, salt. (a) Chemical substance... alanine, N-(2-carboxyethyl)-N- alkyl-, salt (P-89-336) is subject to reporting under this section for the...

  2. The Alanine Racemase of Mycobacterium smegmatis Is Essential for Growth in the Absence of d-Alanine▿ †

    PubMed Central

    Milligan, Daniel L.; Tran, Sieu L.; Strych, Ulrich; Cook, Gregory M.; Krause, Kurt L.

    2007-01-01

    Alanine racemase, encoded by the gene alr, is an important enzyme in the synthesis of d-alanine for peptidoglycan biosynthesis. Strains of Mycobacterium smegmatis with a deletion mutation of the alr gene were found to require d-alanine for growth in both rich and minimal media. This indicates that alanine racemase is the only source of d-alanine for cell wall biosynthesis in M. smegmatis and confirms alanine racemase as a viable target gene for antimycobacterial drug development. PMID:17827284

  3. Isotopic effects in mechanistic studies of biotransformations of fluorine derivatives of L-alanine catalysed by L-alanine dehydrogenase.

    PubMed

    Szymańska-Majchrzak, Jolanta; Pałka, Katarzyna; Kańska, Marianna

    2017-05-01

    Synthesis of 3-fluoro-[2-(2)H]-L-alanine (3-F-[(2)H]-L-Ala) in reductive amination of 3-fluoropyruvic acid catalysed by L-alanine dehydrogenase (AlaDH) was described. Fluorine derivative was used to study oxidative deamination catalysed by AlaDH applied kinetic (for 3-F-L-Ala in H2O - KIE's on Vmax: 1.1; on Vmax/KM: 1.2; for 3-F-L-Ala in (2)H2O - on Vmax: 1.4; on Vmax/KM: 2.1) and solvent isotope effect methods (for 3-F-L-Ala - SIE's on Vmax: 1.0; on Vmax/KM: 0.87; for 3-F-[2-(2)H]-L-Ala - on Vmax: 1.4; on Vmax/KM: 1.5). Studies explain some details of reaction mechanism. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Biomaterial properties evaluation of poly(vinyl acetate- alt-maleic anhydride)/chitosan nanocapsules

    NASA Astrophysics Data System (ADS)

    Raţă, Delia Mihaela; Popa, Marcel; Chailan, Jean-François; Zamfir, Carmen Lăcrămioara; Peptu, Cătălina Anişoara

    2014-08-01

    Nanocapsules with diameter around 100 nm based on a natural polymer (chitosan) and a synthetic polymer poly(vinyl acetate- alt-maleic anhydride) [poly(MAVA)] by interfacial condensation method were prepared. The present study proposes a new type of biocompatible nanocapsules based on poly(vinyl acetate- alt-maleic anhydride-chitosan) (MCS) able to become a reliable support for inclusion and release of drugs. The spherical shape of the nanocapsules was evidenced by scanning electron microscopy. Nanocapsules presented a good Norfloxacin loading and release capacity. Haemocompatibility tests have demonstrated that the nanocapsules present a low toxicity and a good compatibility with sanguine medium. The biocompatibility properties of the nanocapsules after their intraperitoneal administration in rats were evidenced by histopathological examination of different organs (brain, liver, kidney, and lung). The results are encouraging and the nanocapsules can be used as controlled drug delivery systems.

  5. The larval specific lymphatic filarial ALT-2: induction of protection using protein or DNA vaccination.

    PubMed

    Ramachandran, Sabarinathan; Kumar, Mishra Pankaj; Rami, Reddy Maryada Venkata; Chinnaiah, Harinath Basker; Nutman, Thomas; Kaliraj, Perumal; McCarthy, James

    2004-01-01

    Genes from the infective stage of lymphatic filarial parasites expressed at the time of host invasion have been identified as potential vaccine candidates. By screening an L3 cDNA library with sera from uninfected longstanding residents of an area endemic for onchocerciasis, so-called "endemic normals" (EN), we have cloned and characterized one such gene termed the abundant larval transcript two (ALT-2). The stage specificity of ALT-2 gene transcription and protein synthesis was confirmed by PCR using genespecific primers, and by western blot analysis of protein extracts from various stages of the parasite life cycle using specific antisera. Significant differences in antibody response to the recombinant ALT-2 were observed in endemic populations with differing clinical manifestations of lymphatic filariasis with an antibody response present in sera from 18 of 25 (72%) EN subjects compared to 9 of 25 (36%) with subclinical microfilaracmia (MF) and 14 of 25 (52%) of those with chronic lymphatic obstruction (CP) (P=0.01 for comparison of EN to CP or to MF). This differential responsiveness suggests that the protective immunity postulated to account for their uninfected status might be associated with a response to this protein. When the utility of ALT-2 as a vaccine candidate was tested in a murine model using either recombinant protein or a DNA vaccine construct, statistically significant protection was observed when compared to a control filarial gene product expressed across all stages of the parasite lifecycle (SXP-1; P=0.02 for protein and P=0.01 for the DNA vaccine) or compared to adjuvant alone. This level of protection indicates that this vaccine is a promising candidate for further development.

  6. Telomeric overhang length determines structural dynamics and accessibility to telomerase and ALT associated proteins

    PubMed Central

    Hwang, Helen; Kreig, Alex; Calvert, Jacob; Lormand, Justin; Kwon, Yongho; Daley, James M.; Sung, Patrick; Opresko, Patricia L.; Myong, Sua

    2014-01-01

    The G-rich single stranded DNA at the 3′ end of human telomeres can self-fold into G-quaduplex (GQ). However, telomere lengthening by telomerase or the recombination-based alternative lengthening of telomere (ALT) mechanism requires protein loading on the overhang. Using single molecule fluorescence spectroscopy we discovered that lengthening the telomeric overhang also increased the rate of dynamic exchanges between structural conformations. Overhangs with five to seven TTAGGG repeats, compared to four repeats, showed much greater dynamics and accessibility to telomerase binding and activity, and loading of the ALT-associated proteins RAD51, WRN and BLM. Although the eight repeats are highly dynamic, they can fold into two GQs, which limited protein accessibility. In contrast, the telomere-specific protein, POT1 is unique in that it binds independently of repeat number. Our results suggest that the telomeric overhang length and dynamics may contribute to the regulation of telomere extension via telomerase action and the ALT mechanism. PMID:24836024

  7. Alternative Liquid Fuels Simulation Model (AltSim) v. 2.0

    SciTech Connect

    Baker, Arnold; Thomas, Drennan; Williams, Ryan

    2010-02-24

    The Alternative Liquid Fuels Simulation Model (AltSim) is a high-level dynamic simulation model which calculates and compares the production and end use costs, energy balances, and greenhouse gas emissions for several alternative liquid transportation fuels. These fuels include: corn ethanol, cellulosic ethanol from various feedstocks, biodiesel, and diesels derived from natural gas (gas to liquid, or GTL), coal (coal to liquid, or CTL), and coal with biomass (CBTL). AltSim allows for comprehensive sensitivity analyses on capital costs, operation and maintenance costs, renewable and fossil fuel feedstock costs, feedstock conversion efficiency, financial assumptions, tax credits, CO2 taxes, and plant capacity factor. AltSim also includes policy tools to allow for consideration of greenhouse gas offset policies, production tax credits, and land use requirements. The main goal is to allow interested stakeholders to understand the complicated economic and environmental tradeoffs associated with the various options. The software is designed to address policy questions related to the economic competitiveness of technologies under different economic and technical assumptions. This model will be used to inform policy makers and staff about the economic and environmental tradeoffs associated with various fuel alternatives.

  8. Development of PCR-based codominant markers flanking the Alt3 gene in rye.

    PubMed

    Miftahudin; Scoles, G J; Gustafson, J P

    2004-04-01

    Aluminum (Al) toxicity is considered to be a major problem for crop growth and production on acid soils. The ability of crops to overcome Al toxicity varies among crop species and cultivars. Rye (Secale cereale L.) is the most Al-tolerant species among the Triticeae. Our previous study showed that Al tolerance in a rye F6 recombinant inbred line (RIL) population was controlled by a single gene designated as the aluminum tolerance (Alt3) gene on chromosome 4RL. Based on the DNA sequence of a rice (Oryza sativa L.) BAC clone suspected to be syntenic to the Alt3 gene region, we developed two PCR-based codominant markers flanking the gene. These two markers, a sequence-tagged site (STS) marker and a cleaved amplified polymorphic sequence (CAPS) marker, each flanked the Alt3 gene at an approximate distance of 0.4 cM and can be used to facilitate high-resolution mapping of the gene. The markers might also be used for marker-assisted selection in rye or wheat (Triticum aestivum L.) breeding programs to obtain Al-tolerant lines and (or) cultivars.

  9. Twist-3 fragmentation effects for ALT in light hadron production from proton-proton collisions

    DOE PAGES

    Koike, Y.; Pitonyak, D.; Takagi, Y.; ...

    2015-11-11

    Here, we compute the contribution from the twist-3 fragmentation function for light hadron production in collisions between transversely and longitudinally polarized protons, i.e., View the MathML sourcep↑p→→hX, which can cause a double-spin asymmetry (DSA) ALT. This is a naïve T-even twist-3 observable that we analyze in collinear factorization using both Feynman gauge and lightcone gauge as well as give a general proof of color gauge invariance. So far only twist-3 effects in the transversely polarized proton have been studied for ALT in p↑p→→hX. However, there are indications that the naïve T-odd transverse single-spin asymmetry (SSA) AN in p↑p→hX is dominatedmore » not by such distribution effects but rather by a fragmentation mechanism. Therefore, one may expect similarly that the fragmentation contribution is important for ALT. As a result, given possible plans at RHIC to measure this observable, it is timely to provide a calculation of this term.« less

  10. The Alt-Az Initiative for Lightweight Research Telescopes: Scientific Research Programs and Engineering Developments

    NASA Astrophysics Data System (ADS)

    Genet, Russell M.

    2009-05-01

    The Alt-Az Initiative is a catalyst for the development of low cost, lightweight, modest aperture (2 meters and less) alt-az research telescopes. Such telescopes, especially when automated and networked, can be cost-effective tools for dedicated research programs including low and high resolution fiber fed spectroscopy as well as optical, near infrared, and high speed photometry. To date, six two-day workshops and two full conferences have been held. Nearly a dozen technical initiatives have been completed or are underway. These include optical designs, lightweight mirrors, active primary mirror controls, and direct drive motors and controllers. One low cost, lightweight, technical demonstration telescope with lightweight mirrors, a lightweight structure, and direct drives has been completed. Future technical initiatives and technical demonstration telescopes are outlined. A 39-chapter book, Galileo's Legacy: Small Telescopes and Astronomical Research, based on these meetings, initiatives, and the demonstration telescope, is in final editing. A web site, www.AltAzInitiative.org provides details, references, and links.

  11. Absolute quantification of serum microRNA-122 and its correlation with liver inflammation grade and serum alanine aminotransferase in chronic hepatitis C patients.

    PubMed

    Wang, Jiang-hua; Jiang, Dong; Rao, Hui-yng; Zhao, Jing-min; Wang, Yu; Wei, Lai

    2015-01-01

    MicroRNA-122 has been shown to be crucial for efficient HCV RNA replication in vitro. Pretreatment intrahepatic microRNA-122 levels in chronic hepatitis C (CHC) patients have been associated with the outcomes of interferon therapy. Here, we determined microRNA-122 serum levels in CHC patients and healthy donors using an absolute quantification approach and evaluated the correlation with liver inflammation grades and serum alanine aminotransferase (ALT) levels. Serum samples were collected from 105 treatment-naive CHC patients, 11 acute hepatitis patients, and 33 healthy donors. Serum microRNA-122 was measured using the TaqMan RT-qPCR. The cycle threshold values were converted to copy numbers by drawing a standard curve using a chemical synthetic standard. For accurate quantification, copy numbers were further normalized according to the recovery ratios of spiked-in cel-miR-39. Serum levels of microRNA-122 were significantly higher in acute hepatitis and CHC patients than in healthy donors (p<0.001). However, there was no significant association between microRNA-122 and ALT serum levels or liver inflammation grades. The present study showed that serum microRNA-122 was elevated in acute and chronic hepatitis patients. However, this biomarker for acute liver injury did not reflect the liver inflammation activity in CHC patients. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Therapeutic effect of combination of alagebrium (ALT-711) and sildenafil on erectile function in diabetic rats.

    PubMed

    Gurbuz, N; Sagdic, G; Sanli, A; Ciftcioglu, A; Bassorgun, I; Baykal, A; Usta, M F

    2012-01-01

    Recently, the relationship between advanced glycation end products (AGEs) and erectile dysfunction (ED) has been reported. The present study aimed to investigate whether a combination of an AGE cross-link breaker (alagebrium/ALT-711) and sildenafil could enhance the erectile capacity in streptozotocin (STZ) diabetic rats. Additionally, we assessed the effect of that treatment option on some molecules that have been suggested to have crucial roles in AGE-related ED pathways. Four groups of animals were utilized: (1) age-matched control rats, (2) STZ-induced diabetic rats (40 mg kg(-1) i.p.), (3) STZ rats+sildenafil (5 mg kg(-1) p.o.), (4) STZ rats treated with a combination of sildenafil (5 mg kg(-1) p.o)+alagebrium/ALT-711 (10 mg kg(-1) p.o.) for the final 1 month of the 2 months of diabetes period. At 2 months after i.p. injection of STZ, all animals underwent cavernosal nerve stimulation (CNS) to assess erectile function. Penile tissue AGEs, MDA (malondialdehyde), cyclic guanosine monophosphate (cGMP) (ELISA), endothelial nitric oxide (NO) synthase (eNOS), inducible NO synthase (iNOS) (western blot), nuclear factor (NF)-κB, mitogen-activated protein (MAP) kinase (immunohistochemistry) and apoptosis (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling) analyses were performed in all groups of rats. STZ diabetic rats had a significant decrease in erectile function as determined by the peak intracavernosal pressure (ICP) and total ICP (area under the erectile curve) after CNS when compared with control rats (P<0.05). The increase in both ICP and area under the erectile curve of STZ diabetic rats treated with a combination of sildenafil+alagebrium/ALT-711 as well as in STZ diabetic rats treated with sildenafil alone was significantly greater than STZ diabetic rats. Additionally, combination treatment decreased AGE, MDA, iNOS, NF-κB, MAP kinase and apoptosis levels, whereas it preserved cGMP contents in diabetic penile tissue

  13. RNaseH1 regulates TERRA-telomeric DNA hybrids and telomere maintenance in ALT tumour cells.

    PubMed

    Arora, Rajika; Lee, Yongwoo; Wischnewski, Harry; Brun, Catherine M; Schwarz, Tobias; Azzalin, Claus M

    2014-10-21

    A fraction of cancer cells maintain telomeres through the telomerase-independent, 'Alternative Lengthening of Telomeres' (ALT) pathway. ALT relies on homologous recombination (HR) between telomeric sequences; yet, what makes ALT telomeres recombinogenic remains unclear. Here we show that the RNA endonuclease RNaseH1 regulates the levels of RNA-DNA hybrids between telomeric DNA and the long noncoding RNA TERRA, and is a key mediator of telomere maintenance in ALT cells. RNaseH1 associated to telomeres specifically in ALT cells and its depletion led to telomeric hybrid accumulation, exposure of single-stranded telomeric DNA, activation of replication protein A at telomeres and abrupt telomere excision. Conversely, overexpression of RNaseH1 weakened the recombinogenic nature of ALT telomeres and led to telomere shortening. Altering cellular RNaseH1 levels did not perturb telomere homoeostasis in telomerase-positive cells. RNaseH1 maintains regulated levels of telomeric RNA-DNA hybrids at ALT telomeres to trigger HR without compromising telomere integrity too severely.

  14. Modest weight loss and physical activity in overweight patients with chronic liver disease results in sustained improvements in alanine aminotransferase, fasting insulin, and quality of life.

    PubMed

    Hickman, I J; Jonsson, J R; Prins, J B; Ash, S; Purdie, D M; Clouston, A D; Powell, E E

    2004-03-01

    Obesity is a risk factor for progression of fibrosis in chronic liver diseases such as non-alcoholic fatty liver disease and hepatitis C. The aim of this study was to investigate the longer term effect of weight loss on liver biochemistry, serum insulin levels, and quality of life in overweight patients with liver disease and the effect of subsequent weight maintenance or regain. Thirty one patients completed a 15 month diet and exercise intervention. On completion of the intervention, 21 patients (68%) had achieved and maintained weight loss with a mean reduction of 9.4 (4.0)% body weight. Improvements in serum alanine aminotransferase (ALT) levels were correlated with the amount of weight loss (r = 0.35, p = 0.04). In patients who maintained weight loss, mean ALT levels at 15 months remained significantly lower than values at enrollment (p = 0.004), while in regainers (n = 10), mean ALT levels at 15 months were no different to values at enrollment (p = 0.79). Improvements in fasting serum insulin levels were also correlated with weight loss (r = 0.46, p = 0.04), and subsequent weight maintenance sustained this improvement. Quality of life was significantly improved after weight loss. Weight maintainers sustained recommended levels of physical activity and had higher fasting insulin levels (p = 0.03) at enrollment than weight regainers. In summary, these findings demonstrate that maintenance of weight loss and exercise in overweight patients with liver disease results in a sustained improvement in liver enzymes, serum insulin levels, and quality of life. Treatment of overweight patients should form an important component of the management of those with chronic liver disease.

  15. Protective Effect of Hericium erinaceus on Alcohol Induced Hepatotoxicity in Mice

    PubMed Central

    Hao, Lijun; Xie, Yuxi; Wu, Guikai; Cheng, Aibin; Liu, Xiaogang; Zheng, Rongjuan; Huo, Hong; Zhang, Junwei

    2015-01-01

    We investigated the effects of Hericium erinaceus (HEM) on liver injury induced by acute alcohol administration in mice. Mice received ethanol (5 g/kg BW) by gavage every 12 hrs for a total of 3 doses. HEM (200 mg/kg BW) was gavage before ethanol administration. Subsequent serum alanine aminotransferase (ALT) level, aspartate aminotransaminase (AST) level, Maleic dialdehyde (MDA) level, hepatic total antioxidant status (TAOS), and activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were determined by ELISA and immunohistochemistry, respectively. HEM administration markedly (P < 0.05) decreased serum ALT, AST, and MDA levels. The hepatic histopathological observations showed that HEM had a relatively significant role in mice model, which had alcoholic liver damage. In conclusion, we observed that HEM (200 mg/kg BW) supplementation could restrain the hepatic damage caused by acute alcohol exposure. PMID:25960751

  16. Targeting the aluminum tolerance gene Alt3 region in rye, using rice/rye micro-colinearity.

    PubMed

    Miftahudin; Chikmawati, T; Ross, K; Scoles, G J; Gustafson, J P

    2005-03-01

    Characterization and manipulation of aluminum (Al) tolerance genes offers a solution to Al toxicity problems in crop cultivation on acid soil, which composes approximately 40% of all arable land. By exploiting the rice (Oryza sativa L.)/rye (Secale cereale L.) syntenic relationship, the potential for map-based cloning of genes controlling Al tolerance in rye (the most Al-tolerant cereal) was explored. An attempt to clone an Al tolerance gene (Alt3) from rye was initiated by using DNA markers flanking the rye Alt3 gene, from many cereals. Two rice-derived, PCR-based markers flanking the Alt3 gene, B1 and B4, were used to screen 1,123 plants of a rye F2 population segregating for Alt3. Fifteen recombinant plants were identified. Four additional RFLP markers developed from rice genes/putative genes, spanning 10 kb of a 160-kb rice BAC, were mapped to the Alt3 region. Two rice markers flanked the Alt3 locus at a distance of 0.05 cM, while two others co-segregated with it. The rice/rye micro-colinearity worked very well to delineate and map the Alt3 gene region in rye. A rye fragment suspected to be part of the Alt3 candidate gene was identified, but at this level, the rye/rice microsynteny relationship broke down. Because of sequence differences between rice and rye and the complexity of the rye sequence, we have been unable to clone a full-length candidate gene in rye. Further attempts to clone a full-length rye Alt3 candidate gene will necessitate the creation of a rye large-insert library.

  17. Comparison of the super agonist complex, ALT-803, to IL-15 as cancer immunotherapeutics in animal models

    PubMed Central

    Xu, Wenxin; Hong, Hao; Webb, Gabriela M.; Chen, Xiaoyue; Liu, Bai; Zhu, Xiaoyun; Wen, Jinghai; You, Lijing; Kong, Lin; Edwards, Ana C.; Han, Kaiping; Shi, Sixiang; Alter, Sarah; Sacha, Jonah B.; Jeng, Emily K.; Cai, Weibo; Wong, Hing C.

    2015-01-01

    Interleukin-15 (IL-15), a potent stimulant of CD8+ T and NK cells, is a promising cancer immunotherapeutic. ALT-803 is a complex of an IL-15 superagonist mutant and a dimeric IL-15 receptor αSu/Fc fusion protein that was found to exhibit enhanced biologic activity in vivo with a substantially longer serum half-life than recombinant IL-15. A single intravenous dose of ALT-803, but not IL-15, eliminated well-established tumors and prolonged survival of mice bearing multiple myeloma. In this study, we extended these findings to demonstrate the superior antitumor activity of ALT-803 over IL-15 in mice bearing subcutaneous B16F10 melanoma tumors and CT26 colon carcinoma metastases. Tissue biodistribution studies in mice also showed much greater retention of ALT-803 in the lymphoid organs compared to IL-15, consistent with its highly potent immunostimulatory and antitumor activities in vivo. Weekly dosing with 1 mg/kg ALT-803 in C57BL/6 mice was well-tolerated, yet capable of increasing peripheral blood lymphocyte, neutrophil and monocyte counts by >8-fold. ALT-803 dose-dependent stimulation of immune cell infiltration into the lymphoid organs was also observed. Similarly, cynomolgus monkeys treated weekly with ALT-803 showed dose-dependent increases of peripheral blood lymphocyte counts, including NK, CD4+, and CD8+ memory T cell subsets. In vitro studies demonstrated ALT-803-mediated stimulation of mouse and human immune cell proliferation and IFN-γ production without inducing a broad-based release of other proinflammatory cytokines (i.e., cytokine storm). Based on these results, a weekly dosing regimen of ALT-803 has been implemented in multiple clinical studies to evaluate the dose required for effective immune cell stimulation in humans. PMID:26511282

  18. Alanine Racemase Mutants of Burkholderia pseudomallei and Burkholderia mallei and Use of Alanine Racemase as a Non-Antibiotic-Based Selectable Marker

    PubMed Central

    Zajdowicz, Sheryl L. W.; Jones-Carson, Jessica; Vazquez-Torres, Andres; Jobling, Michael G.; Gill, Ronald E.; Holmes, Randall K.

    2011-01-01

    Burkholderia pseudomallei and Burkholderia mallei are category B select agents and must be studied under BSL3 containment in the United States. They are typically resistant to multiple antibiotics, and the antibiotics used to treat B. pseudomallei or B. mallei infections may not be used as selective agents with the corresponding Burkholderia species. Here, we investigated alanine racemase deficient mutants of B. pseudomallei and B. mallei for development of non-antibiotic-based genetic selection methods and for attenuation of virulence. The genome of B. pseudomallei K96243 has two annotated alanine racemase genes (bpsl2179 and bpss0711), and B. mallei ATCC 23344 has one (bma1575). Each of these genes encodes a functional enzyme that can complement the alanine racemase deficiency of Escherichia coli strain ALA1. Herein, we show that B. pseudomallei with in-frame deletions in both bpsl2179 and bpss0711, or B. mallei with an in-frame deletion in bma1575, requires exogenous d-alanine for growth. Introduction of bpsl2179 on a multicopy plasmid into alanine racemase deficient variants of either Burkholderia species eliminated the requirement for d-alanine. During log phase growth without d-alanine, the viable counts of alanine racemase deficient mutants of B. pseudomallei and B. mallei decreased within 2 hours by about 1000-fold and 10-fold, respectively, and no viable bacteria were present at 24 hours. We constructed several genetic tools with bpsl2179 as a selectable genetic marker, and we used them without any antibiotic selection to construct an in-frame ΔflgK mutant in the alanine racemase deficient variant of B. pseudomallei K96243. In murine peritoneal macrophages, wild type B. mallei ATCC 23344 was killed much more rapidly than wild type B. pseudomallei K96243. In addition, the alanine racemase deficient mutant of B. pseudomallei K96243 exhibited attenuation versus its isogenic parental strain with respect to growth and survival in murine peritoneal macrophages

  19. Alanine racemase mutants of Burkholderia pseudomallei and Burkholderia mallei and use of alanine racemase as a non-antibiotic-based selectable marker.

    PubMed

    Zajdowicz, Sheryl L W; Jones-Carson, Jessica; Vazquez-Torres, Andres; Jobling, Michael G; Gill, Ronald E; Holmes, Randall K

    2011-01-01

    Burkholderia pseudomallei and Burkholderia mallei are category B select agents and must be studied under BSL3 containment in the United States. They are typically resistant to multiple antibiotics, and the antibiotics used to treat B. pseudomallei or B. mallei infections may not be used as selective agents with the corresponding Burkholderia species. Here, we investigated alanine racemase deficient mutants of B. pseudomallei and B. mallei for development of non-antibiotic-based genetic selection methods and for attenuation of virulence. The genome of B. pseudomallei K96243 has two annotated alanine racemase genes (bpsl2179 and bpss0711), and B. mallei ATCC 23344 has one (bma1575). Each of these genes encodes a functional enzyme that can complement the alanine racemase deficiency of Escherichia coli strain ALA1. Herein, we show that B. pseudomallei with in-frame deletions in both bpsl2179 and bpss0711, or B. mallei with an in-frame deletion in bma1575, requires exogenous D-alanine for growth. Introduction of bpsl2179 on a multicopy plasmid into alanine racemase deficient variants of either Burkholderia species eliminated the requirement for D-alanine. During log phase growth without D-alanine, the viable counts of alanine racemase deficient mutants of B. pseudomallei and B. mallei decreased within 2 hours by about 1000-fold and 10-fold, respectively, and no viable bacteria were present at 24 hours. We constructed several genetic tools with bpsl2179 as a selectable genetic marker, and we used them without any antibiotic selection to construct an in-frame ΔflgK mutant in the alanine racemase deficient variant of B. pseudomallei K96243. In murine peritoneal macrophages, wild type B. mallei ATCC 23344 was killed much more rapidly than wild type B. pseudomallei K96243. In addition, the alanine racemase deficient mutant of B. pseudomallei K96243 exhibited attenuation versus its isogenic parental strain with respect to growth and survival in murine peritoneal macrophages.

  20. Prevalence, knowledge and attitudes relating to β-alanine use among professional footballers.

    PubMed

    Kelly, Vincent G; Leveritt, Michael D; Brennan, Christopher T; Slater, Gary J; Jenkins, David G

    2017-01-01

    To investigate β-alanine supplementation use and level of knowledge amongst professional footballers. Cross-sectional survey of Australian professional football players. Questionnaires assessing β-alanine supplementation behaviours, level of knowledge and sources of information were completed by professional rugby union (RU) (n=87), rugby league (RL) (n=180) and Australian Rules Football (ARF) (n=303) players. Approximately 61% of athletes reported β-alanine use, however use by ARF football players (44%) was lower than that of RU (80%) and RL players (80%). The majority of respondents were not using β-alanine in accordance with recommendations. Only 35% of the participants were able to correctly identify the potential benefits of β-alanine supplementation. The main information sources that influenced players' decision to use β-alanine were strength and conditioning coach (71%) and dietitian (52%). Forty-eight per cent of athletes never read labels prior to supplementing and only 11% completed their own research on β-alanine. Compared to RL and ARF players, RU players had both a greater knowledge of β-alanine supplementation and better supplementation practices. Despite over half the surveyed professional footballers using β-alanine, the majority of athletes used β-alanine in a manner inconsistent with recommendations. A better understanding of the environment and culture within professional football codes is required before supplement use becomes consistent with evidence based supplement recommendations. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  1. The effect of immunonutrition (glutamine, alanine) on fracture healing

    PubMed Central

    Küçükalp, Abdullah; Durak, Kemal; Bayyurt, Sarp; Sönmez, Gürsel; Bilgen, Muhammed S.

    2014-01-01

    Background There have been various studies related to fracture healing. Glutamine is an amino acid with an important role in many cell and organ functions. This study aimed to make a clinical, radiological, and histopathological evaluation of the effects of glutamine on fracture healing. Methods Twenty rabbits were randomly allocated into two groups of control and immunonutrition. A fracture of the fibula was made to the right hind leg. All rabbits received standard food and water. From post-operative first day for 30 days, the study group received an additional 2 ml/kg/day 20% L-alanine L-glutamine solution via a gastric catheter, and the control group received 2 ml/kg/day isotonic via gastric catheter. At the end of 30 days, the rabbits were sacrificed and the fractures were examined clinically, radiologically, and histopathologically in respect to the degree of union. Results Radiological evaluation of the control group determined a mean score of 2.5 according to the orthopaedists and 2.65 according to the radiologists. In the clinical evaluation, the mean score was 1.875 for the control group and 2.0 for the study group. Histopathological evaluation determined a mean score of 8.5 for the control group and 9.0 for the study group. Conclusion One month after orally administered glutamine–alanine, positive effects were observed on fracture healing radiologically, clinically, and histopathologically, although no statistically significant difference was determined.

  2. Thermodynamics of Deca-alanine Folding in Water.

    PubMed

    Hazel, Anthony; Chipot, Christophe; Gumbart, James C

    2014-07-08

    The determination of the folding dynamics of polypeptides and proteins is critical in characterizing their functions in biological systems. Numerous computational models and methods have been developed for studying structure formation at the atomic level. Due to its small size and simple structure, deca-alanine is used as a model system in molecular dynamics (MD) simulations. The free energy of unfolding in vacuum has been studied extensively using the end-to-end distance of the peptide as the reaction coordinate. However, few studies have been conducted in the presence of explicit solvent. Previous results show a significant decrease in the free energy of extended conformations in water, but the α-helical state is still notably favored over the extended state. Although sufficient in vacuum, we show that end-to-end distance is incapable of capturing the full complexity of deca-alanine folding in water. Using α-helical content as a second reaction coordinate, we deduce a more descriptive free-energy landscape, one which reveals a second energy minimum in the extended conformations that is of comparable free energy to the α-helical state. Equilibrium simulations demonstrate the relative stability of the extended and α-helical states in water as well as the transition between the two states. This work reveals both the necessity and challenge of determining a proper reaction coordinate to fully characterize a given process.

  3. Formation of chloroform during chlorination of alanine in drinking water.

    PubMed

    Chu, Wen-Hai; Gao, Nai-Yun; Deng, Yang; Dong, Bing-Zhi

    2009-11-01

    Currently, dissolved nitrogenous organic matters in water, important precursors of disinfection by-products (DBPs), are of significant concern. This study was to explore the formation of chloroform (CF) during chlorination of alanine (Ala), an important nitrogenous organic compound commonly present in water sources. Our results indicated that the CF yield reached a maximum value of 0.143% at the molar ratio of chlorine atom to nitrogen atom (Cl/N)=1.0 over a Cl/N range of 0.2-5.0 (pH=7.0, reaction time=5d, and initial Ala=0.1mM). At an acidic-neutral condition (pH 4-7), the formation of CF was suppressed. However, the highest CF yield (0.227%) occurred at weakly alkaline condition (pH 8.0) (initial Ala=0.1mM, and Cl/N=1.0). The increase of Br(-) in water can increase total trihalomethanes (THMs) and bromo-THMs. However, the bromo-THMs level reached a plateau at Br(-)/Cl>0.04. Finally, based on the computation of frontier electron density and identification and measurement of key intermediates during Ala chlorination, we proposed a formation pathway of CF from Ala chlorination: Ala-->monochloro-N-alanine (MC-N-Ala)-->acetaldehyde (AAld)-->monochloroacetaldehyde acetaldehyde (MCAld)-->dichloroacetaldehyde (DCAld)-->trichloroacetaldehyde (TCAld)-->CF.

  4. Dorsal foot resurfacing using free anterolateral thigh (ALT) flap in children.

    PubMed

    El-Gammal, Tarek A; El-Sayed, Amr; Kotb, Mohamed M; Saleh, Waleed Riad; Ragheb, Yasser Farouk; El-Refai, Omar; El Fahar, Mohammed Hassan Ali

    2013-05-01

    Very limited literature described the use of the free anterolateral thigh (ALT) among other flaps for pediatric lower limb reconstruction. The aim of this study is to present our experience using the free ALT flap for reconstruction of soft tissue defects over the dorsum of the foot and ankle in children. The study included 42 children aged 2.5-13 years with a mean of 6.18 years. Three children had crush injuries while the rest were victims of run over car accidents. All of the flaps were vascularized by at least two perforators; 88.23% were musculocutaneous and 11.77 were septocutaneous perforators. All flaps were raised in a subfascial plane. Initial thinning was performed in five flaps and 35% required subsequent debulking. Mean Flap surface area was 117.11 cm(2). The recipient arteries were the anterior tibial artery in 38 cases and posterior tibial artery in four cases. Venous anastomosis was performed to one vena commitant and in nine cases the long saphenous vein was additionally used. Mean ischemia time of the flap was 2 hours while total operative time averaged 6.3 hours. About 41% of donor sites were closed primarily while 59% required skin grafting. Primary flap survival rate was 92.8% (39/42 cases). Three flaps showed venous congestion. After venous reanastomosis, two flaps showed partial loss and one flap was lost completely. Post-operative hospital stay averaged 7.5 days. The free ALT flap could be as safe, reliable, and aesthetically appealing option for foot/ankle resurfacing in children after traumatic soft tissue loss.

  5. Serum ALT levels as a surrogate marker for serum HBV DNA levels in HBeAg-negative pregnant women.

    PubMed

    Sangfelt, Per; Von Sydow, Madeleine; Uhnoo, Ingrid; Weiland, Ola; Lindh, Gudrun; Fischler, Björn; Lindgren, Susanne; Reichard, Olle

    2004-01-01

    In Stockholm, Sweden, the majority of pregnant women positive for hepatitis B surface antigen (HBsAg) are hepatitis Be antigen (HBeAg) negative. Newborns to HBeAg positive mothers receive vaccination and hepatitis B immunoglobulin (HBIg). Newborns to HBeAg negative mothers receive vaccine and HBIg only if the mothers have elevated ALT levels. The aim of this study was to retrospectively evaluate ALT levels as a surrogate marker for HBV DNA levels in HBeAg negative carrier mothers. Altogether 8947 pregnant women were screened for HBV markers from 1999 to 2001 at the Virology Department, Karolinska Hospital. Among mothers screened 192 tested positive for HBsAg (2.2%). 13 of these samples could not be retrieved. Of the remaining 179 sera, 8 (4%) tested positive for HBeAg and 171 (95.5%) were HBeAg negative. Among the HBeAg negative mothers, 9 had HBV DNA levels > 10(5) copies/ml, and of these 7 had normal ALT levels indicating low sensitivity of an elevated ALT level as a surrogate marker for high HBV DNA level. Furthermore, no correlation was found between ALT and HBV DNA levels. Hence, it is concluded that the use of ALT as a surrogate marker for high viral replication in HBeAg negative mothers could be questioned.

  6. Expression, crystallization and preliminary X-ray crystallographic analysis of Xoo0352, D-alanine-D-alanine ligase A, from Xanthomonas oryzae pv. oryzae.

    PubMed

    Doan, Thanh Thi Ngoc; Kim, Jin-Kwang; Kim, Hyesoon; Ahn, Yeh-Jin; Kim, Jeong-Gu; Lee, Byoung-Moo; Kang, Lin-Woo

    2008-12-01

    Xanthomonas oryzae pv. oryzae (Xoo) causes bacterial blight (BB), which is one of the most devastating diseases of rice in most rice-growing countries. D-Alanine-D-alanine ligase A (DdlA), coded by the Xoo0352 gene, was expressed, purified and crystallized. DdlA is an enzyme that is involved in D-alanine metabolism and the biosynthesis of an essential bacterial peptidoglycan precursor, in which it catalyzes the formation of D-alanyl-D-alanine from two D-alanines, and is thus an attractive antibacterial drug target against Xoo. The DdlA crystals diffracted to 2.3 A resolution and belonged to the primitive tetragonal space group P4(3)2(1)2, with unit-cell parameters a = b = 83.0, c = 97.6 A. There is one molecule in the asymmetric unit, with a corresponding V(M) of 1.88 A(3) Da(-1) and a solvent content of 34.6%. The initial structure was determined by molecular replacement using D-alanine-D-alanine ligase from Staphylococcus aureus (PDB code 2i87) as a template model.

  7. The Helical Alanine Controversy: An (Ala)6 Insertion Dramatically Increases Helicity

    PubMed Central

    Lin, Jasper C.; Barua, Bipasha

    2013-01-01

    Employing chemical shift melts and hydrogen/deuterium exchange NMR techniques, we have determined the stabilization of the Trp-cage miniprotein due to multiple alanine insertions within the N-terminal α-helix. Alanine is shown to be uniquely helix-stabilizing and this stabilization is reflected in the global fold stability of the Trp-cage. The associated free energy change per alanine can be utilized to calculate the alanine propagation value. From the Lifson–Roig formulation, the calculated value (wAla = 1.6) is comparable to those obtained for short, solubilized, alanine-rich helices and is much larger than the values obtained by prior host–guest techniques or in N-terminally templated helices and peptides bearing long contiguous strings of alanines with no capping or solubilizing units present. PMID:15493925

  8. Involvement of alanine racemase in germination of Bacillus cereus spores lacking an intact exosporium.

    PubMed

    Venir, Elena; Del Torre, Manuela; Cunsolo, Vincenzo; Saletti, Rosaria; Musetti, Rita; Stecchini, Mara Lucia

    2014-02-01

    The L-alanine mediated germination of food isolated Bacillus cereus DSA 1 spores, which lacked an intact exosporium, increased in the presence of D-cycloserine (DCS), which is an alanine racemase (Alr) inhibitor, reflecting the activity of the Alr enzyme, capable of converting L-alanine to the germination inhibitor D-alanine. Proteomic analysis of the alkaline extracts of the spore proteins, which include exosporium and coat proteins, confirmed that Alr was present in the B. cereus DSA 1 spores and matched to that encoded by B. cereus ATCC 14579, whose spore germination was strongly affected by the block of conversion of L- to D-alanine. Unlike ATCC 14579 spores, L-alanine germination of B. cereus DSA 1 spores was not affected by the preincubation with DCS, suggesting a lack of restriction in the reactant accessibility.

