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Sample records for 1c enzymes implications

  1. Enzymes of the AKR1B and AKR1C subfamilies and uterine diseases

    Tea eLanisnik Rizner

    2012-03-01

    Full Text Available Endometrial and cervical cancers, uterine myoma, and endometriosis are very common uterine diseases. Worldwide, more than 800,000 women are affected annually by gynecological cancers, as a result of which, more than 360,000 die. During their reproductive age, about 70% of women develop uterine myomas, 10% to 15% suffer from endometriosis, and 35% to 50% from infertility associated with endometriosis. Uterine diseases are associated with aberrant inflammatory responses and concomitant increased production of prostaglandins (PG. They are also related to decreased differentiation, due to low levels of protective progesterone and retinoic acid, and to enhanced proliferation, due to high local concentrations of estrogens. The pathogenesis of these diseases can thus be attributed to disturbed PG, estrogen and retinoid metabolism and actions. Five human members of the aldo-keto reductase 1B (AKR1B and 1C (AKR1C superfamilies, i.e., AKR1B1, AKR1B10, AKR1C1, AKR1C2 and AKR1C3, have roles in these processes and can thus be implicated in uterine diseases. AKR1B1 and AKR1C3 catalyze the formation of PGF2alpha which stimulates cell proliferation. AKR1C3 converts PGD2 to 9alpha,11beta-PGF2, and thus counteracts the formation of 15deoxy-PGJ2, which can activate pro-apoptotic peroxisome-proliferator-activated receptor beta. AKR1B10 catalyzes the reduction of retinal to retinol, and in thus lessens the formation of retinoic acid, with potential pro-differentiating actions. The AKR1C1-AKR1C3 enzymes also act as 17-keto- and 20-ketosteroid reductases to varying extents, and are implicated in increased estradiol and decreased progesterone levels. This review comprises a short introduction to uterine diseases, followed by an overview of the current literature on the AKR1B and AKR1C expression in the uterus and in uterine diseases. The potential implications of the AKR1B and AKR1C enzymes and their pathophysiologies are then discussed, followed by conclusions and

  2. CD1c-Expression by Monocytes - Implications for the Use of Commercial CD1c+ Dendritic Cell Isolation Kits.

    Martine Schrøder

    Full Text Available Conventional dendritic cells (cDCs comprise a heterogeneous population of cells that are important regulators of immunity and homeostasis. CD1c+ cDCs are present in human blood and tissues, and found to efficiently activate naïve CD4+ T cells. While CD1c is thought to specifically identify this subset of human cDCs, we show here that also classical and intermediate monocytes express CD1c. Accordingly, the commercial CD1c (BDCA-1+ Dendritic Cell Isolation Kit isolates two distinct cell populations from blood: CD1c+CD14- cDCs and CD1c+CD14+ monocytes. CD1c+ cDCs and CD1c+ monocytes exhibited strikingly different properties, including their differential regulation of surface marker expression, their levels of cytokine production, and their ability to stimulate naïve CD4+ T cells. These results demonstrate that a commercial CD1c (BDCA-1+ Dendritic Cell Isolation Kit isolates two functionally different cell populations, which has important implications for the interpretation of previously generated data using this kit to characterize CD1c+ cDCs.

  3. The relationship between HbA(1c) and fasting plasma glucose in patients with increased plasma liver enzyme measurements

    Christiansen, R; Rasmussen, L Melholt; Nybo, H;

    2012-01-01

    levels of increased liver enzyme concentrations. Methods:  Data from 10 065 patients with simultaneous measurement of HbA(1c) , venous fasting plasma glucose, alanine aminotransferase and γ-glutamyl transferase were extracted from our laboratory database. Correlations were investigated in four patient...

  4. Rational design of an AKR1C3-resistant analog of PR-104 for enzyme-prodrug therapy.

    Mowday, Alexandra M; Ashoorzadeh, Amir; Williams, Elsie M; Copp, Janine N; Silva, Shevan; Bull, Matthew R; Abbattista, Maria R; Anderson, Robert F; Flanagan, Jack U; Guise, Christopher P; Ackerley, David F; Smaill, Jeff B; Patterson, Adam V