  9. The helical alanine controversy: an (Ala)6 insertion dramatically increases helicity.

    PubMed

    Lin, Jasper C; Barua, Bipasha; Andersen, Niels H

    2004-10-27

    Employing chemical shift melts and hydrogen/deuterium exchange NMR techniques, we have determined the stabilization of the Trp-cage miniprotein due to multiple alanine insertions within the N-terminal alpha-helix. Alanine is shown to be uniquely helix-stabilizing and this stabilization is reflected in the global fold stability of the Trp-cage. The associated free energy change per alanine can be utilized to calculate the alanine propagation value. From the Lifson-Roig formulation, the calculated value (wAla = 1.6) is comparable to those obtained for short, solubilized, alanine-rich helices and is much larger than the values obtained by prior host-guest techniques or in N-terminally templated helices and peptides bearing long contiguous strings of alanines with no capping or solubilizing units present. Copyright 2004 American Chemical Society

  10. Clinicopathological studies of gastrointestinal tract disorders in sheep with parasitic infection

    PubMed Central

    Kumar, Sarvan; Jakhar, K. K.; Singh, Satyavir; Potliya, Sandeep; Kumar, Kailash; Pal, Madan

    2015-01-01

    Aim: This study was envisaged to elucidate the parasitological aspects of gastrointestinal tract (GIT) disorders of sheep. Materials and Methods: Fecal, blood and serum samples collected from 31 sheep/lambs of Sheep Breeding Farm, Lala Lajpat Rai University of Veterinary & Animal Sciences, Hisar. Results: Of 25 cases, strongyle eggs (12 cases, 48%) were a major infection, followed by Strongyloides spp. (8 cases, 32%) and Moniezia spp. (5 case, 20%). In one case, massive infection of strongyle particularly Haemonchus contortus and Moniezia spp. was observed. All these animals were found negative for hemoprotozoan parasites in blood smear examination. Hematological studies revealed that significantly decreased values of hemoglobin (Hb), packed cell volume (PCV) and total erythrocytic count (TEC). Absolute leukocytic count revealed significant leukocytosis due to neutrophilia, lymphocytosis, monocytosis and eosinophilia. Serum biochemical profiles of diarrheic sheep/lambs in present study were significant decrease in values of total protein, serum globulin, glucose where as significant increase in the albumin: Globulin ratio, aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), alkaline phosphatise (ALKP) and bilirubin. Conclusions: From the present study, it is reasonable to conclude that major parasitic infection of sheep/lamb observed was strongyle, followed by Strongyloides spp. and Moniezia spp. Hemato-biochemical studies revealed significant leukocytosis and increase in AST, ALT, ALKP and bilirubin. PMID:27046991

  11. Hepatoprotective activity of Mammea africana ethanol stem bark extract

    PubMed Central

    Okokon, Jude Efiom; Bawo, Michael Burata; Mbagwu, Herbert Orji

    2016-01-01

    Objective: The stem bark of Mammea africana Sabine (Guttiferae), (M. africana) a common plant that has been traditionally used to treat various diseases and ailments was evaluated for hepatoprotective potentials against paracetamol-induced liver injury in rats. Materials and Methods: The hepatoprotective effect of the stem bark extract (30-90 mg/kg) was evaluated by the assay of liver function parameters, namely total and direct bilirubin, serum protein and albumin, total cholesterol, alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), and alkaline phosphatase activities (ALP), antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH) and histopathological study of the liver. Results: Administration of the stem bark extract caused a significant (p<0.05 – 0.001) dose-dependent reduction of high levels of liver enzymes (ALT, AST and ALP), total cholesterol, direct and total bilirubin as well as elevation of serum levels of total protein, albumin and antioxidant enzymes (SOD, CAT, GPx and GSH). Histology of the liver sections of extract and silymarin-treated animals showed reductions in the pathological features compared to the paracetamol-treated animals. The chemical pathological changes were consistent with histopathological observations suggesting marked hepatoprotective effect of the stem bark extract of M. africana. Conclusion: The results show that the stem bark extract of M. africana has hepatoprotective potential which may be due to its antioxidant activity. PMID:27222838

  12. Transaminase Activity Predicts Survival in Patients with Head and Neck Cancer

    PubMed Central

    Takenaka, Yukinori; Takemoto, Norihiko; Yasui, Toshimichi; Yamamoto, Yoshifumi; Uno, Atsuhiko; Miyabe, Haruka; Ashida, Naoki; Shimizu, Kotaro; Nakahara, Susumu; Hanamoto, Atshushi; Fukusumi, Takahito; Michiba, Takahiro; Cho, Hironori; Yamamoto, Masashi; Inohara, Hidenori

    2016-01-01

    Various serum biomarkers have been developed for predicting head and neck squamous cell carcinoma (HNSCC) prognosis. However, none of them have been proven to be clinically significant. A recent study reported that the ratio of aspartate aminotransaminase (AST) to alanine aminotransaminase (ALT) had a prognostic effect on non-metastatic cancers. This study aimed to examine the effect of the AST/ALT ratio on the survival of patients with HNSCC. Clinical data of 356 patients with locoregionally advanced HNSCC were collected. The effect of the AST/ALT ratio on overall survival was analyzed using a Cox proportional hazard model. Moreover, recursive partitioning analysis (RPA) was used to divide the patients into groups on the basis of the clinical stage and AST/ALT ratio. The prognostic ability of this grouping was validated using an independent data set (N = 167). The AST/ALT ratio ranged from 0.42 to 4.30 (median, 1.42) and was a prognostic factor for overall survival that was independent of age, primary sites, and tumor stage (hazard ratio: 1.36, confidence interval: 1.08−1.68, P = 0.010). RPA divided patients with stage IVA into the following two subgroups: high AST/ALT (≥2.3) and low AST/ALT (<2.3) subgroups. The 5-year survival rate for patients with stage III, stage IVA with a low AST/ALT ratio, stage IVA with a high AST/ALT ratio, and stage IVB were 64.8%, 49.2%, 28.6%, and 33.3%, respectively (p < 0.001). Compared with the low AST/ALT group, the adjusted hazard ratio for death was 2.17 for high AST/ALT group (confidence interval: 1.02–.22 P = 0.045). The AST/ALT ratio was demonstrated to be a prognostic factor of HNSCC. The ratio subdivided patients with stage IVA into low- and high-risk groups. Moreover, intensified treatment for the high-risk group may be considered. PMID:27732629

  13. Telomere extension by telomerase and ALT generates variant repeats by mechanistically distinct processes

    PubMed Central

    Lee, Michael; Hills, Mark; Conomos, Dimitri; Stutz, Michael D.; Dagg, Rebecca A.; Lau, Loretta M.S.; Reddel, Roger R.; Pickett, Hilda A.

    2014-01-01

    Telomeres are terminal repetitive DNA sequences on chromosomes, and are considered to comprise almost exclusively hexameric TTAGGG repeats. We have evaluated telomere sequence content in human cells using whole-genome sequencing followed by telomere read extraction in a panel of mortal cell strains and immortal cell lines. We identified a wide range of telomere variant repeats in human cells, and found evidence that variant repeats are generated by mechanistically distinct processes during telomerase- and ALT-mediated telomere lengthening. Telomerase-mediated telomere extension resulted in biased repeat synthesis of variant repeats that differed from the canonical sequence at positions 1 and 3, but not at positions 2, 4, 5 or 6. This indicates that telomerase is most likely an error-prone reverse transcriptase that misincorporates nucleotides at specific positions on the telomerase RNA template. In contrast, cell lines that use the ALT pathway contained a large range of variant repeats that varied greatly between lines. This is consistent with variant repeats spreading from proximal telomeric regions throughout telomeres in a stochastic manner by recombination-mediated templating of DNA synthesis. The presence of unexpectedly large numbers of variant repeats in cells utilizing either telomere maintenance mechanism suggests a conserved role for variant sequences at human telomeres. PMID:24225324

  14. Transient ALT activation protects human primary cells from chromosome instability induced by low chronic oxidative stress

    PubMed Central

    Coluzzi, Elisa; Buonsante, Rossella; Leone, Stefano; Asmar, Anthony J.; Miller, Kelley L.; Cimini, Daniela; Sgura, Antonella

    2017-01-01

    Cells are often subjected to the effect of reactive oxygen species (ROS) as a result of both intracellular metabolism and exposure to exogenous factors. ROS-dependent oxidative stress can induce 8-oxodG within the GGG triplet found in the G-rich human telomeric sequence (TTAGGG), making telomeres highly susceptible to ROS-induced oxidative damage. Telomeres are nucleoprotein complexes that protect the ends of linear chromosomes and their dysfunction is believed to affect a wide range of cellular and/or organismal processes. Acute oxidative stress was shown to affect telomere integrity, but how prolonged low level oxidative stress, which may be more physiologically relevant, affects telomeres is still poorly investigated. Here, we explored this issue by chronically exposing human primary fibroblasts to a low dose of hydrogen peroxide. We observed fluctuating changes in telomere length and fluctuations in the rates of chromosome instability phenotypes, such that when telomeres shortened, chromosome instability increased and when telomeres lengthened, chromosome instability decreased. We found that telomere length fluctuation is associated with transient activation of an alternative lengthening of telomere (ALT) pathway, but found no evidence of cell death, impaired proliferation, or cell cycle arrest, suggesting that ALT activation may prevent oxidative damage from reaching levels that threaten cell survival. PMID:28240303

  15. Cardiovascular and renal effects of a collagen cross-link breaker (ALT 711) in adult and aged spontaneously hypertensive rats.

    PubMed

    Susic, Dinko; Varagic, Jasmina; Ahn, Jwari; Frohlich, Edward D

    2004-04-01

    Increased formation of advanced glycosylation end-products on body proteins is a consequence of aging and leads to exaggerated collagen cross-linking eventually increasing cardiovascular stiffness. This study reports our initial inquires into the cardiovascular and renal effects of a cross-link breaker (ALT-711) in aged spontaneously hypertensive rats (SHR). The first experiment, in 45-week-old SHR, showed that (among four doses) the dose of 1 mg/kg/d of ALT-711 given for 4 months was most effective in reducing left ventricular and aortic mass indexes. ALT-711 also reduced left ventricular hydroxyproline concentration (5.8 +/- 0.2 v 5.1 +/- 0.3 mg/g in controls, P < .05); however, it did not affect systemic or regional hemodynamics. In older SHR, ALT-711 (1 mg/kg/d) reduced (P < .05) systolic pressure (tail-cuff) (from 203 +/- 3 mm Hg at outset to 187 +/- 3 mm Hg at 8 weeks). Systolic pressure remained unchanged in placebo-treated rats. In addition, left ventricular index (3.09 +/- 0.10 v 3.44 +/- 0.05 mg/g) and aortic mass index (1.54 +/- 0.04 v 1.74 +/- 0.05 mg/mm) were reduced by ALT-711. In the third experiment, 1-year-old SHR were given vehicle or ALT-711 (1 mg/kg/d) or placebo until natural death. After 3 months, ALT-711 markedly reduced urinary protein excretion (74.5 +/- 8.6 v 135.4 +/- 11.8 mg/24 h). Echocardiographic studies, performed at the outset and after 3 and 6 months, revealed two changed indexes. Left ventricular end-diastolic diameter increased more in control than in ALT rats, whereas E-wave deceleration time decreased more in control than in ALT rats. Therapy with ALT-711 exerted beneficial cardiovascular and renal effects in aged SHR, improving systolic pressure, left ventricular mass, geometry, and hydroxyproline content while reducing urinary protein excretion.

  16. AGE-breaker ALT-711 plus insulin could restore erectile function in streptozocin-induced type 1 diabetic rats.

    PubMed

    Wang, Lin; Tian, Wenjie; Uwais, Zaid; Li, Guangyong; Li, Huixi; Guan, Ruili; Gao, Zhezhu; Xin, Zhongcheng

    2014-06-01

    The interaction between advanced glycation end-products (AGEs) and its receptors for AGEs (RAGEs) elicits oxidative stress and mediates the development of erectile dysfunction (ED). ALT-711, an AGE cross-link breaker, has the therapeutic potential for ED but has been less intensively investigated. The aim of this study was to investigate the effects of an AGEs breaker 3-phenacyl-4,5-dimethylthiazolium chloride (ALT-711) plus insulin on erectile function in streptozocin (STZ)-induced type 1 diabetic rats. Fifty 8-week-old Sprague-Dawley rats were randomly distributed into five groups: normal control (C), diabetic (D), insulin-treated diabetic (D + I), ALT-711-treated diabetic (D + ALT-711) and insulin plus ALT-711-treated diabetic (D + I + ALT-711) rats. Diabetes was induced by a single intraperitoneal injection of STZ. Eight weeks after induction of diabetes, ALT-711 was administered by intraperitoneal injection. Two to six units of intermediate-acting insulin were utilized to achieve normal levels of glycemic control. After treatment for 6 weeks, erectile function was determined via measurement of intracavernous pressures (ICPs) following electrostimulation of the cavernous nerve. The deposition of AGEs, expression of RAGEs, superoxide dismutase activity, and lipid peroxidation were measured. We also evaluated penile histological changes such as smooth muscle contents, endothelial cells contents, and apoptotic activity. The main outcome measures were the ratio of ICP/mean arterial pressure (MAP), penile endothelial cells, smooth muscle cells, neuronal nitric oxide synthase, AGE and RAGE expression, malondialdehyde concentration, SOD activity, and apoptosis index. Diabetic rats demonstrated significantly reduced ICP/MAP ratio, penile endothelial cells, smooth muscles cells, increased AGEs and RAGE expression, and increased apoptosis. Insulin and ALT-711 monotherapy partially restored erectile function and histological changes. However, the

  17. Radiolysis of alanine adsorbed in a clay mineral

    SciTech Connect

    Aguilar-Ovando, Ellen Y.; Negron-Mendoza, Alicia

    2013-07-03

    Optical activity in molecules is a chemical characteristic of living beings. In this work, we examine the hypothesis of the influence of different mineral surfaces on the development of a specific chirality in organic molecules when subjected to conditions simulating the primitive Earth during the period of chemical evolution. By using X-ray diffraction techniques and HPLC/ELSD to analyze aqueous suspensions of amino acids adsorbed on minerals irradiated in different doses with a cobalt-60 gamma source, the experiments attempt to prove the hypothesis that some solid surfaces (like clays and meteorite rocks) may have a concentration capacity and protective role against external sources of ionizing radiation (specifically {gamma}-ray) for some organic compounds (like some amino acids) adsorbed on them. Preliminary results show a slight difference in the adsorption and radiolysis of the D-and L-alanine.

  18. Antibacterial Activity of Alanine-Derived Gemini Quaternary Ammonium Compounds.

    PubMed

    Piecuch, Agata; Obłąk, Ewa; Guz-Regner, Katarzyna

    The antibacterial activity of alanine-derived gemini quaternary ammonium salts (chlorides and bromides) with various spacer and alkyl chain lengths was investigated. The studied compounds exhibited a strong bactericidal effect, especially bromides with 10 and 12 carbon alkyl chains and 3 carbon spacer groups (TMPAL-10 Br and TMPAL-12 Br), with a short contact time. Both salts dislodged biofilms of Pseudomonas aeruginosa and Staphylococcus epidermidis, and were lethal to adherent cells of S. epidermidis. Bromide with 2 carbon spacer groups and 12 carbon alkyl chains (TMEAL-12 Br) effectively reduced microbial adhesion by coating polystyrene and silicone surfaces. The results obtained suggest that, after further studies, gemini QAS might be considered as antimicrobial agents in medicine or industry.

  19. Charge dependent photodynamic activity of alanine based zinc phthalocyanines.

    PubMed

    Wang, Ao; Li, Yejing; Zhou, Lin; Yuan, Linxin; Lu, Shan; Lin, Yun; Zhou, Jiahong; Wei, Shaohua

    2014-12-01

    In this paper, to minimize the effects of different structure, three alanine-based zinc phthalocyanines (Pcs) of differing charges were engineered and synthesized with the same basic structure. On this premise, the relationship between nature of charge and photodynamic activity was studied. Besides, further verification and explanation of some inconsistent results were also carried out. The results showed that charge can influence the aggregation state, singlet oxygen generation ability and cellular uptake of Pcs, thereby affecting their photodynamic activity. In addition, the biomolecules inside cells may interact with Pcs of differing charges, which can also influence the aggregation state and singlet oxygen generation of the Pcs, and then influence the relationship between nature of charge and photodynamic activity.

  20. First-principles study of fluorination of L-Alanine

    NASA Astrophysics Data System (ADS)

    Sreepad, H. R.; Ravi, H. R.; Ahmed, Khaleel; Dayananda, H. M.; Umakanth, K.; Manohara, B. M.

    2013-02-01

    First-principles calculations based on Density Functional Theory have been done on effect of fluorination of an important amino acid - L-Alanine. Its structure has been simulated. The unit cell is orthorhombic with lattice parameters a=5.90Å, b=13.85Å and c=5.75Å with volume 470 (Å)3. Bond lengths and bond angles have been estimated. Electronic Density of States calculations show that the material has a band gap of 4.47eV. Electronic band structure indicates that the material can be effectively used for NLO applications. The electronic contribution to the dielectric constant has been calculated and its average value comes out to be 2.165.

  1. Integrating diffusion maps with umbrella sampling: application to alanine dipeptide.

    PubMed

    Ferguson, Andrew L; Panagiotopoulos, Athanassios Z; Debenedetti, Pablo G; Kevrekidis, Ioannis G

    2011-04-07

    Nonlinear dimensionality reduction techniques can be applied to molecular simulation trajectories to systematically extract a small number of variables with which to parametrize the important dynamical motions of the system. For molecular systems exhibiting free energy barriers exceeding a few k(B)T, inadequate sampling of the barrier regions between stable or metastable basins can lead to a poor global characterization of the free energy landscape. We present an adaptation of a nonlinear dimensionality reduction technique known as the diffusion map that extends its applicability to biased umbrella sampling simulation trajectories in which restraining potentials are employed to drive the system into high free energy regions and improve sampling of phase space. We then propose a bootstrapped approach to iteratively discover good low-dimensional parametrizations by interleaving successive rounds of umbrella sampling and diffusion mapping, and we illustrate the technique through a study of alanine dipeptide in explicit solvent.

  2. Alanine Aminotransferase Variants Conferring Diverse NUE Phenotypes in Arabidopsis thaliana

    PubMed Central

    McAllister, Chandra H.; Good, Allen G.

    2015-01-01

    Alanine aminotransferase (AlaAT, E.C. 2.6.1.2), is a pyridoxal-5’-phosphate-dependent (PLP) enzyme that catalyzes the reversible transfer of an amino group from alanine to 2-oxoglutarate to produce glutamate and pyruvate, or vice versa. It has been well documented in both greenhouse and field studies that tissue-specific over-expression of AlaAT from barley (Hordeum vulgare, HvAlaAT) results in a significant increase in plant NUE in both canola and rice. While the physical phenotypes associated with over-expression of HvAlaAT have been well characterized, the role this enzyme plays in vivo to create a more N efficient plant remains unknown. Furthermore, the importance of HvAlaAT, in contrast to other AlaAT enzyme homologues in creating this phenotype has not yet been explored. To address the role of AlaAT in NUE, AlaAT variants from diverse sources and different subcellular locations, were expressed in the wild-type Arabidopsis thaliana Col-0 background and alaat1;2 (alaat1-1;alaat2-1) knockout background in various N environments. The analysis and comparison of both the physical and physiological properties of AlaAT over-expressing transgenic plants demonstrated significant differences between plants expressing the different AlaAT enzymes under different external conditions. This analysis indicates that the over-expression of AlaAT variants other than HvAlaAT in crop plants could further increase the NUE phenotype(s) previously observed. PMID:25830496

  3. Alanine aminotransferase variants conferring diverse NUE phenotypes in Arabidopsis thaliana.

    PubMed

    McAllister, Chandra H; Good, Allen G

    2015-01-01

    Alanine aminotransferase (AlaAT, E.C. 2.6.1.2), is a pyridoxal-5'-phosphate-dependent (PLP) enzyme that catalyzes the reversible transfer of an amino group from alanine to 2-oxoglutarate to produce glutamate and pyruvate, or vice versa. It has been well documented in both greenhouse and field studies that tissue-specific over-expression of AlaAT from barley (Hordeum vulgare, HvAlaAT) results in a significant increase in plant NUE in both canola and rice. While the physical phenotypes associated with over-expression of HvAlaAT have been well characterized, the role this enzyme plays in vivo to create a more N efficient plant remains unknown. Furthermore, the importance of HvAlaAT, in contrast to other AlaAT enzyme homologues in creating this phenotype has not yet been explored. To address the role of AlaAT in NUE, AlaAT variants from diverse sources and different subcellular locations, were expressed in the wild-type Arabidopsis thaliana Col-0 background and alaat1;2 (alaat1-1;alaat2-1) knockout background in various N environments. The analysis and comparison of both the physical and physiological properties of AlaAT over-expressing transgenic plants demonstrated significant differences between plants expressing the different AlaAT enzymes under different external conditions. This analysis indicates that the over-expression of AlaAT variants other than HvAlaAT in crop plants could further increase the NUE phenotype(s) previously observed.

  4. The advanced glycation end product-lowering agent ALT-711 is a low-affinity inhibitor of thiamine diphosphokinase.

    PubMed

    Krautwald, Martina; Leech, Dale; Horne, Stacey; Steele, Megan L; Forbes, Josephine; Rahmadi, Anton; Griffith, Renate; Münch, Gerald

    2011-08-01

    Advanced glycation end products (AGEs) are involved in age-related diseases, including the complications of diabetes and chronic renal impairment with arterial stiffening. Alagebrium chloride (ALT-711) is an AGE-lowering agent with beneficial effects in renal structural and functional parameters in diabetes, decreased diabetes-accelerated atherosclerosis, and age-related myocardial stiffening. ALT-711 exhibits a structural homology to thiamine, and it was suggested to interfere with thiamine metabolism. Thiamine is converted to thiamine diphosphate (TDP) by thiamine diphosphokinase (TDPK). TDP is a cofactor for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase and transketolase. A decreased activity of these enzymes due to TDP deficiency results in disorders such as beriberi and Wernicke-Korsakoff syndrome. Therefore, we investigated whether ALT-711 is an inhibitor of TDPK. Molecular modeling studies showed that ALT-711 fits into the thiamine-binding pocket of TDPK, and there are three interactions between the thiazolium ring and the enzyme, as well as parallel stacking between the phenyl ring and the indole ring of Trp222B. Enzyme kinetic experiments also showed that ALT-711 dose-dependently decreased TDPK activity with K(i)s, calculated by different experiments and fitting models ranging from 0.88 to 1.09 mM. Fitting of the kinetic data favored mixed-mode inhibition with a major role for competitive inhibition. In summary, our results suggest that ALT-711 is a low-affinity inhibitor of TDPK, but is unlikely to interfere with thiamine metabolism at therapeutic concentrations. However, when new AGE-crosslink breakers based on thiamine are designed, care should be taken that they do not act as more potent competitive inhibitors than ALT-711.

  5. The major Alternaria alternata allergen, Alt a 1: A reliable and specific marker of fungal contamination in citrus fruits.

    PubMed

    Gabriel, M F; Uriel, N; Teifoori, F; Postigo, I; Suñén, E; Martínez, J

    2017-09-18

    The ubiquitously present spores of Alternaria alternata can spoil a wide variety of foodstuffs, including a variety of fruits belonging to the Citrus genus. The major allergenic protein of A. alternata, Alt a 1, is a species-specific molecular marker that has been strongly associated with allergenicity and phytopathogenicity of this fungal species. This study aimed to evaluate the potential of the detection of Alt a 1 as a reliable indicator of A. alternata contamination in citrus fruits. To accomplish this aim, sixty oranges were artificially infected with a spore suspension of A. alternata. Internal fruit material was collected at different incubation times (one, two and three weeks after the fungal inoculation) and used for both total RNA extraction and protein extraction. Alt a 1 detection was then performed by polymerase chain reaction (PCR) amplification using Alt a 1 specific primers and by enzyme-linked immunosorbent assay (ELISA). The experimental model presented in this work was effective to simulate the typical Alternaria black rot phenotype and its progression. Although both PCR and ELISA techniques have been successfully carried out for detecting Alt a 1 allergen in A. alternata infected oranges, the PCR method was found to be more sensitive than ELISA. Nevertheless, ELISA results were highly valuable to demonstrate that considerable amounts of Alt a 1 are produced during A. alternata fruit infection process, corroborating the recently proposed hypothesis that this protein plays a role in the pathogenicity and virulence of Alternaria species. Such evidence suggests that the detection of Alt a 1 by PCR-based assay may be used as a specific indicator of the presence of pathogenic and allergenic fungal species, A. alternata, in fruits. This knowledge can be employed to control the fungal infection and mitigate agricultural losses as well as human exposure to A. alternata allergens and toxins. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Efficient L-Alanine Production by a Thermo-Regulated Switch in Escherichia coli.

    PubMed

    Zhou, Li; Deng, Can; Cui, Wen-Jing; Liu, Zhong-Mei; Zhou, Zhe-Min

    2016-01-01

    L-Alanine has important applications in food, pharmaceutical and veterinary and is used as a substrate for production of engineered thermoplastics. Microbial fermentation could reduce the production cost and promote the application of L-alanine. However, the presence of L-alanine significantly inhibit cell growth rate and cause a decrease in the ultimate L-alanine productivity. For efficient L-alanine production, a thermo-regulated genetic switch was designed to dynamically control the expression of L-alanine dehydrogenase (alaD) from Geobacillus stearothermophilus on the Escherichia coli B0016-060BC chromosome. The optimal cultivation conditions for the genetically switched alanine production using B0016-060BC were the following: an aerobic growth phase at 33 °C with a 1-h thermo-induction at 42 °C followed by an oxygen-limited phase at 42 °C. In a bioreactor experiment using the scaled-up conditions optimized in a shake flask, B0016-060BC accumulated 50.3 g biomass/100 g glucose during the aerobic growth phase and 96 g alanine/100 g glucose during the oxygen-limited phase, respectively. The L-alanine titer reached 120.8 g/l with higher overall and oxygen-limited volumetric productivities of 3.09 and 4.18 g/l h, respectively, using glucose as the sole carbon source. Efficient cell growth and L-alanine production were reached separately, by switching cultivation temperature. The results revealed the application of a thermo-regulated strategy for heterologous metabolic production and pointed to strategies for improving L-alanine production.

  7. Development of a prodrug of salicylic acid, salicylic acid-L-alanine conjugate, utilizing hydrolysis by rabbit intestinal microorganisms.

    PubMed

    Nakamura, J; Tagami, C; Nishida, K; Sasaki, H

    1992-04-01

    The hydrolysis of salicylic acid-L-alanine conjugate (salicyl-L-alanine) following oral, intravenous, intracaecal and rectal administration (60, 10, 5 and 5 mg kg-1, respectively: salicylic acid equivalent) was examined in rabbits. Salicylic acid was detected in the blood 2 h after oral administration of salicyl-L-alanine and reached a maximum concentration at 10 h, whereas salicyl-L-alanine was rapidly eliminated. In contrast, unchanged salicyl-L-alanine only was found following intravenous administration of salicyl-L-alanine, suggesting that presystemic de-conjugation of salicyl-L-alanine was involved. The intestinal mucosal de-conjugation of salicyl-L-alanine was not recognized in the in-situ intestinal sac preparation with complete mesenteric venous blood collection. Immediate and very extensive salicylic acid formation in the caecum was found following intracaecal administration of salicyl-L-alanine. After oral pretreatment of rabbits with kanamycin sulphate, a significant inhibition of salicylic acid formation following intracaecal administration of salicyl-L-alanine was observed, indicating that the intestinal microorganisms were responsible for the biotransformation of salicyl-L-alanine. In-vitro incubation of salicyl-L-alanine with gut contents showed that the major source of its hydrolysis was the hind gut. Consequently, the blood concentration of salicylic acid was prolonged extensively following rectal administration of salicyl-L-alanine, suggesting the usefulness of salicyl-L-alanine as a prodrug of salicylic acid.

  8. Ephedra alte (joint pine): an invasive, problematic weedy species in forestry and fruit tree orchards in Jordan.

    PubMed

    Qasem, Jamal R

    2012-01-01

    A field survey was carried out to record plant species climbed by Ephedra alte in certain parts of Jordan during 2008-2010. Forty species of shrubs, ornamental, fruit, and forest trees belonging to 24 plant families suffered from the climbing habit of E. alte. Growth of host plants was adversely affected by E. alte growth that extended over their vegetation. In addition to its possible competition for water and nutrients, the extensive growth it forms over host species prevents photosynthesis, smothers growth and makes plants die underneath the extensive cover. However, E. alte did not climb all plant species, indicating a host preference range. Damaged fruit trees included Amygdalus communis, Citrus aurantifolia, Ficus carica, Olea europaea, Opuntia ficus-indica, and Punica granatum. Forestry species that were adversely affected included Acacia cyanophylla, Ceratonia siliqua, Crataegus azarolus, Cupressus sempervirens, Pinus halepensis, Pistacia atlantica, Pistacia palaestina, Quercus coccifera, Quercus infectoria, Retama raetam, Rhamnus palaestina, Rhus tripartita, and Zizyphus spina-christi. Woody ornamentals attacked were Ailanthus altissima, Hedera helix, Jasminum fruticans, Jasminum grandiflorum, Nerium oleander, and Pyracantha coccinea. Results indicated that E. alte is a strong competitive for light and can completely smother plants supporting its growth. A. communis, F. carica, R. palaestina, and C. azarolus were most frequently attacked.

  9. Ephedra alte (Joint Pine): An Invasive, Problematic Weedy Species in Forestry and Fruit Tree Orchards in Jordan

    PubMed Central

    Qasem, Jamal R.

    2012-01-01

    A field survey was carried out to record plant species climbed by Ephedra alte in certain parts of Jordan during 2008–2010. Forty species of shrubs, ornamental, fruit, and forest trees belonging to 24 plant families suffered from the climbing habit of E. alte. Growth of host plants was adversely affected by E. alte growth that extended over their vegetation. In addition to its possible competition for water and nutrients, the extensive growth it forms over host species prevents photosynthesis, smothers growth and makes plants die underneath the extensive cover. However, E. alte did not climb all plant species, indicating a host preference range. Damaged fruit trees included Amygdalus communis, Citrus aurantifolia, Ficus carica, Olea europaea, Opuntia ficus-indica, and Punica granatum. Forestry species that were adversely affected included Acacia cyanophylla, Ceratonia siliqua, Crataegus azarolus, Cupressus sempervirens, Pinus halepensis, Pistacia atlantica, Pistacia palaestina, Quercus coccifera, Quercus infectoria, Retama raetam, Rhamnus palaestina, Rhus tripartita, and Zizyphus spina-christi. Woody ornamentals attacked were Ailanthus altissima, Hedera helix, Jasminum fruticans, Jasminum grandiflorum, Nerium oleander, and Pyracantha coccinea. Results indicated that E. alte is a strong competitive for light and can completely smother plants supporting its growth. A. communis, F. carica, R. palaestina, and C. azarolus were most frequently attacked. PMID:22645486

  10. [Impact analysis of shuxuetong injection on abnormal changes of ALT based on generalized boosted models propensity score weighting].

    PubMed

    Yang, Wei; Yi, Dan-Hui; Xie, Yan-Ming; Yang, Wei; Dai, Yi; Zhi, Ying-Jie; Zhuang, Yan; Yang, Hu

    2013-09-01

    To estimate treatment effects of Shuxuetong injection on abnormal changes on ALT index, that is, to explore whether the Shuxuetong injection harms liver function in clinical settings and to provide clinical guidance for its safe application. Clinical information of traditional Chinese medicine (TCM) injections is gathered from hospital information system (HIS) of eighteen general hospitals. This is a retrospective cohort study, using abnormal changes in ALT index as an outcome. A large number of confounding biases are taken into account through the generalized boosted models (GBM) and multiple logistic regression model (MLRM) to estimate the treatment effects of Shuxuetong injections on abnormal changes in ALT index and to explore possible influencing factors. The advantages and process of application of GBM has been demonstrated with examples which eliminate the biases from most confounding variables between groups. This serves to modify the estimation of treatment effects of Shuxuetong injection on ALT index making the results more reliable. Based on large scale clinical observational data from HIS database, significant effects of Shuxuetong injection on abnormal changes in ALT have not been found.

  11. Diorganosilacetylene-alt-diorganosilvinylene polymers and a process densifying porous silicon-carbide bodies

    DOEpatents

    Barton, T.J.; Ijadi-Maghsoodi, S.; Pang, Y.

    1994-05-17

    The present invention provides linear organosilicon polymers including acetylene and vinylene moieties, and a process for their preparation. These diorganosilacetylene-alt-diorganosilvinylene linear polymers can be represented by the formula: --[--(R[sup 1])(R[sup 2])Si--C[triple bond]C-(R[sup 3])(R[sup 4])Si--CH[double bond]CH--][sub n]--, wherein n[>=]2; and each R[sup 1], R[sup 2], R[sup 3], and R[sup 4] is independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, aryl, and aralkyl radicals. The polymers are soluble in organic solvents, air stable, and can be pulled into fibers or cast into films. They can be thermally converted into silicon carbide ceramic materials.

  12. Diorganosilacetylene-alt-diorganosilvinylene polymers and a process densifying porous silicon-carbide bodies

    DOEpatents

    Barton, Thomas J.; Ijadi-Maghsoodi, Sina; Pang, Yi

    1994-05-17

    The present invention provides linear organosilicon polymers including acetylene and vinylene moieties, and a process for their preparation. These diorganosilacetylene-alt-diorganosilvinylene linear polymers can be represented by the formula: --[--(R.sup.1)(R.sup.2)Si--C.tbd.C--(R.sup.3)(R.sup.4)Si--CH=CH--].sub.n-- , wherein n.gtoreq.2; and each R.sup.1, R.sup.2, R.sup.3, and R.sup.4 is independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, aryl, and aralkyl radicals. The polymers are soluble in organic solvents, air stable, and can be pulled into fibers or cast into films. They can be thermally converted into silicon carbide ceramic materials.

  13. Intrachain versus interchain electron transport in poly(fluorene-alt-benzothiadiazole): a quantum-chemical insight.

    PubMed

    Van Vooren, Antoine; Kim, Ji-Seon; Cornil, Jérôme

    2008-05-16

    Poly(9,9-di-n-octylfluorene-alt-benzothiadiazole) [F8BT], displays very different charge-transport properties for holes versus electrons when comparing annealed and pristine thin films and transport parallel (intrachain) and perpendicular (interchain) to the polymer axes. The present theoretical contribution focuses on the electron-transport properties of F8BT chains and compares the efficiency of intrachain versus interchain transport in the hopping regime. The theoretical results rationalize significantly lowered electron mobility in annealed F8BT thin films and the smaller mobility anisotropy (mu( parallel)/mu( perpendicular)) measured for electrons in aligned films (i.e. 5-7 compared to 10-15 for holes).

  14. Segmental dynamics of polyethylene-alt-propylene studied by NMR spin echo techniques

    NASA Astrophysics Data System (ADS)

    Lozovoi, A.; Mattea, C.; Hofmann, M.; Saalwaechter, K.; Fatkullin, N.; Stapf, S.

    2017-06-01

    Segmental dynamics of a highly entangled melt of linear polyethylene-alt-propylene with a molecular weight of 200 kDa was studied with a novel proton nuclear magnetic resonance (NMR) approach based upon 1H → 2H isotope dilution as applied to a solid-echo build-up function ISE(t), which is constructed from the NMR spin echo signals arising from the Hahn echo (HE) and two variations of the solid-echo pulse sequence. The isotope dilution enables the separation of inter- and intramolecular contributions to this function and allows one to extract the segmental mean-squared displacements in the millisecond time range, which is hardly accessible by other experimental methods. The proposed technique in combination with time-temperature superposition yields information about segmental translation in polyethylene-alt-propylene over 6 decades in time from 10-6 s up to 1 s. The time dependence of the mean-squared displacement obtained in this time range clearly shows three regimes of power law with exponents, which are in good agreement with the tube-reptation model predictions for the Rouse model, incoherent reptation and coherent reptation regimes. The results at short times coincide with the fast-field cycling relaxometry and neutron spin echo data, yet, significantly extending the probed time range. Furthermore, the obtained data are verified as well by the use of the dipolar-correlation effect on the Hahn echo, which was developed before by the co-authors. At the same time, the amplitude ratio of the intermolecular part of the proton dynamic dipole-dipole correlation function over the intramolecular part obtained from the experimental data is not in agreement with the predictions of the tube-reptation model for the regimes of incoherent and coherent reptation.

  15. Prevention and reversal of diabetic nephropathy in db/db mice treated with alagebrium (ALT-711).

    PubMed

    Peppa, Melpomeni; Brem, Harold; Cai, Weijing; Zhang, Jiang-Gang; Basgen, John; Li, Zhu; Vlassara, Helen; Uribarri, Jaime

    2006-01-01

    Alagebrium (ALT-711) has been shown to improve renal dysfunction in animal models of diabetes. To test its effects in diabetic nephropathy (DN), ALT-711 was administered (1 mg/kg daily i.p.) to 9-week-old female db/db mice (n = 15, group A1) for 3 weeks and to 3-month-old (n = 15, group A2), 7-month-old (n = 7, group A3), and 12-month-old (n = 5, group A4) female db/db mice for 12 weeks, while a similar number of diabetic and nondiabetic mice were used as controls. The epsilonN-carboxymethyllysine (CML) levels in serum, urine, skin, and kidney tissue were measured by enzyme-linked immunosorbent assay. The renal morphometric parameters were assessed by electron and light microscopy. By the 3rd week of treatment, the serum CML level decreased by 41%, and the urinary CML concentration increased by 138% from baseline, while the urinary albumin/creatinine ratio was lower (p < 0.05) in diabetic and nondiabetic group A1 mice. After 3 months of treatment, serum, skin, and kidney CML levels and urinary albumin/creatinine ratio were lower (p < 0.05) and the urinary CML levels higher (p < 0.05) in treated group A2, A3, and A4 animals compared with groups which received phosphate-buffered saline, with a similar pattern observed in nondiabetic mice. The renal morphological parameters characteristic of DN decreased in treated compared with untreated mice. Alagebrium may prevent, delay, and/or reverse established DN in db/db mice by reducing the systemic advanced glycation end product pools and facilitating the urinary excretion of advanced glycation end products. Copyright (c) 2006 S. Karger AG, Basel.

  16. Increased frequency of HLA DR13 in hepatitis C virus carriers with persistently normal ALT levels.

    PubMed

    Kuzushita, N; Hayashi, N; Katayama, K; Hiramatsu, N; Yasumaru, M; Murata, H; Shimizu, Y; Yamazaki, T; Fushimi, H; Kotoh, K; Kasahara, A; Fusamoto, H; Kamada, T

    1996-01-01

    The aim of this study was to clarify the relationship between human leukocyte antigen DR allele distribution and the degree of liver cell injury of hepatitis C virus (HCV) carriers in Japan. The subjects, 68 HCV carriers, were divided into two groups according to the laboratory data and liver histology. Those in the asymptomatic carrier group (n = 19) had normal ALT levels persistently for 8-153 months (mean 25.7 months) and were diagnosed histologically as normal liver, nonspecific reactive hepatitis or chronic persistent hepatitis. Those in the chronic active hepatitis group (n = 49) had elevated ALT levels and were diagnosed histologically with chronic active hepatitis. The human leukocyte antigen DR alleles of all subjects were defined using the polymerase chain reaction restriction fragment length polymorphism method. The expression of human leukocyte antigen class I antigen and intercellular adhesion molecule 1 on the hepatocyte membrane were also examined in 14 patients from each group using an indirect immunohistochemical method. The frequency of DR13 (42.1%) in the asymptomatic carrier group was significantly higher (Pc < 0.003) than that of the chronic active hepatitis group (4.1%). There were no significant differences for the other DR alleles. The frequencies of expression of human leukocyte antigen class I antigen and intercellular adhesion molecule 1 on the hepatocyte membrane of the asymptomatic carrier group were significantly less than those of the chronic hepatitis group (64% vs. 100% P < 0.05, 29% vs. 71% P < 0.05, respectively), although there was no significant difference in the serum HCV-RNA titer between the two groups (10(6.4 +/- 1.1) vs. 10(6.5 +/- 0.7) copies/mL). These results demonstrate that the cellular immune response of the asymptomatic carrier group is less activated than the response of the chronic active hepatitis group and that HLA DR13 may be closely associated with this low activity of hepatitis among HCV carriers.

  17. Telomere-based crisis: functional differences between telomerase activation and ALT in tumor progression

    PubMed Central

    Chang, Sandy; Khoo, Christine M.; Naylor, Maria L.; Maser, Richard S.; DePinho, Ronald A.

    2003-01-01

    Telomerase activation is a common feature of most advanced human cancers and is postulated to restore genomic stability to a level permissive for cell viability and tumor progression. Here, we used genetically defined transformed mouse embryonic fibroblast (MEF) cultures derived from late generation mTerc−/− Ink4a/Arf−/− mice to explore more directly how telomere-based crisis relates to the evolution of cancer cell genomes and to tumor biology. An exhaustive serial analysis of cytogenetic profiles over extensive passage in culture revealed that the emergence of chromosomal fusions (including dicentrics) coincided with onset of deletions and complex nonreciprocal translocations (NRTs), whereas mTerc-transduced cultures maintained intact chromosomes and stable genomes. Despite a high degree of telomere dysfunction and genomic instability, transformed late passage mTerc−/− Ink4a/Arf−/− cultures retained the capacity to form subcutaneous tumors in immunocompromised mice. However, even moderate levels of telomere dysfunction completely abrogated the capacity of these cells to form lung metastases after tail-vein injection, whereas mTerc reconstitution alone conferred robust metastatic activity in these cells. Finally, serial subcutaneous tumor formation using late passage transformed mTerc−/− Ink4a/Arf−/− cultures revealed clear evidence of telomerase-independent alternative lengthening of telomeres (ALT). Significantly, despite a marked increase in telomere reserve, cells derived from the ALT+ subcutaneous tumors were unable to generate lung metastases, indicating in vivo functional differences in these principal mechanisms of telomere maintenance. Together, these results are consistent with the model that although telomere dysfunction provokes chromosomal aberrations that initiate carcinogenesis, telomerase-mediated telomere maintenance enables such initiated cells to efficiently achieve a fully malignant endpoint, including metastasis. PMID

  18. Orthologous Allergens and Diagnostic Utility of Major Allergen Alt a 1

    PubMed Central

    Moreno, Antonio; Alcover, Javier; Rodríguez, David; Palacios, Ricardo; Martínez-Naves, Eduardo

    2016-01-01

    Purpose Hypersensitivity to fungi is associated with rhinoconjunctivitis and asthma. For some fungi, such as Alternaria alternata (A. alternata), the symptoms of asthma are persistent, increasing disease severity and the risk of fatal outcomes. There are a large number of species of fungi but knowledge of them remains limited. This, together with the difficulties in obtaining adequate standardized extracts, means that there remain significant challenges in the diagnosis and immunotherapy of allergy associated with fungi. The type of indoor fungi related to asthma/allergy varies according to geographic, climatic, and seasonal factors, making their study difficult. The aim of this study was to determine hypersensitivity to indoor fungi in a population from Cuenca, Spain. Methods Thirty-five patients with symptoms compatible with rhinitis or asthma who showed clear worsening of their symptoms in their homes or workplace were included. In vivo and in vitro tests were made with a battery of fungal allergens, including the species isolated in the home or workplace. Results Ulocladium botrytis (U. botrytis) and A. alternata were the most representative species as a source of home sensitization. These species showed very high concordance in skin tests, specific IgE, and histamine release. The allergen Alt a 1, which was recognized in all patients, was detected in A. alternata, U. botrytis, and Stemphylium botryosum (S. botryosum). Conclusions U. botrytis and A. alternata were the most representative species as a source of home sensitization. Alt a 1 was recognized in all patients and may be considered a non-species-specific allergen that could be used as a diagnostic source of sensitization to some species of the Pleosporaceae family. PMID:27334781

  19. 40 CFR 721.520 - Alanine, N-(2-carboxyethyl)-N-alkyl-, salt.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-, salt. 721.520 Section 721.520 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.520 Alanine, N-(2-carboxyethyl)-N-alkyl-, salt. (a) Chemical substance... alanine, N-(2-carboxyethyl)-N- alkyl-, salt (P-89-336) is subject to reporting under this section for...

  20. 40 CFR 721.520 - Alanine, N-(2-carboxyethyl)-N-alkyl-, salt.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-, salt. 721.520 Section 721.520 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.520 Alanine, N-(2-carboxyethyl)-N-alkyl-, salt. (a) Chemical substance... alanine, N-(2-carboxyethyl)-N- alkyl-, salt (P-89-336) is subject to reporting under this section for...

  1. 40 CFR 721.520 - Alanine, N-(2-carboxyethyl)-N-alkyl-, salt.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-, salt. 721.520 Section 721.520 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.520 Alanine, N-(2-carboxyethyl)-N-alkyl-, salt. (a) Chemical substance... alanine, N-(2-carboxyethyl)-N- alkyl-, salt (P-89-336) is subject to reporting under this section for...

  2. 40 CFR 721.520 - Alanine, N-(2-carboxyethyl)-N-alkyl-, salt.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-, salt. 721.520 Section 721.520 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.520 Alanine, N-(2-carboxyethyl)-N-alkyl-, salt. (a) Chemical substance... alanine, N-(2-carboxyethyl)-N- alkyl-, salt (P-89-336) is subject to reporting under this section for...

  3. Polymerization of alanine in the presence of a non-swelling montmorillonite

    NASA Technical Reports Server (NTRS)

    Paecht-Horowitz, M.; Lahav, N.

    1977-01-01

    Alanine, starting from alanine-adenylate, has been polymerized in the presence of non-swelling Al-montmorillonite. The yield of polymerization is much lower than that obtained in the presence of swelling Na-montmorillonite. The possibility that the changing interlayer spacing in Na-montmorillonite might be responsible for its catalytic properties, is discussed.

  4. Regulation of the ald gene encoding alanine dehydrogenase by AldR in Mycobacterium smegmatis.

    PubMed

    Jeong, Ji-A; Baek, Eun-Young; Kim, Si Wouk; Choi, Jong-Soon; Oh, Jeong-Il

    2013-08-01

    The regulatory gene aldR was identified 95 bp upstream of the ald gene encoding L-alanine dehydrogenase in Mycobacterium smegmatis. The AldR protein shows sequence similarity to the regulatory proteins of the Lrp/AsnC family. Using an aldR deletion mutant, we demonstrated that AldR serves as both activator and repressor for the regulation of ald gene expression, depending on the presence or absence of L-alanine. The purified AldR protein exists as a homodimer in the absence of L-alanine, while it adopts the quaternary structure of a homohexamer in the presence of L-alanine. The binding affinity of AldR for the ald control region was shown to be increased significantly by L-alanine. Two AldR binding sites (O1 and O2) with the consensus sequence GA-N₂-ATC-N₂-TC and one putative AldR binding site with the sequence GA-N₂-GTT-N₂-TC were identified upstream of the ald gene. Alanine and cysteine were demonstrated to be the effector molecules directly involved in the induction of ald expression. The cellular level of L-alanine was shown to be increased in M. smegmatis cells grown under hypoxic conditions, and the hypoxic induction of ald expression appears to be mediated by AldR, which senses the intracellular level of alanine.

  5. A Human Long Non-Coding RNA ALT1 Controls the Cell Cycle of Vascular Endothelial Cells Via ACE2 and Cyclin D1 Pathway.

    PubMed

    Li, Wen; Wang, Rui; Ma, Jie-Yi; Wang, Mian; Cui, Jin; Wu, Wei-Bin; Liu, Rui-Ming; Zhang, Chun-Xiang; Li, Wen; Wang, Shen-Ming

    2017-10-05

    ALT1 is a novel long non-coding RNA derived from the alternatively spliced transcript of the deleted in lymphocytic leukemia 2 (DLEU2). To date, ALT1 biological roles in human vascular endothelial cells have not been reported. ALT1 was knocked down by siRNAs. Cell proliferation was analyzed by cck-8. The existence and sequence of human ALT1 were identified by 3' rapid amplification of cDNA ends. The interaction between lncRNA and proteins was analyzed by RNA-Protein pull down assay, RNA immunoprecipitation, and mass spectrometry analysis. ALT1 was expressed in human umbilical vein endothelial cells (HUVECs). The expression of ALT1 was significantly downregulated in contact-inhibited HUVECs and in hypoxia-induced, growth-arrested HUVECs. Knocking down of ALT1 inhibited the proliferation of HUVECs by G0/G1 cell cycle arrest. We observed that angiotensin converting enzyme Ⅱ(ACE2) was a direct target gene of ALT1. Knocking-down of ALT1 or its target gene ACE2 could efficiently decrease the expression of cyclin D1 via the enhanced ubiquitination and degradation, in which HIF-1α and protein von Hippel-Lindau (pVHL) might be involved. The results suggested the human long non-coding RNA ALT1 is a novel regulator for cell cycle of HUVECs via ACE2 and cyclin D1 pathway. © 2017 The Author(s). Published by S. Karger AG, Basel.

  6. Thermal decomposition behavior of potassium and sodium jarosite synthesized in the presence of methylamine and alanine

    SciTech Connect

    J. Michelle Kotler; Nancy W. Hinman; C. Doc Richardson; Jill R. Scott

    2010-10-01

    Biomolecules, methylamine and alanine, found associated with natural jarosite samples peaked the interest of astrobiologists and planetary geologists. How the biomolecules are associated with jarosite remains unclear although the mechanism could be important for detecting biosignatures in the rock record on Earth and other planets. A series of thermal gravimetric experiments using synthetic K-jarosite and Na-jarosite were conducted to determine if thermal analysis could differentiate physical mixtures of alanine and methylamine with jarosite from samples where the methylamine or alanine was incorporated into the synthesis procedure. Physical mixtures and synthetic experiments with methylamine and alanine could be differentiated from one another and from the standards by thermal analysis for both the K-jarosite and Na-jarosite end-member suites. Changes included shifts in on-set temperatures, total temperature changes from on-set to final, and the presence of indicator peaks for methylamine and alanine in the physical mixture experiments.

  7. How similar is the electronic structures of β-lactam and alanine?

    NASA Astrophysics Data System (ADS)

    Chatterjee, Subhojyoti; Ahmed, Marawan; Wang, Feng

    2016-02-01

    The C1s spectra of β-lactam i.e. 2-azetidinone (C3H5NO), a drug and L-alanine (C3H7NO2), an amino acid, exhibit striking similarities, which may be responsible for the competition between 2-azetidinone and the alanyl-alanine moiety in biochemistry. The present study is to reveal the degree of similarities and differences between their electronic structures of the two model molecular pairs. It is found that the similarities in C1s and inner valence binding energy spectra are due to their bonding connections but other properties such as ring structure (in 2-azetidinone) and chiral carbon (alanine) can be very different. Further, the inner valence region of ionization potential greater than 18 eV for 2-azetidinone and alanine is also significantly similar. Finally the strained lactam ring exhibits more chemical reactivity measured at all non-hydrogen atoms by Fukui functions with respect to alanine.

  8. Synthesis and GGCT Inhibitory Activity of N-Glutaryl-L-alanine Analogues.

    PubMed

    Ii, Hiromi; Yoshiki, Tatsuhiro; Hoshiya, Naoyuki; Uenishi, Jun'ichi

    2016-01-01

    γ-Glutamylcyclotransferase (GGCT) is an important enzyme that cleaves γ-glutamyl-amino acid in the γ-glutamyl cycle to release 5-oxoproline and amino acid. Eighteen N-acyl-L-alanine analogues including eleven new compounds have been synthesized and examined for their inhibitory activity against recombinant human GGCT protein. Simple N-glutaryl-L-alanine was found to be the most potent inhibitor for GGCT. Other N-glutaryl-L-alanine analogues having methyl and dimethyl substituents at the 2-position were moderately effective, while N-(3R-aminoglutary)-L-alanine, the substrate having an (R)-amino group at the 3-position or N-(N-methyl-3-azaglutaryl)-L-alanine, the substrate having an N-methyl substituent on the 3-azaglutaryl carbon, in constract, exhibited excellent inhibition properties.

  9. Impact of charged amino acid substitution in the transmembrane domain of L-alanine exporter, AlaE, of Escherichia coli on the L-alanine export.

    PubMed

    Kim, Seryoung; Ihara, Kohei; Katsube, Satoshi; Ando, Tasuke; Isogai, Emiko; Yoneyama, Hiroshi

    2017-01-01

    The Escherichia coli alaE gene encodes the L-alanine exporter, AlaE, that catalyzes active export of L-alanine using proton electrochemical potential. The transporter comprises only 149 amino acid residues and four predicted transmembrane domains (TMs), which contain three charged amino acid residues. The AlaE-deficient L-alanine non-metabolizing cells (ΔalaE cells) appeared hypersusceptible to L-alanyl-L-alanine showing a minimum inhibitory concentration (MIC) of 2.5 µg/ml for the dipeptide due to a toxic accumulation of L-alanine. To elucidate the mechanism by which AlaE exports L-alanine, we replaced charged amino acid residues in the TMs, glutamic acid-30 (TM-I), arginine-45 (TM-II), and aspartic acid-84 (TM-III) with their respective charge-conserved amino acid or a net neutral cysteine. The ΔalaE cells producing R45K or R45C appeared hypersusceptible to the dipeptide, indicating that arginine-45 is essential for AlaE activity. MIC of the dipeptide in the ΔalaE cells expressing E30D and E30C was 156 µg/ml and >10,000 µg/ml, respectively, thereby suggesting that a negative charge at this position is not essential. The ΔalaE cells expressing D84E or D84C showed an MIC >10,000 and 78 µg/ml, respectively, implying that a negative charge is required at this position. These results were generally consistent with that of the L-alanine accumulation experiments in intact cells. We therefore concluded that charged amino acid residues (R45 and D84) in the AlaE transmembrane domain play a pivotal role in L-alanine export. Replacement of three cysteine residues at C22, C28 (both in TM-I), and C135 (C-terminal region) with alanine showed only a marginal effect on L-alanine export.

  10. Effect of beta-alanine, with and without sodium bicarbonate, on 2000-m rowing performance.

    PubMed

    Hobson, Ruth M; Harris, Roger C; Martin, Dan; Smith, Perry; Macklin, Ben; Gualano, Bruno; Sale, Craig

    2013-10-01

    To examine the effect of beta-alanine only and beta-alanine with sodium bicarbonate supplementation on 2,000-m rowing performance. Twenty well-trained rowers (age 23 ± 4 y; height 1.85 ± 0.08 m; body mass 82.5 ± 8.9 kg) were assigned to either a placebo or beta-alanine (6.4 g · d(-1) for 4 weeks) group. A 2,000-m rowing time trial (TT) was performed before supplementation (Baseline) and after 28 and 30 days of supplementation. The post supplementation trials involved supplementation with either maltodextrin or sodium bicarbonate in a double-blind, crossover design, creating four study conditions (placebo with maltodextrin; placebo with sodium bicarbonate; beta-alanine with maltodextrin; beta-alanine with sodium bicarbonate). Blood lactate, pH, bicarbonate, and base excess were measured pre-TT, immediately post-TT and at TT+5 min. Performance data were analyzed using magnitude based inferences. Beta-alanine supplementation was very likely to be beneficial to 2,000-m rowing performance (6.4 ± 8.1 s effect compared with placebo), with the effect of sodium bicarbonate having a likely benefit (3.2 ± 8.8 s). There was a small (1.1 ± 5.6 s) but possibly beneficial additional effect when combining chronic beta-alanine supplementation with acute sodium bicarbonate supplementation compared with chronic beta-alanine supplementation alone. Sodium bicarbonate ingestion led to increases in plasma pH, base excess, bicarbonate, and lactate concentrations. Both chronic beta-alanine and acute sodium bicarbonate supplementation alone had positive effects on 2,000-m rowing performance. The addition of acute sodium bicarbonate to chronic beta-alanine supplementation may further enhance rowing performance.

  11. Ergogenic Effects of β-Alanine and Carnosine: Proposed Future Research to Quantify Their Efficacy

    PubMed Central

    Caruso, John; Charles, Jessica; Unruh, Kayla; Giebel, Rachel; Learmonth, Lexis; Potter, William

    2012-01-01

    β-alanine is an amino acid that, when combined with histidine, forms the dipeptide carnosine within skeletal muscle. Carnosine and β-alanine each have multiple purposes within the human body; this review focuses on their roles as ergogenic aids to exercise performance and suggests how to best quantify the former’s merits as a buffer. Carnosine normally makes a small contribution to a cell’s total buffer capacity; yet β-alanine supplementation raises intracellular carnosine concentrations that in turn improve a muscle’s ability to buffer protons. Numerous studies assessed the impact of oral β-alanine intake on muscle carnosine levels and exercise performance. β-alanine may best act as an ergogenic aid when metabolic acidosis is the primary factor for compromised exercise performance. Blood lactate kinetics, whereby the concentration of the metabolite is measured as it enters and leaves the vasculature over time, affords the best opportunity to assess the merits of β-alanine supplementation’s ergogenic effect. Optimal β-alanine dosages have not been determined for persons of different ages, genders and nutritional/health conditions. Doses as high as 6.4 g day−1, for ten weeks have been administered to healthy subjects. Paraesthesia is to date the only side effect from oral β-alanine ingestion. The severity and duration of paraesthesia episodes are dose-dependent. It may be unwise for persons with a history of paraesthesia to ingest β-alanine. As for any supplement, caution should be exercised with β-alanine supplementation. PMID:22852051

  12. Metabolic response of muscle to alanine, glutamine, and valine supplementation during severe illness.

    PubMed

    Gore, Dennis C; Wolfe, Robert R

    2003-01-01

    Alanine and glutamine are released from muscle in response to critical illness. Subsequent depletion of glutamine from muscle is proposed as a principal factor in the limitation of muscle protein synthesis in severely ill patients. The objective of this study was to assess the peripheral metabolic response to enteral supplementation of alanine, glutamine, and valine in critically ill patients. Isotopic tracers of alanine, glutamine, and phenylalanine were given IV to 6 critically ill patients and 6 healthy volunteers. Blood sampling from the femoral artery and vein along with muscle biopsies provided assessment of leg (ie, muscle) kinetics. Measurements were obtained during enteral nutrition alone and then with combined alanine (11.25 g), glutamine (7.5 g) and valine (11.25 g) supplementation for 3 hours. Compared with healthy volunteers, critically ill patients had significantly reduced concentrations of alanine and glutamine in arterial plasma (p < .05), which increased significantly with amino acid supplementation. Muscle glutamine concentrations were significantly less in the patients and were not significantly affected by supplementation. Alanine and glutamine transport into and out of muscle and the rates of alanine and glutamine incorporation into and production from muscle were not affected by supplementation. Phenylalanine kinetics, as a marker of muscle protein metabolism, were not significantly altered by alanine, glutamine, and valine intake. These results demonstrate that alanine, glutamine, and valine administration fails to significantly affect muscle glutamine availability or muscle protein metabolism. These findings suggest that accelerated muscle catabolism in critically ill patients is not in response to any deficiency in alanine or glutamine availability.

  13. The 'Führerschule' in Alt Rehse: A character school for the physicians of National Socialist Germany.

    PubMed

    Hansson, N; Maiboum, T; Nilsson, P M

    2011-12-01

    This contribution traces the international contacts and impact of the leader school for German doctors ('Führerschule der deutschen Arzteschaft') in Alt Rehse 1935-1943 through studies of a visitors' book and of biographies.We suggest that the 'Föhrerschule', an institution providing political and ideological education for health professionals, interested non-German physicians to a larger extent than earlier described. This paper also highlights a few examples of non-German physicians who, for various reasons, visited the 'Führerschule' in Alt Rehse.

  14. Approach & Landing Test (ALT) - Shuttle Free-Flight (FF)-2 - New Release - Dryden Flight Research Center (DFRC), CA

    NASA Image and Video Library

    1977-09-13

    S77-28136 (13 Sept 1977) --- The Orbiter 101 "Enterprise" is seen separating from the NASA 747 carrier aircraft during the second free flight of the Shuttle Approach and Landing Tests (ALTs) conducted on September 13, 1977 at Dryden Flight Research Center in Southern California. Astronauts Joe H. Engle, and Richard H. Truly were the crew of the "Enterprise." The ALT free flights are designed to verify Orbiter subsonic airworthiness, integrated systems operations and pilot-guided approach and landing capability and satisfying prerequisites to automatic flight control and navigation mode.

  15. Alanine synthesis from glyceraldehyde and ammonium ion in aqueous solution

    NASA Technical Reports Server (NTRS)

    Weber, A. L.

    1985-01-01

    The formation of alanine (ala) form C(14)-glyceraldehyde and ammonium phosphate in the presence or absence of a thiol is reported. At ambient temperature, ala synthesis was six times more rapid in the presence of 3-mercaptopropionic acid than in its absence (0.6 and 0.1 percent, respectively, after 60 days). Similarly, the presence of another thiol, N-acetylcysteinate, increased the production of ala, as well as of lactate. The reaction pathway of thiol-catalyzed synthesis of ala, with the lactic acid formed in a bypath, is suggested. In this, dehydration of glyceraldehyde is followed by the formation of hemithioacetal. In the presence of ammonia, an imine is formed, which eventually yields ala. This pathway is consistent with the observation that the rate ratio of ala/lactate remains constant throughout the process. The fact that the reaction takes place under anaerobic conditions in the presence of H2O and with the low concentrations of simple substrates and catalysts makes it an attractive model prebiotic reaction in the process of molecular evolution.

  16. Alanine synthesis from glyceraldehyde and ammonium ion in aqueous solution

    NASA Technical Reports Server (NTRS)

    Weber, A. L.

    1985-01-01

    The formation of alanine (ala) form C(14)-glyceraldehyde and ammonium phosphate in the presence or absence of a thiol is reported. At ambient temperature, ala synthesis was six times more rapid in the presence of 3-mercaptopropionic acid than in its absence (0.6 and 0.1 percent, respectively, after 60 days). Similarly, the presence of another thiol, N-acetylcysteinate, increased the production of ala, as well as of lactate. The reaction pathway of thiol-catalyzed synthesis of ala, with the lactic acid formed in a bypath, is suggested. In this, dehydration of glyceraldehyde is followed by the formation of hemithioacetal. In the presence of ammonia, an imine is formed, which eventually yields ala. This pathway is consistent with the observation that the rate ratio of ala/lactate remains constant throughout the process. The fact that the reaction takes place under anaerobic conditions in the presence of H2O and with the low concentrations of simple substrates and catalysts makes it an attractive model prebiotic reaction in the process of molecular evolution.

  17. Alanine racemase mutants of Mycobacterium tuberculosis require D-alanine for growth and are defective for survival in macrophages and mice.

    PubMed

    Awasthy, Disha; Bharath, Sowmya; Subbulakshmi, Venkita; Sharma, Umender

    2012-02-01

    Alanine racemase (Alr) is an essential enzyme in most bacteria; however, some species (e.g. Listeria monocytogenes) can utilize d-amino acid transaminase (Dat) to generate d-alanine, which renders Alr non-essential. In addition to the conflicting reports on gene knockout of alr in Mycobacterium smegmatis, a recent study concluded that depletion of Alr does not affect the growth of M. smegmatis. In order to get an unambiguous answer on the essentiality of Alr in Mycobacterium tuberculosis and validate it as a drug target in vitro and in vivo, we have inactivated the alr gene of M. tuberculosis and found that it was not possible to generate an alr knockout in the absence of a complementing gene copy or d-alanine in the growth medium. The growth kinetics of the alr mutant revealed that M. tuberculosis requires very low amounts of d-alanine (5-10 µg ml(-1)) for optimum growth. Survival kinetics of the mutant in the absence of d-alanine indicated that depletion of this amino acid results in rapid loss of viability. The alr mutant was found to be defective for growth in macrophages. Analysis of phenotype in mice suggested that non-availability of d-alanine in mice leads to clearance of bacteria followed by stabilization of bacterial number in lungs and spleen. Additionally, reversal of d-cycloserine inhibition in the presence of d-alanine in M. tuberculosis suggested that Alr is the primary target of d-cycloserine. Thus, Alr of M. tuberculosis is a valid drug target and inhibition of Alr alone should result in loss of viability in vitro and in vivo.

  18. Enzymatic characterization and crystal structure analysis of the D-alanine-D-alanine ligase from Helicobacter pylori.

    PubMed

    Wu, Dalei; Zhang, Liang; Kong, Yunhua; Du, Jiamu; Chen, Shuai; Chen, Jing; Ding, Jianping; Jiang, Hualiang; Shen, Xu

    2008-09-01

    D-Alanine-D-alanine ligase is the second enzyme in the D-Ala branch of bacterial cell wall peptidoglycan assembly, and recognized as an attractive antimicrobial target. In this work, the D-Ala-D-Ala ligase of Helicobacter pylori strain SS1 (HpDdl) was kinetically and structurally characterized. The determined apparent K(m) of ATP (0.87 microM), the K(m1) (1.89 mM) and K(m2) of D-Ala (627 mM), and the k(cat) (115 min(-1)) at pH 8.0 indicated its relatively weak binding affinity and poor catalytic activity against the substrate D-Ala in vitro. However, by complementary assay of expressing HpDdl in Escherichia coli Delta ddl mutant, HpDdl was confirmed to be capable of D-Ala-D-Ala ligating in vivo. Through sequence alignment with other members of the D-Ala-D-X ligase superfamily, HpDdl keeps two conservatively substituted residues (Ile16 and Leu241) and two nonconserved residues (Leu308 and Tyr311) broadly located in the active region of the enzyme. Kinetic analyses against the corresponding HpDdl mutants (I16V, L241Y, L241F, L308T, and Y311S) suggested that these residues, especially Leu308 and Tyr311, might partly contribute to the unique catalytic properties of the enzyme. This was fairly proved by the crystal structure of HpDdl, which revealed that there is a 3(10)-helix (including residues from Gly306 to Leu312) near the D-Ala binding region in the C-terminal domain, where HpDdl has two sequence deletions compared with other homologs. Such 3(10)-helix may participate in D-Ala binding and conformational change of the enzyme. Our present work hopefully provides useful information for understanding the D-Ala-D-Ala ligase of Helicobacter pylori.

  19. The ribavirin analog ICN 17261 demonstrates reduced toxicity and antiviral effects with retention of both immunomodulatory activity and reduction of hepatitis-induced serum alanine aminotransferase levels.

    PubMed

    Tam, R C; Ramasamy, K; Bard, J; Pai, B; Lim, C; Averett, D R

    2000-05-01

    The demonstrated utility of the nucleoside analog ribavirin in the treatment of certain viral diseases can be ascribed to its multiple distinct properties. These properties may vary in relative importance in differing viral disease conditions and include the direct inhibition of viral replication, the promotion of T-cell-mediated immune responses via an enhanced type 1 cytokine response, and a reduction of circulating alanine aminotransferase (ALT) levels associated with hepatic injury. Ribavirin also has certain known toxicities, including the induction of anemia upon chronic administration. To determine if all these properties are linked, we compared the D-nucleoside ribavirin to its L-enantiomer (ICN 17261) with regard to these properties. Strong similarities were seen for these two compounds with respect to induction of type 1 cytokine bias in vitro, enhancement of type 1 cytokine responses in vivo, and the reduction of serum ALT levels in a murine hepatitis model. In contrast, ICN 17261 had no in vitro antiviral activity against a panel of RNA and DNA viruses, while ribavirin exhibited its characteristic activity profile. Importantly, the preliminary in vivo toxicology profile of ICN 17261 is significantly more favorable than that of ribavirin. Administration of 180 mg of ICN 17261 per kg of body weight to rats by oral gavage for 4 weeks generated substantial serum levels of drug but no observable clinical pathology, whereas equivalent doses of ribavirin induced a significant anemia and leukopenia. Thus, structural modification of ribavirin can dissociate its immunomodulatory properties from its antiviral and toxicologic properties, resulting in a compound (ICN 17261) with interesting therapeutic potential.

  20. ALT-associated promyelocytic leukaemia body (APB) detection as a reproducible tool to assess alternative lengthening of telomere stability in liposarcomas.

    PubMed

    Venturini, L; Erdas, R; Costa, A; Gronchi, A; Pilotti, S; Zaffaroni, N; Daidone, Mg

    2008-03-01

    Most cancers maintain telomeres by activating telomerase, but a significant minority, mainly of mesenchymal origin, utilize an alternative lengthening of telomeres (ALT) mechanism. We previously showed the presence of ALT, as detected by ALT-associated promyelocytic leukaemia bodies (APBs) by combined promyelocytic leukaemia immunofluorescence and telomere fluorescence-in situ hybridization, in approximately 25% of frozen specimens obtained from adult patient liposarcomas and proved that ALT negatively affects patient prognosis. In the present study, we assessed the reproducibility of APB detection on frozen versus formalin-fixed, paraffin-embedded specimens from the same liposarcoma specimens and investigated the eventual stability of ALT in 103 different lesions from 40 adult patients followed during their disease. Irrespective of liposarcoma subtype, we (1) confirmed the presence of ALT in 21.4% of tumours; (2) demonstrated the reliability of ALT-associated promyelocytic leukaemia body detection in formalin-fixed, paraffin-embedded sections (with qualitative concordance between matched frozen and formalin-fixed, paraffin-embedded samples in 29/30 specimens, and high quantitative agreement, as indicated by a Spearman correlation coefficient of 0.85); and (3) suggested the stability of ALT status during disease evolution, since the ALT mechanism was never acquired in the 29 patients with initially ALT-negative lesions and lost over time in only two of 11 patients with initially ALT-positive liposarcomas. In conclusion, these results confirm the possibility of investigating the ALT mechanism in archival specimens to obtain biologically relevant information on liposarcoma progression, even when the primary lesion is not available.

  1. In Quest of the Alanine R3 Radical: Multivariate EPR Spectral Analyses of X-Irradiated Alanine in the Solid State.

    PubMed

    Jåstad, Eirik O; Torheim, Turid; Villeneuve, Kathleen M; Kvaal, Knut; Hole, Eli O; Sagstuen, Einar; Malinen, Eirik; Futsaether, Cecilia M

    2017-09-28

    The amino acid l-α-alanine is the most commonly used material for solid-state electron paramagnetic resonance (EPR) dosimetry, due to the formation of highly stable radicals upon irradiation, with yields proportional to the radiation dose. Two major alanine radical components designated R1 and R2 have previously been uniquely characterized from EPR and electron-nuclear double resonance (ENDOR) studies as well as from quantum chemical calculations. There is also convincing experimental evidence of a third minor radical component R3, and a tentative radical structure has been suggested, even though no well-defined spectral signature has been observed experimentally. In the present study, temperature dependent EPR spectra of X-ray irradiated polycrystalline alanine were analyzed using five multivariate methods in further attempts to understand the composite nature of the alanine dosimeter EPR spectrum. Principal component analysis (PCA), maximum likelihood common factor analysis (MLCFA), independent component analysis (ICA), self-modeling mixture analysis (SMA), and multivariate curve resolution (MCR) were used to extract pure radical spectra and their fractional contributions from the experimental EPR spectra. All methods yielded spectral estimates resembling the established R1 spectrum. Furthermore, SMA and MCR consistently predicted both the established R2 spectrum and the shape of the R3 spectrum. The predicted shape of the R3 spectrum corresponded well with the proposed tentative spectrum derived from spectrum simulations. Thus, results from two independent multivariate data analysis techniques strongly support the previous evidence that three radicals are indeed present in irradiated alanine samples.

  2. Carnosine and anserine homeostasis in skeletal muscle and heart is controlled by β-alanine transamination.

    PubMed

    Blancquaert, Laura; Baba, Shahid P; Kwiatkowski, Sebastian; Stautemas, Jan; Stegen, Sanne; Barbaresi, Silvia; Chung, Weiliang; Boakye, Adjoa A; Hoetker, J David; Bhatnagar, Aruni; Delanghe, Joris; Vanheel, Bert; Veiga-da-Cunha, Maria; Derave, Wim; Everaert, Inge

    2016-09-01

    Using recombinant DNA technology, the present study provides the first strong and direct evidence indicating that β-alanine is an efficient substrate for the mammalian transaminating enzymes 4-aminobutyrate-2-oxoglutarate transaminase and alanine-glyoxylate transaminase. The concentration of carnosine and anserine in murine skeletal and heart muscle depends on circulating availability of β-alanine, which is in turn controlled by degradation of β-alanine in liver and kidney. Chronic oral β-alanine supplementation is a popular ergogenic strategy in sports because it can increase the intracellular carnosine concentration and subsequently improve the performance of high-intensity exercises. The present study can partly explain why the β-alanine supplementation protocol is so inefficient, by demonstrating that exogenous β-alanine can be effectively routed toward oxidation. The metabolic fate of orally ingested β-alanine is largely unknown. Chronic β-alanine supplementation is becoming increasingly popular for improving high-intensity exercise performance because it is the rate-limiting precursor of the dipeptide carnosine (β-alanyl-l-histidine) in muscle. However, only a small fraction (3-6%) of the ingested β-alanine is used for carnosine synthesis. Thus, the present study aimed to investigate the putative contribution of two β-alanine transamination enzymes, namely 4-aminobutyrate-2-oxoglutarate transaminase (GABA-T) and alanine-glyoxylate transaminase (AGXT2), to the homeostasis of carnosine and its methylated analogue anserine. We found that, when transfected into HEK293T cells, recombinant mouse and human GABA-T and AGXT2 are able to transaminate β-alanine efficiently. The reaction catalysed by GABA-T is inhibited by vigabatrin, whereas both GABA-T and AGXT2 activity is inhibited by aminooxyacetic acid (AOA). Both GABA-T and AGXT2 are highly expressed in the mouse liver and kidney and the administration of the inhibitors effectively reduced their enzyme

  3. Effects of Monovalent Cations on the Sodium-Alanine Interaction in Rabbit Ileum

    PubMed Central

    Frizzell, Raymond A.; Schultz, Stanley G.

    1970-01-01

    H, K, Rb, and Li inhibit Na-dependent alanine influx across the brush border of rabbit ileum. Kinetic analysis indicates that H and K behave as competitive inhibitors of influx so that increasing the concentration of H or K in the mucosal solution is kinetically indistinguishable from decreasing the Na concentration. In addition the coupling between alanine and Na influxes is markedly reduced at pH 2.5. With the exception of H and Li, none of these monovalent cations significantly affects carrier-mediated alanine influx in the absence of Na indicating that their inhibitory effects are largely restricted to the Na-dependent fraction of influx. Increasing H concentration from 0.03 to 3 mM does not affect influx in the absence of Na but markedly inhibits influx in the presence of Na. Li significantly enhances alanine influx in the absence of Na. Ag, UO2, and La also inhibit the Na-dependent fraction of alanine influx. These findings suggest that anionic groups having a pKa of approximately 4 are involved in the interaction between Na and the alanine-carrier complex; present evidence implicates carboxylate groups however, phosphoryl residues cannot be ruled out. The previously proposed kinetic model for the Na-alanine interaction has been extended to accommodate these effects of H and other monovalent cations. The mechanistic and physiological implications of these findings are discussed. PMID:5507092

  4. Alanine-EPR as a transfer standard dosimetry system for low energy X radiation

    NASA Astrophysics Data System (ADS)

    Khoury, H. J.; da Silva, E. J.; Mehta, K.; de Barros, V. S.; Asfora, V. K.; Guzzo, P. L.; Parker, A. G.

    2015-11-01

    The purpose of this paper is to evaluate the use of alanine-EPR as a transfer standard dosimetry system for low energy X radiation, such as that in RS-2400, which operates in the range from 25 to 150 kV and 2 to 45 mA. Two types of alanine dosimeters were investigated. One is a commercial alanine pellets from Aérial-Centre de Ressources Technologiques, France and one was prepared in our laboratory (LMRI-DEN/UFPE). The EPR spectra of the irradiated dosimeters were recorded in the Nuclear Energy Department of UFPE, using a Bruker EMX10 EPR spectrometer operating in the X-band. The alanine-EPR dosimetry system was calibrated in the range of 20-220 Gy in this X-ray field, against an ionization chamber calibrated at the relevant X-ray energy with traceability to PTB. The results showed that both alanine dosimeters presented a linear dose response the same sensitivity, when the EPR signal was normalized to alanine mass. The total uncertainty in the measured dose was estimated to be about 3%. The results indicate that it is possible to use the alanine-EPR dosimetry system for validation of a low-energy X ray irradiator, such as RS-2400.

  5. Characterization of alanine catabolism in Pseudomonas aeruginosa and its importance for proliferation in vivo.

    PubMed

    Boulette, Megan L; Baynham, Patricia J; Jorth, Peter A; Kukavica-Ibrulj, Irena; Longoria, Aissa; Barrera, Karla; Levesque, Roger C; Whiteley, Marvin

    2009-10-01

    The opportunistic pathogen Pseudomonas aeruginosa causes a variety of infections in immunocompromised individuals, including individuals with the heritable disease cystic fibrosis. Like the carbon sources metabolized by many disease-causing bacteria, the carbon sources metabolized by P. aeruginosa at the host infection site are unknown. We recently reported that l-alanine is a preferred carbon source for P. aeruginosa and that two genes potentially involved in alanine catabolism (dadA and dadX) are induced during in vivo growth in the rat peritoneum and during in vitro growth in sputum (mucus) collected from the lungs of individuals with cystic fibrosis. The goals of this study were to characterize factors required for alanine catabolism in P. aeruginosa and to assess the importance of these factors for in vivo growth. Our results reveal that dadA and dadX are arranged in an operon and are required for catabolism of l-alanine. The dad operon is inducible by l-alanine, d-alanine, and l-valine, and induction is dependent on the transcriptional regulator Lrp. Finally, we show that a mutant unable to catabolize dl-alanine displays decreased competitiveness in a rat lung model of infection.

  6. Revised mechanism of D-alanine incorporation into cell wall polymers in Gram-positive bacteria.

    PubMed

    Reichmann, Nathalie T; Cassona, Carolina Picarra; Gründling, Angelika

    2013-09-01

    Teichoic acids (TAs) are important for growth, biofilm formation, adhesion and virulence of Gram-positive bacterial pathogens. The chemical structures of the TAs vary between bacteria, though they typically consist of zwitterionic polymers that are anchored to either the peptidoglycan layer as in the case of wall teichoic acid (WTA) or the cell membrane and named lipoteichoic acid (LTA). The polymers are modified with D-alanines and a lack of this decoration leads to increased susceptibility to cationic antimicrobial peptides. Four proteins, DltA-D, are essential for the incorporation of d-alanines into cell wall polymers and it has been established that DltA transfers D-alanines in the cytoplasm of the cell onto the carrier protein DltC. However, two conflicting models have been proposed for the remainder of the mechanism. Using a cellular protein localization and membrane topology analysis, we show here that DltC does not traverse the membrane and that DltD is anchored to the outside of the cell. These data are in agreement with the originally proposed model for D-alanine incorporation through a process that has been proposed to proceed via a D-alanine undecaprenyl phosphate membrane intermediate. Furthermore, we found that WTA isolated from a Staphylococcus aureus strain lacking LTA contains only a small amount of D-alanine, indicating that LTA has a role, either direct or indirect, in the efficient D-alanine incorporation into WTA in living cells.

  7. ALT1, a Snf2 family chromatin remodeling ATPase, negatively regulates alkaline tolerance through enhanced defense against oxidative stress in rice.

    PubMed

    Guo, Mingxin; Wang, Ruci; Wang, Juan; Hua, Kai; Wang, Yueming; Liu, Xiaoqiang; Yao, Shanguo

    2014-01-01

    Alkaline salt stress adversely affects rice growth, productivity and grain quality. However, the mechanism underlying this process remains elusive. We characterized here an alkaline tolerant mutant, alt1 in rice. Map-based cloning revealed that alt1 harbors a mutation in a chromatin remodeling ATPase gene. ALT1-RNAi transgenic plants under different genetic background mimicked the alt1 phenotype, exhibiting tolerance to alkaline stress in a transcript dosage-dependent manner. The predicted ALT1 protein belonged to the Ris1 subgroup of the Snf2 family and was localized in the nucleus, and transcription of ALT1 was transiently suppressed after alkaline treatment. Although the absorption of several metal ions maintained well in the mutant under alkaline stress, expression level of the genes involved in metal ions homeostasis was not altered in the alt1 mutant. Classification of differentially expressed abiotic stress related genes, as revealed by microarray analysis, found that the majority (50/78) were involved in ROS production, ROS scavenging, and DNA repair. This finding was further confirmed by that alt1 exhibited lower levels of H2O2 under alkaline stress and tolerance to methyl viologen treatment. Taken together, these results suggest that ALT1 negatively functions in alkaline tolerance mainly through the defense against oxidative damage, and provide a potential two-step strategy for improving the tolerance of rice plants to alkaline stress.

  8. ALT1, a Snf2 Family Chromatin Remodeling ATPase, Negatively Regulates Alkaline Tolerance through Enhanced Defense against Oxidative Stress in Rice

    PubMed Central

    Guo, Mingxin; Wang, Ruci; Wang, Juan; Hua, Kai; Wang, Yueming; Liu, Xiaoqiang; Yao, Shanguo

    2014-01-01

    Alkaline salt stress adversely affects rice growth, productivity and grain quality. However, the mechanism underlying this process remains elusive. We characterized here an alkaline tolerant mutant, alt1 in rice. Map-based cloning revealed that alt1 harbors a mutation in a chromatin remodeling ATPase gene. ALT1-RNAi transgenic plants under different genetic background mimicked the alt1 phenotype, exhibiting tolerance to alkaline stress in a transcript dosage-dependent manner. The predicted ALT1 protein belonged to the Ris1 subgroup of the Snf2 family and was localized in the nucleus, and transcription of ALT1 was transiently suppressed after alkaline treatment. Although the absorption of several metal ions maintained well in the mutant under alkaline stress, expression level of the genes involved in metal ions homeostasis was not altered in the alt1 mutant. Classification of differentially expressed abiotic stress related genes, as revealed by microarray analysis, found that the majority (50/78) were involved in ROS production, ROS scavenging, and DNA repair. This finding was further confirmed by that alt1 exhibited lower levels of H2O2 under alkaline stress and tolerance to methyl viologen treatment. Taken together, these results suggest that ALT1 negatively functions in alkaline tolerance mainly through the defense against oxidative damage, and provide a potential two-step strategy for improving the tolerance of rice plants to alkaline stress. PMID:25473841

  9. Serum Alanine Aminotransferase Levels, Hematocrit Rate and Body Weight Correlations Before and After Hemodialysis Session

    PubMed Central

    Lopes, Edmundo Pessoa; Sette, Luis Henrique B. C.; Sette, Jorge Bezerra C.; Luna, Carlos F.; Andrade, Amaro M.; Moraes, Maviael; Sette, Paulo C. A.; Menezes, Roberto; Cavalcanti, Rui L.; Conceição, Sergio C.