    2016-09-15

    The clinical stage anti-cancer agent PR-104 has potential utility as a cytotoxic prodrug for exogenous bacterial nitroreductases expressed from replicating vector platforms. However substrate selectivity is compromised due to metabolism by the human one- and two-electron oxidoreductases cytochrome P450 oxidoreductase (POR) and aldo-keto reductase 1C3 (AKR1C3). Using rational drug design we developed a novel mono-nitro analog of PR-104A that is essentially free of this off-target activity in vitro and in vivo. Unlike PR-104A, there was no biologically relevant cytotoxicity in cells engineered to express AKR1C3 or POR, under aerobic or anoxic conditions, respectively. We screened this inert prodrug analog, SN34507, against a type I bacterial nitroreductase library and identified E. coli NfsA as an efficient bioactivator using a DNA damage response assay and recombinant enzyme kinetics. Expression of E. coli NfsA in human colorectal cancer cells led to selective cytotoxicity to SN34507 that was associated with cell cycle arrest and generated a robust 'bystander effect' at tissue-like cell densities when only 3% of cells were NfsA positive. Anti-tumor activity of SN35539, the phosphate pre-prodrug of SN34507, was established in 'mixed' tumors harboring a minority of NfsA-positive cells and demonstrated marked tumor control following heterogeneous suicide gene expression. These experiments demonstrate that off-target metabolism of PR-104 can be avoided and identify the suicide gene/prodrug partnership of E. coli NfsA/SN35539 as a promising combination for development in armed vectors.

  5. Long-term In Vitro Treatment of Human Glioblastoma Cells with Temozolomide Increases Resistance In Vivo through Up-regulation of GLUT Transporter and Aldo-Keto Reductase Enzyme AKR1C Expression

    Benjamin Le Calvé

    2010-09-01

    Full Text Available Glioblastoma (GBM is the most frequent malignant glioma. Treatment of GBM patients is multimodal with maximum surgical resection, followed by concurrent radiation and chemotherapy with the alkylating drug temozolomide (TMZ. The present study aims to identify genes implicated in the acquired resistance of two human GBM cells of astrocytic origin, T98G and U373, to TMZ. Resistance to TMZ was induced by culturing these cells in vitro for months with incremental TMZ concentrations up to 1 mM. Only partial resistance to TMZ has been achieved and was demonstrated in vivo in immunocompromised mice bearing orthotopic U373 and T98G xenografts. Our data show that long-term treatment of human astroglioma cells with TMZ induces increased expression of facilitative glucose transporter/solute carrier GLUT/SLC2A family members, mainly GLUT-3, and of the AKR1C family of proteins. The latter proteins are phase 1 drug-metabolizing enzymes involved in the maintenance of steroid homeostasis, prostaglandin metabolism, and metabolic activation of polycyclic aromatic hydrocarbons. GLUT-3 has been previously suggested to exert roles in GBM neovascularization processes, and TMZ was found to exert antiangiogenic effects in experimental gliomas. AKR1C1 was previously shown to be associated with oncogenic potential, with proproliferative effects similar to AKR1C3 in the latter case. Both AKR1C1 and AKR1C2 proteins are involved in cancer pro-proliferative cell chemoresistance. Selective targeting of GLUT-3 in GBM and/or AKR1C proteins (by means of jasmonates, for example could thus delay the acquisition of resistance to TMZ of astroglioma cells in the context of prolonged treatment with this drug.

  6. Elevated AKR1C3 expression promotes prostate cancer cell survival and prostate cell-mediated endothelial cell tube formation: implications for prostate cancer progressioan

    Davis Jeffrey S

    2010-12-01

    Full Text Available Abstract Background Aldo-keto reductase (AKR 1C family member 3 (AKR1C3, one of four identified human AKR1C enzymes, catalyzes steroid, prostaglandin, and xenobiotic metabolism. In the prostate, AKR1C3 is up-regulated in localized and advanced prostate adenocarcinoma, and is associated with prostate cancer (PCa aggressiveness. Here we propose a novel pathological function of AKR1C3 in tumor angiogenesis and its potential role in promoting PCa progression. Methods To recapitulate elevated AKR1C3 expression in cancerous prostate, the human PCa PC-3 cell line was stably transfected with an AKR1C3 expression construct to establish PC3-AKR1C3 transfectants. Microarray and bioinformatics analysis were performed to identify AKR1C3-mediated pathways of activation and their potential biological consequences in PC-3 cells. Western blot analysis, reverse transcription-polymerase chain reaction (RT-PCR, enzyme-linked immunosorbent assay (ELISA, and an in vitro Matrigel angiogenesis assays were applied to validate the pro-angiogenic activity of PC3-AKR1C3 transfectants identified by bioinformatics analysis. Results Microarray and bioinformatics analysis suggested that overexpression of AKR1C3 in PC-3 cells modulates estrogen and androgen metabolism, activates insulin-like growth factor (IGF-1 and Akt signaling pathways, as well as promotes tumor angiogenesis and aggressiveness. Levels of IGF-1 receptor (IGF-1R and Akt activation as well as vascular endothelial growth factor (VEGF expression and secretion were significantly elevated in PC3-AKR1C3 transfectants in comparison to PC3-mock transfectants. PC3-AKR1C3 transfectants also promoted endothelial cell (EC tube formation on Matrigel as compared to the AKR1C3-negative parental PC-3 cells and PC3-mock transfectants. Pre-treatment of PC3-AKR1C3 transfectants with a selective IGF-1R kinase inhibitor (AG1024 or a non-selective phosphoinositide 3-kinases (PI3K inhibitor (LY294002 abolished ability of the cells

  7. Bioequivalence studies of tibolone in premenopausal women and effects on expression of the tibolone-metabolizing enzyme AKR1C (aldo-keto reductase) family caused by estradiol.