    2009-01-01

    PURPOSE To evaluate alanine aminotransferase levels before and after a hemodialysis session and to correlate these values with the hematocrit rate and weight loss during hemodialysis. PATIENTS AND METHODS The serum alanine aminotransferase levels, hematocrit rate and body weight were measured and correlated before and after a single hemodialysis session for 146 patients with chronic renal failure. An receiver operating characteristic (ROC) curve for the serum alanine aminotransferase levels collected before and after hemodialysis was plotted to identify hepatitis C virus-infected patients. RESULTS The mean weight loss of the 146 patients during hemodialysis was 5.3% (p < 0.001). The mean alanine aminotransferase levels before and after hemodialysis were 18.8 and 23.9 IU/, respectively, denoting a significant 28.1% increase. An equally significant increase of 16.4% in the hematocrit rate also occurred after hemodialysis. The weight loss was inversely correlated with the rise in both the alanine aminotransferase level (r = 0.3; p < 0.001) and hematocrit rate (r = 0.5; p < 0.001). A direct correlation was found between the rise in alanine aminotransferase levels and the hematocrit during the hemodialysis session (r = 0.4; p < 0.001). Based on the ROC curve, the upper limit of the normal alanine aminotransferase level should be reduced by 40% relative to the upper limit of normal if the blood samples are collected before the hemodialysis session or by 60% if blood samples are collected after the session. CONCLUSION In the present study, significant elevations in the serum alanine aminotransferase levels and hematocrit rates occurred in parallel to a reduction in body weight after the hemodialysis session. These findings suggest that one of the factors for low alanine aminotransferase levels prior to hemodialysis could be hemodilution in patients with chronic renal failure. PMID:19841699

  10. Determination of D- and L-alanine concentrations using a pyruvic acid sensor.

    PubMed

    Inaba, Yohei; Hamada-Sato, Naoko; Kobayashi, Takeshi; Imada, Chiaki; Watanabe, Etsuo

    2003-08-01

    The concentrations of D- and L-alanine in bivalves are useful as indicators of environmental pollution. Amino acid oxidase with a low substrate specificity catalyzes the oxidation of various amino acids. Among the various amino acids, pyruvic acid can be generated from alanine only by the catalytic oxidative reaction of this oxidase. Therefore, in this study, the concentrations of D- and L-alanine were determined from the concentration of pyruvic acid, which was determined from the consumption of oxygen based on the oxidative reaction of pyruvate oxidase. From this point of view, there is a very strong possibility that biosensors utilizing enzymes with a low substrate specificity can be developed. The results obtained were as follows. (1) The optimum conditions for the use of pyruvic acid sensor were as follows: temperature of 25 degrees C, pH of 6.8, flow rate of 0.1 ml/min, thiamin diphosphate concentration of 1.5 mM, and injection volume of 50 microl. (2) D-Alanine and L-alanine optimally reacted with D- and L-amino acid oxidase at 30 degrees C, pH 8.2, for 30 min and at 37 degrees C, pH 7.8, for 90 min, respectively. (3) The linear relationships between the concentrations of D- and L-alanine and the output of the sensor were obtained at 3.56-106.8 microg of D-alanine and 5.34-71.3 microg of L-alanine. (4) The concentrations of D- and L-alanine in Meretrix iusoria, Patinopecten yessonsi, and Corbicula leana obtained by the proposed assay were in good agreement with those determined by a conventional method.

  11. Mitochondrial defects associated with β-alanine toxicity: relevance to hyper-beta-alaninemia

    PubMed Central

    Shetewy, Aza; Shimada-Takaura, Kayoko; Warner, Danielle; Jong, Chian Ju; Mehdi, Abu-Bakr Al; Alexeyev, Mikhail; Takahashi, Kyoko; Schaffer, Stephen W.

    2016-01-01

    Hyper-beta-alaninemia is a rare metabolic condition that results in elevated plasma and urinary β-alanine levels and is characterized by neurotoxicity, hypotonia, and respiratory distress. It has been proposed that at least some of the symptoms are caused by oxidative stress; however, only limited information is available on the mechanism of reactive oxygen species generation. The present study examines the hypothesis that β-alanine reduces cellular levels of taurine, which are required for normal respiratory chain function; cellular taurine depletion is known to reduce respiratory function and elevate mitochondrial superoxide generation. To test the taurine hypothesis, isolated neonatal rat cardiomyocytes and mouse embryonic fibroblasts were incubated with medium lacking or containing β-alanine. β-alanine treatment led to mitochondrial superoxide accumulation in conjunction with a decrease in oxygen consumption. The defect in β-alanine-mediated respiratory function was detected in permeabilized cells exposed to glutamate/malate but not in cells utilizing succinate, suggesting that β-alanine leads to impaired complex I activity. Taurine treatment limited mitochondrial superoxide generation, supporting a role for taurine in maintaining complex I activity. Also affected by taurine is mitochondrial morphology, as β-alanine-treated fibroblasts undergo fragmentation, a sign of unhealthy mitochondria that is reversed by taurine treatment. If left unaltered, β-alanine-treated fibroblasts also undergo mitochondrial apoptosis, as evidenced by activation of caspases 3 and 9 and the initiation of the mitochondrial permeability transition. Together, these data show that β-alanine mediates changes that reduce ATP generation and enhance oxidative stress, factors that contribute to heart failure. PMID:27023909

  12. Importance of intrahepatic mechanisms to gluconeogenesis from alanine during exercise and recovery

    SciTech Connect

    Wasserman, D.H.; Williams, P.E.; Lacy, D.B.; Green, D.R.; Cherrington, A.D.

    1988-04-01

    These studies were performed to assess the importance of intrahepatic mechanisms to gluconeogenesis in the dog during 150 min of treadmill exercise and 90 min of recovery. Sampling catheters were implanted in an artery and portal and hepatic veins 16 days before experimentation. Infusions of (U-/sup 14/C)alanine, (3-/sup 3/H)glucose, and indocyanine green were used to assess gluconeogenesis. During exercise, a decline in arterial and portal vein plasma alanine and in hepatic blood flow led to a decrease in hepatic alanine delivery. During recovery, hepatic blood flow was restored to basal, causing an increase in hepatic alanine delivery beyond exercise rates but still below resting rates. Hepatic fractional alanine extraction increased from 0.26 +/- 0.02 at rest to 0.64 +/- 0.03 during exercise and remained elevated during recovery. Net hepatic alanine uptake was 2.5 +/- 0.2 mumol.kg-1.min-1 at rest and remained unchanged during exercise but was increased during recovery. The conversion rate of (/sup 14/C)alanine to glucose had increased by 248 +/- 38% by 150 min of exercise and had increased further during recovery. The efficiency with which alanine was channeled into glucose in the liver was accelerated to a rate of 338 +/- 55% above basal by 150 min of exercise but declined slightly during recovery. In conclusion, 1) gluconeogenesis from alanine is accelerated during exercise, due to an increase in the hepatic fractional extraction of the amino acid and through intrahepatic mechanisms that more efficiently channel it into glucose.

  13. Solvation Free Energies of Alanine Peptides: The Effect of Flexibility

    SciTech Connect

    Kokubo, Hironori; Harris, Robert C.; Asthagiri, Dilip; Pettitt, Bernard M.

    2013-12-03

    The electrostatic (?Gel), cavity-formation (?Gvdw), and total (?G) solvation free energies for 10 alanine peptides ranging in length (n) from 1 to 10 monomers were calculated. The free energies were computed both with xed, extended conformations of the peptides and again for some of the peptides without constraints. The solvation free energies, ?Gel, ?Gvdw, and ?G, were found to be linear in n, with the slopes of the best-fit lines being gamma_el, gamma_vdw, and gamma, respectively. Both gamma_el and gamma were negative for fixed and flexible peptides, and gamma_vdw was negative for fixed peptides. That gamma_vdw was negative was surprising, as experimental data on alkanes, theoretical models, and MD computations on small molecules and model systems generally suggest that gamma_vdw should be positive. A negative gamma_vdw seemingly contradicts the notion that ?Gvdw drives the initial collapse of the protein when it folds by favoring conformations with small surface areas, but when we computed ?Gvdw for the flexible peptides, thereby allowing the peptides to assume natural ensembles of more compact conformations, gamma-vdw was positive. Because most proteins do not assume extended conformations, a ?Gvdw that increases with increasing surface area may be typical for globular proteins. An alternative hypothesis is that the collapse is driven by intramolecular interactions. We show that the intramolecular van der Waal's interaction energy is more favorable for the flexible than for the extended peptides, seemingly favoring this hypothesis, but the large fluctuations in this energy may make attributing the collapse of the peptide to this intramolecular energy difficult.

  14. Perspectives on English Education in the Japanese Public School System: The Views of Foreign Assistant Language Teachers (ALTs)

    ERIC Educational Resources Information Center

    Amaki, Yuki

    2008-01-01

    Public school students in Japan must take English as a required subject for three years in junior high school and for three more years in senior high school. In spite of the amount of classroom time invested, and in spite of the available learning support services, the foreign Assistant Language Teacher (ALT) system included, the English…

  15. An ALMT1 gene cluster controlling aluminium (aluminum) tolerance at the Alt4 locus of rye (Secale cereale L.)

    USDA-ARS?s Scientific Manuscript database

    Aluminium toxicity is a major problem in agriculture worldwide. Among the cultivated triticeae, rye (Secale cereale L.) is one of the most Al-tolerant and represents an important potential source of Al-tolerance for improvement of wheat. The Alt4 Al-tolerance locus of rye contains a cluster of genes...

  16. The effect of IFN-based therapies on the short-term dynamics of alt in HCV-infected patients

    SciTech Connect

    Ribeiro, R. M.; Talal, A. H.; Layden, J. E.; Powers, K. A.; Layden, T. J.; Perelson, Alan S.,

    2002-01-01

    IFN therapy of HCV-infection has been shown to reduce production of virus from infected cells, but its effect on hepatocytes is less well understood. One indicator of liver damage is ALT, which has been used as an associated diagnostic for HCV infection.

  17. Applicability of EPR/alanine dosimetry for quality assurance in proton eye radiotherapy.

    PubMed

    Michalec, B; Mierzwinska, G; Ptaszkiewicz, M; Sowa, U; Stolarczyk, L; Weber, A

    2014-06-01

    A new quality assurance and quality control method for proton eye radiotherapy based on electron paramagnetic resonance (EPR)/alanine dosimetry has been developed. It is based on Spread-Out Bragg Peak entrance dose measurement with alanine detectors. The entrance dose is well correlated with the dose at the facility isocenter, where, during the therapeutic irradiation, the tumour is placed. The unique alanine detector features namely keeping the dose record in a form of stable radiation-induced free radicals trapped in the material structure, and the non-destructive read-out makes this type of detector a good candidate for additional documentation of the patient's exposure over the therapy course.

  18. Progress towards an alanine/ESR therapy level reference dosimetry service at NPL.

    PubMed

    Sharpe, P H; Rajendran, K; Sephton, J P

    1996-01-01

    This paper describes work being carried out at the National Physical Laboratory towards the establishment of an alanine reference dosimetry service for radiotherapy applications. A precision fused quartz holder has been constructed to allow precise positioning of alanine dosimeters in the ESR cavity. A novel method of signal analysis based on spectrum fitting has been developed to minimize the effect of baseline distortions. Data are also presented on the relative response of alanine to 60Co gamma rays and high energy photons (4-12 MeV).

  19. Interactions of L-alanine with alumina as studied by vibrational spectroscopy.

    PubMed

    Garcia, Ana R; de Barros, Ricardo Brito; Fidalgo, Alexandra; Ilharco, Laura M

    2007-09-25

    The interactions of L-alanine with gamma- and alpha-alumina have been investigated by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). L-alanine/alumina samples were dried from aqueous suspensions, at 36.5 degrees C, with two amino acid concentrations (0.4 and 0.8 mmol g-1) and at different pH values (1, 6, and 13). The vibrational spectra proved that the nature of L-alanine interactions with both aluminas is the same (hydrogen bonding), although the groups involved depend on the L-alanine form and on alumina surface groups, both controlled by the pH. For samples prepared at pH 1, cationic L-alanine [CH3CH(NH3+)COOH] displaces physisorbed water from alumina, and strong hydrogen bonds are established between the carbonyl groups of alanine, as electron donors, and the surface Al-OH2+ groups of alumina. This occurs at the expense of alanine dimer dissociation and breaking of intramolecular bonds. When samples are prepared at pH 6, the interacting groups are Al-OH2+ and the carboxylate groups of zwitterionic L-alanine [CH3CH(NH3+)COO-]. The affinity of L-alanine toward alumina decreases, as the strong NH3+...-OOC intermolecular hydrogen bonds prevail over the interactions with alumina. Thus, for a load of 0.8 mmol g-1, phase segregation is observed. On alpha-alumina, crystal deposition is even observed for a load of 0.4 mmol g-1. At pH 13, the carboxylate groups of anionic L-alanine [CH3CH(NH2)COO-] are not affected by alumina. Instead, hydrogen bond interactions occur between NH2 and the Al-OH surface groups of the substrate. Complementary N2 adsorption-desorption isotherms showed that adsorption of L-alanine occurs onto the alumina pore network for samples prepared at pH 1 and 13, whereas at pH 6 the amino acid/alumina interactions are not strong enough to promote adsorption. The mesoporous structure and the high specific surface area of gamma-alumina make it a more efficient substrate for adsorption of L-alanine. For each alumina, however, it is

  20. Temperature dependences of piezoelectric, elastic and dielectric constants of L-alanine crystal

    NASA Astrophysics Data System (ADS)

    Tylczyński, Z.; Sterczyńska, A.; Wiesner, M.

    2011-09-01

    Temperature changes in the components of piezoelectric, elastic and dielectric tensors were studied in L-alanine crystals in the range 100-300 K. A jumpwise increase in the c55 component of the elastic stiffness accompanied by maxima in damping of all face-shear modes observed at 199 K in L-alanine crystal were interpreted as a result of changes in the NH3+ vibrations occurring through electron-phonon coupling. All components of the piezoelectric tensor show small anomalies in this temperature range. The components of the electromechanical coupling coefficient determined indicate that L-alanine is a weak piezoelectric.

  1. Optical and Spectral Studies on β Alanine Metal Halide Hybrid Crystals

    NASA Astrophysics Data System (ADS)

    Sweetlin, M. Daniel; Selvarajan, P.; Perumal, S.; Ramalingom, S.

    2011-10-01

    We have synthesized and grown β alanine metal halide hybrid crystals viz. β alanine cadmium chloride (BACC), an amino acid transition metal halide complex crystal and β alanine potassium chloride (BAPC), an amino acid alkali metal halide complex crystal by slow evaporation method. The grown crystals were found to be transparent and have well defined morphology. The optical characteristics of the grown crystals were carried out with the help of UV-Vis Spectroscopy. The optical transmittances of the spectrums show that BAPC is more transparent than BACC. The Photoluminescence of the materials were determined by the Photoluminescent Spectroscopy

  2. Temperature dependences of piezoelectric, elastic and dielectric constants of L-alanine crystal.

    PubMed

    Tylczyński, Z; Sterczyńska, A; Wiesner, M

    2011-09-07

    Temperature changes in the components of piezoelectric, elastic and dielectric tensors were studied in L-alanine crystals in the range 100-300 K. A jumpwise increase in the c(55) component of the elastic stiffness accompanied by maxima in damping of all face-shear modes observed at 199 K in L-alanine crystal were interpreted as a result of changes in the NH(3)(+) vibrations occurring through electron-phonon coupling. All components of the piezoelectric tensor show small anomalies in this temperature range. The components of the electromechanical coupling coefficient determined indicate that L-alanine is a weak piezoelectric.

  3. Alagebrium (ALT-711) improves the anti-hypertensive efficacy of nifedipine in diabetic-hypertensive rats.

    PubMed

    Zhang, Bing; He, Kunlun; Chen, Wei; Cheng, Xianfa; Cui, Hao; Zhong, Wu; Li, Song; Wang, Lili

    2014-10-01

    Combining drugs with complementary mechanisms of action may contribute to improved hypertension control in diabetic patients. Advanced glycation end-product (AGE) breakers, a new class of candidate drugs targeting aging-related cardiovascular dysfunction, may be useful as novel adjuvant agents to improve the efficacy of diabetic hypertension (DH) treatment. This study evaluated the effects of alagebrium (ALT-711), an AGE breaker, combined with nifedipine, a Ca(2+) channel blocker, in a rat model of streptozotocin-induced DH. Compared with monotherapy, combination treatment significantly decreased systolic and diastolic blood pressure values, increased the pulse pressure, and decreased the coefficient of variation of the systolic blood pressure. Plasma biochemistry indicated that the concentrations of prostacyclin and nitric oxide were increased. Gene expression analysis showed significantly decreased prepro-endothelin-1expression in the aorta. These results reveal that alagebrium significantly improves the anti-hypertensive actions of nifedipine in a rat model of DH and suggest its potential use in the successful control of clinical DH.

  4. Structure of Poly(styrene-b-ethylene-alt-propylene) Diblock Copolymer Micelles in Squalane

    SciTech Connect

    Choi, Soo-Hyung; Bates, Frank S.; Lodge, Timothy P.

    2009-11-04

    The temperature dependence of the micellar structures formed by poly(styrene-b-ethylene-alt-propylene) (SEP) diblock copolymers in squalane, a highly selective solvent for the PEP blocks, has been studied using dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS). Four SEP diblock copolymers were prepared by sequential anionic polymerization of styrene and isoprene, followed by hydrogenation of the isoprene blocks, to yield SEP(17-73), SEP(26-66), SEP(36-69), and SEP(42-60), where the numbers indicate block molecular weights in kDa. All four polymers formed well-defined spherical micelles. In dilute solution, DLS provided the temperature-dependent mean hydrodynamic radius, R{sub h}, and its distribution, while detailed fitting of the SAXS profiles gave the core radius, R{sub c}, the equivalent hard sphere radius, R{sub hs}, and an estimate of the aggregation number, N{sub agg}. In general, the micelles became smaller as the critical micelle temperature (CMT) was approached, which was well above the glass transition of the core block. As concentration increased the micelles packed onto body centered cubic lattices for all four copolymers, which underwent order-disorder transitions upon heating near the dilute solution CMTs. The results are discussed in terms of current understanding of block copolymer solution self-assembly, and particular attention is paid to the issue of equilibration, given the high glass transition temperature of the core block.

  5. Flexible Polyimide Aerogel Cross-linked by Poly(maleic Anhydride-alt-alkylene)

    NASA Technical Reports Server (NTRS)

    Guo, Haiquan; Meador, Mary Ann B.; Wilkewitz, Brittany Marie

    2014-01-01

    Aerogels are potential materials for aerospace applications due to their lower thermal conductivity, lighter weight, and low dielectric constant. However, silica aerogels are restricted due to their inherent fragility, hygroscopic nature, and poor mechanical properties, especially in extreme aerospace environments. In order to fit the needs of aerospace applications, developing new thermal insulation materials that are flexible, and moisture resistant is needed. To this end, we fabricated a series of polyimide aerogels crosslinked with different poly(maleic anhydride-alt-alkylene)s as seen in Scheme 1. The polyimide oligomers were made with 3,3,4,4-biphenyltetracarboxylic dianhydride (BPDA), and different diamines or diamine combinations. The resulting aerogels have low density (0.06 gcm3 to 0.16 gcm3) and high surface area (240-440 m2g). The effect of the different backbone structures on density, shrinkage, porosity, surface area, mechanical properties, moisture resistance and thermal properties will be discussed. These novel polyalkylene-imide aerogels may be potential candidates for applications such as space suit insulation for planetary surface missions, insulation for inflatable structures for habitats, inflatable aerodynamic decelerators for entry, descent and landing (EDL) operations, and cryotank insulation for advance space propulsion systems. Scheme 1. Network of polyimide aerogels crosslinked with deifferent poly(maleic anhydride).

  6. "Control-alt-delete": rebooting solutions for the E-waste problem.

    PubMed

    Li, Jinhui; Zeng, Xianlai; Chen, Mengjun; Ogunseitan, Oladele A; Stevels, Ab

    2015-06-16

    A number of efforts have been launched to solve the global electronic waste (e-waste) problem. The efficiency of e-waste recycling is subject to variable national legislation, technical capacity, consumer participation, and even detoxification. E-waste management activities result in procedural irregularities and risk disparities across national boundaries. We review these variables to reveal opportunities for research and policy to reduce the risks from accumulating e-waste and ineffective recycling. Full regulation and consumer participation should be controlled and reinforced to improve local e-waste system. Aiming at standardizing best practice, we alter and identify modular recycling process and infrastructure in eco-industrial parks that will be expectantly effective in countries and regions to handle the similar e-waste stream. Toxicity can be deleted through material substitution and detoxification during the life cycle of electronics. Based on the idea of "Control-Alt-Delete", four patterns of the way forward for global e-waste recycling are proposed to meet a variety of local situations.

  7. Morphological control of calcium oxalate particles in the presence of poly-(styrene-alt-maleic acid)

    NASA Astrophysics Data System (ADS)

    Yu, Jiaguo; Tang, Hua; Cheng, Bei; Zhao, Xiujian

    2004-10-01

    Calcium oxalate (CaOx) particles exhibiting different shapes and phase structures were fabricated by a simple precipitation reaction of sodium oxalate with calcium chloride in the absence and presence of poly-(styrene-alt-maleic acid) (PSMA) as a crystal modifier at room temperature. The as-obtained products were characterized with scanning electron microscopy (SEM) and X-ray diffraction (XRD). The effects of reaction conditions including pH, [Ca2+]/[C2O42-] ratio and concentration of PSMA and CaC2O4 on the crystal forms and morphologies of the as-obtained calcium oxalate were investigated. The results show that various crystal morphologies of calcium oxalate, such as parallelograms, plates, spheres, bipyramids etc. can be obtained depending on the experimental conditions. Higher polymer concentration favors formation of the metastable calcium oxalate dihydrate (COD) crystals. Lower pH is beneficial to the formation of plate-like CaOx crystals. Especially, the monodispersed parallelogram-like CaOx crystals can be produced by PSMA as an additive at pH 2. PSMA may act as a good inhibitor for urolithiasis since it induces the formation of COD and reduces the particle size of CaOx. This research may provide new insight into the morphological control of CaOx particles and the prevention of urolithiasis.

  8. The LTDP ALTS Project: Contributing to the Continued Understanding and Exploitation of the ATSR Time Series

    NASA Astrophysics Data System (ADS)

    Clarke, Hannah; Done, Fay; Casadio, Stefano; Mackin, Stephen; Dinelli, Bianca Maria; Castelli, Elisa

    2016-08-01

    The long time-series of observations made by the Along Track Scanning Radiometers (ATSR) missions represents a valuable resource for a wide range of research and EO applications.With the advent of ESA's Long-TermData Preservation (LTDP) programme, thought has turned to the preservation and improved understanding of such long time-series, to support their continued exploitation in both existing and new areas of research, bringing the possibility of improving the existing data set and to inform and contribute towards future missions. For this reason, the 'Long Term Stability of the ATSR Instrument Series: SWIR Calibration, Cloud Masking and SAA' project, commonly known as the ATSR Long Term Stability (or ALTS) project, is designed to explore the key characteristics of the data set and new and innovative ways of enhancing and exploiting it.Work has focussed on: A new approach to the assessment of Short Wave Infra-Red (SWIR) channel calibration.; Developmentof a new method for Total Column Water Vapour (TCWV) retrieval.; Study of the South Atlantic Anomaly (SAA).; Radiative Transfer (RT) modelling for ATSR.; Providing AATSR observations with their location in the original instrument grid.; Strategies for the retrieval and archiving of historical ATSR documentation.; Study of TCWV retrieval over land; Development of new methods for cloud masking This paper provides an overview of these activities and illustrates the importance of preserving and understanding 'old' data for continued use in the future.

  9. Characterization of the l-alanine exporter AlaE of Escherichia coli and its potential role in protecting cells from a toxic-level accumulation of l-alanine and its derivatives.

    PubMed

    Kim, Seryoung; Ihara, Kohei; Katsube, Satoshi; Hori, Hatsuhiro; Ando, Tasuke; Isogai, Emiko; Yoneyama, Hiroshi

    2015-08-01

    We previously reported that the alaE gene of Escherichia coli encodes the l-alanine exporter AlaE. The objective of this study was to elucidate the mechanism of the AlaE exporter. The minimum inhibitory concentration of l-alanine and l-alanyl-l-alanine in alaE-deficient l-alanine-nonmetabolizing cells MLA301ΔalaE was 4- and >4000-fold lower, respectively, than in the alaE-positive parent cells MLA301, suggesting that AlaE functions as an efflux pump to avoid a toxic-level accumulation of intracellular l-alanine and its derivatives. Furthermore, the growth of the alaE-deficient mutant derived from the l-alanine-metabolizing strain was strongly inhibited in the presence of a physiological level of l-alanyl-l-alanine. Intact MLA301ΔalaE and MLA301ΔalaE/pAlaE cells producing plasmid-borne AlaE, accumulated approximately 200% and 50%, respectively, of the [(3) H]l-alanine detected in MLA301 cells, suggesting that AlaE exports l-alanine. When 200 mmol/L l-alanine-loaded inverted membrane vesicles prepared from MLA301ΔalaE/pAlaE were placed in a solution containing 200 mmol/L or 0.34 μmol/L l-alanine, energy-dependent [(3) H]l-alanine accumulation occurred under either condition. This energy-dependent uphill accumulation of [(3) H]l-alanine was strongly inhibited in the presence of carbonyl cyanide m-chlorophenylhydrazone but not by dicyclohexylcarbodiimide, suggesting that the AlaE-mediated l-alanine extrusion was driven by proton motive force. Based on these results, physiological roles of the l-alanine exporter are discussed.

  10. Characterization of the l-alanine exporter AlaE of Escherichia coli and its potential role in protecting cells from a toxic-level accumulation of l-alanine and its derivatives

    PubMed Central

    Kim, Seryoung; Ihara, Kohei; Katsube, Satoshi; Hori, Hatsuhiro; Ando, Tasuke; Isogai, Emiko; Yoneyama, Hiroshi

    2015-01-01

    We previously reported that the alaE gene of Escherichia coli encodes the l-alanine exporter AlaE. The objective of this study was to elucidate the mechanism of the AlaE exporter. The minimum inhibitory concentration of l-alanine and l-alanyl-l-alanine in alaE-deficient l-alanine-nonmetabolizing cells MLA301ΔalaE was 4- and >4000-fold lower, respectively, than in the alaE-positive parent cells MLA301, suggesting that AlaE functions as an efflux pump to avoid a toxic-level accumulation of intracellular l-alanine and its derivatives. Furthermore, the growth of the alaE-deficient mutant derived from the l-alanine-metabolizing strain was strongly inhibited in the presence of a physiological level of l-alanyl-l-alanine. Intact MLA301ΔalaE and MLA301ΔalaE/pAlaE cells producing plasmid-borne AlaE, accumulated approximately 200% and 50%, respectively, of the [3H]l-alanine detected in MLA301 cells, suggesting that AlaE exports l-alanine. When 200 mmol/L l-alanine-loaded inverted membrane vesicles prepared from MLA301ΔalaE/pAlaE were placed in a solution containing 200 mmol/L or 0.34 μmol/L l-alanine, energy-dependent [3H]l-alanine accumulation occurred under either condition. This energy-dependent uphill accumulation of [3H]l-alanine was strongly inhibited in the presence of carbonyl cyanide m-chlorophenylhydrazone but not by dicyclohexylcarbodiimide, suggesting that the AlaE-mediated l-alanine extrusion was driven by proton motive force. Based on these results, physiological roles of the l-alanine exporter are discussed. PMID:26073055

  11. Rapid Ti(III) reduction of perchlorate in the presence of beta-alanine: kinetics, pH effect, complex formation, and beta-alanine effect.

    PubMed

    Wang, Chao; Huang, Zhengdao; Lippincott, Lee; Meng, Xiaoguang

    2010-03-15

    Ti(III) reduction of perchlorate might be a useful method for the treatment of highly perchlorate-contaminated water. Though the reaction rate was usually low, we observed that beta-alanine (HOOCCH(2)CH(2)NH(2)) could significantly promote the reaction. A complete (>99.9%) perchlorate removal was obtained in a solution containing [ClO(4)(-)]=1.0mM, [Ti(III)]=40 mM, and [beta-alanine]=120 mM after 2.5h of reaction under 50 degrees C. The effects of both pH and complex formation on the reaction were then studied. The results showed that without beta-alanine the optimal pH was 2.3. When pH increased from 1.6 to 2.3, the reduction rate increased remarkably. In the pH range >2.3, however, the reduction was significantly inhibited, attributed to the formation of Ti(III) precipitate. The presence of beta-alanine at a molar ratio of [beta-alanine]:[Ti(III)]=3:1 significantly increased the reduction rate of perchlorate even at near neutral pH. This is because beta-alanine formed complexes with Ti(III), which greatly improved the total soluble [Ti(III)] in the pH range between 3.5 and 6. The findings may lead to the development of rapid treatment methods for intermittent and small stream of highly perchlorate-contaminated water, which are resulted from the manufacturing, storage, handling, use and/or disposal of large quantities of perchlorate salts.

  12. Na+-coupled alanine transport in LLC-PK1 cells: the relationship between the Km for Na+ at low [Alanine] and potential dependence for the system.

    PubMed

    Wilson, J J; Randles, J; Kimmich, G A

    1998-10-01

    Analysis of the mechanistic basis by which sodium-coupled transport systems respond to changes in membrane potential is inherently complex. Algebraic expressions for the primary kinetic parameters (Km and Vmax) consist of multiple terms that encompass most rate constants in the transport cycle. Even for a relatively simple cotransport system such as the Na+/alanine cotransporter in LLC-PK1 cells (1:1 Na+ to substrate coupling, and an ordered binding sequence), the algebraic expressions for Km for either substrate includes ten of the twelve rate constants necessary for modeling the full transport cycle. We show here that the expression of Km of the first-bound substrate (Na+) simplifies markedly if the second-bound substrate (alanine) is held at a low concentration so that its' binding becomes the rate limiting step. Under these conditions, the expression for the KNam includes rate constants for only two steps in the full cycle: (i) binding/dissociation of Na+, and (ii) conformational 'translocation' of the substrate-free protein. The influence of imposed changes in membrane potential on the apparent KNam for the LLC-PK1 alanine cotransporter at low alanine thus provides insight to potential dependence at these sites. The data show no potential dependence for KNam at 5 micron alanine, despite marked potential dependence at 2 mm alanine when the full algebraic expression applies. The results suggest that neither translocation of the substrate-free form of the transporter nor binding/dissociation of extracellular sodium are potential dependent events for this transport system.

  13. A comparative study on the growth and characterization of nonlinear optical amino acid crystals: L-alanine (LA) and L-alanine alaninium nitrate (LAAN).

    PubMed

    Aravindan, A; Srinivasan, P; Vijayan, N; Gopalakrishnan, R; Ramasamy, P

    2008-11-15

    A comparative study on the properties of L-alanine and LAAN crystals has been made and discussed. It may be concluded that the protonation of the amino group in the L-alanine molecule is the key factor in increasing the relative SHG efficiency of LAAN. The protonation is justified by the crystal structure analysis, FTIR and photoluminescence studies. The factor group vibrations are compared and found that there is an increase in vibrational modes of LA when reacted with nitric acid forming LAAN.

  14. Determination of the carbon, hydrogen and nitrogen contents of alanine and their uncertainties using the certified reference material L-alanine (NMIJ CRM 6011-a).

    PubMed

    Itoh, Nobuyasu; Sato, Ayako; Yamazaki, Taichi; Numata, Masahiko; Takatsu, Akiko

    2013-01-01

    The carbon, hydrogen, and nitrogen (CHN) contents of alanine and their uncertainties were estimated using a CHN analyzer and the certified reference material (CRM) L-alanine. The CHN contents and their uncertainties, as measured using the single-point calibration method, were 40.36 ± 0.20% for C, 7.86 ± 0.13% for H, and 15.66 ± 0.09% for N; the results obtained using the bracket calibration method were also comparable. The method described in this study is reasonable, convenient, and meets the general requirement of having uncertainties ≤ 0.4%.

  15. Inducible L-alanine exporter encoded by the novel gene ygaW (alaE) in Escherichia coli.

    PubMed

    Hori, Hatsuhiro; Yoneyama, Hiroshi; Tobe, Ryuta; Ando, Tasuke; Isogai, Emiko; Katsumata, Ryoichi

    2011-06-01

    We previously isolated a mutant hypersensitive to L-alanyl-L-alanine from a non-L-alanine-metabolizing Escherichia coli strain and found that it lacked an inducible l-alanine export system. Consequently, this mutant showed a significant accumulation of intracellular L-alanine and a reduction in the L-alanine export rate compared to the parent strain. When the mutant was used as a host to clone a gene(s) that complements the dipeptide-hypersensitive phenotype, two uncharacterized genes, ygaW and ytfF, and two characterized genes, yddG and yeaS, were identified. Overexpression of each gene in the mutant resulted in a decrease in the intracellular l-alanine level and enhancement of the L-alanine export rate in the presence of the dipeptide, suggesting that their products function as exporters of L-alanine. Since ygaW exhibited the most striking impact on both the intra- and the extracellular L-alanine levels among the four genes identified, we disrupted the ygaW gene in the non-L-alanine-metabolizing strain. The resulting isogenic mutant showed the same intra- and extracellular L-alanine levels as observed in the dipeptide-hypersensitive mutant obtained by chemical mutagenesis. When each gene was overexpressed in the wild-type strain, which does not intrinsically excrete alanine, only the ygaW gene conferred on the cells the ability to excrete alanine. In addition, expression of the ygaW gene was induced in the presence of the dipeptide. On the basis of these results, we concluded that YgaW is likely to be the physiologically most relevant exporter for L-alanine in E. coli and proposed that the gene be redesignated alaE for alanine export.

  16. Inducible l-Alanine Exporter Encoded by the Novel Gene ygaW (alaE) in Escherichia coli ▿

    PubMed Central

    Hori, Hatsuhiro; Yoneyama, Hiroshi; Tobe, Ryuta; Ando, Tasuke; Isogai, Emiko; Katsumata, Ryoichi

    2011-01-01

    We previously isolated a mutant hypersensitive to l-alanyl-l-alanine from a non-l-alanine-metabolizing Escherichia coli strain and found that it lacked an inducible l-alanine export system. Consequently, this mutant showed a significant accumulation of intracellular l-alanine and a reduction in the l-alanine export rate compared to the parent strain. When the mutant was used as a host to clone a gene(s) that complements the dipeptide-hypersensitive phenotype, two uncharacterized genes, ygaW and ytfF, and two characterized genes, yddG and yeaS, were identified. Overexpression of each gene in the mutant resulted in a decrease in the intracellular l-alanine level and enhancement of the l-alanine export rate in the presence of the dipeptide, suggesting that their products function as exporters of l-alanine. Since ygaW exhibited the most striking impact on both the intra- and the extracellular l-alanine levels among the four genes identified, we disrupted the ygaW gene in the non-l-alanine-metabolizing strain. The resulting isogenic mutant showed the same intra- and extracellular l-alanine levels as observed in the dipeptide-hypersensitive mutant obtained by chemical mutagenesis. When each gene was overexpressed in the wild-type strain, which does not intrinsically excrete alanine, only the ygaW gene conferred on the cells the ability to excrete alanine. In addition, expression of the ygaW gene was induced in the presence of the dipeptide. On the basis of these results, we concluded that YgaW is likely to be the physiologically most relevant exporter for l-alanine in E. coli and proposed that the gene be redesignated alaE for alanine export. PMID:21531828

  17. Titration of Alanine Monitored by NMR Spectroscopy: A Biochemistry Laboratory Experiment

    ERIC Educational Resources Information Center

    Waller, Francis J.; And Others

    1977-01-01

    The experiment described here involves simultaneous monitoring of pH and NMR chemical shifts during an aqueous titration of alpha- and beta-alanine. This experiment is designed for use in an undergraduate biochemistry course. (MR)

  18. Alanine blends for ESR measurements of thermal neutron fluence in a mixed radiation field.

    PubMed

    Marrale, M; Brai, M; Gennaro, G; Triolo, A; Bartolotta, A; D'Oca, M C; Rosi, G

    2007-01-01

    In this paper, the results of a study on the electron spin resonance (ESR) dosimetry to measure thermal neutron fluence in a mixed radiation field (neutron and photons) are presented. The ESR responses of alanine dosemeters with different additives are compared. In particular, the (10)B-acid boric and the Gd-oxide were chosen to enhance the sensitivity of alanine dosemeters to thermal neutrons. Irradiations were carried out inside the thermal column of the TAPIRO reactor of the ENEA center, Casaccia Rome. The main results are a greater neutron sensitivity and a smaller lowest detectable fluence for the dosemeters with gadolinium than for dosemeters of alanine with (10)B, which is well known to be much more sensitive to thermal neutrons than simple alanine.

  19. Titration of Alanine Monitored by NMR Spectroscopy: A Biochemistry Laboratory Experiment

    ERIC Educational Resources Information Center

    Waller, Francis J.; And Others

    1977-01-01

    The experiment described here involves simultaneous monitoring of pH and NMR chemical shifts during an aqueous titration of alpha- and beta-alanine. This experiment is designed for use in an undergraduate biochemistry course. (MR)

  20. Second harmonic generation studies in L-alanine single crystals grown from solution

    NASA Astrophysics Data System (ADS)

    Boomadevi, Shanmugam; Pandiyan, Krishnamoorthy

    2014-01-01

    Single crystals of L-alanine of dimensions 2×1.1×0.5 cm3 were grown by evaporation method using deionised water as a solvent. The morphology of the grown crystals had (1 2 0) and (0 1 1) as their prominent faces. UV-vis-near IR spectrum shows the transparency range of L-alanine crystal available for frequency doubling from 250 to 1400 nm. Phase-matched second harmonic generation was observed in L-alanine sample by using 7 ns Q-switched Nd:YAG laser with OPO set up. In the present work, phase matching was achieved by angle and wavelength tuning. The angular and spectral phase-matching bandwidths were determined experimentally for a 1.5 mm thick L-alanine crystal and the results have been compared with their theoretical results. Further the possible reasons for the broadening of SHG spectrum have been discussed.

  1. Low-frequency electromagnetic fields induce a stress effect upon higher plants, as evident by the universal stress signal, alanine.

    PubMed

    Ben-Izhak Monselise, Edna; Parola, Abraham H; Kost, Daniel

    2003-03-07

    15N NMR analysis reveals alanine production in Duckweed plants exposed to low intensity sinusoidally varying magnetic fields (SVMF) at 60 and 100Hz, and fed by 15N-labeled ammonium chloride. Alanine does not accumulate in the absence of SVMF. Addition of vitamin C, a radical scavenger, reduced alanine production by 82%, indicating the roll of free radicals in the process. Alanine accumulation in plants and animals in response to exposure to a variety of stress conditions, including SVMF, is a general phenomenon. It is proposed that alanine is a universal first stress signal expressed by cells.

  2. Repeated Supramaximal Exercise-Induced Oxidative Stress: Effect of β-Alanine Plus Creatine Supplementation

    PubMed Central

    Belviranli, Muaz; Okudan, Nilsel; Revan, Serkan; Balci, Serdar; Gokbel, Hakki

    2016-01-01

    Background: Carnosine is a dipeptide formed from the β-alanine and histidine amino acids and found in mainly in the brain and muscle, especially fast twitch muscle. Carnosine and creatine has an antioxidant effect and carnosine accounts for about 10% of the muscle's ability to buffer the H+ ions produced by exercise. Objectives: The aim of the study was to investigate the effects of beta alanine and/or creatine supplementation on oxidant and antioxidant status during repeated Wingate tests (WTs). Patients and Methods: Forty four sedentary males participated in the study. Participants performed three 30s WTs with 2 minutes rest between exercise bouts. After the first exercise session, the subjects were assigned to one of four groups: Placebo, Creatine, Beta-alanine and Beta-alanine plus creatine. Participants ingested twice per day for 22 consecutive days, then four times per day for the following 6 days. After the supplementation period the second exercise session was applied. Blood samples were taken before and immediately after the each exercise session for the analysis of oxidative stress and antioxidant markers. Results: Malondialdehyde levels and superoxide dismutase activities were affected by neither supplementation nor exercise. During the pre-supplementation session, protein carbonyl reduced and oxidized glutathione (GSH and GSSG) levels increased immediately after the exercise. However, during the post-supplementation session GSH and GSSG levels increased in beta-alanine and beta-alanine plus creatine groups immediately after the exercise compared to pre-exercise. In addition, during the post-supplementation session total antioxidant capacity increased in beta-alanine group immediately after the exercise. Conclusions: Beta-alanine supplementation has limited antioxidant effect during the repeated WTs. PMID:27217925

  3. SU-E-T-643: Pure Alanine Dosimeter for Verification Dosimetry in IMRT

    SciTech Connect

    Al-Karmi, Anan M.; Zraiqat, Fadi

    2015-06-15

    Purpose: The objective of this study was evaluation of accuracy of pure alanine dosimeters measuring intensity-modulated radiation therapy (IMRT) dose distributions in a thorax phantom. Methods: Alanine dosimeters were prepared in the form of 110 mg pure L-α-alanine powder filled into clear tissue-equivalent polymethylmethacrylate (PMMA) plastic tubes with the dimensions 25 mm length, 3 mm inner diameter, and 1 mm wall thickness. A dose-response calibration curve was established for the alanine by placing the dosimeters at 1.5 cm depth in a 30×30×30 cm{sup 3} solid water phantom and then irradiating on a linac with 6 MV photon beam at 10×10 cm{sup 2} field size to doses ranging from 1 to 5 Gy. Electron paramagnetic resonance (EPR) spectroscopy was used to determine the absorbed dose in alanine. An IMRT treatment plan was designed for a commercial heterogeneous CIRS thorax phantom and the dose values were calculated at three different points located in tissue, lung, and bone equivalent materials. A set of dose measurements was carried out to compare measured and calculated dose values by placing the alanine dosimeters at those selected locations inside the thorax phantom and delivering the IMRT to the phantom. Results: The alanine dose measurements and the IMRT plan dose calculations were found to be in agreement within ±2%. Specifically, the deviations were −0.5%, 1.3%, and −1.7% for tissue, lung, and bone; respectively. The slightly large deviations observed for lung and bone may be attributed to tissue inhomogeneity, steep dose gradients in these regions, and uncontrollable changes in spectrometer conditions. Conclusion: The results described herein confirmed that pure alanine dosimeter was suitable for in-phantom dosimetry of IMRT beams because of its high sensitivity and acceptable accuracy. This makes the dosimeter a promising option for quality control of the therapeutic beams, complementing the commonly used ionization chambers, TLDs, and films.

  4. Effect of beta-alanine treatment on mitochondrial taurine level and 5-taurinomethyluridine content.

    PubMed

    Jong, Chian Ju; Ito, Takashi; Mozaffari, Mahmood; Azuma, Junichi; Schaffer, Stephen

    2010-08-24

    The beta-amino acid, taurine, is a nutritional requirement in some species. In these species, the depletion of intracellular stores of taurine leads to the development of severe organ dysfunction. The basis underlying these defects is poorly understood, although there is some suggestion that oxidative stress may contribute to the abnormalities. Recent studies indicate that taurine is required for normal mitochondrial protein synthesis and normal electron transport chain activity; it is known that defects in these events can lead to severe mitochondrial oxidative stress. The present study examines the effect of taurine deficiency on the first step of mitochondrial protein synthesis regulation by taurine, namely, the formation of taurinomethyluridine containing tRNA. Isolated rat cardiomyocytes were rendered taurine deficient by incubation with medium containing the taurine transport inhibitor, beta-alanine. The time course of cellular and mitochondrial taurine depletion was measured. The primer extension method was employed to evaluate the effect of beta-alanine treatment on taurinomethyluridine content of tRNALeu. The protein levels of ND6 were also determined by Western blot analysis. beta-alanine caused a time-dependent decrease in cellular taurine content, which were reduced in half after 48 hrs of incubation. The amount of taurine in the mitochondria was considerably less than that in the cytosol and was unaffected by beta-alanine treatment. Approximately 70% of the tRNALeu in the untreated cell lacked taurinomethyluridine and these levels were unchanged following beta-alanine treatment. Protein content of ND6, however, was significantly reduced after 48 hours incubation with beta-alanine. The taurine levels of the cytosol and the mitochondria are not directly coupled. The beta-alanine-mediated reduction in taurine levels is too small to affect taurinomethyluridine levels. Nonetheless, it interferes with mitochondrial protein synthesis, as exemplified by a

  5. Effect of abomasal glucose infusion on alanine metabolism and urea production in sheep.

    PubMed

    Obitsu, T; Bremner, D; Milne, E; Lobley, G E

    2000-08-01

    The effect of abomasal infusion of glucose (120 kJ/d per kg body weight (BW)0.75, 758 mmol/d) on urea production, plasma alanine-N flux rate and the conversion of alanine-N to urea was studied in sheep offered a low-N diet at limited energy intake (500 kJ/d per kg BW0.75), based on hay and grass pellets. Glucose provision reduced urinary N (P = 0.040) and urea (P = 0.009) elimination but this was offset by poorer N digestibility. Urea-N production was significantly reduced (822 v. 619 mmol/d, P = 0.024) by glucose while plasma alanine-N flux rate was elevated (295 v. 342 mmol/d, P = 0.011). The quantity of urea-N derived from alanine tended to be decreased by glucose (127 v. 95 mmol/d) but the fraction of urea production from alanine was unaltered (15%). Plasma urea and alanine concentrations (plus those of the branched chain amino acids) decreased in response to exogenous glucose, an effect probably related to enhanced anabolic usage of amino acids and lowered urea production.

  6. Electrochemical analysis of the alanine phenylthiohydantoin derivative by cathodic stripping voltammetry.

    PubMed

    Vilaseca, C; Quintana, M C; Vicente, J; Hernández, P; Hernández, L

    2008-08-01

    A square-wave cathodic stripping voltammetry method for alanine determination as its phenylthiohydantoin (PTH-alanine) derivative is developed. To this end, all the chemical and instrumental variables affecting the determination of PTH-alanine are optimized. From studies of the mechanisms governing the electrochemical response of PTH-alanine, it was concluded that it is an electrochemically irreversible system with a diffusive-adsorptive reduction phenomenon. Under optimal conditions, the variation of analytical signal (I(p)) with PTH-alanine concentration is linear in the 2.4x10(-8)-4.8x10(-7) M range, with a LOD of 1.2x10(-8) M and a LOQ of 4.2x10(-8) M, a RSD (%) less than 11%, and a E(r) (%) less than 10%. The optimized method was applied to the determination of PTH-alanine obtained from a synthetic protein after Edman reaction and the results were corroborated by high-performance liquid chromatography with UV detection.

  7. [Alanine solution as enzyme reaction buffer used in A to O blood group conversion].

    PubMed

    Li, Su-Bo; Zhang, Xue; Zhang, Yin-Ze; Tan, Ying-Xia; Bao, Guo-Qiang; Wang, Ying-Li; Ji, Shou-Ping; Gong, Feng; Gao, Hong-Wei

    2014-06-01

    The aim of this study was to investigate the effect of alanine solution as α-N-acetylgalactosaminidase enzyme reaction buffer on the enzymatic activity of A antigen. The binding ability of α-N-acetylgalactosaminidase with RBC in different reaction buffer such as alanine solution, glycine solution, normal saline (0.9% NaCl), PBS, PCS was detected by Western blot. The results showed that the efficiency of A to O conversion in alanine solution was similar to that in glycine solution, and Western blot confirmed that most of enzymes blinded with RBC in glycine or alanine solution, but few enzymes blinded with RBC in PBS, PCS or normal saline. The evidences indicated that binding of enzyme with RBC was a key element for A to O blood group conversion, while the binding ability of α-N-acetylgalactosaminidase with RBC in alanine or glycine solution was similar. It is concluded that alanine solution can be used as enzyme reaction buffer in A to O blood group conversion. In this buffer, the α-N-acetylgalactosaminidase is closely blinded with RBC and α-N-acetylgalactosaminidase plays efficient enzymatic activity of A antigen.

  8. A radiometric and petrographic approach to risk assessment at Alte Madonie Mounts region (Sicily, Italy).

    PubMed

    Lanzo, G; Rizzo, S; Tomarchio, E

    2014-03-01

    The main goal of this work was to assess the radiological hazard at Alte Madonie Mounts region (north-central Sicily, Italy) in response to rumours of an increase in the incidence of cancer in this area. A correlation between the natural radionuclide contents and the petrographic features of the soil and rock samples was also evaluated. A total of 41 samples of selected soils and rocks were collected, powdered, dried and sealed in 'Marinelli' beakers for 20 d prior to measurement to ensure that a radioactive equilibrium between (226)Ra and (214)Bi had been reached. A gamma-ray spectrometer was used to quantify the radioactivity concentrations. To determine (238)U and (232)Th activities, the 609.3-keV line from (214)Bi in secular equilibrium with (226)Ra and the 911-keV line from (228)Ac, with which (232)Th can be assumed to be in equilibrium, were used, respectively. The gamma transition of 1461 keV was used to determine (40)K activity. The average values of the concentrations of (214)Bi, (228)Ac and (40)K were 30, 17 and 227 Bq kg(-1), respectively, whereas the greatest values were 134, 59 and 748 Bq kg(-1), respectively. A linear relationship was found between the activity values of (214)Bi, (228)Ac and (40)K. An exception was found for a group of samples in which the (214)Bi activities were much higher than expected. The chemical compositions and mineralogical features of the samples permitted the justification of these anomalies. The results of the primordial radionuclide contents are reassuring from a radiation protection point of view because the activities of the uranium and thorium series products and of the (40)K do not present a significant radiological hazard.

  9. Self-healing pH-sensitive poly[(methyl vinyl ether)-alt-(maleic acid)]-based supramolecular hydrogels formed by inclusion complexation between cyclodextrin and adamantane.

    PubMed

    Ma, Xiaoe; Zhou, Naizhen; Zhang, Tianzhu; Hu, Wanjun; Gu, Ning

    2017-04-01

    Self-healing materials are of interest for drug delivery, cell and gene therapy, tissue engineering, and other biomedical applications. In this work, on the base of biocompatible polymer poly(methyl vinyl ether-alt-maleic acid) (P(MVE-alt-MA)), host polymer β-cyclodextrin-grafted P(MVE-alt-MA) (P(MVE-alt-MA)-g-β-CD) and guest polymer adamantane-grafted P(MVE-alt-MA) (P(MVE-alt-MA)-g-Ad) were first prepared. Then through taking advantage of the traditional host-guest interaction of β-cyclodextrin and adamantane, a novel self-healing pH-sensitive physical P(MVE-alt-MA)-g-β-CD/P(MVE-alt-MA)-g-Ad supramolecular hydrogels were obtained after simply mixing the aqueous solution of host polymer and guest polymer. This kind of supramolecular hydrogels not only possess pH-sensitivity, but also possess the ability to repair themselves after being damaged. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. ESR response to gamma-rays of alanine pellets containing B(OH)3 or Gd2O3.

    PubMed

    Brai, M; Gennaro, G; Marrale, M; Bartolotta, A; D'Oca, M C

    2007-04-01

    ESR response to gamma-irradiation (1-50 Gy) of blends containing alanine and either B(OH)(3) or Gd(2)O(3) is reported. The sensitivity of the alanine--B(OH)(3) blend is comparable to the sensitivity of pure alanine, although its lowest detectable dose, LDD, is smaller ( approximately 1.3 Gy) than that of pure alanine ( approximately 2.9 Gy). Alanine with Gd(2)O(3) is about two times more sensitive than pure alanine, and its LDD is 0.8 Gy. The better sensitivity and LDD are probably due to the high atomic number (Z=64) of gadolinium, which enhances the interaction probability with photons and, consequently, the radical yield. This study suggests that other high-Z atoms may be useful for increasing the sensitivity of the response of alanine to gamma-radiation.

  11. Expression, crystallization and preliminary X-ray crystallographic analysis of D-alanine-D-alanine ligase from OXA-23-producing Acinetobacter baumannii K0420859.

    PubMed

    Huynh, Kim-Hung; Tran, Huyen-Thi; Pham, Tan-Viet; Ngo, Ho-Phuong-Thuy; Cha, Sun-Shin; Chung, Kyung Min; Lee, Sang Hee; Kang, Lin-Woo

    2014-04-01

    Acinetobacter baumannii causes bacteraemia, pneumonia, other respiratory-tract and urinary-tract infections in humans. OXA-23 carbapenemase-producing A. baumannii K0420859 (A. baumannii OXA-23) is resistant to carbapenem, a common antibacterial drug. To develop an efficient and novel antibacterial drug against A. baumannii OXA-23, D-alanine-D-alanine ligase, which is essential in bacterial cell-wall synthesis, is of interest. Here, the D-alanine-D-alanine ligase (AbDdl) gene from A. baumannii OXA-23 was cloned and expressed, and the AbDdl protein was purified and crystallized; this enzyme can be used as a novel target for an antibacterial drug against A. baumannii OXA-23. The AbDdl crystal diffracted to a resolution of 2.8 Å and belonged to the orthorhombic space group P212121, with unit-cell parameters a = 113.4, b = 116.7, c = 176.5 Å, a corresponding VM of 2.8 Å(3) Da(-1) and a solvent content of 56.3%, and six protomers in the asymmetric unit.

  12. The Symptoms of Gastroesophageal Reflux Disease Correlate with High Body Mass Index, the Aspartate Aminotransferase/Alanine Aminotransferase Ratio and Insulin Resistance in Japanese Patients with Non-alcoholic Fatty Liver Disease.

    PubMed

    Fujiwara, Motoshi; Eguchi, Yuichiro; Fukumori, Norio; Eguchi, Hitoshi; Tomonaga, Motosuke; Yoshioka, Tsuneaki; Hyakutake, Masaki; Sakanishi, Yuta; Kyoraku, Itaru; Sugioka, Takashi; Fujimoto, Kazuma; Kusano, Motoyasu; Yamashita, Shu-ichi

    2015-01-01

    This study was designed to compare the association between the body mass index (BMI) and symptoms of gastroesophageal reflux disease (GERD) in allegedly normal subjects undergoing regular medical checkups and subjects diagnosed with non-alcoholic fatty liver disease (NAFLD). Additionally, the correlation between the BMI and GERD symptoms was evaluated in subjects with NAFLD. This study included 50 patients with NAFLD and 228 normal subjects evaluated during regular medical checkups. The height, weight, BMI, frequency scale for the symptoms of GERD (FSSG), and serum concentrations of triglycerides and γ-GTP were compared between the two groups. In the NAFLD group, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations were measured and insulin resistance was calculated using the quantitative insulin sensitivity check index (QUICKI). The total FSSG score moderately correlated with the BMI in the NAFLD group (r=0.342, p=0.015), but correlated negatively in the control group (r=-0.014, p=0.831). The FSSG score in the NAFLD group also negatively correlated with the AST/ALT ratio (r=-0.319) and insulin resistance calculated using the QUICKI score (r=-0.288). The BMI in the NAFLD group moderately correlated with the acid-reflux related score on the FSSG (r=0.389), and both the AST/ALT ratio (r=-0.344) and QUICKI score (r=-0.330) negatively correlated with the dyspepsia score on the FSSG. Obesity evaluated by the BMI was a significant risk factor for the exacerbation of GERD symptoms in subjects with NAFLD.

  13. Effect of Commiphora mukul gum resin on hepatic marker enzymes, lipid peroxidation and antioxidants status in pancreas and heart of streptozotocin induced diabetic rats

    PubMed Central

    Ramesh, B; Karuna, R; Sreenivasa, Reddy S; Haritha, K; Sai, Mangala D; Sasi, Bhusana Rao B; Saralakumari, D

    2012-01-01

    Objective To study the antioxidant efficacy of Commiphora mukul (C. mukul) gum resin ethanolic extract in streptozotocin (STZ) induced diabetic rats. Methods The male Wistar albino rats were randomly divided into four groups of eight animals each: Control group (C), CM-treated control group (C+CMEE), Diabetic control group (D), CM- treated diabetic group (D+CMEE). Diabetes was induced by intraperitoneal injection of STZ (55 mg/kg/ bwt). After being confirmed the diabetic rats were treated with C. mukul gum resin ethanolic extract (CMEE) for 60 days. The biochemical estimations like antioxidant, oxidative stress marker enzymes and hepatic marker enzymes of tissues were performed. Results The diabetic rats showed increased level of enzymatic activities aspartate aminotransaminase (AST), alanine aminotransaminase (ALT) in liver and kidney and oxidative markers like lipid peroxidation (LPO) and protein oxidation (PO) in pancreas and heart. Antioxidant enzyme activities were significantly decreased in the pancreas and heart compared to control group. Administration of CMEE (200 mg/kg bw) to diabetic rats for 60 days significantly reversed the above parameters towards normalcy. Conclusions In conclusion, our data indicate the preventive role of C. mukul against STZ-induced diabetic oxidative stress; hence this plant could be used as an adjuvant therapy for the prevention and/or management of diabetes and aggravated antioxidant status. PMID:23569867

  14. Simple synthesis of P(Cbz-alt-TBT) and PCDTBT by combining direct arylation with suzuki polycondensation of heteroaryl chlorides.

    PubMed

    Lombeck, Florian; Matsidik, Rukiya; Komber, Hartmut; Sommer, Michael

    2015-01-01

    Direct arylation (DA) of 2-chlorothiophene and 2-chloro-3-hexylthiophene with 4,7-dibromo-2,1,3-benzothiadiazole is used to synthesize 4,7-bis(5-chloro-2-thienyl)-2,1,3-benzothiadiazole (TBTCl2) and 4,7-bis(5-chloro-4-hexyl-2-thienyl)-2,1,3-benzothiadiazole (DH-TBTCl2) in one step. Suitable conditions of the Suzuki polycondensations (SPC) of TBTCl2 and DH-TBTCl2 with the carbazole comonomer CbzPBE2 are established, furnishing PCDTBT and P(Cbz-alt-TBT) with high molecular weight and yield. Compared with control samples made from the corresponding dibromides, high-temperature NMR and UV-vis spectroscopy indicate similar properties for PCDTBT but an increased content of Cbz-Cbz homocouplings for P(Cbz-alt-TBT).

  15. Comparison Study II: Double Star Measurements Made Using an Equatorial Mounted Refractor and an Alt-Az Mounted Reflector

    NASA Astrophysics Data System (ADS)

    Frey, Thomas G.; Coombs, Lee C.

    2012-07-01

    Eight double stars with separations between 13 and 48 arc seconds were studied. Their separations and position angles were measured using an equatorial mounted refractor and and alt-az mounted reflector. A 2x Barlow lens was used along with a Celestron Micro Guide eyepiece to magnify the separation. Comparison of the possible effect of magnitude difference on the separation and position angle measurements was investigated.

  16. Clinico-biochemical factors to early predict biliary etiology of acute pancreatitis: age, female gender, and ALT

    PubMed Central

    Zarnescu, NO; Costea, R; Zarnescu (Vasiliu), EC; Neagu, S

    2015-01-01

    Background/ Aims: Despite the existence of an easy tool to diagnose biliary tract disease as an etiology for acute pancreatitis (AP), the sensitivity of abdominal ultrasound is around 80%, which can be even lower in certain conditions. Methodology: We have retrospectively reviewed data of 146 patients admitted for acute pancreatitis between 1999 and 2013. Bivariate analysis for clinical and biochemical variables was performed with respect to etiology of AP (biliary versus non-biliary). Multivariate analysis was performed by using binary logistic regression. Results: There were 87 males (59.6%) and 59 females (40.4%), with a median age of 51. The etiology of acute pancreatitis was biliary in 71 patients (48.6%). Bivariate analysis found the following as significant association (p=0.001) with biliary pancreatitis: older age, female gender, and elevated AST, ALT. A binary logistic regression analysis identified as predictor factors for biliary etiology of acute pancreatitis: age OR = 1.031 (95% CI 1.004 - 1.059, p = 0.024), sex (female) OR = 2.34 (95% CI 1.022 - 5.359, p = 0.044) and ALT OR = 1.004 (95% CI 1.001 - 1.007, p =0.004). The two clinical scores included the three variables (A.S.ALT scores) in categorical format were generated and then checked with the ROC curves (areas under curve are 0.768 and 0.778). Conclusions: Age, female gender, and elevated ALT can help identifying cases with biliary etiology of acute pancreatitis. PMID:26664483

  17. FTIR spectra and conformational structure of deutero-β-alanine isolated in argon matrices

    NASA Astrophysics Data System (ADS)

    Stepanian, Stepan G.; Ivanov, Alexander Yu; Adamowicz, Ludwik

    2016-02-01

    Low temperature FTIR spectra of β-alanine-d3 isolated in argon matrices are used to determine the conformational composition of this compound. UV irradiation of the matrix samples is found to change the relative populations of the β-alanine-d3 conformers. The populations of conformers I and II with an Nsbnd D⋯O intramolecular H-bond decrease after the UV irradiation while the populations of conformer V with an N⋯Dsbnd O H-bond and conformer IV which has no intramolecular H-bonds increase. This behavior of the β-alanine-d3 conformers are used to separate the bands of the different conformers. The analysis of the experimental FTIR spectra is based on the calculated harmonic B3LYP/6-311++G(df,pd) frequencies and on the MP2/aug-cc-pVDZ frequencies calculated with a method that includes anharmonic effects. Polynomial scaling of the calculated frequencies is used to achieve better agreement with the experimental data. The observation of the wide band of the OD stretching vibration at 2201 cm-1 is a direct evidence of the presence of the β-alanine-d3 conformer V in the Ar matrix. In total ten bands of conformer V are detected. The influence of the matrix environment on the structures and the IR spectra of the β-alanine and β-alanine-d3 conformers is investigated. This involves performing calculations of the β-alanine conformers embedded in argon clusters containing from 163 to 166 argon atoms using the M06-2X and B3LYP(GD3BJ) density-functional methods. Good agreement between the calculated and the experimental matrix splitting is demonstrated.

  18. Glucose and Alanine Metabolism in Children with Maple Syrup Urine Disease

    PubMed Central

    Haymond, Morey W.; Ben-Galim, Ehud; Strobel, Karen E.

    1978-01-01

    In vitro studies have suggested that catabolism of branched chain amino acids is linked with alanine and glutamine formed in, and released from, muscle. To explore this possibility in vivo, static and kinetic studies were performed in three patients with classical, and one patient with partial, branched chain α-ketoacid decarboxylase deficiency (maple syrup urine disease, MSUD) and compared to similar studies in eight age-matched controls. The subjects underwent a 24-30-h fast, and a glucose-alanine flux study using stable isotopes. Basal plasma leucine concentrations were elevated (P <0.001) in patients with MSUD (1,140±125 μM vs. 155±18 μM in controls); and in contrast to the controls, branched chain amino acid concentrations in plasma increased during the fast in the MSUD patients. Basal plasma alanine concentrations were lower (P <0.01) in patients with classical MSUD (153±8 μM vs. 495±27 μM in controls). This discrepancy was maintained throughout the fast despite a decrease in alanine concentrations in both groups. Plasma alanine and leucine concentrations in the patient with partial MSUD were intermediate between those of the controls and the subjects with the classical form of the disease. Circulating ketone bodies and glucoregulatory hormones concentrations were similar in the MSUD and normal subjects during the fast. Alanine flux rates in two patients with classical MSUD (3.76 and 4.00 μmol/Kg per min) and the patient with partial MSUD (5.76 μmol/Kg per min) were clearly lower than those of the controls (11.72±2.53 [SD] μmol/Kg per min). After short-term starvation, glucose flux and fasting concentrations were similar in the MSUD patients and normal subjects. These data indicate that branched chain amino acid catabolism is an important rate limiting event for alanine production in vivo. PMID:670400

  19. Elevation of Alanine Aminotransferase Activity Occurs after Activation of the Cell-Death Signaling Initiated by Pattern-Recognition Receptors ‎but before Activation of Cytolytic Effectors in NK or CD8+ T Cells in the Liver During Acute HCV Infection

    PubMed Central

    Choi, Youkyung H.; Jin, Nancy; Kelly, Fiona; Sakthivel, SenthilKumar K.; Yu, Tianwei

    2016-01-01

    Pattern-recognition receptors (PRRs) promote host defenses against HCV infection by binding to their corresponding adapter molecules leading to the initiation of innate immune responses including cell death. We investigated the expression of PRR genes, biomarkers of liver cell-death, and T cell and NK cell activation/inhibition-related genes in liver and serum obtained from three experimentally infected chimpanzees with acute HCV infection, and analyzed the correlation between gene expression levels and clinical profiles. Our results showed that expression of hepatic RIG-I, TLR3, TLR7, 2OAS1, and CXCL10 mRNAs was upregulated as early as 7 days post-inoculation and peaked 12 to 83 days post-inoculation. All of the three HCV infected chimpanzees exhibited significant elevations of serum alanine aminotransferase (ALT) activity between 70 and 95 days after inoculation. Elevated levels of serum cytokeratin 18 (CK-18) and caspases 3 and 7 activity coincided closely with the rise of ALT activity, and were preceded by significant increases in levels of caspase 3 and caspase 7 mRNAs in the liver. Particularly we found that significant positive auto-correlations were observed between RIG-I, TLR3, CXCL10, 2OAS1, and PD-L1 mRNA and ALT activity at 3 to 12 days before the peak of ALT activity. However, we observed substantial negative auto-correlations between T cell and NK cell activation/inhibition-related genes and ALT activity at 5 to 32 days after the peak of ALT activity. Our results indicated cell death signaling is preceded by early induction of RIG-I, TLR3, 2OAS1, and CXCL10 mRNAs which leads to elevation of ALT activity and this signaling pathway occurs before the activation of NK and T cells during acute HCV infection. Our study suggests that PRRs and type I IFN response may play a critical role in development of liver cell injury related to viral clearance during acute HCV infection. PMID:27788241

  20. The metabolism of histamine in the Drosophila optic lobe involves an ommatidial pathway: β-alanine recycles through the retina.

    PubMed

    Borycz, Janusz; Borycz, Jolanta A; Edwards, Tara N; Boulianne, Gabrielle L; Meinertzhagen, Ian A

    2012-04-15

    Flies recycle the photoreceptor neurotransmitter histamine by conjugating it to β-alanine to form β-alanyl-histamine (carcinine). The conjugation is regulated by Ebony, while Tan hydrolyses carcinine, releasing histamine and β-alanine. In Drosophila, β-alanine synthesis occurs either from uracil or from the decarboxylation of aspartate but detailed roles for the enzymes responsible remain unclear. Immunohistochemically detected β-alanine is present throughout the fly's entire brain, and is enhanced in the retina especially in the pseudocone, pigment and photoreceptor cells of the ommatidia. HPLC determinations reveal 10.7 ng of β-alanine in the wild-type head, roughly five times more than histamine. When wild-type flies drink uracil their head β-alanine increases more than after drinking l-aspartic acid, indicating the effectiveness of the uracil pathway. Mutants of black, which lack aspartate decarboxylase, cannot synthesize β-alanine from l-aspartate but can still synthesize it efficiently from uracil. Our findings demonstrate a novel function for pigment cells, which not only screen ommatidia from stray light but also store and transport β-alanine and carcinine. This role is consistent with a β-alanine-dependent histamine recycling pathway occurring not only in the photoreceptor terminals in the lamina neuropile, where carcinine occurs in marginal glia, but vertically via a long pathway that involves the retina. The lamina's marginal glia are also a hub involved in the storage and/or disposal of carcinine and β-alanine.

  1. [Levels of aspartate aminotransferase and alanine aminotransferase in two factories with various hepato-toxic risks].

    PubMed

    Bavazzano, P; Benassi, S; Forzieri, R; Petrioli, G

    1981-12-01

    The Authors have studied AST and ALT enzymatic activities in the workers of two firms, the former of which (tannery) with a high and the latter (boot and shoe factory) with a low level of hepatic-toxic risk. The influence of various trouble factors such as age, sex and seniority was eliminated through appropriate statistical techniques. A significant difference was evidenced between AST and ALT levels in two firms, chiefly attributable to the quantity and quality of the substances utilized in the two technological cycles: trichloroethylene, chromium, sulphuric acid, mineral oils, ammonia, N-hexane, pentanes acetone, ciclo hexane, methanol, ethyl acetate, isopropyl acetate, toluene, methylene chloride.

  2. Posttranslational alanine trans-stimulation of zwitterionic amino acid transport systems in human intestinal Caco-2 cells.

    PubMed

    Pan, Ming; Souba, Wiley W; Wolfgang, Christopher L; Karinch, Anne M; Stevens, Bruce R

    2002-05-01

    Neutral dietary amino acids, such as alanine, are transported across the gut lumen by both Na(+)-dependent (System B) and Na(+)-independent (System L) carriers, but the nature of the acute phase of substrate-induced uptake is unknown. This study examined the effects of acute amino acid substrate exposure on the rapid modulation of apical membrane alanine transport in cultured human intestinal cells. System B and System L transport activity kinetics, as well as ATB(0) mRNA levels, were measured in confluent Caco-2 monolayers treated with various metabolic agents during short-term and extended time periods. Depleting the incubation medium of alanine attenuated both System B and System L uptake activities within 30 mins, with a complete return to baseline values within 3 h. Extracellular alanine added to depleted Caco-2 cells rapidly (within 5 min) increased alanine transport activities. Kinetic analysis showed that acute alanine exposure increased both K(m) and V(max) of each transport system, indicative of a trans-stimulation effect. Augmenting intracellular alanine levels using the cytosolic alanine aminotransferase inhibitor, aminooxyacetic acid, increased alanine uptake activity. Acute exposure to other substrates of Systems B and L also increased the uptake of alanine, while nonsubstrates did not affect alanine uptake. Cycloheximide or actinomycin did not affect substrate acute activation of System B, and the steady-state level of ATB(0) mRNA was not altered by amino acid exposure. Increasing alanine availability to intestinal cells, by either exogenous substrate exposure or inhibition of intracellular catabolism, acutely and reversibly increases apical membrane alanine transport activity via a posttranslation trans-stimulation mechanism.

  3. Supplementation with l-arginine stabilizes plasma arginine and nitric oxide metabolites, suppresses elevated liver enzymes and peroxidation in sickle cell anaemia.

    PubMed

    Jaja, S I; Ogungbemi, S O; Kehinde, M O; Anigbogu, C N

    2016-06-01

    The effect of l-arginine on liver function in SCD has received little or no attention. The effect of a chronic, oral, low-dose supplementation with l-arginine (1gm/day for 6 weeks) on some liver enzymes, lipid peroxidation and nitric oxide metabolites was studied in 20 normal (non-sickle cell anaemia; NSCA) subjects and 20 sickle cell anaemia (SCA) subjects. Ten milliliters of blood was withdrawn from an ante-cubital vein for the estimation of plasma arginine concentration ([R]), alanine aminotransaminase (ALT), aspartate aminotransaminase (AST) and alkaline phosphatase (ALP), plasma total bilirubin concentration [TB], malondialdehyde concentration [MDA] and nitric oxide metabolites concentration [NOx]. Before supplementation, ALT, AST, ALP (p<0.05 respectively) and TB (p<0.001) were higher in SCA subjects than in NSCA subjects. [R] and [NOx] were higher in NSCA subjects (p<0.001 and p<0.05 respectively). Supplementation caused greater percent increases in [R], and [NOX] in SCA than in NSCA subjects (p<0.001 in each case). l-Arginine caused greater percent reductions in ALT and AST in SCA subjects but greater percent reduction in ALP in NSCA subjects (p<0.001 in each case). Changes in [MDA] and [TB] in the two groups were similar. Study shows that chronic, oral, low-dose supplementation with l-arginine improved liver function, oxidative stress, plasma arginine concentration and nitric oxide metabolites levels in NSCA and SCA subjects. Responses in SCA subjects to l-arginine were more sensitive than in NSCA subjects.

  4. Liver enzymes and trace elements in the acute phase of sickle cell anaemia.

    PubMed

    Kehinde, M O; Jaja, S I; Adewumi, O M; Adeniyi, I M; Nezianya, M O; Ayinla, E O

    2010-01-01

    Trace elements are required for the performance of numerous functions of immune cells. It is not clear whether levels of trace elements are elevated and whether there is a relationship between the levels of liver enzymes and trace elements in patients with sickle cell anaemia in crisis. To compare the plasma levels of liver enzymes and trace elements in non sickle cell anaemia (NSCA), sickle cell anaemia subjects in the steady state (SCASS) and sickle cell anaemia patients in crisis (SCAC). Haematological parameters, liver enzymes and trace elements were determined in 20 NSCA subjects, 20 SCASS subjects and 18 SCAC subjects. Variables studied included aspartate aminotransferase (AST) , alanine aminotransaminase (ALT), alkaline phosphatase (ALP), and the trace elements copper, zinc, and manganese. Levels of liver enzymes were higher in the SCAC subjects than in the NSCA or SCASS subjects (p<0.001). Plasma Cu++, Zn++ and Mn++ were also higher in the SCAC subjects than in the NSCA or SCASS subjects (p<0.001). Correlationships were high and strong between AST and ALT (r=+0.7; p=0.03), AST and ALP (r=+0.9; p=0.001), Zn++ and Fe++ (r=+0.9; p=0.001) in SCAC. During crisis in sickle cell anaemia, liver enzymes, as well as the trace elements of Cu++, Zn++ and Mn++ are increased; levels of aspartate aminotransaminase are strongly correlated with those of ALT and ALP. Levels of liver enzymes do not appear to be related to those of the trace elements in painful sickle cell crisis.

  5. Perturbation correction for alanine dosimeters in different phantom materials in high-energy photon beams.

    PubMed

    von Voigts-Rhetz, P; Anton, M; Vorwerk, H; Zink, K

    2016-02-07

    In modern radiotherapy the verification of complex treatments plans is often performed in inhomogeneous or even anthropomorphic phantoms. For dose verification small detectors are necessary and therefore alanine detectors are most suitable. Though the response of alanine for a wide range of clinical photon energies in water is well know, the knowledge about the influence of the surrounding phantom material on the response of alanine is sparse. Therefore we investigated the influence of twenty different surrounding/phantom materials for alanine dosimeters in clinical photon fields via Monte Carlo simulations. The relative electron density of the used materials was in the range [Formula: see text] up to 1.69, covering almost all materials appearing in inhomogeneous or anthropomorphic phantoms used in radiotherapy. The investigations were performed for three different clinical photon spectra ranging from 6 to 25 MV-X and Co-60 and as a result a perturbation correction [Formula: see text] depending on the environmental material was established. The Monte Carlo simulation show, that there is only a small dependence of [Formula: see text] on the phantom material and the photon energy, which is below  ±0.6%. The results confirm the good suitability of alanine detectors for in-vivo dosimetry.

  6. Effect of 10 week beta-alanine supplementation on competition and training performance in elite swimmers.

    PubMed

    Chung, Weiliang; Shaw, Greg; Anderson, Megan E; Pyne, David B; Saunders, Philo U; Bishop, David J; Burke, Louise M

    2012-10-09

    Although some laboratory-based studies show an ergogenic effect with beta-alanine supplementation, there is a lack of field-based research in training and competition settings. Elite/Sub-elite swimmers (n = 23 males and 18 females, age = 21.7 ± 2.8 years; mean ± SD) were supplemented with either beta-alanine (4 weeks loading phase of 4.8 g/day and 3.2 g/day thereafter) or placebo for 10 weeks. Competition performance times were log-transformed, then evaluated before (National Championships) and after (international or national selection meet) supplementation. Swimmers also completed three standardized training sets at baseline, 4 and 10 weeks of supplementation. Capillary blood was analyzed for pH, bicarbonate and lactate concentration in both competition and training. There was an unclear effect (0.4%; ± 0.8%, mean, ± 90% confidence limits) of beta-alanine on competition performance compared to placebo with no meaningful changes in blood chemistry. While there was a transient improvement on training performance after 4 weeks with beta-alanine (-1.3%; ± 1.0%), there was an unclear effect at ten weeks (-0.2%; ± 1.5%) and no meaningful changes in blood chemistry. Beta-alanine supplementation appears to have minimal effect on swimming performance in non-laboratory controlled real-world training and competition settings.

  7. Absorbed dose determination in kilovoltage X-ray synchrotron radiation using alanine dosimeters.

    PubMed

    Butler, D J; Lye, J E; Wright, T E; Crossley, D; Sharpe, P H G; Stevenson, A W; Livingstone, J; Crosbie, J C

    2016-12-01

    Alanine dosimeters from the National Physical Laboratory (NPL) in the UK were irradiated using kilovoltage synchrotron radiation at the imaging and medical beam line (IMBL) at the Australian Synchrotron. A 20 × 20 mm(2) area was irradiated by scanning the phantom containing the alanine through the 1 mm × 20 mm beam at a constant velocity. The polychromatic beam had an average energy of 95 keV and nominal absorbed dose to water rate of 250 Gy/s. The absorbed dose to water in the solid water phantom was first determined using a PTW Model 31014 PinPoint ionization chamber traceable to a graphite calorimeter. The alanine was read out at NPL using correction factors determined for (60)Co, traceable to NPL standards, and a published energy correction was applied to correct for the effect of the synchrotron beam quality. The ratio of the doses determined by alanine at NPL and those determined at the synchrotron was 0.975 (standard uncertainty 0.042) when alanine energy correction factors published by Waldeland et al. (Waldeland E, Hole E O, Sagstuen E and Malinen E, Med. Phys. 2010, 37, 3569) were used, and 0.996 (standard uncertainty 0.031) when factors by Anton et al. (Anton M, Büermann L., Phys Med Biol. 2015 60 6113-29) were used. The results provide additional verification of the IMBL dosimetry.

  8. Effect of 10 Week Beta-Alanine Supplementation on Competition and Training Performance in Elite Swimmers

    PubMed Central

    Chung, Weiliang; Shaw, Greg; Anderson, Megan E.; Pyne, David B.; Saunders, Philo U.; Bishop, David J.; Burke, Louise M.

    2012-01-01

    Although some laboratory-based studies show an ergogenic effect with beta-alanine supplementation, there is a lack of field-based research in training and competition settings. Elite/Sub-elite swimmers (n = 23 males and 18 females, age = 21.7 ± 2.8 years; mean ± SD) were supplemented with either beta-alanine (4 weeks loading phase of 4.8 g/day and 3.2 g/day thereafter) or placebo for 10 weeks. Competition performance times were log-transformed, then evaluated before (National Championships) and after (international or national selection meet) supplementation. Swimmers also completed three standardized training sets at baseline, 4 and 10 weeks of supplementation. Capillary blood was analyzed for pH, bicarbonate and lactate concentration in both competition and training. There was an unclear effect (0.4%; ±0.8%, mean, ±90% confidence limits) of beta-alanine on competition performance compared to placebo with no meaningful changes in blood chemistry. While there was a transient improvement on training performance after 4 weeks with beta-alanine (−1.3%; ±1.0%), there was an unclear effect at ten weeks (−0.2%; ±1.5%) and no meaningful changes in blood chemistry. Beta-alanine supplementation appears to have minimal effect on swimming performance in non-laboratory controlled real-world training and competition settings. PMID:23201763

  9. Theoretical and experimental study of valence photoelectron spectrum of D,L-alanine amino acid.

    PubMed

    Farrokhpour, H; Fathi, F; De Brito, A Naves

    2012-07-05

    In this work, the He-I (21.218 eV) photoelectron spectrum of D,L-alanine in the gas phase is revisited experimentally and theoretically. To support the experiment, the high level ab initio calculations were used to calculate and assign the photoelectron spectra of the four most stable conformers of gaseous alanine, carefully. The symmetry adapted cluster/configuration interaction (SAC-CI) method based on single and double excitation operators (SD-R) and its more accurate version, termed general-R, was used to separately calculate the energies and intensities of the ionization bands of the L- and D-alanine conformers. The intensities of ionization bands were calculated based on the monopole approximation. Also, natural bonding orbital (NBO) calculations were employed for better spectral band assignment. The relative electronic energy, Gibbs free energy, and Boltzmann population ratio of the conformers were calculated at the experimental temperature (403 K) using several theoretical methods. The theoretical photoelectron spectrum of alanine was calculated by summing over the spectra of individual D and L conformers weighted by different population ratios. Finally, the population ratio of the four most stable conformers of alanine was estimated from the experimental photoelectron spectrum using theoretical calculations for the first time.

  10. Perturbation correction for alanine dosimeters in different phantom materials in high-energy photon beams

    NASA Astrophysics Data System (ADS)

    von Voigts-Rhetz, P.; Anton, M.; Vorwerk, H.; Zink, K.

    2016-02-01

    In modern radiotherapy the verification of complex treatments plans is often performed in inhomogeneous or even anthropomorphic phantoms. For dose verification small detectors are necessary and therefore alanine detectors are most suitable. Though the response of alanine for a wide range of clinical photon energies in water is well know, the knowledge about the influence of the surrounding phantom material on the response of alanine is sparse. Therefore we investigated the influence of twenty different surrounding/phantom materials for alanine dosimeters in clinical photon fields via Monte Carlo simulations. The relative electron density of the used materials was in the range {{n}e}/{{n}e,\\text{w}}=0.20 up to 1.69, covering almost all materials appearing in inhomogeneous or anthropomorphic phantoms used in radiotherapy. The investigations were performed for three different clinical photon spectra ranging from 6 to 25 MV-X and Co-60 and as a result a perturbation correction {{k}\\text{env}} depending on the environmental material was established. The Monte Carlo simulation show, that there is only a small dependence of {{k}\\text{env}} on the phantom material and the photon energy, which is below  ±0.6%. The results confirm the good suitability of alanine detectors for in-vivo dosimetry.