    Kang, Keon W; Kim, Yoon G

    2008-12-01

    This study aimed to investigate the bioequivalence of a test formulation of tibolone with the marketed reference formulation in 24 young healthy female volunteers. Tibolone is a synthetic steroid hormone for menopausal women. Volunteers were treated with the 2 formulations of tibolone (total dose of active ingredient 2.5 mg) according to a 2 x 2 crossover design with a 1-week washout period. Plasma concentrations of 3alpha- and 3beta-hydroxytibolone, which are major metabolites of tibolone, were assayed in timed samples over a 24-hour period with a validated gas chromatography/mass spectrometry (GC/MS) method that had a lower limit of quantification of 0.5 ng/mL. The reference and test formulations gave a mean 3alpha-hydroxytibolone C(max) of 5.0 and 5.2 ng/mL, respectively, and a mean 3beta-hydroxytibolone C(max) of 16.4 and 16.5 ng/mL, respectively. The mean AUC(t) of 3alpha-hydroxytibolone was 24.7 and 24.3 ng h/mL, whereas the mean AUC(t) of 3beta-hydroxytibolone was 57.6 and 54.8 ng h/mL for the test and reference formulations, respectively. The authors did not find significant differences in pharmacokinetic parameters between the 2 formulations, but metabolite formation was different from reports in postmenopausal women. The authors therefore measured the effects of estradiol on the expression of the tibolone-metabolizing enzymes, from the aldo-keto reductase (AKR1C) family, using HepG2 cell (human hepatoma cells) and MCF-7 cell (human breast cancer cells). Estradiol increased mRNA levels of AKR1C1, AKR1C2, and AKR1C3 and protein levels of total AKR1C in HepG2 cells. Estradiol selectively enhanced levels of AKR1C2 mRNA in MCF-7 cells. Thus, changes in the major metabolites of tibolone might result from changes in AKR1C family expression by patient estrogen status.

  8. Implications of iron deficiency/anemia on the classification of diabetes using HbA1c

    Attard, S M; Herring, A H; Wang, H; Howard, A-G; Thompson, A L; Adair, L S; Mayer-Davis, E J; Gordon-Larsen, P

    2015-01-01

    Background/Objectives: Nonglycemic factors like iron deficiency (ID) or anemia may interfere with classification of diabetes and prediabetes using hemoglobin A1c (HbA1c). However, few population-based studies of diabetes in areas with endemic ID/anemia have been conducted. We aimed to determine how mutually exclusive categories of ID alone, anemia alone and iron-deficiency anemia (IDA) were each associated with prediabetes and diabetes prevalence using fasting blood glucose (FBG) versus HbA1c in a population-based study of adults with endemic ID/anemia. Subjects/Methods: We used data from the China Health and Nutrition Survey, a longitudinal, population-based study across 228 communities within nine provinces of China. This analysis included 7308 adults seen in the 2009 survey aged 18–75 years. We used descriptive and covariate-adjusted models to examine relative risk of prediabetes and diabetes using FBG alone, HbA1c alone, HbA1c and FBG, or neither (normoglycemia) by anemia alone, ID alone, IDA or normal iron/hemoglobin. Results: Approximately 65% of individuals with diabetes in our sample were concordantly classified with diabetes using both FBG and HbA1c, while 35% had a discordant diabetes classification: they were classified using either FBG or HbA1c, but not both. Fewer participants with ID alone versus normal iron/hemoglobin were classified with diabetes using HbA1c only. From covariate-adjusted, multinomial regression analyses, the adjusted prevalence of prediabetes using HbA1c only was 22% for men with anemia alone, but 13% for men with normal iron/hemoglobin. In contrast, the predicted prevalence of prediabetes using HbA1c only was 8% for women with ID alone, compared with 13% for women with normal iron/hemoglobin. Conclusions: These findings suggest potential misclassification of diabetes using HbA1c in areas of endemic ID/anemia. Estimating diabetes prevalence using HbA1c may result in under-diagnosis in women with ID and over-diagnosis in men with

  9. Solvent effects on enzymes - Implications for extraterrestrial life.

    Heinrich, M. R.

    1972-01-01

    Review of several studies on the alterations taking place in the structure, catalytic activity, specificity, and stability of an enzyme when some or all of the water in the medium is replaced by another solvent. These studies show the utility of solvents as a tool for probing enzyme function. They also suggest that solvents other than water should be investigated as media for controlling and directing enzyme reactions.

  10. Paradoxical Roles of Antioxidant Enzymes: Basic Mechanisms and Health Implications.

    Lei, Xin Gen; Zhu, Jian-Hong; Cheng, Wen-Hsing; Bao, Yongping; Ho, Ye-Shih; Reddi, Amit R; Holmgren, Arne; Arnér, Elias S J

    2016-01-01

    Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated from aerobic metabolism, as a result of accidental electron leakage as well as regulated enzymatic processes. Because ROS/RNS can induce oxidative injury and act in redox signaling, enzymes metabolizing them will inherently promote either health or disease, depending on the physiological context. It is thus misleading to consider conventionally called antioxidant enzymes to be largely, if not exclusively, health protective. Because such a notion is nonetheless common, we herein attempt to rationalize why this simplistic view should be avoided. First we give an updated summary of physiological phenotypes triggered in mouse models of overexpression or knockout of major antioxidant enzymes. Subsequently, we focus on a series of striking cases that demonstrate "paradoxical" outcomes, i.e., increased fitness upon deletion of antioxidant enzymes or disease triggered by their overexpression. We elaborate mechanisms by which these phenotypes are mediated via chemical, biological, and metabolic interactions of the antioxidant enzymes with their substrates, downstream events, and cellular context. Furthermore, we propose that novel treatments of antioxidant enzyme-related human diseases may be enabled by deliberate targeting of dual roles of the pertaining enzymes. We also discuss the potential of "antioxidant" nutrients and phytochemicals, via regulating the expression or function of antioxidant enzymes, in preventing, treating, or aggravating chronic diseases. We conclude that "paradoxical" roles of antioxidant enzymes in physiology, health, and disease derive from sophisticated molecular mechanisms of redox biology and metabolic homeostasis. Simply viewing antioxidant enzymes as always being beneficial is not only conceptually misleading but also clinically hazardous if such notions underpin medical treatment protocols based on modulation of redox pathways.

  11. Carbonic Anhydrase: An Efficient Enzyme with Possible Global Implications

    Christopher D. Boone

    2013-01-01

    Full Text Available As the global atmospheric emissions of carbon dioxide (CO2 and other greenhouse gases continue to grow to record-setting levels, so do the demands for an efficient and inexpensive carbon sequestration system. Concurrently, the first-world dependence on crude oil and natural gas provokes concerns for long-term availability and emphasizes the need for alternative fuel sources. At the forefront of both of these research areas are a family of enzymes known as the carbonic anhydrases (CAs, which reversibly catalyze the hydration of CO2 into bicarbonate. CAs are among the fastest enzymes known, which have a maximum catalytic efficiency approaching the diffusion limit of 108 M−1s−1. As such, CAs are being utilized in various industrial and research settings to help lower CO2 atmospheric emissions and promote biofuel production. This review will highlight some of the recent accomplishments in these areas along with a discussion on their current limitations.

  12. Enzyme

    Enzymes are complex proteins that cause a specific chemical change in all parts of the body. For ... use them. Blood clotting is another example of enzymes at work. Enzymes are needed for all body ...

  13. A1C test

    HbA1C test; Glycated hemoglobin test; Glycosylated hemoglobin test; Hemoglobin glycosylated test; Glycohemoglobin test ... have recently eaten does not affect the A1C test, so you do not need to fast to ...

  14. Extensive Lysine Methylation in Hyperthermophilic Crenarchaea: Potential Implications for Protein Stability and Recombinant Enzymes

    Catherine H. Botting

    2010-01-01

    Full Text Available In eukarya and bacteria, lysine methylation is relatively rare and is catalysed by sequence-specific lysine methyltransferases that typically have only a single-protein target. Using RNA polymerase purified from the thermophilic crenarchaeum Sulfolobus solfataricus, we identified 21 methyllysines distributed across 9 subunits of the enzyme. The modified lysines were predominantly in α-helices and showed no conserved sequence context. A limited survey of the Thermoproteus tenax proteome revealed widespread modification with 52 methyllysines in 30 different proteins. These observations suggest the presence of an unusual lysine methyltransferase with relaxed specificity in the crenarchaea. Since lysine methylation is known to enhance protein thermostability, this may be an adaptation to a thermophilic lifestyle. The implications of this modification for studies and applications of recombinant crenarchaeal enzymes are discussed.

  15. Quantitative comparison of catalytic mechanisms and overall reactions in convergently evolved enzymes: implications for classification of enzyme function.