  11. Role of Alanine Dehydrogenase of Mycobacterium tuberculosis during Recovery from Hypoxic Nonreplicating Persistence

    PubMed Central

    Giffin, Michelle M.; Shi, Lanbo; Gennaro, Maria L.; Sohaskey, Charles D.

    2016-01-01

    Mycobacterium tuberculosis can maintain a nonreplicating persistent state in the host for decades, but must maintain the ability to efficiently reactivate and produce active disease to survive and spread in a population. Among the enzymes expressed during this dormancy is alanine dehydrogenase, which converts pyruvate to alanine, and glyoxylate to glycine concurrent with the oxidation of NADH to NAD. It is involved in the metabolic remodeling of M. tuberculosis through its possible interactions with both the glyoxylate and methylcitrate cycle. Both mRNA levels and enzymatic activities of isocitrate lyase, the first enzyme of the glyoxylate cycle, and alanine dehydrogenase increased during entry into nonreplicating persistence, while the gene and activity for the second enzyme of the glyoxylate cycle, malate synthase were not. This could suggest a shift in carbon flow away from the glyoxylate cycle and instead through alanine dehydrogenase. Expression of ald was also induced in vitro by other persistence-inducing stresses such as nitric oxide, and was expressed at high levels in vivo during the initial lung infection in mice. Enzyme activity was maintained during extended hypoxia even after transcription levels decreased. An ald knockout mutant of M. tuberculosis showed no reduction in anaerobic survival in vitro, but resulted in a significant lag in the resumption of growth after reoxygenation. During reactivation the ald mutant had an altered NADH/NAD ratio, and alanine dehydrogenase is proposed to maintain the optimal NADH/NAD ratio during anaerobiosis in preparation of eventual regrowth, and during the initial response during reoxygenation. PMID:27203084

  12. The IL-15-based ALT-803 complex enhances FcγRIIIa-triggered NK cell responses and in vivo clearance of B cell lymphomas

    PubMed Central

    Rosario, Maximillian; Bai, Liu; Kong, Lin; Collins, Lynne I.; Schneider, Stephanie E.; Chen, Xiaoyue; Han, Kaiping; Jeng, Emily K.; Rhode, Peter R.; Leong, Jeffrey W.; Schappe, Timothy; Jewell, Brea A.; Keppel, Catherine R.; Shah, Keval; Hess, Brian; Romee, Rizwan; Piwnica-Worms, David R.; Cashen, Amanda F.; Bartlett, Nancy L.; Wong, Hing C.; Fehniger, Todd A.

    2015-01-01

    PURPOSE Anti-CD20 monoclonal antibodies (mAbs) are an important immunotherapy for B cell lymphoma, and provide evidence that the immune system may be harnessed as an effective lymphoma treatment approach. ALT-803 is a super-agonist IL-15 mutant and IL-15Rα–Fc fusion complex that activates the IL-15 receptor constitutively expressed on NK cells. We hypothesized that ALT-803 would enhance anti-CD20 mAb-directed NK cell responses and antibody-dependent cellular cytotoxicity (ADCC). EXPERIMENTAL DESIGN We tested this hypothesis by adding ALT-803 immunostimulation to anti-CD20 mAb triggering of NK cells in vitro and in vivo. Cell lines and primary human lymphoma cells were utilized as targets for primary human NK cells. Two complementary in vivo mouse models were used, which included human NK cell xenografts in NOD-SCID-γc−/− mice. REULTS We demonstrate that short-term ALT-803 stimulation significantly increased degranulation, IFN-γ production, and ADCC by human NK cells against B-cell lymphoma cell lines or primary follicular lymphoma cells. ALT-803 augmented cytotoxicity and the expression of granzyme B and perforin, providing one potential mechanism for this enhanced functionality. Moreover, in two distinct in vivo B cell lymphoma models, the addition of ALT-803 to anti-CD20 mAb therapy resulted in significantly reduced tumor cell burden and increased survival. Long-term ALT-803 stimulation of human NK cells induced proliferation and NK cell subset changes with preserved ADCC. CONCLUSIONS ALT-803 represents a novel immunostimulatory drug that enhances NK cell anti-lymphoma responses in vitro and in vivo, thereby supporting the clinical investigation of ALT-803 plus anti-CD20 mAbs in patients with indolent B cell lymphoma. PMID:26423796

  13. Glutamine synthetase and alanine transaminase expression are decreased in livers of aged vs. young beef cows and GS can be upregulated by 17β-estradiol implants.

    PubMed

    Miles, E D; McBride, B W; Jia, Y; Liao, S F; Boling, J A; Bridges, P J; Matthews, J C

    2015-09-01

    Aged beef cows (≥ 8 yr of age) produce calves with lower birth and weaning weights. In mammals, aging is associated with reduced hepatic expression of glutamine synthetase (GS) and alanine transaminase (ALT), thus impaired hepatic Gln-Glu cycle function. To determine if the relative protein content of GS, ALT, aspartate transaminase (AST), glutamate transporters (EAAC1, GLT-1), and their regulating protein (GTRAP3-18) differed in biopsied liver tissue of (a) aged vs. young (3 to 4 yr old) nonlactating, nongestating Angus cows (Exp. 1 and 2) and (b) aged mixed-breed cows with and without COMPUDOSE (17β-estradiol) ear implants (Exp. 3), Western blot analyses were performed. In Exp. 1, 12 young (3.62 ± 0.01 yr) and 13 aged (10.08 ± 0.42 yr) cows grazed the same mixed forage for 42 d (August-October). In Exp. 2, 12 young (3.36 ± 0.01 yr) and 12 aged (10.38 ± 0.47 yr) cows were individually fed (1.03% of BW) a corn-silage-based diet to maintain BW for 20 d. For both Exp. 1 and 2, the effect of cow age was assessed by ANOVA using the MIXED procedure of SAS. Cow BW did not change ( ≥ 0.17). Hepatic ALT (78% and 61%) and GS (52% and 71%) protein content (Exp. 1 and 2, respectively) was decreased ( ≤ 0.01), whereas GTRAP3-18 (an inhibitor of EAAC1 activity) increased ( ≤ 0.01; 170% and 136%) and AST, GLT-1, and EAAC1 contents did not differ ( ≥ 0.17) in aged vs. young cows. In Exp. 2, free concentrations (nmol/g) of Glu, Ala, Gln, Arg, and Orn in liver homogenates were determined. Aged cows tended to have less ( = 0.10) free Gln (15.0%) than young cows, whereas other AA concentrations did not differ ( 0.26). In Exp. 3, 14 aged (> 10 yr) cows were randomly allotted ( = 7) to sham or COMPUDOSE (25.7 mg of 17β-estradiol) implant treatment (TRT), and had ad libitum access to alfalfa hay for 28 d. Blood and liver biopsies were collected 14 and 28 d after implant treatment. Treatment, time after implant (DAY), and TRT × DAY effects were assessed by ANOVA using

  14. Sensitivity of alanine dosimeters with gadolinium exposed to 6 MV photons at clinical doses.

    PubMed

    Marrale, M; Longo, A; Spanò, M; Bartolotta, A; D'Oca, M C; Brai, M

    2011-12-01

    In this study we analyzed the ESR signal of alanine dosimeters with gadolinium exposed to 6 MV linear accelerator photons. We observed that the addition of gadolinium brings about an improvement in the sensitivity to photons because of its high atomic number. The experimental data indicated that the addition of gadolinium increases the sensitivity of the alanine to 6 MV photons. This enhancement was better observed at high gadolinium concentrations for which the tissue equivalence is heavily reduced. However, information about the irradiation setup and of the radiation beam features allows one to correct for this difference. Monte Carlo simulations were carried out to obtain information on the expected effect of the addition of gadolinium on the dose absorbed by the alanine molecules inside the pellets. These results are compared with the experimental values, and the agreement is discussed.

  15. Intramitochondrial localization of alanine aminotransferase in rat-liver mitochondria: comparison with glutaminase and aspartate aminotransferase.

    PubMed

    Masola, B; Devlin, T M

    1995-12-01

    The removal of the outer mitochondrial membrane and hence of constituents of the intermembrane space in rat-liver mitochondria using digitonin showed that phosphate-dependent glutaminase, alanine and aspartate aminotransferase were localized in the mitoplasts. Further fractionation of mitoplasts following their sonication resulted in 90% of glutaminase, 98% of alanine aminotransferase and 48% of aspartate aminotransferase being recovered in the soluble fraction while the remainder of each enzyme was recovered in the sonicated vesicles fraction. These results indicated that glutaminase and alanine aminotransferase were soluble matrix enzymes, the little of each enzyme recovered in the sonicated vesicles fraction being probably due to entrapment in the vesicles. Aspartate aminotransferase had dual localization, in the inner membrane and matrix with the high specific activity in sonicated vesicles confirming its association with the membrane. Activation experiments suggested that the membrane-bound enzyme was localized on the inner side of the inner mitochondrial membrane.

  16. Combined TL and 10B-alanine ESR dosimetry for BNCT.

    PubMed

    Bartolotta, A; D'Oca, M C; Lo Giudice, B; Brai, M; Borio, R; Forini, N; Salvadori, P; Manera, S

    2004-01-01

    The dosimetric technique described in this paper is based on electron spin resonance (ESR) detectors using an alanine-boric compound acid enriched with (10)B, and beryllium oxide thermoluminescent (TL) detectors; with this combined dosimetry, it is possible to discriminate the doses due to thermal neutrons and gamma radiation in a mixed field. Irradiations were carried out inside the thermal column of a TRIGA MARK II water-pool-type research nuclear reactor, also used for Boron Neutron Capture therapy (BNCT) applications, with thermal neutron fluence from 10(9) to 10(14) nth cm(-2). The ESR dosemeters using the alanine-boron compound indicated ESR signals about 30-fold stronger than those using only alanine. Moreover, a negligible correction for the gamma contribution, measured with TL detectors, almost insensitive to thermal neutrons, was necessary. Therefore, a simultaneous analysis of our TL and ESR detectors allows discrimination between thermal neutron and gamma doses, as required in BNCT.

  17. On the roles of the alanine and serine in the β-sheet structure of fibroin.

    PubMed

    Carrascoza Mayen, Juan Francisco; Lupan, Alexandru; Cosar, Ciprian; Kun, Attila-Zsolt; Silaghi-Dumitrescu, Radu

    2015-02-01

    In its silk II form, fibroin is almost exclusively formed from layers of β-sheets, rich in glycine, alanine and serine. Reported here are computational results on fibroin models at semi-empirical, DFT levels of theory and molecular dynamics (MD) for (Gly)10, (Gly-Ala)5 and (Gly-Ser)5 decapeptides. While alanine and serine introduce steric repulsions, the alanine side-chain adds to the rigidity of the sheet, allowing it to maintain a properly pleated structure even in a single β-sheet, and thus avoiding two alternative conformations which would interfere with the formation of the multi-layer pleated-sheet structure. The role of the serine is proposed to involve modulation of the hydrophobicity in order to construct the supramolecular assembly as opposed to random precipitation due to hydrophobicity.

  18. A photoactivable amino acid based on a novel functional coumarin-6-yl-alanine.

    PubMed

    Fonseca, Andrea S C; Gonçalves, M Sameiro T; Costa, Susana P G

    2012-12-01

    A novel fluorescent amino acid, L-4-chloromethylcoumarin-6-yl-alanine, was obtained from tyrosine by a Pechmann reaction. The assembly of the heterocyclic ring at the tyrosine side chain could be achieved before or after incorporation of tyrosine into a dipeptide, and amino acid and dipeptide ester conjugates were obtained by coupling to a model N-protected alanine. The behaviour of one of the fluorescent conjugates towards irradiation was studied in a photochemical reactor at different wavelengths (254, 300, 350 and 419 nm). The photoreaction course in methanol/HEPES buffer solution (80:20) was followed by HPLC/UV monitoring. It was found that the novel unnatural amino acid could act as a fluorescent label, due to its fluorescence properties, and, more importantly, as a photoactivable unit, due to the short irradiation times necessary to cleave the ester bond between the model amino acid and the coumarin-6-yl-alanine.

  19. Antimicrobial activity of antihypertensive food-derived peptides and selected alanine analogues.

    PubMed

    McClean, Stephen; Beggs, Louise B; Welch, Robert W

    2014-03-01

    This study evaluated four food-derived peptides with known antihypertensive activities for antimicrobial activity against pathogenic microorganisms, and assessed structure-function relationships using alanine analogues. The peptides (EVSLNSGYY, barley; PGTAVFK, soybean; TTMPLW, α-casein; VHLPP, α-zein) and the six alanine substitution peptides of PGTAVFK were synthesised, characterised and evaluated for antimicrobial activity using the bacteria, Escherichia coli, Staphylococcus aureus, and Micrococcus luteus and the yeast, Candida albicans. The peptides TTMPLW and PGTAVFK inhibited growth of all four microorganisms tested, with activities of a similar order of magnitude to ampicillin and ethanol controls. EVSLNSGYY inhibited the growth of the bacteria, but VHLPP showed no antimicrobial activity. The alanine analogue, PGAAVFK showed the highest overall antimicrobial activity and PGTAVFA showed no activity; overall, the activities of the analogues were consistent with their structures. Some peptides with antihypertensive activity also show antimicrobial activity, suggesting that food-derived peptides may exert beneficial effects via a number of mechanisms.

  20. The effect of a high protein diet on leucine and alanine turnover in acid maltase deficiency.

    PubMed Central

    Umpleby, A M; Trend, P S; Chubb, D; Conaglen, J V; Williams, C D; Hesp, R; Scobie, I N; Wiles, C M; Spencer, G; Sönksen, P H

    1989-01-01

    Leucine and alanine production rate was measured in 5 patients with acid maltase deficiency in the postabsorptive state, following 6 months on a normal diet with placebo and 6 months on an isocaloric high protein diet (16-22% protein). Whole body leucine production rate, a measure of protein degradation, expressed in terms of lean body mass was significantly greater than in five control subjects. Following the high protein diet, leucine production rate was decreased in four of the five patients but this was not statistically significant. Alanine production rate expressed in terms of lean body mass was significantly greater than in control subjects. After the high protein diet, alanine production rate and concentration were significantly decreased (p less than 0.05). There were no significant improvements in any of the clinically relevant variables measured in these patients. It is possible that a larger increase in protein intake over a longer time period may have a clinical effect. PMID:2507747

  1. Nucleation kinetics, growth and studies of β-alanine single crystals

    NASA Astrophysics Data System (ADS)

    Shanthi, D.; Selvarajan, P.; HemaDurga, K. K.; Lincy Mary Ponmani, S.

    2013-06-01

    Solubility and metastable zone width for the re-crystallized salt of β-alanine was determined. Induction period measurement for the selected supersaturation ratios at room temperature (31 °C) was carried out for supersaturated aqueous solutions of β-alanine and it is noticed that induction period decreases with increase of supersaturation ratio. The nucleation parameters such as Gibbs free energy change, radius and number of molecules of the critical nucleus, interfacial tension and the nucleation rate have been evaluated by classical nucleation theory. Single crystals of β-alanine were grown using the optimized nucleation parameters by solution method and grown crystals have been subjected to various studies like XRD studies, FTIR, optical, thermal and SHG studies.

  2. Probing the Catalytic Charge-Relay System in Alanine Racemase with Genetically Encoded Histidine Mimetics.

    PubMed

    Sharma, Vangmayee; Wang, Yane-Shih; Liu, Wenshe R

    2016-12-16

    Histidine is a unique amino acid with an imidazole side chain in which both of the nitrogen atoms are capable of serving as a proton donor and proton acceptor in hydrogen bonding interactions. In order to probe the functional role of histidine involved in hydrogen bonding networks, fine-tuning the hydrogen bonding potential of the imidazole side chain is required but not feasible through traditional mutagenesis methods. Here, we show that two close mimetics of histidine, 3-methyl-histidine and thiazole alanine, can be genetically encoded using engineered pyrrolysine incorporation machinery. Replacement of the three histidine residues predicted to be involved in an extended charge-relay system in alanine racemase with 3-methyl-histidine or thiazole alanine shows a dramatic loss in the enzyme's catalytic efficiency, implying the role of this extended charge-relay system in activating the active site residue Y265, a general acid/base catalyst in the enzyme.

  3. Substrate Specificity of the Aspartate:Alanine Antiporter (AspT) of Tetragenococcus halophilus in Reconstituted Liposomes*

    PubMed Central

    Sasahara, Ayako; Nanatani, Kei; Enomoto, Masaru; Kuwahara, Shigefumi; Abe, Keietsu

    2011-01-01

    The aspartate:alanine antiporter (AspT) of the lactic acid bacterium Tetragenococcus halophilus is a member of the aspartate:alanine exchanger (AAEx) transporter family. T. halophilus AspT catalyzes the electrogenic exchange of l-aspartate1− with l-alanine0. Although physiological functions of AspT were well studied, l-aspartate1−:l-alanine0 antiport mechanisms are still unsolved. Here we report that the binding sites of l-aspartate and l-alanine are independently present in AspT by means of the kinetic studies. We purified His6-tagged T. halophilus AspT and characterized its kinetic properties when reconstituted in liposomes (Km = 0.35 ± 0.03 mm for l-aspartate, Km = 0.098 ± 0 mm for d-aspartate, Km = 26 ± 2 mm for l-alanine, Km = 3.3 ± 0.2 mm for d-alanine). Competitive inhibition by various amino acids of l-aspartate or l-alanine in self-exchange reactions revealed that l-cysteine selectively inhibited l-aspartate self-exchange but only weakly inhibited l-alanine self-exchange. Additionally, l-serine selectively inhibited l-alanine self-exchange but barely inhibited l-aspartate self-exchange. The aspartate analogs l-cysteine sulfinic acid, l-cysteic acid, and d-cysteic acid competitively and strongly inhibited l-aspartate self-exchange compared with l-alanine self-exchange. Taken together, these kinetic data suggest that the putative binding sites of l-aspartate and l-alanine are independently located in the substrate translocation pathway of AspT. PMID:21719707

  4. Substrate specificity of the aspartate:alanine antiporter (AspT) of Tetragenococcus halophilus in reconstituted liposomes.

    PubMed

    Sasahara, Ayako; Nanatani, Kei; Enomoto, Masaru; Kuwahara, Shigefumi; Abe, Keietsu

    2011-08-19

    The aspartate:alanine antiporter (AspT) of the lactic acid bacterium Tetragenococcus halophilus is a member of the aspartate:alanine exchanger (AAEx) transporter family. T. halophilus AspT catalyzes the electrogenic exchange of L-aspartate(1-) with L-alanine(0). Although physiological functions of AspT were well studied, L-aspartate(1-):L-alanine(0) antiport mechanisms are still unsolved. Here we report that the binding sites of L-aspartate and L-alanine are independently present in AspT by means of the kinetic studies. We purified His(6)-tagged T. halophilus AspT and characterized its kinetic properties when reconstituted in liposomes (K(m) = 0.35 ± 0.03 mm for L-aspartate, K(m) = 0.098 ± 0 mm for D-aspartate, K(m) = 26 ± 2 mm for L-alanine, K(m) = 3.3 ± 0.2 mm for D-alanine). Competitive inhibition by various amino acids of L-aspartate or L-alanine in self-exchange reactions revealed that L-cysteine selectively inhibited L-aspartate self-exchange but only weakly inhibited L-alanine self-exchange. Additionally, L-serine selectively inhibited L-alanine self-exchange but barely inhibited L-aspartate self-exchange. The aspartate analogs L-cysteine sulfinic acid, L-cysteic acid, and D-cysteic acid competitively and strongly inhibited L-aspartate self-exchange compared with L-alanine self-exchange. Taken together, these kinetic data suggest that the putative binding sites of L-aspartate and L-alanine are independently located in the substrate translocation pathway of AspT.

  5. Spontaneous excretion of D-alanine in urine in mutant mice lacking D-amino-acid oxidase.

    PubMed Central

    Konno, R; Nagata, Y; Niwa, A; Yasumura, Y

    1989-01-01

    Urine from mutant mice lacking D-amino-acid oxidase contained a large amount of alanine compared with that from normal mice. Urinary alanine of the mutant mice was sensitive to D-amino-acid oxidase. H.p.l.c. showed that about 94% of the urinary alanine had the D-configuration. These results suggest that D-amino-acid oxidase functions to decompose D-amino acid(s) in normal mice. Images Fig. 1. PMID:2570568

  6. The crystal structure of the D-alanine-D-alanine ligase from Acinetobacter baumannii suggests a flexible conformational change in the central domain before nucleotide binding.

    PubMed

    Huynh, Kim-Hung; Hong, Myoung-ki; Lee, Clarice; Tran, Huyen-Thi; Lee, Sang Hee; Ahn, Yeh-Jin; Cha, Sun-Shin; Kang, Lin-Woo

    2015-11-01

    Acinetobacter baumannii, which is emerging as a multidrug-resistant nosocomial pathogen, causes a number of diseases, including pneumonia, bacteremia, meningitis, and skin infections. With ATP hydrolysis, the D-alanine-D-alanine ligase (DDL) catalyzes the synthesis of D-alanyl-D-alanine, which is an essential component of bacterial peptidoglycan. In this study, we determined the crystal structure of DDL from A. baumannii (AbDDL) at a resolution of 2.2 Å. The asymmetric unit contained six protomers of AbDDL. Five protomers had a closed conformation in the central domain, while one protomer had an open conformation in the central domain. The central domain with an open conformation did not interact with crystallographic symmetry-related protomers and the conformational change of the central domain was not due to crystal packing. The central domain of AbDDL can have an ensemble of the open and closed conformations before the binding of substrate ATP. The conformational change of the central domain is important for the catalytic activity and the detail information will be useful for the development of inhibitors against AbDDL and putative antibacterial agents against A. baumannii. The AbDDL structure was compared with that of other DDLs that were in complex with potent inhibitors and the catalytic activity of AbDDL was confirmed using enzyme kinetics assays.

  7. Relative response of the alanine dosimeter to medium energy x-rays.

    PubMed

    Anton, M; Büermann, L

    2015-08-07

    The response of the alanine dosimeter to kilovoltage x-rays with respect to the dose to water was measured, relative to the response to Co-60 radiation.Two series of x-ray qualities were investigated, one ranging from 30 kV to 100 kV tube voltage (TW series), the other one ranging from 70 kV to 280 kV (TH series). Due to the use of the water calorimeter as a primary standard, the uncertainty of the delivered dose is significantly lower than for other published data. The alanine response was measured as described in a previous publication (Anton et al 2013 Phys. Med. Biol. 58 3259-82). The uncertainty component due to the alanine measurement and analysis is ⩽0.4%, the major part of the combined uncertainty of the relative response originates from the uncertainty of the delivered dose. The relative uncertainties of the relative response vary from ⩽2% for the TW series to ⩽1.1% for the TH series.Different from the behaviour of the alanine dosimeter for megavoltage x-rays or electrons, the relative response drops significantly from unity for Co-60 radiation to less than 64% for the TW quality with a tube voltage of 30 kV. In order to reproduce this behaviour through Monte Carlo simulations, not only the ratio of the absorbed dose to alanine to the absorbed dose to water has to be known, but also the intrinsic efficiency, i.e. the dependence of the number of free radicals generated per unit of absorbed dose on the photon energy. This quantity is not yet accessible for the TW series.For a possible use of the alanine dosimeter for kilovoltage x-rays, for example in electronic brachytherapy, users should rely on the measured data for the relative response which have become available with this publication.

  8. Exchange of aspartate and alanine. Mechanism for development of a proton-motive force in bacteria.

    PubMed

    Abe, K; Hayashi, H; Maloney, P C; Malone, P C

    1996-02-09

    We examined the idea that aspartate metabolism by Lactobacillus subsp. M3 is organized as a proton-motive metabolic cycle by using reconstitution to monitor the activity of the carrier, termed AspT, expected to carry out the electrogenic exchange of precursor (aspartate) and product (alanine). Membranes of Lactobacillus subsp. M3 were extracted with 1.25% octyl glucoside in the presence of 0. 4% Escherichia coli phospholipid and 20% glycerol. The extracts were then used to prepare proteoliposomes loaded with either aspartate or alanine. Aspartate-loaded proteoliposomes accumulated external [3H]aspartate by exchange with internal substrate; this homologous self-exchange (Kt = 0.4 mm) was insensitive to potassium or proton ionophores and was unaffected by the presence or absence of Na+, K+, or Mg2+. Alanine-loaded proteoliposomes also took up [3H]aspartate in a heterologous antiport reaction that was stimulated or inhibited by an inside-positive or inside-negative membrane potential, respectively. Several lines of evidence suggest that these homologous and heterologous exchange reactions were catalyzed by the same functional unit. Thus, [3H]aspartate taken up by AspT during self-exchange was released by a delayed addition of alanine. In addition, the spontaneous loss of AspT activity that occurs when a detergent extract is held at 37 degrees C prior to reconstitution was prevented by the presence of either aspartate (KD(aspartate) = 0.3 mm) or alanine (KD(alanine) > or = 10 mm), indicating that both substrates interact directly with AspT. These findings are consistent with operation of a proton-motive metabolic cycle during aspartate metabolism by Lactobacillus subsp. M3.

  9. The energy dependence of lithium formate and alanine EPR dosimeters for medium energy x rays

    SciTech Connect

    Waldeland, Einar; Hole, Eli Olaug; Sagstuen, Einar; Malinen, Eirik

    2010-07-15

    Purpose: To perform a systematic investigation of the energy dependence of alanine and lilthium formate EPR dosimeters for medium energy x rays. Methods: Lithium formate and alanine EPR dosimeters were exposed to eight different x-ray beam qualities, with nominal potentials ranging from 50 to 200 kV. Following ionometry based on standards of absorbed dose to water, the dosimeters were given two different doses of approximately 3 and 6 Gy for each radiation quality, with three dosimeters for each dose. A reference series was also irradiated to three different dose levels at a {sup 60}Co unit. The dose to water energy response, that is, the dosimeter reading per absorbed dose to water relative to that for {sup 60}Co {gamma}-rays, was estimated for each beam quality. In addition, the energy response was calculated by Monte Carlo simulations and compared to the experimental energy response. Results: The experimental energy response estimates ranged from 0.89 to 0.94 and from 0.68 to 0.90 for lithium formate and alanine, respectively. The uncertainties in the experimental energy response estimates were typically 3%. The relative effectiveness, that is, the ratio of the experimental energy response to that following Monte Carlo simulations was, on average, 0.96 and 0.94 for lithium formate and alanine, respectively. Conclusions: This work shows that lithium formate dosimeters are less dependent on x-ray energy than alanine. Furthermore, as the relative effectiveness for both lithium formate and alanine were systematically less than unity, the yield of radiation-induced radicals is decreased following x-irradiation compared to irradiation with {sup 60}Co {gamma}-rays.

  10. The effect of β-alanine supplementation on cycling time trials of different length.

    PubMed

    Bellinger, Phillip M; Minahan, Clare L

    2016-10-01

    The varying results reported in response to β-alanine supplementation may be related to the duration and nature of the exercise protocol employed. We investigated the effects of β-alanine supplementation on a wide range of cycling performance tests in order to produce a clear concise set of criteria for its efficacy. Fourteen trained cyclists (Age = 24.8 ± 6.7 years; VO2max = 65.4 ± 10.2 mL·kg·min(-1)) participated in this placebo-controlled, double-blind study. Prior to supplementation, subjects completed two (familiarization and baseline) supramaximal cycling bouts until exhaustion (120% pre-supplementation VO2max) and two 1-, 4- and 10-km cycling time trial (TT). Subjects then supplemented orally for 4 weeks with 6.4 g/d placebo or β-alanine and repeated the battery of performance tests. Blood lactate was measured pre-exercise, post-exercise and 5  min post-exercise. β-alanine supplementation elicited significant increases in time to exhaustion (TTE) (17.6 ± 11.5 s; p = 0.013, effect compared with placebo) and was likely to be beneficial to 4-km TT performance time (-7.8 ± 8.1 s; 94% likelihood), despite not being statistically different (p = 0.060). Performance times in the 1- and 10-km TT were not affected by treatment. For the highly trained cyclists in the current study, β-alanine supplementation significantly extended supramaximal cycling TTE and may have provided a worthwhile improvement to 4-km TT performance. However, 1- and 10-km cycling TT performance appears to be unaffected by β-alanine supplementation.

  11. Bacillus cereus Spores Release Alanine that Synergizes with Inosine to Promote Germination

    PubMed Central

    Dodatko, Tetyana; Akoachere, Monique; Muehlbauer, Stefan M.; Helfrich, Forrest; Howerton, Amber; Ross, Christian; Wysocki, Vicki; Brojatsch, Jürgen; Abel-Santos, Ernesto

    2009-01-01

    Background The first step of the bacterial lifecycle is the germination of bacterial spores into their vegetative form, which requires the presence of specific nutrients. In contrast to closely related Bacillus anthracis spores, Bacillus cereus spores germinate in the presence of a single germinant, inosine, yet with a significant lag period. Methods and Findings We found that the initial lag period of inosine-treated germination of B. cereus spores disappeared in the presence of supernatants derived from already germinated spores. The lag period also dissipated when inosine was supplemented with the co-germinator alanine. In fact, HPLC-based analysis revealed the presence of amino acids in the supernatant of germinated B. cereus spores. The released amino acids included alanine in concentrations sufficient to promote rapid germination of inosine-treated spores. The alanine racemase inhibitor D-cycloserine enhanced germination of B. cereus spores, presumably by increasing the L-alanine concentration in the supernatant. Moreover, we found that B. cereus spores lacking the germination receptors gerI and gerQ did not germinate and release amino acids in the presence of inosine. These mutant spores, however, germinated efficiently when inosine was supplemented with alanine. Finally, removal of released amino acids in a washout experiment abrogated inosine-mediated germination of B. cereus spores. Conclusions We found that the single germinant inosine is able to trigger a two-tier mechanism for inosine-mediated germination of B. cereus spores: Inosine mediates the release of alanine, an essential step to complete the germination process. Therefore, B. cereus spores appear to have developed a unique quorum-sensing feedback mechanism to monitor spore density and to coordinate germination. PMID:19636427

  12. Effect of β-alanine treatment on mitochondrial taurine level and 5-taurinomethyluridine content

    PubMed Central

    2010-01-01

    Background The β-amino acid, taurine, is a nutritional requirement in some species. In these species, the depletion of intracellular stores of taurine leads to the development of severe organ dysfunction. The basis underlying these defects is poorly understood, although there is some suggestion that oxidative stress may contribute to the abnormalities. Recent studies indicate that taurine is required for normal mitochondrial protein synthesis and normal electron transport chain activity; it is known that defects in these events can lead to severe mitochondrial oxidative stress. The present study examines the effect of taurine deficiency on the first step of mitochondrial protein synthesis regulation by taurine, namely, the formation of taurinomethyluridine containing tRNA. Methods Isolated rat cardiomyocytes were rendered taurine deficient by incubation with medium containing the taurine transport inhibitor, β-alanine. The time course of cellular and mitochondrial taurine depletion was measured. The primer extension method was employed to evaluate the effect of β-alanine treatment on taurinomethyluridine content of tRNALeu. The protein levels of ND6 were also determined by Western blot analysis. Results β-alanine caused a time-dependent decrease in cellular taurine content, which were reduced in half after 48 hrs of incubation. The amount of taurine in the mitochondria was considerably less than that in the cytosol and was unaffected by β-alanine treatment. Approximately 70% of the tRNALeu in the untreated cell lacked taurinomethyluridine and these levels were unchanged following β-alanine treatment. Protein content of ND6, however, was significantly reduced after 48 hours incubation with β-alanine. Conclusions The taurine levels of the cytosol and the mitochondria are not directly coupled. The β-alanine-mediated reduction in taurine levels is too small to affect taurinomethyluridine levels. Nonetheless, it interferes with mitochondrial protein synthesis

  13. Effect of combined β-alanine and sodium bicarbonate supplementation on cycling performance.

    PubMed

    Bellinger, Phillip M; Howe, Samuel T; Shing, Cecilia M; Fell, James W

    2012-08-01

    The purpose of this study was to investigate the effects of 28 d of β-alanine supplementation on 4-min cycling time trial performance and to determine whether there was an additive effect of combined β-alanine and sodium bicarbonate (NaHCO3) supplementation on high-intensity cycling performance. Fourteen highly trained cyclists (mean ± SD: age = 25.4 ± 7.2 yr, mass = 71.1 ± 7.1 kg, V˙O(2max) = 66.6 ± 5.7 mL·kg·min) supplemented for 28 d with β-alanine (65 mg·kg body mass each day) or placebo. A maximal 4-min bout of cycling was performed before supplementation (baseline) and twice after supplementation: after ingestion of NaHCO3 (300 mg·kg body mass) and ingestion of a placebo using a randomized crossover design with 2 d between trials. Blood pH and HCO3 concentration were determined before loading (postsupplementation trials) and at pretest and posttest. In the acute NaHCO3 loading trials, blood pH and HCO3 were elevated from before loading to pretest, and the magnitude of the change in HCO3 from pretest to posttest was significantly greater compared with the acute placebo loading trial (P < 0.001). Average power output in the 4-min cycling performance trial was increased in placebo + NaHCO3 (+3.1% ± 1.8%) and β-alanine + NaHCO3 (+3.3% ± 3.0%) compared with baseline (P < 0.05). β-alanine + placebo did not significantly improve average power output compared with baseline (+1.6% ± 1.7%, P = 0.20); however, magnitude-based inferences demonstrated that β-alanine + placebo was associated with a 37% likelihood of producing average power improvements. In trained cyclists, β-alanine supplementation did not significantly improve 4-min cycling performance; however, there may be a small meaningful improvement in performance. Acute NaHCO3 supplementation significantly improved 4-min cycling performance. There seemed to be a minimal additive effect of combined β-alanine and NaHCO3 supplementation.

  14. On the fragmentation of biomolecules: Fragmentation of alanine dipeptide along the polypeptide chain

    SciTech Connect

    Solov'yov, I. A. Yakubovich, A. V.; Solov'yov, A. V.; Greiner, W.

    2006-09-15

    The interaction potential between amino acids in alanine dipeptide has been studied for the first time taking into account exact molecular geometry. Ab initio calculation has been performed in the framework of density functional theory taking into account all electrons in the system. The fragmentation of dipeptide along the polypeptide chain, as well as the interaction between alanines, has been considered. The energy of the system has been analyzed as a function of the distance between fragments for all possible dipeptide fragmentation channels. Analysis of the energy barriers makes it possible to estimate the characteristic fragmentation times and to determine the degree of applicability of classical electrodynamics for describing the system energy.

  15. Fragmentation of α- and β-alanine molecules by ions at Bragg-peak energies

    NASA Astrophysics Data System (ADS)

    Bari, S.; Sobocinski, P.; Postma, J.; Alvarado, F.; Hoekstra, R.; Bernigaud, V.; Manil, B.; Rangama, J.; Huber, B.; Schlathölter, T.

    2008-02-01

    The interaction of keV He+, He2+, and O5+ ions with isolated α and β isomers of the amino acid alanine was studied by means of high resolution coincidence time-of-flight mass spectrometry. We observed a strong isomer dependence of characteristic fragmentation channels which manifests in strongly altered branching ratios. Despite the ultrashort initial perturbation by the incoming ion, evidence for molecular rearrangement leading to the formation of H3+ was found. The measured kinetic energies of ionic alanine fragments can be sufficient to induce secondary damage to DNA in a biological environment.

  16. Self-organized structure of Alanine on Cu(111) Studied with STM

    NASA Astrophysics Data System (ADS)

    Jia, Jinfeng; Xue, Qukun; Seiberling, Liz

    2002-03-01

    There is an increasing interest in the interaction between organic molecules and metal surfaces. One reason for this is that well-ordered biological layers on metal surfaces have many important technological applications in biocatalysis, bioelectronics, biomaterials and nano-technology. The self-organized surface structure of alanine adsorbed on Cu(111) was studied with scanning tunneling microscopy. Well-ordered alanine islands are observed on the Cu(111) surface and the unit cell is about 20A x 20A. Based on our STM images, a structure model is proposed.

  17. Association Mapping Provides Insights into the Origin and the Fine Structure of the Sorghum Aluminum Tolerance Locus, AltSB

    PubMed Central

    Caniato, Fernanda F.; Hamblin, Martha T.; Guimaraes, Claudia T.; Zhang, Zhiwu; Schaffert, Robert E.; Kochian, Leon V.; Magalhaes, Jurandir V.

    2014-01-01

    Root damage caused by aluminum (Al) toxicity is a major cause of grain yield reduction on acid soils, which are prevalent in tropical and subtropical regions of the world where food security is most tenuous. In sorghum, Al tolerance is conferred by SbMATE, an Al-activated root citrate efflux transporter that underlies the major Al tolerance locus, AltSB, on sorghum chromosome 3. We used association mapping to gain insights into the origin and evolution of Al tolerance in sorghum and to detect functional variants amenable to allele mining applications. Linkage disequilibrium across the AltSB locus decreased much faster than in previous reports in sorghum, and reached basal levels at approximately 1000 bp. Accordingly, intra-locus recombination events were found to be extensive. SNPs and indels highly associated with Al tolerance showed a narrow frequency range, between 0.06 and 0.1, suggesting a rather recent origin of Al tolerance mutations within AltSB. A haplotype network analysis suggested a single geographic and racial origin of causative mutations in primordial guinea domesticates in West Africa. Al tolerance assessment in accessions harboring recombinant haplotypes suggests that causative polymorphisms are localized to a ∼6 kb region including intronic polymorphisms and a transposon (MITE) insertion, whose size variation has been shown to be positively correlated with Al tolerance. The SNP with the strongest association signal, located in the second SbMATE intron, recovers 9 of the 14 highly Al tolerant accessions and 80% of all the Al tolerant and intermediately tolerant accessions in the association panel. Our results also demonstrate the pivotal importance of knowledge on the origin and evolution of Al tolerance mutations in molecular breeding applications. Allele mining strategies based on associated loci are expected to lead to the efficient identification, in diverse sorghum germplasm, of Al tolerant accessions able maintain grain yields under Al

  18. Association mapping provides insights into the origin and the fine structure of the sorghum aluminum tolerance locus, AltSB.

    PubMed

    Caniato, Fernanda F; Hamblin, Martha T; Guimaraes, Claudia T; Zhang, Zhiwu; Schaffert, Robert E; Kochian, Leon V; Magalhaes, Jurandir V

    2014-01-01

    Root damage caused by aluminum (Al) toxicity is a major cause of grain yield reduction on acid soils, which are prevalent in tropical and subtropical regions of the world where food security is most tenuous. In sorghum, Al tolerance is conferred by SbMATE, an Al-activated root citrate efflux transporter that underlies the major Al tolerance locus, AltSB, on sorghum chromosome 3. We used association mapping to gain insights into the origin and evolution of Al tolerance in sorghum and to detect functional variants amenable to allele mining applications. Linkage disequilibrium across the AltSB locus decreased much faster than in previous reports in sorghum, and reached basal levels at approximately 1000 bp. Accordingly, intra-locus recombination events were found to be extensive. SNPs and indels highly associated with Al tolerance showed a narrow frequency range, between 0.06 and 0.1, suggesting a rather recent origin of Al tolerance mutations within AltSB. A haplotype network analysis suggested a single geographic and racial origin of causative mutations in primordial guinea domesticates in West Africa. Al tolerance assessment in accessions harboring recombinant haplotypes suggests that causative polymorphisms are localized to a ∼6 kb region including intronic polymorphisms and a transposon (MITE) insertion, whose size variation has been shown to be positively correlated with Al tolerance. The SNP with the strongest association signal, located in the second SbMATE intron, recovers 9 of the 14 highly Al tolerant accessions and 80% of all the Al tolerant and intermediately tolerant accessions in the association panel. Our results also demonstrate the pivotal importance of knowledge on the origin and evolution of Al tolerance mutations in molecular breeding applications. Allele mining strategies based on associated loci are expected to lead to the efficient identification, in diverse sorghum germplasm, of Al tolerant accessions able maintain grain yields under Al

  19. Predictors of treatment requirement in HBeAg-negative chronic hepatitis B patients with persistently normal alanine aminotransferase and high serum HBV DNA levels.