    Daniel E Almonacid

    2010-03-01

    Full Text Available Functionally analogous enzymes are those that catalyze similar reactions on similar substrates but do not share common ancestry, providing a window on the different structural strategies nature has used to evolve required catalysts. Identification and use of this information to improve reaction classification and computational annotation of enzymes newly discovered in the genome projects would benefit from systematic determination of reaction similarities. Here, we quantified similarity in bond changes for overall reactions and catalytic mechanisms for 95 pairs of functionally analogous enzymes (non-homologous enzymes with identical first three numbers of their EC codes from the MACiE database. Similarity of overall reactions was computed by comparing the sets of bond changes in the transformations from substrates to products. For similarity of mechanisms, sets of bond changes occurring in each mechanistic step were compared; these similarities were then used to guide global and local alignments of mechanistic steps. Using this metric, only 44% of pairs of functionally analogous enzymes in the dataset had significantly similar overall reactions. For these enzymes, convergence to the same mechanism occurred in 33% of cases, with most pairs having at least one identical mechanistic step. Using our metric, overall reaction similarity serves as an upper bound for mechanistic similarity in functional analogs. For example, the four carbon-oxygen lyases acting on phosphates (EC 4.2.3 show neither significant overall reaction similarity nor significant mechanistic similarity. By contrast, the three carboxylic-ester hydrolases (EC 3.1.1 catalyze overall reactions with identical bond changes and have converged to almost identical mechanisms. The large proportion of enzyme pairs that do not show significant overall reaction similarity (56% suggests that at least for the functionally analogous enzymes studied here, more stringent criteria could be used to

  16. Guava leaves polyphenolics-rich extract inhibits vital enzymes implicated in gout and hypertension in vitro

    Irondi, Emmanuel Anyachukwu; Agboola, Samson Olalekan; Oboh, Ganiyu; Boligon, Aline Augusti; Athayde, Margareth Linde; Shode, Francis O.

    2016-01-01

    Background/Aim: Elevated uric acid level, an index of gout resulting from the over-activity of xanthine oxidase (XO), increases the risk of developing hypertension. However, research has shown that plant-derived inhibitors of XO and angiotensin 1-converting enzyme (ACE), two enzymes implicated in gout and hypertension, respectively, can prevent or ameliorate both diseases, without noticeable side effects. Hence, this study characterized the polyphenolics composition of guava leaves extract and evaluated its inhibitory effect on XO and ACE in vitro. Materials and Methods: The polyphenolics (flavonoids and phenolic acids) were characterized using high-performance liquid chromatography (HPLC) coupled with diode array detection (DAD). The XO, ACE, and Fe2+-induced lipid peroxidation inhibitory activities, and free radicals (2,2-diphenylpicrylhydrazyl [DPPH]* and 2,2´-azino-bis-3-ethylbenzthiazoline-6-sulphonic [ABTS]*+) scavenging activities of the extract were determined using spectrophotometric methods. Results: Flavonoids were present in the extract in the order of quercetin > kaempferol > catechin > quercitrin > rutin > luteolin > epicatechin; while phenolic acids were in the order of caffeic acid > chlorogenic acid > gallic acids. The extract effectively inhibited XO, ACE and Fe2+-induced lipid peroxidation in a dose-dependent manner; having half-maximal inhibitory concentrations (IC50) of 38.24 ± 2.32 μg/mL, 21.06 ± 2.04 μg/mL and 27.52 ± 1.72 μg/mL against XO, ACE and Fe2+-induced lipid peroxidation, respectively. The extract also strongly scavenged DPPH* and ABTS*+. Conclusion: Guava leaves extract could serve as functional food for managing gout and hypertension and attenuating the oxidative stress associated with both diseases. PMID:27104032

  17. Targeted mutagenesis of mitochondrial carbonic anhydrases VA and VB implicates both enzymes in ammonia detoxification and glucose metabolism

    Shah, Gul N.; Rubbelke, Timothy S.; Hendin, Joshua; Nguyen, Hien; Waheed, Abdul; Shoemaker, James D.; Sly, William S.

    2013-01-01

    Prior studies with carbonic anhydrase (CA) inhibitors implicated mitochondrial CA in ureagenesis and gluconeogenesis. Subsequent studies identified two mitochondrial CAs. To distinguish the contribution of each enzyme, we studied the effects of targeted disruption of the murine CA genes, called Car5A and Car5B. The Car5A mutation had several deleterious consequences. Car5A null mice were smaller than wild-type littermates and bred poorly. However, on sodium–potassium citrate-supplemented wate...

  18. A simple assay for mammalian spermine oxidase: a polyamine catabolic enzyme implicated in drug response and disease.

    Goodwin, Andrew C; Murray-Stewart, Tracy R; Casero, Robert A

    2011-01-01

    Spermine oxidase (SMO), the most recently characterized polyamine metabolic enzyme, catalyzes the direct back-conversion of spermine to spermidine in an FAD-dependent reaction that also yields the byproducts hydrogen peroxide (H(2)O(2)) and 3-aminopropanal. These metabolites, particularly H(2)O(2), have been implicated in cytotoxic cellular responses to specific antitumor polyamine analogs, as well as in the inflammation-associated generation of DNA damage. This chapter describes a rapid, sensitive, and inexpensive method for the chemiluminescent measurement of SMO (or alternatively, N (1)-acetyl polyamine oxidase, APAO) enzyme activity in cultured cell lysates, without the need for radioactive reagents or the use of high performance liquid chromatography (HPLC). Specifically, H(2)O(2) production by SMO is coupled to chemiluminescence generated by the horseradish peroxidase-catalyzed oxidation of luminol. Detailed protocols for preparation of reagents, harvesting cell lysates, generation of a standard curve, assaying of samples, and calculation of SMO enzyme activity are presented.

  19. Short communication: expression of transporters and metabolizing enzymes in the female lower genital tract: implications for microbicide research.

    Zhou, Tian; Hu, Minlu; Cost, Marilyn; Poloyac, Samuel; Rohan, Lisa

    2013-11-01

    Topical vaginal microbicides have been considered a promising option for preventing the male-to-female sexual transmission of HIV; however, clinical trials to date have not clearly demonstrated robust and reproducible effectiveness results. While multiple approaches may help enhance product effectiveness observed in clinical trials, increasing the drug exposure in lower genital tract tissues is a compelling option, given the difficulty in achieving sufficient drug exposure and positive correlation between tissue exposure and microbicide efficacy. Since many microbicide drug candidates are substrates of transporters and/or metabolizing enzymes, there is emerging interest in improving microbicide exposure and efficacy through local modulation of transporters and enzymes in the female lower genital tract. However, no systematic information on transporter/enzyme expression is available for ectocervical and vaginal tissues of premenopausal women, the genital sites most relevant to microbicide drug delivery. The current study utilized reverse transcriptase polymerase chain reaction (RT-PCR) to examine the mRNA expression profile of 22 transporters and 19 metabolizing enzymes in premenopausal normal human ectocervix and vagina. Efflux and uptake transporters important for antiretroviral drugs, such as P-gp, BCRP, OCT2, and ENT1, were found to be moderately or highly expressed in the lower genital tract as compared to liver. Among the metabolizing enzymes examined, most CYP isoforms were not detected while a number of UGTs such as UGT1A1 were highly expressed. Moderate to high expression of select transporters and enzymes was also observed in mouse cervix and vagina. The implications of this information on microbicide research is also discussed, including microbicide pharmacokinetics, the utilization of the mouse model in microbicide screening, as well as the in vivo functional studies of cervicovaginal transporters and enzymes.

  20. Hemoglobina glucosilada a1c (a1c)

    Mendivil Anaya, Carlos Olimpo; Pérez Gualdrón, Clara Eugenia; Sierra Ariza, Iván Dario; Pinzón, Giuliana Andrea

    2014-01-01

    Antecedentes. La Hemoglobina GlucosiladaA1c es un examen de laboratorio empleado paraevaluar el control glucémico en pacientes condiabetes. Clásicamente el personal de atenciónen salud asume que solamente la glucemia promediodetermina el valor de A1c. Sin embargoalgunos estudios han encontrado variación en laA1c de acuerdo a la edad y el sexo.Objetivos. El objetivo principal de este estudioera determinar si existía alguna tendencia o patrónde comportamiento de los niveles de A1c adiferentes e...

  1. Proteinaceous inhibitors of carbohydrate-active enzymes in cereals: implication in agriculture, cereal processing and nutrition

    Juge, N.; Svensson, Birte

    2006-01-01

    Enzymes that degrade, modify, or create glycosidic bonds are involved in carbohydrate biosynthesis and remodelling. Microbial carbohydrate-active enzymes form the basis of current green technology in the food, feed, starch, paper and pulp industries and the revolution in genomics may offer long......-term gains on the quality and quantity of the raw materials. Proteinaceous inhibitors of carbohydrate-active enzymes (alpha-amylase, limit-dextrinase, polygalacturonase, pectin lyase, pectin methylesterase, invertase and xyloglucan endoglucanase) naturally occur in plants where they are involved in various...... roles from plant defence to metabolism. Xylanase inhibitors represent the latest addition to this growing family. In this review, we will focus on the inhibitors of carbohydrate-active enzymes present in cereals, mostly represented by et-amylase and xylanase inhibitors, and summarise the existing...

  2. Crystal Structures of Trypanosoma cruzi UDP-Galactopyranose Mutase Implicate Flexibility of the Histidine Loop in Enzyme Activation

    Dhatwalia, Richa; Singh, Harkewal; Oppenheimer, Michelle; Sobrado, Pablo; Tanner, John J. (Virginia Tech); (UMC)