    PubMed

    Ormeci, Aslı; Aydın, Yucel; Sumnu, Abdullah; Baran, Bulent; Soyer, Ozlem Mutluay; Pınarbasi, Binnur; Gokturk, Suut; Gulluoglu, Mine; Onel, Derya; Badur, Selim; Akyuz, Filiz; Karaca, Cetin; Demir, Kadir; Besisik, Fatih; Kaymakoglu, Sabahattin

    2016-11-01

    Serum alanine aminotransferase (ALT) is a controversial marker for disease monitoring in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. The aim of this study was to determine the fibrosis stage and histological activity index (HAI) in HBeAg-negative CHB patients with persistently normal ALT (PNALT) and high serum HBV DNA (≥2000 IU/ml) and to investigate clinical risk factors for the requirement of treatment through the examination of liver biopsy specimens. HBeAg-negative CHB patients with PNALT (≤40 IU/l) and high serum HBV DNA (≥2000 IU/ml) were included. HBV fibrosis stage and HAI were scored according to the Ishak system. Multivariate logistic regression analysis was used to estimate the independent risk factors for fibrosis stage ≥2 and/or HAI ≥6. Receiver operating characteristic curve analysis was used to determine an optimal age cut-off for liver biopsy. A total 120 patients were enrolled. These patients had a mean HBV DNA level of 123680±494500 IU/ml; the HBV DNA load was 2000-20000 IU/ml in 68 patients (56.6%) and ≥20000 IU/ml in 52 (43.4%). Eighteen patients (15%) had moderate-to-severe histological activity (HAI ≥6). Forty-three patients (35.9%) had a fibrosis stage ≥2. Forty-eight patients (40%) had a fibrosis stage ≥2 and/or HAI ≥6. On multivariate logistic regression analysis, independent variables associated with fibrosis stage ≥2 and/or HAI ≥6 included age and HBV DNA viral load. Patients with HBV DNA 2000-20000 IU/ml were more likely to require treatment compared to those with a viral load ≥20000 IU/ml. The optimal age cut-off to predict fibrosis stage ≥2 and/or HAI ≥6 was 46 years. Significant liver damage was detected in 40% of CHB patients with PNALT and high HBV DNA upon biopsy. Age and HBV DNA viral load were independent predictors of significant liver damage. A biopsy to determine the degree of liver damage is advisable for CHB patients older than 46 years. Copyright © 2016 The

  20. A Styrene-alt-Maleic Acid Copolymer Is an Effective Inhibitor of R5 and X4 Human Immunodeficiency Virus Type 1 Infection

    PubMed Central

    Pirrone, Vanessa; Passic, Shendra; Wigdahl, Brian; Rando, Robert F.; Labib, Mohamed; Krebs, Fred C.

    2010-01-01

    An alternating copolymer of styrene and maleic acid (alt-PSMA) differs from other polyanionic antiviral agents in that the negative charges of alt-PSMA are provided by carboxylic acid groups instead of sulfate or sulfonate moieties. We hypothesized that alt-PSMA would have activity against human immunodeficiency virus type 1 (HIV-1) comparable to other polyanions, such as the related compound, poly(sodium 4-styrene sulfonate) (PSS). In assays using cell lines and primary immune cells, alt-PSMA was characterized by low cytotoxicity and effective inhibition of infection by HIV-1 BaL and IIIB as well as clinical isolates of subtypes A, B, and C. In mechanism of action assays, in which each compound was added to cells and subsequently removed prior to HIV-1 infection (“washout” assay), alt-PSMA caused no enhancement of infection, while PSS washout increased infection 70% above control levels. These studies demonstrate that alt-PSMA is an effective HIV-1 inhibitor with properties that warrant further investigation. PMID:20589074

  1. Effects of glycine, beta-alanine and diazepam upon morphine-tolerant-dependent mice.

    PubMed

    Contreras, E; Tamayo, L

    1980-05-01

    The effects in mice of glycine, beta-alanine and diazepam on the analgesic response to morphine, on the intensity of tolerance and on the physical dependence on the analgesic have been examined. The two amino acids increased the analgesic response to morphine in a dose-related manner. However, both compounds were ineffective in the analgesic test (hot plate) when administered without morphine. Diazepam was ineffective in the analgesic test and it did not alter morphine analgesia, except when administered in a high dose which decreased and analgesic response. Glycine, either in single or repeated doses, did not modify tolerance to morphine, whereas beta-alanine induced a dose-related partial antagonism, which promptly reached a plateau. Diazepam induced a small decrease in the intensity of tolerance to the analgesic. The abstinence syndrome to morphine, induced by naloxone administration to primed mice, was reduced by single doses of glycine or beta-alanine. Diazepam behaved as a weak inhibitor of the abstinence syndrome when administered at a high dose. The potentiation of morphine analgesia and the antagonism of the abstinence syndrome induced by the amino acids may be related to their hyperpolarizing action in the c.n. system. The effects of beta-alanine on morphine tolerance cannot be explained by the same mechanism.

  2. Beta-alanine/alpha-ketoglutarate aminotransferase for 3-hydroxypropionic acid production

    DOEpatents

    Jessen, Holly Jean [Chanhassen, MN; Liao, Hans H [Eden Prairie, MN; Gort, Steven John [Apple Valley, MN; Selifonova, Olga V [Plymouth, MN

    2011-10-04

    The present disclosure provides novel beta-alanine/alpha ketoglutarate aminotransferase nucleic acid and protein sequences having increased biological activity. Also provided are cells containing such enzymes, as well as methods of their use, for example to produce malonyl semialdehyde and downstream products thereof, such as 3-hydroxypropionic acid and derivatives thereof.

  3. Positron and electron scattering by glycine and alanine: Shape resonances and methylation effect

    NASA Astrophysics Data System (ADS)

    Nunes, Fernanda B.; Bettega, Márcio H. F.; Sanchez, Sergio d'Almeida

    2016-12-01

    We report integral cross sections (ICSs) for both positron and electron scattering by glycine and alanine amino acids. These molecules differ only by a methyl group. We computed the scattering cross sections using the Schwinger multichannel method for both glycine and alanine in different levels of approximation for both projectiles. The alanine ICSs are greater in magnitude than the glycine ICSs for both positron and electron scattering, probably due to the larger size of the molecule. In electron scattering calculations, we found two resonances for each molecule. Glycine presents one at 1.8 eV, and another centered at around 8.5 eV, in the static-exchange plus polarization (SEP) approximation. The ICS for alanine shows one resonance at 2.5 eV and another at around 9.5 eV, also in SEP approximation. The results are in good agreement with most of the data present in the literature. The comparison of the electron scattering ICSs for both molecules indicates that the methylation of glycine destabilizes the resonances, shifting them to higher energies.

  4. Investigation on physical properties of L-alanine: An effect of Methylene blue dye

    NASA Astrophysics Data System (ADS)

    Shkir, Mohd.; Yahia, I. S.; Al-Qahtani, A. M. A.; Ganesh, V.; AlFaify, S.

    2017-03-01

    In the present investigation, a bulk size (35 mm × 25 mm × 15 mm) single crystal of 0.1 wt% Methylene blue dye (MLB) added L-alanine is grown at room temperature using solution technique for the first time. The L-alanine crystals with higher concentrations of dye (0.5 and 1 wt%) were also grown. Solubility study was performed at different temperatures. Structural, vibrational and good quality was inveterate by powder XRD, FT-Raman and SEM analyses. High transmittance in dyed crystals was confirmed. The presence of MLB dye was confirmed by an absorption band centered at 650 nm. Optical band gap was calculated for pure and dyed L-alanine crystals and found to be 5.45 and 4.49 eV respectively. Photoluminescence intensity of UV-A emission band centered at 332 nm was found to be enhanced due to the presence of dye. The dielectric measurement was done in the wide frequency range. Furthermore, the third order nonlinear optical parameters are enhanced in dyed L-alanine crystals determined by Z-scan technique.

  5. Role of alanine racemase mutations in Mycobacterium tuberculosis D-cycloserine resistance.

    PubMed

    Nakatani, Yoshio; Opel-Reading, Helen K; Merker, Matthias; Machado, Diana; Andres, Sönke; Kumar, S Siva; Moradigaravand, Danesh; Coll, Francesc; Perdigão, João; Portugal, Isabel; Schön, Thomas; Nair, Dina; Devi, K R Uma; Kohl, Thomas A; Beckert, Patrick; Clark, Taane G; Maphalala, Gugu; Khumalo, Derrick; Diel, Roland; Klaos, Kadri; Aung, Htin Lin; Cook, Gregory M; Parkhill, Julian; Peacock, Sharon J; Swaminathan, Soumya; Viveiros, Miguel; Niemann, Stefan; Krause, Kurt L; Köser, Claudio U

    2017-10-02

    Screening of more than 1,500 drug-resistant strains of Mycobacterium tuberculosis revealed evolutionary patterns characteristic of positive selection for three alanine racemase (Alr) mutations. We investigated these mutations using molecular modeling, in vitro MIC testing, as well as direct measurements of enzymatic activity, which demonstrated that these mutations likely confer resistance to D-cycloserine. Copyright © 2017 Nakatani et al.

  6. Effect of alpha interferon on glucose and alanine transport by rat renal brush border membrane vesicles

    SciTech Connect

    Batuman, V.; Chadha, I. New Jersey Medical School, Newark )

    1990-01-01

    To investigate the pathogenetic mechanisms of interferon nephrotoxicity, we studied the effect of recombinant interferon alfa-2b on the uptake of {sup 14}C-D-glucose and {sup 14}C-L-alanine by rat renal brush-border-membrane vesicles. Interferon significantly inhibited 20 sec. sodium-dependent and 5 and 10 min. equilibrium uptake of both glucose and alanine. The inhibitory effect was dose dependent with maximum effect achieved at interferon concentration of 5 {times} 10{sup {minus}8}M in the uptake media. The half-maximal inhibitory concentrations, IC{sub 50}, of interferon on glucose uptake was 1.8 {times} 10{sup {minus}8}M, and 5.4 {times} 10{sup {minus}9}M on alanine uptake. Dixon plot analysis of uptake data was consistent with pure non-competitive inhibition. The inhibition constants, K{sub i}, 1.5 {times} 10{sup {minus}8}M for glucose uptake, and 7.3 {times} 10{sup {minus}9}M for alanine uptake, derived from Dixon plots were in close agreement with the IC{sub 50}s calculated from the semilog dose response curves. These observations reveal that direct interactions at the proximal tubule cell membrane are involved in the pathogenesis of interferon nephrotoxicity, and that its mechanism of nephrotoxicity is similar to that of other low molecular weight proteins.

  7. Protein Homeostasis Defects of Alanine-Glyoxylate Aminotransferase: New Therapeutic Strategies in Primary Hyperoxaluria Type I

    PubMed Central

    Pey, Angel L.; Albert, Armando; Salido, Eduardo

    2013-01-01

    Alanine-glyoxylate aminotransferase catalyzes the transamination between L-alanine and glyoxylate to produce pyruvate and glycine using pyridoxal 5′-phosphate (PLP) as cofactor. Human alanine-glyoxylate aminotransferase is a peroxisomal enzyme expressed in the hepatocytes, the main site of glyoxylate detoxification. Its deficit causes primary hyperoxaluria type I, a rare but severe inborn error of metabolism. Single amino acid changes are the main type of mutation causing this disease, and considerable effort has been dedicated to the understanding of the molecular consequences of such missense mutations. In this review, we summarize the role of protein homeostasis in the basic mechanisms of primary hyperoxaluria. Intrinsic physicochemical properties of polypeptide chains such as thermodynamic stability, folding, unfolding, and misfolding rates as well as the interaction of different folding states with protein homeostasis networks are essential to understand this disease. The view presented has important implications for the development of new therapeutic strategies based on targeting specific elements of alanine-glyoxylate aminotransferase homeostasis. PMID:23956997

  8. Partial enzymatic elimination and quantification of sarcosine from alanine using liquid chromatography-tandem mass spectrometry.

    PubMed

    Burton, Casey; Gamagedara, Sanjeewa; Ma, Yinfa

    2013-04-01

    Since sarcosine and D,L-alanine co-elute on reversed-phase high-performance liquid chromatography (HPLC) columns and the tandem mass spectrometer cannot differentiate them due to equivalent parent and fragment ions, derivatization is often required for analysis of sarcosine in LC/MS systems. This study offers an alternative to derivatization by employing partial elimination of sarcosine by enzymatic oxidation. The decrease in apparent concentration from the traditionally merged sarcosine-alanine peak associated with the enzymatic elimination has been shown to be proportional to the total sarcosine present (R(2) = 0.9999), allowing for determinations of urinary sarcosine. Sarcosine oxidase was shown to eliminate only sarcosine in the presence of D,L-alanine, and was consequently used as the selective enzyme. This newly developed technique has a method detection limit of 1 μg/L (parts per billion) with a linear range of 3 ppb-1 mg/L (parts per million) in urine matrices. The method was further validated through spiked recoveries of real urine samples, as well as the analysis of 35 real urine samples. The average recoveries for low, middle, and high sarcosine concentration spikes were 111.7, 90.8, and 90.1 %, respectively. In conclusion, this simple enzymatic approach coupled with HPLC/MS/MS is able to resolve sarcosine from D,L-alanine leading to underivatized quantification of sarcosine.

  9. High-velocity intermittent running: effects of beta-alanine supplementation.

    PubMed

    Smith-Ryan, Abbie E; Fukuda, David H; Stout, Jeffrey R; Kendall, Kristina L

    2012-10-01

    The use of β-alanine in sport is widespread. However, the effects across all sport activities are inconclusive. The purpose of this study was to evaluate the effects of β-alanine supplementation on high-intensity running performance and critical velocity (CV) and anaerobic running capacity (ARC). Fifty recreationally trained men were randomly assigned, in a double-blind fashion, to a β-alanine group (BA, 2 × 800 mg tablets, 3 times daily; CarnoSyn; n = 26) or placebo group (PL, 2 × 800 mg maltodextrin tablets, 3 times daily; n = 24). A graded exercise test (GXT) was performed to establish peak velocity (PV). Three high-speed runs to exhaustion were performed at 110, 100, and 90% of PV, with 15 minutes of rest between bouts. The distances achieved were plotted over the time to exhaustion (TTE). Linear regression was used to determine the slope (CV) and y-intercept (ARC) of these relationships to assess aerobic and anaerobic performances, respectively. There were no significant treatment effects (p > 0.05) on CV or ARC for either men or women. Additionally, no TTE effects were evident for bouts at 90-110%PV lasting 1.95-5.06 minutes. There seems to be no ergogenic effect of β-alanine supplementation on CV, ARC, or high-intensity running lasting approximately 2-5 minutes in either men or women in the current study.

  10. Vibrational Raman optical activity characterization of poly(l-proline) II helix in alanine oligopeptides.

    PubMed

    McColl, Iain H; Blanch, Ewan W; Hecht, Lutz; Kallenbach, Neville R; Barron, Laurence D

    2004-04-28

    A vibrational Raman optical activity (ROA) study of a series of alanine peptides in aqueous solution is presented. The seven-alanine peptide Acetyl-OOAAAAAAAOO-Amide (OAO), recently shown by NMR and UVCD to adopt a predominantly poly(l-proline II) (PPII) helical conformation in aqueous solution, gave an ROA spectrum very similar to that of disordered poly(l-glutamic acid) which has long been considered to adopt the PPII conformation, both being dominated by a strong positive extended amide III ROA band at approximately 1319 cm-1 together with weak positive amide I ROA intensity at approximately 1675 cm-1. A series of alanine peptides Ala2-Ala6 studied in their cationic states in aqueous solution at low pH displayed ROA spectra which steadily evolved toward that of OAO with increasing chain length. As well as confirming that alanine peptides can support the PPII conformation in aqueous solution, our results also confirm the previous ROA band assignments for PPII structure, thereby reinforcing the foundation for ongoing ROA studies of unfolded and partially folded proteins.

  11. Synthesis of silver nanoparticles using DL-alanine for ESR dosimetry applications

    NASA Astrophysics Data System (ADS)

    Guidelli, Eder José; Ramos, Ana Paula; Zaniquelli, Maria Elisabete D.; Nicolucci, Patricia; Baffa, Oswaldo

    2012-03-01

    The potential use of alanine for the production of nanoparticles is presented here for the first time. Silver nanoparticles were synthesized using a simple green method, namely the thermal treatment of silver nitrate aqueous solutions with DL-alanine. The latter compound was employed both as a reducing and a capping agent. Particles with average size equal to 7.5 nm, face-centered cubic crystalline structure, narrow size distribution, and spherical shape were obtained. Interaction between the silver ions present on the surface of the nanoparticles and the amine group of the DL-alanine molecule seems to be responsible for reduction of the silver ions and for the stability of the colloid. The bio-hybrid nano-composite was used as an ESR dosimeter. The amount of silver nanoparticles in the nanocomposite was not sufficient to cause considerable loss of tissue equivalency. Moreover, the samples containing nanoparticles presented increased sensitivity and reduced energetic dependence as compared with pure DL-alanine, contributing to the construction of small-sized dosimeters.

  12. Influence of beta-alanine supplementation on skeletal muscle carnosine concentrations and high intensity cycling capacity.

    PubMed

    Hill, C A; Harris, R C; Kim, H J; Harris, B D; Sale, C; Boobis, L H; Kim, C K; Wise, J A

    2007-02-01

    Muscle carnosine synthesis is limited by the availability of beta-alanine. Thirteen male subjects were supplemented with beta-alanine (CarnoSyn) for 4 wks, 8 of these for 10 wks. A biopsy of the vastus lateralis was obtained from 6 of the 8 at 0, 4 and 10 wks. Subjects undertook a cycle capacity test to determine total work done (TWD) at 110% (CCT(110%)) of their maximum power (Wmax). Twelve matched subjects received a placebo. Eleven of these completed the CCT(110%) at 0 and 4 wks, and 8, 10 wks. Muscle biopsies were obtained from 5 of the 8 and one additional subject. Muscle carnosine was significantly increased by +58.8% and +80.1% after 4 and 10 wks beta-alanine supplementation. Carnosine, initially 1.71 times higher in type IIa fibres, increased equally in both type I and IIa fibres. No increase was seen in control subjects. Taurine was unchanged by 10 wks of supplementation. 4 wks beta-alanine supplementation resulted in a significant increase in TWD (+13.0%); with a further +3.2% increase at 10 wks. TWD was unchanged at 4 and 10 wks in the control subjects. The increase in TWD with supplementation followed the increase in muscle carnosine.

  13. Synthesis, characterization, and biocompatible properties of alanine-grafted chitosan copolymers.

    PubMed

    Park, Gyu Han; Kang, Min-Sil; Knowles, Jonathan C; Gong, Myoung-Seon

    2016-04-01

    In order to overcome major problems regarding the lack of affinity to solvents and limited reactivity of the free amines of chitosan, introduction of appropriate spacer arms having terminal amine function is considered of interest. L-Alanine-N-carboxyanhydride was grafted onto chitosan via anionic ring-opening polymerization. The chemical and structural characterizations of L-alanine-grafted chitosan (Ala-g-Cts) were confirmed through Fourier transform infrared spectroscopy and proton nuclear magnetic resonance spectroscopy ((1)H NMR). In addition, the viscoelastic properties of Ala-g-Cts were examined by means of a rotational viscometer, and thermal analysis was carried out with a thermogravimetric analyzer and differential scanning calorimetry. Morphological changes in the chitosan L-alanine moiety were determined by x-ray diffraction. To determine the feasibility of using these films as biomedical materials, we investigated the effects of their L-alanine content on physical and mechanical properties. The biodegradation results of crosslinked Ala-g-Cts films were evaluated in phosphate-buffered solution containing lysozyme at 37℃. Proliferation of MC3T3-E1 cells on crosslinked Ala-g-Cts films was also investigated with use of the CCK-8 assay.

  14. Growth and characterization of pure and semiorganic nonlinear optical Lithium Sulphate admixtured l-alanine crystal

    NASA Astrophysics Data System (ADS)

    Vela, T.; Selvarajan, P.; Freeda, T. H.; Balasubramanian, K.

    2013-04-01

    Lithium sulphate admixtured l-alanine (LSLA) salt was synthesized and the solubility of the commercially available l-alanine and the synthesized LSLA sample was determined in de-ionized water at various temperatures. In accordance with the solubility data, the saturated aqueous solutions of l-alanine and lithium admixtured l-alanine were prepared separately and the single crystals of the samples were grown by the solution method with a slow evaporation technique. Studying single x-ray diffraction shows that pure and LSLA crystal belong to the orthorhombic system with a non-centrosymmetric space group P212121. Using the powder x-ray diffraction study, the crystallinity of the grown crystals is confirmed and the diffraction peaks are indexed. The various functional groups present in the pure and LSLA crystal are elucidated from Fourier transform infrared spectroscopy study. UV-visible transmittance is recorded to study the optical transmittance range for the grown crystals. The powder second harmonic generation test confirms the nonlinear optical property of the grown crystals. From the microhardness test, the hardness of the grown crystals is estimated. The dielectric behaviour, such as the dielectric constant and the loss of the sample, are measured as a function of temperature and frequency. The ac conductivity of the grown crystals is also studied and the activation energy is calculated.

  15. [Temperature-dependent optical activity and birefringence study of D-alanine single crystal].

    PubMed

    Li, Zong-Sheng; Gong, Yan; Wang, Wen-Qing; Du, Wei-Min

    2006-02-01

    The measurement of the anisotropy of optical acitivity and birefringence is one of the most important clues to studying physical properties of a biaxial crystal of D-alanine. In order to investigate a second-order phase transition predicted by A. Salam between two states of D-alanine, the behavior of birefringence and optical activity is useful for the phenomenological approach to the transition mechanism. The optical activity as a peculiar quantity can respond to the modulation of the crystal lattice and to the change in the bonding nature of constituent atoms. In the present paper, the authors use the PEM-90 photoelastic modulator to study the conformation change of D-alanine at the temperature ranging from 220 to 290 K. The temperature dependence of I(2f)/I(dc) showed that the conformation of D-alanine molecule in single crystal changed around 250 K. The obtained results provide an obvious evidence of optical rotation phase transition predicted by Salam.

  16. Probing the interaction of the amino acid alanine with the surface of ZnO(1010).

    PubMed

    Gao, Y K; Traeger, F; Shekhah, O; Idriss, H; Wöll, C

    2009-10-01

    The adsorption modes and stability of the amino acid alanine (NH(2)-CH(CH(3))-COOH) have been studied on the nonpolar single crystal surface of zinc oxide, ZnO(1010), experimentally by X-ray photoelectron spectroscopy (XPS) and computationally using density functional theory (DFT). Deposition at 200 K was found to lead to the formation of multilayers identified by an XPS N1s peak at 401.7 eV assigned to the NH(3)(+) group, a fingerprint of the zwitterionic structure of alanine in the solid state. Heating to 300 K resulted in the removal of most of the multilayers with the remaining surface coverage estimated to 0.4 with respect to Zn cations. At this temperature most of the alanine molecules are found to be deprotonated (dissociated), yielding a carboxylate species (NH(2)-CH(CH(3))-COO(-) (a) + OH (s); where O is surface oxygen, (a) for adsorbed and (s) for surface species). Further heating of the surface resulted in a gradual decrease of the surface coverage and by 500 K a large fraction of adsorbed alanine molecules have desorbed from the surface. Total energy DFT computations of different adsorbate species identified two stable dissociative adsorption modes: bidentate and monodentate. The bidentate species with adsorption energy of 1.75 eV was found to be more stable than the monodentate species by about 0.7 eV.

  17. Spectral characterization of a non-centrosymmetric organic compound: D-(-)-alanine

    NASA Astrophysics Data System (ADS)

    Moovendaran, K.; Martin Britto Dhas, S. A.; Natarajan, S.

    2013-08-01

    The crystal growth of D-(-)-alanine (1), a non-centrosymmetric solid is reported. It was characterized by NMR, infrared, Raman, UV-Vis-NIR and CD spectra. Experimental vibrational frequencies are compared with theoretically calculated values. Second harmonic generation (SHG) and first hyperpolarizability measurements are reported.

  18. Spectral characterization of a non-centrosymmetric organic compound: D-(-)-alanine.

    PubMed

    Moovendaran, K; Martin Britto Dhas, S A; Natarajan, S

    2013-08-01

    The crystal growth of D-(-)-alanine (1), a non-centrosymmetric solid is reported. It was characterized by NMR, infrared, Raman, UV-Vis-NIR and CD spectra. Experimental vibrational frequencies are compared with theoretically calculated values. Second harmonic generation (SHG) and first hyperpolarizability measurements are reported.

  19. Multiple state transition interface sampling of alanine dipeptide in explicit solvent

    NASA Astrophysics Data System (ADS)

    Du, Wei-Na; Marino, Kristen A.; Bolhuis, Peter G.

    2011-10-01

    We have applied the recently developed multiple state transition interface sampling approach to alanine dipeptide in explicit water. We extract the rate constant matrix for configurational changes between each pair of metastable states. The results are comparable with values from previous literature and show that the method is applicable to biomolecular systems.

  20. Beta-alanine/alpha-ketoglutarate aminotransferase for 3-hydroxypropionic acid production

    SciTech Connect

    Jessen, Holly Jean; Liao, Hans H; Gort, Steven John; Selifonova, Olga V

    2014-11-18

    The present disclosure provides novel beta-alanine/alpha ketoglutarate aminotransferase nucleic acid and protein sequences having increased biological activity. Also provided are cells containing such enzymes, as well as methods of their use, for example to produce malonyl semialdehyde and downstream products thereof, such as 3-hydroxypropionic acid and derivatives thereof.

  1. An aldonolactonase AltA from Penicillium oxalicum mitigates the inhibition of β-glucosidase during lignocellulose biodegradation.

    PubMed

    Peng, Shengjuan; Cao, Qing; Qin, Yuqi; Li, Xuezhi; Liu, Guodong; Qu, Yinbo

    2017-02-04

    Efficient deconstruction of lignocellulose is achieved by the synergistic action of various hydrolytic and oxidative enzymes. However, the aldonolactones generated by oxidative enzymes have inhibitory effects on some cellulolytic enzymes. In this work, D-glucono-1,5-lactone was shown to have a much stronger inhibitory effect than D-glucose and D-gluconate on β-glucosidase, a vital enzyme during cellulose degradation. AltA, a secreted enzyme from Penicillium oxalicum, was identified as an aldonolactonase which can catalyze the hydrolysis of D-glucono-1,5-lactone to D-gluconic acid. In the course of lignocellulose saccharification conducted by cellulases from P. oxalicum or Trichoderma reesei, supplementation of AltA was able to relieve the decrease of β-glucosidase activity obviously with a stimulation of glucose yield. This boosting effect disappeared when sodium azide and ethylenediaminetetraacetic acid (EDTA) were added to the saccharification system to inhibit the activities of oxidative enzymes. In summary, we describe the first heterologous expression of a fungal secreted aldonolactonase and its application as an efficient supplement of cellulolytic enzyme system for lignocellulose biodegradation.

  2. Frederick W. Alt received the 2015 Szent-Györgi Prize for Progress in Cancer Research.

    PubMed

    Scully, Peter; Zhao, Jie; Ba, Sujuan

    2016-02-03

    The Szent-Györgyi Prize for Progress in Cancer Research is a prestigious scientific award established by the National Foundation for Cancer Research (NFCR)--a leading cancer research charitable organization in the United States that is committed to supporting scientific research and public education relating to the prevention, early diagnosis, better treatments, and ultimately, a cure for cancer. Each year, the Szent-Györgyi Prize honors an outstanding researcher, nominated by colleagues or peers, who has contributed outstanding, significant research to the fight against cancer, and whose accomplishments have helped improve treatment options for cancer patients. The Prize also promotes public awareness of the importance of basic cancer research and encourages the sustained investment needed to accelerate the translation of these research discoveries into new cancer treatments. This report highlights the pioneering work led by the 2015 Prize winner, Dr. Frederick Alt. Dr. Alt's work in the area of cancer genetics over four decades has helped to shape the very roots of modern cancer research. His work continues to profoundly impact the approaches that doctors around the globe use to diagnose and treat cancer. In particular, his seminal discoveries of gene amplification and his pioneering work on molecular mechanisms of DNA damage repair have helped to usher in the era of genetically targeted therapy and personalized medicine.

  3. Knockout of the alanine racemase gene in Aeromonas hydrophila HBNUAh01 results in cell wall damage and enhanced membrane permeability.

    PubMed

    Liu, Dong; Zhang, Lu; Xue, Wen; Wang, Yaping; Ju, Jiansong; Zhao, Baohua

    2015-07-01

    This study focused on the alanine racemase gene (alr-2), which is involved in the synthesis of d-alanine that forms the backbone of the cell wall. A stable alr-2 knockout mutant of Aeromonas hydrophila HBNUAh01 was constructed. When the mutant was supplemented with d-alanine, growth was unaffected; deprivation of d-alanine caused the growth arrest of the starved mutant cells, but not cell lysis. No alanine racemase activity was detected in the culture of the mutant. Additionally, a membrane permeability assay showed increasing damage to the cell wall during d-alanine starvation. No such damage was observed in the wild type during culture. Scanning and transmission electron microscopy analyses revealed deficiencies of the cell envelope and perforation of the cell wall. Leakage of UV-absorbing substances from the mutants was also observed. Thus, the partial viability of the mutants and their independence of d-alanine for growth indicated that inactivation of alr-2 does not impose an auxotrophic requirement for d-alanine.

  4. Effects of endogenous D-alanine synthesis and autoinhibition of Bacillus anthracis germination on in vitro and in vivo infections.

    PubMed

    McKevitt, Matthew T; Bryant, Katie M; Shakir, Salika M; Larabee, Jason L; Blanke, Steven R; Lovchik, Julie; Lyons, C Rick; Ballard, Jimmy D

    2007-12-01

    Bacillus anthracis transitions from a dormant spore to a vegetative bacillus through a series of structural and biochemical changes collectively referred to as germination. The timing of germination is important during early steps in infection and may determine if B. anthracis survives or succumbs to responsive macrophages. In the current study experiments determined the contribution of endogenous D-alanine production to the efficiency and timing of B. anthracis spore germination under in vitro and in vivo conditions. Racemase-mediated production of endogenous D-alanine by B. anthracis altered the kinetics for initiation of germination over a range of spore densities and exhibited a threshold effect wherein small changes in spore number resulted in major changes in germination efficiency. This threshold effect correlated with D-alanine production, was prevented by an alanine racemase inhibitor, and required L-alanine. Interestingly, endogenous production of inhibitory levels of D-alanine was detected under experimental conditions that did not support germination and in a germination-deficient mutant of B. anthracis. Racemase-dependent production of D-alanine enhanced survival of B. anthracis during interaction with murine macrophages, suggesting a role for inhibition of germination during interaction with these cells. Finally, in vivo experiments revealed an approximately twofold decrease in the 50% lethal dose of B. anthracis spores administered in the presence of D-alanine, indicating that rates of germination may be directly influenced by the levels of this amino acid during early stages of disease.

  5. Persistent GABAA/C responses to gabazine, taurine and beta-alanine in rat hypoglossal motoneurons.

    PubMed

    Chesnoy-Marchais, D

    2016-08-25

    In hypoglossal motoneurons, a sustained anionic current, sensitive to a blocker of ρ-containing GABA receptors, (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) and insensitive to bicuculline, was previously shown to be activated by gabazine. In order to better characterize the receptors involved, the sensitivity of this atypical response to pentobarbital (30μM), allopregnanolone (0.3μM) and midazolam (0.5μM) was first investigated. Pentobarbital potentiated the response, whereas the steroid and the benzodiazepine were ineffective. The results indicate the involvement of hybrid heteromeric receptors, including at least a GABA receptor ρ subunit and a γ subunit, accounting for the pentobarbital-sensitivity. The effects of the endogenous β amino acids, taurine and β-alanine, which are released under various pathological conditions and show neuroprotective properties, were then studied. In the presence of the glycine receptor blocker strychnine (1μM), both taurine (0.3-1mM) and β-alanine (0.3mM) activated sustained anionic currents, which were partly blocked by TPMPA (100μM). Thus, both β amino acids activated ρ-containing GABA receptors in hypoglossal motoneurons. Bicuculline (20μM) reduced responses to taurine and β-alanine, but small sustained responses persisted in the presence of both strychnine and bicuculline. Responses to β-alanine were slightly increased by allopregnanolone, indicating a contribution of the bicuculline- and neurosteroid-sensitive GABAA receptors underlying tonic inhibition in these motoneurons. Since sustained activation of anionic channels inhibits most mature principal neurons, the ρ-containing GABA receptors permanently activated by taurine and β-alanine might contribute to some of their neuroprotective properties under damaging overexcitatory situations. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. A glia–neuron alanine/ammonium shuttle is central to energy metabolism in bee retina

    PubMed Central

    Coles, Jonathan A; Martiel, Jean-Louis; Laskowska, Karolina

    2008-01-01

    It has been proposed that glial cells may supply carbon fuel to neurons and also that there are fluxes of ammonium from neurons to glia. We have investigated both these proposals in Apis retinal slices, in which virtually all the mitochondria are in the photoreceptor neurons. Normally the superfusate contained no substrate of energy metabolism; addition of glucose or alanine did not increase oxygen consumption , confirming that the neurons received adequate substrate from glycogen in the glia. 1,4-Dideoxy-1,4-imino-d-arabinitol (DAB, 100 μm), an inhibitor of glycogen phosphorylase, progressively decreased . This decrease was reversed by alanine but not glucose. Ammonium-sensitive microelectrodes did not detect significant extracellular [NH4+] ([NH4+]e) in slices superfused with normal superfusate. Removal of Cl−, necessary for cotransport of NH4+ into the glia, increased [NH4+]e so that at the end of 2 min photostimulation mean [NH4+]e was 0.442 mm (s.e.m.= 0.082 mm, n = 16). In 0 Cl−, [NH4+]e was reduced by 2-(methylamino)isobutyrate (MeAIB) an inhibitor of alanine transport. MeAIB also blocked oxidation of alanine in the presence of DAB, but did not decrease in normal superfusate. Lactate (l and d) and pyruvate (but not glucose) increased in DAB and decreased [NH4+]e in 0 Cl−. These results strengthen the evidence that in superfused retinal slices, glucose is metabolized exclusively in the glia, which supply alanine to the neurons, and that ammonium returns to the glia. They also show that another fuel (perhaps lactate) can be supplied by the glia to the neurons. PMID:18276731

  7. Thermal Condensation of Glycine and Alanine on Metal Ferrite Surface: Primitive Peptide Bond Formation Scenario.

    PubMed

    Iqubal, Md Asif; Sharma, Rachana; Jheeta, Sohan; Kamaluddin

    2017-03-27

    The amino acid condensation reaction on a heterogeneous mineral surface has been regarded as one of the important pathways for peptide bond formation. Keeping this in view, we have studied the oligomerization of the simple amino acids, glycine and alanine, on nickel ferrite (NiFe₂O₄), cobalt ferrite (CoFe₂O₄), copper ferrite (CuFe₂O₄), zinc ferrite (ZnFe₂O₄), and manganese ferrite (MnFe₂O₄) nanoparticles surfaces, in the temperature range from 50-120 °C for 1-35 days, without applying any wetting/drying cycles. Among the metal ferrites tested for their catalytic activity, NiFe₂O₄ produced the highest yield of products by oligomerizing glycine to the trimer level and alanine to the dimer level, whereas MnFe₂O₄ was the least efficient catalyst, producing the lowest yield of products, as well as shorter oligomers of amino acids under the same set of experimental conditions. It produced primarily diketopiperazine (Ala) with a trace amount of alanine dimer from alanine condensation, while glycine was oligomerized to the dimer level. The trend in product formation is in accordance with the surface area of the minerals used. A temperature as low as 50 °C can even favor peptide bond formation in the present study, which is important in the sense that the condensation process is highly feasible without any sort of localized heat that may originate from volcanoes or hydrothermal vents. However, at a high temperature of 120 °C, anhydrides of glycine and alanine formation are favored, while the optimum temperature for the highest yield of product formation was found to be 90 °C.

  8. Thermal Condensation of Glycine and Alanine on Metal Ferrite Surface: Primitive Peptide Bond Formation Scenario

    PubMed Central

    Iqubal, Md. Asif; Sharma, Rachana; Jheeta, Sohan; Kamaluddin

    2017-01-01

    The amino acid condensation reaction on a heterogeneous mineral surface has been regarded as one of the important pathways for peptide bond formation. Keeping this in view, we have studied the oligomerization of the simple amino acids, glycine and alanine, on nickel ferrite (NiFe2O4), cobalt ferrite (CoFe2O4), copper ferrite (CuFe2O4), zinc ferrite (ZnFe2O4), and manganese ferrite (MnFe2O4) nanoparticles surfaces, in the temperature range from 50–120 °C for 1–35 days, without applying any wetting/drying cycles. Among the metal ferrites tested for their catalytic activity, NiFe2O4 produced the highest yield of products by oligomerizing glycine to the trimer level and alanine to the dimer level, whereas MnFe2O4 was the least efficient catalyst, producing the lowest yield of products, as well as shorter oligomers of amino acids under the same set of experimental conditions. It produced primarily diketopiperazine (Ala) with a trace amount of alanine dimer from alanine condensation, while glycine was oligomerized to the dimer level. The trend in product formation is in accordance with the surface area of the minerals used. A temperature as low as 50 °C can even favor peptide bond formation in the present study, which is important in the sense that the condensation process is highly feasible without any sort of localized heat that may originate from volcanoes or hydrothermal vents. However, at a high temperature of 120 °C, anhydrides of glycine and alanine formation are favored, while the optimum temperature for the highest yield of product formation was found to be 90 °C. PMID:28346388

  9. Glutamate Racemase Is the Primary Target of β-Chloro-d-Alanine in Mycobacterium tuberculosis

    PubMed Central

    Rodenburg, Anne; Khoury, Hania; de Chiara, Cesira; Howell, Steve; Snijders, Ambrosius P.

    2016-01-01

    The increasing global prevalence of drug resistance among many leading human pathogens necessitates both the development of antibiotics with novel mechanisms of action and a better understanding of the physiological activities of preexisting clinically effective drugs. Inhibition of peptidoglycan (PG) biosynthesis and cross-linking has traditionally enjoyed immense success as an antibiotic target in multiple bacterial pathogens, except in Mycobacterium tuberculosis, where it has so far been underexploited. d-Cycloserine, a clinically approved antituberculosis therapeutic, inhibits enzymes within the d-alanine subbranch of the PG-biosynthetic pathway and has been a focus in our laboratory for understanding peptidoglycan biosynthesis inhibition and for drug development in studies of M. tuberculosis. During our studies on alternative inhibitors of the d-alanine pathway, we discovered that the canonical alanine racemase (Alr) inhibitor β-chloro–d-alanine (BCDA) is a very poor inhibitor of recombinant M. tuberculosis Alr, despite having potent antituberculosis activity. Through a combination of enzymology, microbiology, metabolomics, and proteomics, we show here that BCDA does not inhibit the d-alanine pathway in intact cells, consistent with its poor in vitro activity, and that it is instead a mechanism-based inactivator of glutamate racemase (MurI), an upstream enzyme in the same early stage of PG biosynthesis. This is the first report to our knowledge of inhibition of MurI in M. tuberculosis and thus provides a valuable tool for studying this essential and enigmatic enzyme and a starting point for future MurI-targeted antibacterial development. PMID:27480853

  10. Effect of beta-alanine and carnosine supplementation on muscle contractility in mice.

    PubMed

    Everaert, Inge; Stegen, Sanne; Vanheel, Bert; Taes, Youri; Derave, Wim

    2013-01-01

    Enhanced carnosine levels have been shown to be ergogenic for high-intensity exercise performances, although the role of carnosine in the control of muscle function is poorly understood. Therefore, the aim of this study was to investigate the effect of long-term supplementation with increasing doses of carnosine and beta-alanine on muscle carnosine, anserine, and taurine levels and on in vitro contractility and fatigue in mice. Male Naval Medical Research Institute mice (n = 66) were control fed or supplemented with either carnosine (0.1%, 0.5%, or 1.8%) or beta-alanine (0.6 or 1.2%) in their drinking water for 8-12 wk. Soleus and extensor digitorum longus (EDL) were tested for in vitro contractile properties, and carnosine, anserine, and taurine content were measured in EDL and tibialis anterior by high-performance liquid chromatography. Only supplementation with 1.8% carnosine and 1.2% beta-alanine resulted in markedly higher carnosine (up to +160%) and anserine levels (up to +46%) compared with control mice. Beta-alanine supplementation (1.2%) resulted in increased fatigue resistance in the beginning of the fatigue protocol in soleus (+2%-4%) and a marked leftward shift of the force-frequency relation in EDL (10%-31% higher relative forces). Comparable with humans, beta-alanine availability seems to be the rate-limiting step for synthesis of muscle histidine-containing dipeptides in mice. Moreover, muscle histidine-containing dipeptides loading in mice moderately and muscle dependently affects excitation-contraction coupling and fatigue.