    2012-11-01

    Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. Here we report crystal structures of the galactofuranose biosynthetic enzyme UDP-galactopyranose mutase (UGM) from T. cruzi, which are the first structures of this enzyme from a protozoan parasite. UGM is an attractive target for drug design because galactofuranose is absent in humans but is an essential component of key glycoproteins and glycolipids in trypanosomatids. Analysis of the enzyme-UDP noncovalent interactions and sequence alignments suggests that substrate recognition is exquisitely conserved among eukaryotic UGMs and distinct from that of bacterial UGMs. This observation has implications for inhibitor design. Activation of the enzyme via reduction of the FAD induces profound conformational changes, including a 2.3 {angstrom} movement of the histidine loop (Gly60-Gly61-His62), rotation and protonation of the imidazole of His62, and cooperative movement of residues located on the si face of the FAD. Interestingly, these changes are substantially different from those described for Aspergillus fumigatus UGM, which is 45% identical to T. cruzi UGM. The importance of Gly61 and His62 for enzymatic activity was studied with the site-directed mutant enzymes G61A, G61P, and H62A. These mutations lower the catalytic efficiency by factors of 10-50, primarily by decreasing k{sub cat}. Considered together, the structural, kinetic, and sequence data suggest that the middle Gly of the histidine loop imparts flexibility that is essential for activation of eukaryotic UGMs. Our results provide new information about UGM biochemistry and suggest a unified strategy for designing inhibitors of UGMs from the eukaryotic pathogens.

  3. Technological Implications of Modifying the Extent of Cell Wall-Proanthocyanidin Interactions Using Enzymes

    Ana Belén Bautista-Ortín

    2016-01-01

    Full Text Available The transference and reactivity of proanthocyanidins is an important issue that affects the technological processing of some fruits, such as grapes and apples. These processes are affected by proanthocyanidins bound to cell wall polysaccharides, which are present in high concentrations during the processing of the fruits. Therefore, the effective extraction of proanthocyanidins from fruits to their juices or derived products will depend on the ability to manage these associations, and, in this respect, enzymes that degrade these polysaccharides could play an important role. The main objective of this work was to test the role of pure hydrolytic enzymes (polygalacturonase and cellulose and a commercial enzyme containing these two activities on the extent of proanthocyanidin-cell wall interactions. The results showed that the modification promoted by enzymes reduced the amount of proanthocyanidins adsorbed to cell walls since they contributed to the degradation and release of the cell wall polysaccharides, which diffused into the model solution. Some of these released polysaccharides also presented some reactivity towards the proanthocyanidins present in a model solution.

  4. Extensive lysine methylation in hyperthermophilic crenarchaea : potential implications for protein stability and recombinant enzymes

    Botting, Catherine H.; Paul Talbot; Sonia Paytubi; White, Malcolm F

    2010-01-01

    In eukarya and bacteria, lysine methylation is relatively rare and is catalysed by sequence-specific lysine methyltransferases that typically have only a single-protein target. Using RNA polymerase purified from the thermophilic crenarchaeum Sulfolobus solfataricus, we identified 21 methyllysines distributed across 9 subunits of the enzyme. The modified lysines were predominantly in alpha-helices and showed no conserved sequence context. A limited survey of the Thermoproteus tenax proteome re...

  5. Polyphenols as enzyme inhibitors in different degraded peat soils: Implication for microbial metabolism in rewetted peatlands

    Zak, Dominik; Roth, Cyril; Gelbrecht, Jörg; Fenner, Nathalie; Reuter, Hendrik

    2015-04-01

    Recently, more than 30,000 ha of drained minerotrophic peatlands (= fens) in NE Germany were rewetted to restore their ecological functions. Due to an extended drainage history, a re-establishment of their original state is not expected in the short-term. Elevated concentrations of dissolved organic carbon, ammonium and phosphate have been measured in the soil porewater of the upper degraded peat layers of rewetted fens at levels of one to three orders higher than the values in pristine systems; an indicator of increased microbial activity in the upper degraded soil layers. On the other hand there is evidence that the substrate availability within the degraded peat layer is lowered since the organic matter has formerly been subject to intense decomposition over the decades of drainage and intense agricultural use of the areas. Previously however, it was suggested that inhibition of hydrolytic enzymes by polyphenolic substances is suspended during aeration of peat soils mainly due to the decomposition of the inhibiting polyphenols by oxidising enzymes such as phenol oxidase. Accordingly we hypothesised a lack of enzyme inhibiting polyphenols in degraded peat soils of rewetted fens compared to less decomposed peat of more natural fens. We collected both peat samples at the soil surface (0-20 cm) and fresh roots of dominating vascular plants and mosses (as peat parent material) from five formerly drained rewetted sites and five more natural sites of NE Germany and NW Poland. Less decomposed peat and living roots were used to obtain an internal standard for polyphenol analysis and to run enzyme inhibition tests. For all samples we determined the total phenolic contents and in addition we distinguished between the contents of hydrolysable and condensed tannic substances. From a methodical perspective the advantage of internal standards compared to the commercially available standards cyanidin chloride and tannic acid became apparent. Quantification with cyanidin or

  6. County-Scale Spatial Distribution of Soil Enzyme Activities and Enzyme Activity Indices in Agricultural Land: Implications for Soil Quality Assessment

    Xiangping Tan; Baoni Xie; Junxing Wang; Wenxiang He; Xudong Wang; Gehong Wei

    2014-01-01

    Here the spatial distribution of soil enzymatic properties in agricultural land was evaluated on a county-wide (567 km2) scale in Changwu, Shaanxi Province, China. The spatial variations in activities of five hydrolytic enzymes were examined using geostatistical methods. The relationships between soil enzyme activities and other soil properties were evaluated using both an integrated total enzyme activity index (TEI) and the geometric mean of enzyme activities (GME). At the county scale, soil...