  11. Alanine racemase is essential for the growth and interspecies competitiveness of Streptococcus mutans

    PubMed Central

    Wei, Yuan; Qiu, Wei; Zhou, Xue-Dong; Zheng, Xin; Zhang, Ke-Ke; Wang, Shi-Da; Li, Yu-Qing; Cheng, Lei; Li, Ji-Yao; Xu, Xin; Li, Ming-Yun

    2016-01-01

    D-alanine (D-Ala) is an essential amino acid that has a key role in bacterial cell wall synthesis. Alanine racemase (Alr) is a unique enzyme that interconverts L-alanine and D-alanine in most bacteria, making this enzyme a potential target for antimicrobial drug development. Streptococcus mutans is a major causative factor of dental caries. The factors involved in the survival, virulence and interspecies interactions of S. mutans could be exploited as potential targets for caries control. The current study aimed to investigate the physiological role of Alr in S. mutans. We constructed alr mutant strain of S. mutans and evaluated its phenotypic traits and interspecies competitiveness compared with the wild-type strain. We found that alr deletion was lethal to S. mutans. A minimal supplement of D-Ala (150 μg·mL−1) was required for the optimal growth of the alr mutant. The depletion of D-alanine in the growth medium resulted in cell wall perforation and cell lysis in the alr mutant strain. We also determined the compromised competitiveness of the alr mutant strain relative to the wild-type S. mutans against other oral streptococci (S. sanguinis or S. gordonii), demonstrated using either conditioned medium assays or dual-species fluorescent in situ hybridization analysis. Given the importance and necessity of alr to the growth and competitiveness of S. mutans, Alr may represent a promising target to modulate the cariogenicity of oral biofilms and to benefit the management of dental caries. PMID:27740612

  12. Alanine racemase is essential for the growth and interspecies competitiveness of Streptococcus mutans.

    PubMed

    Wei, Yuan; Qiu, Wei; Zhou, Xue-Dong; Zheng, Xin; Zhang, Ke-Ke; Wang, Shi-Da; Li, Yu-Qing; Cheng, Lei; Li, Ji-Yao; Xu, Xin; Li, Ming-Yun

    2016-12-16

    D-alanine (D-Ala) is an essential amino acid that has a key role in bacterial cell wall synthesis. Alanine racemase (Alr) is a unique enzyme that interconverts L-alanine and D-alanine in most bacteria, making this enzyme a potential target for antimicrobial drug development. Streptococcus mutans is a major causative factor of dental caries. The factors involved in the survival, virulence and interspecies interactions of S. mutans could be exploited as potential targets for caries control. The current study aimed to investigate the physiological role of Alr in S. mutans. We constructed alr mutant strain of S. mutans and evaluated its phenotypic traits and interspecies competitiveness compared with the wild-type strain. We found that alr deletion was lethal to S. mutans. A minimal supplement of D-Ala (150 μg·mL(-1)) was required for the optimal growth of the alr mutant. The depletion of D-alanine in the growth medium resulted in cell wall perforation and cell lysis in the alr mutant strain. We also determined the compromised competitiveness of the alr mutant strain relative to the wild-type S. mutans against other oral streptococci (S. sanguinis or S. gordonii), demonstrated using either conditioned medium assays or dual-species fluorescent in situ hybridization analysis. Given the importance and necessity of alr to the growth and competitiveness of S. mutans, Alr may represent a promising target to modulate the cariogenicity of oral biofilms and to benefit the management of dental caries.

  13. Structural and functional characterization of the alanine racemase from Streptomyces coelicolor A3(2).

    PubMed

    Tassoni, Raffaella; van der Aart, Lizah T; Ubbink, Marcellus; van Wezel, Gilles P; Pannu, Navraj S

    2017-01-29

    The conversion of l-alanine (L-Ala) into d-alanine (D-Ala) in bacteria is performed by pyridoxal phosphate-dependent enzymes called alanine racemases. D-Ala is an essential component of the bacterial peptidoglycan and hence required for survival. The Gram-positive bacterium Streptomyces coelicolor has at least one alanine racemase encoded by alr. Here, we describe an alr deletion mutant of S. coelicolor which depends on D-Ala for growth and shows increased sensitivity to the antibiotic d-cycloserine (DCS). The crystal structure of the alanine racemase (Alr) was solved with and without the inhibitors DCS or propionate, at 1.64 Å and 1.51 Å resolution, respectively. The crystal structures revealed that Alr is a homodimer with residues from both monomers contributing to the active site. The dimeric state of the enzyme in solution was confirmed by gel filtration chromatography, with and without L-Ala or d-cycloserine. The activity of the enzyme was 66 ± 3 U mg(-1) for the racemization of L- to D-Ala, and 104 ± 7 U mg(-1) for the opposite direction. Comparison of Alr from S. coelicolor with orthologous enzymes from other bacteria, including the closely related d-cycloserine-resistant Alr from S. lavendulae, strongly suggests that structural features such as the hinge angle or the surface area between the monomers do not contribute to d-cycloserine resistance, and the molecular basis for resistance therefore remains elusive.

  14. Structural features and kinetic characterization of alanine racemase from Staphylococcus aureus (Mu50).

    PubMed

    Scaletti, Emma R; Luckner, Sylvia R; Krause, Kurt L

    2012-01-01

    Staphylococcus aureus is an opportunistic Gram-positive bacterium which causes a wide variety of diseases ranging from minor skin infections to potentially fatal conditions such as pneumonia, meningitis and septicaemia. The pathogen is a leading cause of nosocomial acquired infections, a problem that is exacerbated by the existence of methicillin- and glycopeptide antibiotic-resistant strains which can be challenging to treat. Alanine racemase (Alr) is a pyridoxal-5'-phosphate-dependent enzyme which catalyzes reversible racemization between enantiomers of alanine. As D-alanine is an essential component of the bacterial cell-wall peptidoglycan, inhibition of Alr is lethal to prokaryotes. Additionally, while ubiquitous amongst bacteria, this enzyme is absent in humans and most eukaryotes, making it an excellent antibiotic drug target. The crystal structure of S. aureus alanine racemase (Alr(Sas)), the sequence of which corresponds to that from the highly antibiotic-resistant Mu50 strain, has been solved to 2.15 Å resolution. Comparison of the Alr(Sas) structure with those of various alanine racemases demonstrates a conserved overall fold, with the enzyme sharing most similarity to those from other Gram-positive bacteria. Structural examination indicates that the active-site binding pocket, dimer interface and active-site entryway of the enzyme are potential targets for structure-aided inhibitor design. Kinetic constants were calculated in this study and are reported here. The potential for a disulfide bond in this structure is noted. This structural and biochemical information provides a template for future structure-based drug-development efforts targeting Alr(Sas).

  15. A preliminary optimization of alanine blends for ESR dosimetry in a mixed n-γ field: Monte Carlo simulation

    NASA Astrophysics Data System (ADS)

    Hoseininaveh, M.; Ranjbar, A. H.

    2016-04-01

    In this study, a preliminary work on the enhancement of ESR response of several arrangements of alanine and boron compounds, exposed to a thermal neutron beam, is presented using FLUKA code. A multi-layer dosimeter consist of consecutive layers of alanine and boron compounds showed that the amount of energy deposited in the alanine layers is maximized when their thickness is 5 μm and the thickness of boron compound layers are between 2 and 3 μm. Furthermore, the optimum number of 10B layers in the dosimeter was found to be 35 layers. Moreover, the alanine samples consisting of small spherical grains of boron compounds, arranged regularly in the middle plane of the dosimeters, exposed to a thermal neutron beam, were modeled. The dependence of energy deposition in the alanine material on the size of grains, and on their composition were also studied, as well.

  16. Glycolysis and the tricarboxylic acid cycle are linked by alanine aminotransferase during hypoxia induced by waterlogging of Lotus japonicus.

    PubMed

    Rocha, Marcio; Licausi, Francesco; Araújo, Wagner L; Nunes-Nesi, Adriano; Sodek, Ladaslav; Fernie, Alisdair R; van Dongen, Joost T

    2010-03-01

    The role of nitrogen metabolism in the survival of prolonged periods of waterlogging was investigated in highly flood-tolerant, nodulated Lotus japonicus plants. Alanine production revealed to be a critical hypoxic pathway. Alanine is the only amino acid whose biosynthesis is not inhibited by nitrogen deficiency resulting from RNA interference silencing of nodular leghemoglobin. The metabolic changes that were induced following waterlogging can be best explained by the activation of alanine metabolism in combination with the modular operation of a split tricarboxylic acid pathway. The sum result of this metabolic scenario is the accumulation of alanine and succinate and the production of extra ATP under hypoxia. The importance of alanine metabolism is discussed with respect to its ability to regulate the level of pyruvate, and this and all other changes are discussed in the context of current models concerning the regulation of plant metabolism.

  17. Difference in serum complement component C4a levels between hepatitis C virus carriers with persistently normal alanine aminotransferase levels or chronic hepatitis C.

    PubMed

    Imakiire, Kazuyuki; Uto, Hirofumi; Sato, Yuko; Sasaki, Fumisato; Mawatari, Seiichi; Ido, Akio; Shimoda, Kazuya; Hayashi, Katsuhiro; Stuver, Sherri O; Ito, Yoshito; Okanoue, Takeshi; Tsubouchi, Hirohito

    2012-08-01

    Certain hepatitis C virus (HCV) carriers exhibit persistently normal alanine aminotransferase (ALT) levels (PNALT) (≤ 30 IU/l) accompanied by normal platelet counts (≥ 15 x 10(4)/µl); these individuals show milder disease activity and slower progression to cirrhosis. This study aimed to elucidate the characteristics of HCV carriers with PNALT using serum proteomics. The first group of subjects, who underwent clinical evaluation in the hospital, consisted of 19 HCV carriers with PNALT (PNALT-1) and 20 chronic hepatitis C (CHC-1) patients. The second group of subjects was part of a cohort study on the natural history of liver disease, and included 37 PNALT (PNALT-2) and 30 CHC (CHC-2) patients. Affinity bead-purified serum protein was subjected to matrix-assisted laser desorption ionization time-of-flight mass spectrometry analysis. Serum proteomics showed that 6 protein peaks with mass-to-charge ratios ranging from 1,000 to 3,000 differed significantly between the PNALT-1 and CHC-1 groups. Among these peaks, a 1738-m/z peak protein was identified as a fragment of complement component 4 (C4) and correlated significantly with serum C4a concentrations as determined by enzyme immunoassay. Serum C4a levels were also significantly higher in the PNALT-2 group compared to the CHC-2 group and healthy volunteers. Furthermore, in the PNALT-2 group, serum C4a levels negatively correlated with transaminase levels, but not with other biochemical tests, HCV core antigen levels, peripheral blood cell counts or serum hepatic fibrosis markers. This study indicates that host factors such as C4a not only differ between HCV carriers with PNALT and CHC, but that proteomic approaches could also contribute to the elucidation of factors in PNALT as more differences are discovered.

  18. Characterization of the metabolic effect of β-alanine on markers of oxidative metabolism and mitochondrial biogenesis in skeletal muscle

    PubMed Central

    Sunderland, Kyle L.; Kuennen, Matthew R.; Vaughan, Roger A.

    2016-01-01

    [Purpose] β-alanine is a common component of numerous sports supplements purported to improve athletic performance through enhanced carnosine biosynthesis and related intracellular buffering. To date, the effects of β-alanine on oxidative metabolism remain largely unexplored. This work investigated the effects of β-alanine on the expression of proteins which regulate cellular energetics. [Methods] C2C12 myocytes were cultured and differentiated under standard conditions followed by treatment with either β-alanine or isonitrogenous non-metabolizable control D-alanine at 800μM for 24 hours. Metabolic gene and protein expression were quantified by qRT-PCR and immunoblotting, respectively. Glucose uptake and oxygen consumption were measured via fluorescence using commercially available kits. [Results] β-alanine-treated myotubes displayed significantly elevated markers of improved oxidative metabolism including elevated peroxisome proliferator-activated receptor β/δ (PPARβ/δ) and mitochondrial transcription factor a (TFAM) which led to increased mitochondrial content (evidenced by concurrent increases in cytochrome c content). Additionally, β-alanine-treated cells exhibited significantly increased oxygen consumption compared to control in a PPARβ/δ-dependent manner. β-alanine significantly enhanced expression of myocyte enhancer factor 2 (MEF-2) leading to increased glucose transporter 4 (GLUT4) content. [Conclusion] β-alanine appears to increase cellular oxygen consumption as well as the expression of several cellular proteins associated with improved oxidative metabolism, suggesting β-alanine supplementation may provide additional metabolic benefit (although these observations require in vivo experimental verification). PMID:27508152

  19. L-alanine uptake in membrane vesicles from Mytilus edulis gills

    SciTech Connect

    Pajor, A.M.; Wright, S.H.

    1986-03-05

    Previous studies have shown that gills from M. edulis can accumulate L-alanine from seawater by a saturable process specific for ..cap alpha..-neutral amino acids. This uptake occurs against chemical gradients in excess of 10/sup 6/ to 1. To further characterize this uptake, membrane vesicles were prepared from M. edulis gill tissue by differential centrifugation. Enrichments of putative enzyme markers (relative to that in combined initial fractions) were as follows: ..gamma..-Glutamyltranspeptidase, 25-30x; Alkaline Phosphatase, 5-6x; K/sup +/-dependent para-Nitrophenyl Phosphatase, 3-5x; Succinate Dehydrogenase 0.1-0.2x. These results suggest that the preparation is enriched in plasma membranes, although histochemical studies will be needed to verify this. The time course of /sup 14/C-L-alanine uptake in the presence of inwardly-directed Na/sup +/ gradient showed a transient overshoot (3-5 fold) at 10 minutes which decreased to equilibrium after six hours. The size of the overshoot and early uptake rates depended on the size of the inwardly-directed Na/sup +/ gradient. No overshoot was seen in the presence of inwardly-directed gradients of LiCl or choline-Cl, or with equilibrium concentrations NaCl or mannitol. A reduced overshoot was seen with a gradient of NaSCN. A small overshoot was seen with an inwardly-directed gradient of KCl. Transport of L-alanine included saturable and diffusive components. Uptake of 6 ..mu..M L-alanine was inhibited more than 80% by 100 ..mu..M ..cap alpha..-zwitterionic amino acids (alanine, leucine, glycine); by 30 to 75% by proline, aspartate and lysine; and less than 20% by a ..beta..-amino acid, taurine. The results of these experiments agree with those from intact gill studies and support the hypothesis that L-alanine is transported into gill epithelial cells by a secondary active transport process involving Na/sup +/.

  20. The alanine detector in BNCT dosimetry: dose response in thermal and epithermal neutron fields.

    PubMed

    Schmitz, T; Bassler, N; Blaickner, M; Ziegner, M; Hsiao, M C; Liu, Y H; Koivunoro, H; Auterinen, I; Serén, T; Kotiluoto, P; Palmans, H; Sharpe, P; Langguth, P; Hampel, G

    2015-01-01

    The response of alanine solid state dosimeters to ionizing radiation strongly depends on particle type and energy. Due to nuclear interactions, neutron fields usually also consist of secondary particles such as photons and protons of diverse energies. Various experiments have been carried out in three different neutron beams to explore the alanine dose response behavior and to validate model predictions. Additionally, application in medical neutron fields for boron neutron capture therapy is discussed. Alanine detectors have been irradiated in the thermal neutron field of the research reactor TRIGA Mainz, Germany, in five experimental conditions, generating different secondary particle spectra. Further irradiations have been made in the epithermal neutron beams at the research reactors FiR 1 in Helsinki, Finland, and Tsing Hua open pool reactor in HsinChu, Taiwan ROC. Readout has been performed with electron spin resonance spectrometry with reference to an absorbed dose standard in a (60)Co gamma ray beam. Absorbed doses and dose components have been calculated using the Monte Carlo codes fluka and mcnp. The relative effectiveness (RE), linking absorbed dose and detector response, has been calculated using the Hansen & Olsen alanine response model. The measured dose response of the alanine detector in the different experiments has been evaluated and compared to model predictions. Therefore, a relative effectiveness has been calculated for each dose component, accounting for its dependence on particle type and energy. Agreement within 5% between model and measurement has been achieved for most irradiated detectors. Significant differences have been observed in response behavior between thermal and epithermal neutron fields, especially regarding dose composition and depth dose curves. The calculated dose components could be verified with the experimental results in the different primary and secondary particle fields. The alanine detector can be used without

  1. The alanine detector in BNCT dosimetry: Dose response in thermal and epithermal neutron fields

    SciTech Connect

    Schmitz, T.; Bassler, N.; Blaickner, M.; Ziegner, M.; Hsiao, M. C.; Liu, Y. H.; Koivunoro, H.; Auterinen, I.; Serén, T.; Kotiluoto, P.; Palmans, H.; Sharpe, P.; Langguth, P.; Hampel, G.

    2015-01-15

    Purpose: The response of alanine solid state dosimeters to ionizing radiation strongly depends on particle type and energy. Due to nuclear interactions, neutron fields usually also consist of secondary particles such as photons and protons of diverse energies. Various experiments have been carried out in three different neutron beams to explore the alanine dose response behavior and to validate model predictions. Additionally, application in medical neutron fields for boron neutron capture therapy is discussed. Methods: Alanine detectors have been irradiated in the thermal neutron field of the research reactor TRIGA Mainz, Germany, in five experimental conditions, generating different secondary particle spectra. Further irradiations have been made in the epithermal neutron beams at the research reactors FiR 1 in Helsinki, Finland, and Tsing Hua open pool reactor in HsinChu, Taiwan ROC. Readout has been performed with electron spin resonance spectrometry with reference to an absorbed dose standard in a {sup 60}Co gamma ray beam. Absorbed doses and dose components have been calculated using the Monte Carlo codes FLUKA and MCNP. The relative effectiveness (RE), linking absorbed dose and detector response, has been calculated using the Hansen and Olsen alanine response model. Results: The measured dose response of the alanine detector in the different experiments has been evaluated and compared to model predictions. Therefore, a relative effectiveness has been calculated for each dose component, accounting for its dependence on particle type and energy. Agreement within 5% between model and measurement has been achieved for most irradiated detectors. Significant differences have been observed in response behavior between thermal and epithermal neutron fields, especially regarding dose composition and depth dose curves. The calculated dose components could be verified with the experimental results in the different primary and secondary particle fields. Conclusions: The

  2. Synthesis and evaluation of 18F labeled alanine derivatives as potential tumor imaging agents

    PubMed Central

    Wang, Limin; Zha, Zhihao; Qu, Wenchao; Qiao, Hongwen; Lieberman, Brian P.; Plössl, Karl; Kung, Hank F.

    2012-01-01

    Introduction This paper reports the synthesis and labeling of 18F alanine derivatives. We also investigate their biological characteristics as potential tumor imaging agents mediated by alanine-serine-cysteine preferring (ASC) transporter system. Methods Three new 18F alanine derivatives were prepared from corresponding tosylate-precursors through a two-step labelling reaction. In vitro uptake studies to evaluate and to compare these three analogs were carried out in 9L glioma and PC-3 prostate cancer cell lines. Potential transport mechanisms, protein incorporation and stability of 3-(1-[18F]fluoromethyl)-L-alanine (L[18F]FMA) were investigated in 9L glioma cells. Its biodistribution was determined in a rat-bearing 9L tumor model. PET imaging studies were performed on rat bearing 9L glioma tumors and transgenic mouse carrying spontaneous generated M/tomND tumor (mammary gland adenocarcinoma). Results New 18F alanine derivatives were prepared with 7–34% uncorrected radiochemical yields, excellent enantiomeric purity (>99%) and good radiochemical purity (>99%). In vitro uptake of the L-[18F]FMA in 9L glioma and PC-3 prostate cancer cells was higher than those observed for other two alanine derivatives and [18F]FDG in first 1 h. Inhibition of cell uptake studies suggested that L-[18F]FMA uptake in 9L glioma was predominantly via transport system ASC. After entering into cells, L-[18F]FMA remained stable and was not incorporated into protein within 2 h. In vivo biodistribution studies demonstrated that L-[18F]FMA had relatively high uptake in liver and kidney. Tumor uptake was fast, reaching a maximum within 30 min. The tumor-to-muscle, tumor-to-blood and tumor-to-brain ratios at 60 min post injection were 2.2, 1.9 and 3.0, respectively. In PET imaging studies, tumors were visualized with L-[18F]FMA in both 9L rat and transgenic mouse. Conclusion L-[18F]FMA showed promising properties as a PET imaging agent for up-regulated ASC transporter associated with tumor

  3. β-N-Methylamino-L-alanine (BMAA) perturbs alanine, aspartate and glutamate metabolism pathways in human neuroblastoma cells as determined by metabolic profiling.

    PubMed

    Engskog, Mikael K R; Ersson, Lisa; Haglöf, Jakob; Arvidsson, Torbjörn; Pettersson, Curt; Brittebo, Eva

    2017-02-04

    β-Methylamino-L-alanine (BMAA) is a non-proteinogenic amino acid that induces long-term cognitive deficits, as well as an increased neurodegeneration and intracellular fibril formation in the hippocampus of adult rodents following short-time neonatal exposure and in vervet monkey brain following long-term exposure. It has also been proposed to be involved in the etiology of neurodegenerative disease in humans. The aim of this study was to identify metabolic effects not related to excitotoxicity or oxidative stress in human neuroblastoma SH-SY5Y cells. The effects of BMAA (50, 250, 1000 µM) for 24 h on cells differentiated with retinoic acid were studied. Samples were analyzed using LC-MS and NMR spectroscopy to detect altered intracellular polar metabolites. The analysis performed, followed by multivariate pattern recognition techniques, revealed significant perturbations in protein biosynthesis, amino acid metabolism pathways and citrate cycle. Of specific interest were the BMAA-induced alterations in alanine, aspartate and glutamate metabolism and as well as alterations in various neurotransmitters/neuromodulators such as GABA and taurine. The results indicate that BMAA can interfere with metabolic pathways involved in neurotransmission in human neuroblastoma cells.

  4. 3D culture of tonsil-derived mesenchymal stem cells in poly(ethylene glycol)-poly(L-alanine-co-L-phenyl alanine) thermogel.

    PubMed

    Park, Min Hee; Yu, Yeonsil; Moon, Hyo Jung; Ko, Du Young; Kim, Han Su; Lee, Hyukjin; Ryu, Kyung Ha; Jeong, Byeongmoon

    2014-11-01

    Poly(ethylene glycol)-poly(L-alanine-co-L-phenyl alanine) (PEG-PAF) aqueous solutions undergo sol-to-gel transition as the temperature increases. The transition is driven by the micelle aggregation involving the partial dehydration of the PEG block and the partial increase in β-sheet content of the PAF block. Tonsil-tissue-derived mesenchymal stem cells (TMSCs), a new stem cell resource, are encapsulated through the sol-to-gel transition of the TMSC-suspended PEG-PAF aqueous solutions. The encapsulated TMSCs are in vitro 3D cultured by using induction media supplemented with adipogenic, osteogenic, or chondrogenic factors, where the TMSCs preferentially undergo chondrogenesis with high expressions of type II collagen and sulfated glycosaminoglycan. As a feasibility study of the PEG-PAF thermogel for injectable tissue engineering, the TMSCs encapsulated in hydrogels are implanted in the subcutaneous layer of mice by injecting the TMSC suspended PEG-PAF aqueous solution. The in vivo studies also prove that TMSCs undergo chondrogenesis with high expression of the chondrogenic biomarkers. This study suggests that the TMSCs can be an excellent resource of MSCs, and the thermogelling PEG-PAF is a promising injectable tissue engineering scaffold, particularly for chondrogenic differentiation of the stem cells. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Isotope labeling studies on the formation of multiple addition products of alanine in the pyrolysis residue of glucose/alanine mixtures by high-resolution ESI-TOF-MS.

    PubMed

    Chu, Fong Lam; Sleno, Lekha; Yaylayan, Varoujan A

    2011-11-09

    Pyrolysis was used as a microscale sample preparation tool to generate glucose/alanine reaction products to minimize the use of expensive labeled precursors in isotope labeling studies. The residue remaining after the pyrolysis at 250 °C was analyzed by electrospray time-of-flight mass spectrometry (ESI-TOF-MS). It was observed that a peak at m/z 199.1445 in the ESI-TOF-MS spectrum appeared only when the model system contained at least 2-fold excess alanine. The accurate mass determination indeed indicated the presence of two nitrogen atoms in the molecular formula (C(10)H(18)N(2)O(2)). To verify the origin of the carbon atoms in this unknown compound, model studies with [(13)U(6)]glucose, [(13)C-1]alanine, [(13)C-2]alanine, [(13)C-3]alanine, and [(15)N]alanine were also performed. Glucose furnished six carbon atoms, and alanine provides four carbon (2 × C-2 and 2 × C-3) and two nitrogen atoms. When commercially available fructosylalanine (N-attached to C-1) was reacted with only 1 mol of alanine, a peak at m/z 199.1445 was once again observed. In addition, when 3-deoxyglucosone (3-DG) was reacted with a 2-fold excess of alanine, a peak at m/z 199.1433 was also generated, confirming the points of attachment of the two amino acids at C-1 and C-2 atoms of 3-DG. These studies have indicated that amino acids can undergo multiple addition reactions with 1,2-dicarbonyl compounds such as 3-deoxyglucosone and eventually form a tetrahydropyrazine moiety.

  6. Biochemical and molecular mechanisms of N-acetyl cysteine and silymarin-mediated protection against maneb- and paraquat-induced hepatotoxicity in rats.

    PubMed

    Ahmad, Israr; Shukla, Smriti; Kumar, Ashutosh; Singh, Brajesh Kumar; Kumar, Vinod; Chauhan, Amit Kumar; Singh, Dhirendra; Pandey, Haushila Prasad; Singh, Chetna

    2013-01-25

    Oxidative stress is one of the major players in the pathogenesis of maneb (MB) and paraquat (PQ)-induced disorders. N-acetyl cysteine (NAC), a glutathione (GSH) precursor and silymarin (SIL), a naturally occurring antioxidant, encounter oxidative stress-mediated cellular damage. The present study was aimed to investigate the effects of NAC and SIL against MB and/or PQ-induced hepatotoxicity in rats. The levels of hepatotoxicity markers - alanine aminotransaminase (ALT), aspartate aminotransaminase (AST) and total bilirubin, histological changes, oxidative stress indices, phase I and phase II xenobiotic metabolizing enzymes - cytochrome P450 (CYP) and glutathione S-transferase (GST) and pro-inflammatory molecules - inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured in animals treated with MB and/or PQ in the presence or absence of NAC and SIL. MB and/or PQ augmented ALT, AST, total bilirubin, lipid peroxidation and nitrite contents and catalytic activities of superoxide dismutase and glutathione peroxidase however, the GSH content was attenuated. NAC and SIL restored the above-mentioned alterations towards basal levels but the restorations were more pronounced in SIL treated groups. Similarly, MB and/or PQ-mediated histopathological symptoms and changes in the catalytic activities/expressions of CYP1A2, CYP2E1, iNOS, TNF-α, and IL-1β were alleviated by NAC and SIL. Conversely, MB and/or PQ-induced GSTA4-4 expression/activity was further increased by NAC/SIL and glutathione reductase activity was also increased. The results obtained thus suggest that NAC and SIL protect MB and/or PQ-induced hepatotoxicity by reducing oxidative stress, inflammation and by modulating xenobitic metabolizing machinery and SIL seems to be more effective.

  7. Hepatoprotective activity of the extract of Homalium letestui stem against paracetamol-induced liver injury

    PubMed Central

    Okokon, Jude Efiom; Simeon, Joseph Oyepata; Umoh, Emem Ekpo

    2017-01-01

    Objective: H omalium letestui Pellegr (Flacourtiaceae) has been traditionally used by the Ibibios of Southern Nigeria to treat stomach ulcer, malaria and other inflammatory diseases and Yorubas of western Nigeria as an antidote. This study evaluates the hepatoprotective properties of the ethanol extract of the plant stem. Materials and Methods: The hepatoprotective effect of the extract of the stem of the plant (200-600 mg/kg) was evaluated by the assay of liver function parameters, namely total and direct bilirubin, serum protein and albumin, total cholesterol, alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), and alkaline phosphatase activities (ALP), antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), reduced glutathione (GSH) and histopathological study of the liver. Also, GCMS analysis of n-butanol fraction of the extract was carried out. Results: Administration of the extract of the stem of the plant caused a significant (p<0.05 – 0.001) dose-dependent reduction of high levels of liver enzymes (ALT, AST and ALP), total cholesterol, direct and total bilirubin as well as elevation of serum levels of total protein, albumin and antioxidant enzymes (SOD, CAT, GPx and GSH). Histology of the liver sections from extract and silymarin-treated animals showed reductions in the pathological features compared to the paracetamol-treated animals. The chemical pathological changes were consistent with histopathological observations suggesting marked hepatoprotective effect of the extract of H. letestui stem. GCMS analysis of n-butanol fraction revealed the presence of 16 bioactive compounds. Conclusion: The results show that the extract of H. letestui has hepatoprotective potential which may be due to the antioxidant activity of its phytoconstituents. PMID:28265544

  8. 'Arzteführerschule Alt-Rehse'--the main educational centre for promotion of Nazi medicine ideology in Germany during 1935 - 1943.

    PubMed

    Nilsson, Peter M; Bergkvist, Göran; Peters, Anja; Köpp, Wolfgang

    2006-01-01

    In Nazi Germany 1933-1945 the medical profession played an important role, not only within the health sector but also for ideological purposes. Some physicians committed criminal acts during the war, for example in concentration camps, and where later put on trial at the Nuremberg Trials in 1946-1947, some of them also sentenced to death. What is little known outside Germany is the existence of a specialised political leader school for physicians, dentists, midwives, pharmacists, and health officials at Alt-Rehse, a small village north of Berlin in the province of Mecklenburg, Northern Germany. Supported by historical documents it can be shown that the ideological training at Alt-Rehse was structured, politically effective, and well appreciated by the many attending students visiting the school. There is reason to believe that former Alt-Rehse students took part in Nazi criminal acts of war, but this is hard to prove as all documents were captured by the Russian Army at the end of the Second World War and have until now not been traced. Documents have shown that also many foreign visitors came to Alt-Rehse, from the UK, Sweden, Japan, and other countries during the pre-war years. The lessons from Alt-Rehse include how a totalitarian ideology can shape the professional role of health workers.

  9. AltMV TGB1 Nucleolar Localization Requires Homologous Interaction and Correlates with Cell Wall Localization Associated with Cell-to-Cell Movement.

    PubMed

    Nam, Jiryun; Nam, Moon; Bae, Hanhong; Lee, Cheolho; Lee, Bong-Chun; Hammond, John; Lim, Hyoun-Sub

    2013-12-01

    The Potexvirus Alternanthera mosaic virus (AltMV) has multifunctional triple gene block (TGB) proteins, among which our studies have focused on the properties of the TGB1 protein. The TGB1 of AltMV has functions including RNA binding, RNA silencing suppression, and cell-to-cell movement, and is known to form homologous interactions. The helicase domains of AltMV TGB1 were separately mutated to identify which regions are involved in homologous TGB1 interactions. The yeast two hybrid system and Bimolecular Fluorescence Complementation (BiFC) in planta were utilized to examine homologous interactions of the mutants. Helicase motif I of AltMV TGB1 was found to be critical to maintain homologous interactions. Mutations in the remaining helicase motifs did not inhibit TGB1 homologous interactions. In the absence of homologous interaction of TGB1, subcellular localization of helicase domain I mutants showed distinctively different patterns from that of WT TGB1. These results provide important information to study viral movement and replication of AltMV.

  10. The AGE-Breaker ALT-711 Restores High Blood Flow–Dependent Remodeling in Mesenteric Resistance Arteries in a Rat Model of Type 2 Diabetes

    PubMed Central

    Freidja, Mohamed L.; Tarhouni, Kahena; Toutain, Bertrand; Fassot, Céline; Loufrani, Laurent; Henrion, Daniel

    2012-01-01

    Flow-mediated remodeling of resistance arteries is essential for revascularization in ischemic diseases, but this is impaired in diabetes. We hypothesized that breaking advanced glycation end product (AGE) cross-links could improve remodeling in mesenteric resistance arteries in Zucker diabetic fatty (ZDF) rats compared with lean Zucker (LZ) rats. Arteries, exposed to high (HF) or normal (NF) blood flow after alternate arterial ligation in vivo, were collected after 2 weeks. In LZ rats, HF artery diameter was larger than for NF vessels, but this was not the case in ZDF rats. Endothelium-mediated dilation in ZDF rats, which was lower than in LZ rats, was further decreased in HF arteries. Treatment of rats with the AGE-breaker 4,5-dimethyl-3-phenacylthiazolium chloride (ALT-711) (3 mg/kg/day; 3 weeks) reversed diabetes-induced impairment of HF-dependent remodeling. ALT-711 also improved endothelium nitric oxide–dependent relaxation in mesenteric resistance arteries. Reactive oxygen species reduction restored relaxation in ZDF rats but not in LZ or ALT-711–treated rats. AGEs were reduced in ALT-711–treated ZDF rats compared with ZDF rats. Metalloproteinase activity, necessary for HF-dependent remodeling, was reduced in ZDF rats compared with LZ rats and restored by ALT-711. Thus, targeting AGE cross-links may provide a therapeutic potential for overcoming microvascular complications in ischemic disorders occurring in diabetes. PMID:22415880

  11. The AGE-breaker ALT-711 restores high blood flow-dependent remodeling in mesenteric resistance arteries in a rat model of type 2 diabetes.

    PubMed

    Freidja, Mohamed L; Tarhouni, Kahena; Toutain, Bertrand; Fassot, Céline; Loufrani, Laurent; Henrion, Daniel

    2012-06-01

    Flow-mediated remodeling of resistance arteries is essential for revascularization in ischemic diseases, but this is impaired in diabetes. We hypothesized that breaking advanced glycation end product (AGE) cross-links could improve remodeling in mesenteric resistance arteries in Zucker diabetic fatty (ZDF) rats compared with lean Zucker (LZ) rats. Arteries, exposed to high (HF) or normal (NF) blood flow after alternate arterial ligation in vivo, were collected after 2 weeks. In LZ rats, HF artery diameter was larger than for NF vessels, but this was not the case in ZDF rats. Endothelium-mediated dilation in ZDF rats, which was lower than in LZ rats, was further decreased in HF arteries. Treatment of rats with the AGE-breaker 4,5-dimethyl-3-phenacylthiazolium chloride (ALT-711) (3 mg/kg/day; 3 weeks) reversed diabetes-induced impairment of HF-dependent remodeling. ALT-711 also improved endothelium nitric oxide-dependent relaxation in mesenteric resistance arteries. Reactive oxygen species reduction restored relaxation in ZDF rats but not in LZ or ALT-711-treated rats. AGEs were reduced in ALT-711-treated ZDF rats compared with ZDF rats. Metalloproteinase activity, necessary for HF-dependent remodeling, was reduced in ZDF rats compared with LZ rats and restored by ALT-711. Thus, targeting AGE cross-links may provide a therapeutic potential for overcoming microvascular complications in ischemic disorders occurring in diabetes.

  12. CHK1-driven histone H3.3 serine 31 phosphorylation is important for chromatin maintenance and cell survival in human ALT cancer cells

    PubMed Central

    Chang, Fiona T. M.; Chan, F. Lyn; R. McGhie, James D.; Udugama, Maheshi; Mayne, Lynne; Collas, Philippe; Mann, Jeffrey R.; Wong, Lee H.

    2015-01-01

    Human ALT cancers show high mutation rates in ATRX and DAXX. Although it is well known that the absence of ATRX/DAXX disrupts H3.3 deposition at heterochromatin, its impact on H3.3 deposition and post-translational modification in the global genome remains unclear. Here, we explore the dynamics of phosphorylated H3.3 serine 31 (H3.3S31ph) in human ALT cancer cells. While H3.3S31ph is found only at pericentric satellite DNA repeats during mitosis in most somatic human cells, a high level of H3.3S31ph is detected on the entire chromosome in ALT cells, attributable to an elevated CHK1 activity in these cells. Drug inhibition of CHK1 activity during mitosis and expression of mutant H3.3S31A in these ALT cells result in a decrease in H3.3S31ph levels accompanied with increased levels of phosphorylated H2AX serine 139 on chromosome arms and at the telomeres. Furthermore, the inhibition of CHK1 activity in these cells also reduces cell viability. Our findings suggest a novel role of CHK1 as an H3.3S31 kinase, and that CHK1-mediated H3.3S31ph plays an important role in the maintenance of chromatin integrity and cell survival in ALT cancer cells. PMID:25690891

  13. Comparison of immunogenicity, protective efficacy of single and cocktail DNA vaccine of Brugia malayi abundant larval transcript (ALT-2) and thioredoxin peroxidase (TPX) in mice.

    PubMed

    Anand, Setty Balakrishnan; Murugan, Vadivel; Prabhu, Prince Rajaiah; Anandharaman, Veerabhadran; Reddy, Maryada Venkata Rami; Kaliraj, Perumal

    2008-08-01

    Although DNA vaccines have several advantages over conventional vaccines, antibody production and protection are often not adequate, particularly in single plasmid vaccine formulation. In the present study we evaluated the efficacy of a cocktail vaccine based on plasmids encoding larval (L3) stage-specific Brugia malayi abundant larval transcript (BmALT-2) and antioxidant detoxification enzyme B. malayi thioredoxin peroxidase (BmTPX) to induce antibodies, protective efficacy and cell-mediated immune response in mice. Mice immunized with cocktail DNA vaccines containing the pVAX ALT-2+TPX developed higher titers of anti-BmALT-2+TPX (1:5000) antibodies, compared to the mice immunized with single DNA vaccine of pVAX ALT-2 or pVAX TPX (1:2000). Correlating with this, the mice administered with cocktail vaccine induced up to 78% of cytotoxicity against B. malayi mf. This cytotoxicity was high compared to 34% induced by the pVAX-ALT2 or 37% by pVAX-TPX. Moreover, cocktail vaccination of mice resulted in significantly higher level of cellular proliferative response associated with raised levels of IFN-gamma that skewed towards Th1 type of response compared to vaccination using either of the components. Taken together, these data suggest that the combination of two or more antigens maybe an effective vaccine development strategy to improve protection and immunogenicity against human lymphatic filariasis.

  14. Synthesis, characterization and biological evaluation of poly [LA-co-(Glc-alt-Lys)] for nerve regeneration scaffold

    NASA Astrophysics Data System (ADS)

    Yin, Yi-Xia; Yi, Ji-Ling; Xie, Li-Juan; Yan, Qiong-Jiao; Dai, Hong-Lian; Li, Shi-Pu

    2014-03-01

    A novel nerve repairing material poly [LA-co-(Glc-alt-Lys)] (PLGL) was synthesized. The viability and growth of Schwann cells (SCs) co-cultured with poly (D, Llactic acid) (PDLLA) films (control group) and PLGL films were evaluated by MTTassay and SEM observation. Then, contact angle measurement, histological assessment and enzyme-linked immunosorbent assay (ELISA) testing on inflammatory-related cytokines such as IL-10 and TGF-β1 were performed. The results showed that, compared with PDLLA, PLGL films possesses better hydrophilicity, biocompatibility, degradation property and less inflammatory reaction. The present study indicated that PLGL scaffolds would meet the requirements of artificial nerve scaffold and have a potential application in the fields of nerve regeneration.

  15. The exogenous opioid peptides and DPPIV serum activity in infants with apnoea expressed as apparent life threatening events (ALTE).

    PubMed

    Wasilewska, Jolanta; Sienkiewicz-Szłapka, Edyta; Kuźbida, Ewa; Jarmołowska, Beata; Kaczmarski, Maciej; Kostyra, Elżbieta

    2011-06-01

    Casein-derived peptides have been suggested to play a role in sudden infant death syndrome (SIDS). In this study, we have determined the content of bovine β-casomorphin-7 (bBCM-7) and the activity of dipeptidyl peptidase-IV (DPPIV) in sera of infants with apparent life threatening events (ALTE syndromes, 'near miss SIDS'). We have found that the sera of some infants after an apnoea event contained more β-casomorphin-7 than that of the healthy infants in the same age. In all the children after an apnoea event, however, a lowered DPPIV was detected. We suspect that the low activity of that peptidase may be responsible for opioid-induced respiratory depression, induced by bBCM-7 in the general circulation.

  16. Electronic structure disorder, vibronic coupling, and charge transfer excitons in poly(fluorene-alt-bithiophene):fullerene films

    SciTech Connect

    Riisness, I.; Gordon, M. J.

    2013-03-18

    Charge transfer processes in conjugated polymer:fullerene blends play an important role in the operation of organic solar cells and organic light emitting diodes. Herein, near-infrared emission