  7. Serglycin proteoglycan is not implicated in localizing exocrine pancreas enzymes to zymogen granules

    Niemann, Carsten U; Cowland, Jack B; Ralfkiaer, Elisabeth;

    2009-01-01

    Storage and release of proteins from granules forms the basis of cellular functions as diverse as cell mediated cytotoxicity, neuronal communication, activation of muscle fibres, and release of hormones or digestive enzymes from endocrine and exocrine glands, such as the pancreas. Serglycin...... in rat. We here present data showing that serglycin is not present at the protein level in human or murine pancreas. Furthermore, the amount and localization of three exocrine pancreas zymogens (amylase, trypsinogen, and carboxypeptidase A) is not affected by the absence of serglycin in a serglycin knock...

  8. Retinoblastoma protein co-purifies with proteasomal insulin-degrading enzyme: Implications for cell proliferation control

    Radulescu, Razvan T., E-mail: ratura@gmx.net [Molecular Concepts Research (MCR), Muenster (Germany); Duckworth, William C. [Department of Medicine, Phoenix VA Health Care System, Phoenix, AZ (United States); Levy, Jennifer L. [Research Service, Phoenix VA Health Care System, Phoenix, AZ (United States); Fawcett, Janet, E-mail: janet.fawcett@va.gov [Research Service, Phoenix VA Health Care System, Phoenix, AZ (United States)

    2010-04-30

    Previous investigations on proteasomal preparations containing insulin-degrading enzyme (IDE; EC 3.4.24.56) have invariably yielded a co-purifying protein with a molecular weight of about 110 kDa. We have now found both in MCF-7 breast cancer and HepG2 hepatoma cells that this associated molecule is the retinoblastoma tumor suppressor protein (RB). Interestingly, the amount of RB in this protein complex seemed to be lower in HepG2 vs. MCF-7 cells, indicating a higher (cytoplasmic) protein turnover in the former vs. the latter cells. Moreover, immunofluorescence showed increased nuclear localization of RB in HepG2 vs. MCF-7 cells. Beyond these subtle differences between these distinct tumor cell types, our present study more generally suggests an interplay between RB and IDE within the proteasome that may have important growth-regulatory consequences.

  9. Differences in activities of the enzymes of nucleotide metabolism and its implications for cardiac xenotransplantation.

    Yuen, A H Y; Khalpey, Z; Lavitrano, M; McGregor, C G A; Kalsi, K K; Yacoub, M H; Smolenski, R T

    2006-01-01

    Xenotransplantation is one be possible solution for a severe shortage of human organs available for transplantation. However, only a few studies addressed metabolic compatibility of transplanted animal organs. Our aim was to compare activities of adenosine metabolizing enzymes in the heart of different species that are relevant to clinical or experimental xenotransplantation. We noted fundamental differences: ecto-5' nucleotidease (E5' N) activity was 4-fold lower in pig and baboon hearts compared to the human hearts while mouse activity was compatible with human and rat activity was three times higher than human. There also were significant differences in AMP-deaminase (AMPD), adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) activities. We conclude that differences in nucleotide metabolism may contribute to organ dysfunction after xenotransplantation.

  10. Somatostatin modulates insulin-degrading-enzyme metabolism: implications for the regulation of microglia activity in AD.

    Grazia Tundo

    Full Text Available The deposition of β-amyloid (Aβ into senile plaques and the impairment of somatostatin-mediated neurotransmission are key pathological events in the onset of Alzheimer's disease (AD. Insulin-degrading-enzyme (IDE is one of the main extracellular protease targeting Aβ, and thus it represents an interesting pharmacological target for AD therapy. We show that the active form of somatostatin-14 regulates IDE activity by affecting its expression and secretion in microglia cells. A similar effect can also be observed when adding octreotide. Following a previous observation where somatostatin directly interacts with IDE, here we demonstrate that somatostatin regulates Aβ catabolism by modulating IDE proteolytic activity in IDE gene-silencing experiments. As a whole, these data indicate the relevant role played by somatostatin and, potentially, by analogue octreotide, in preventing Aβ accumulation by partially restoring IDE activity.

  11. Transcriptional co-regulation of secondary metabolism enzymes in Arabidopsis: functional and evolutionary implications.

    Gachon, Claire M M; Langlois-Meurinne, Mathilde; Henry, Yves; Saindrenan, Patrick

    2005-05-01

    The combined knowledge of the Arabidopsis genome and transcriptome now allows to get an integrated view of the dynamics and evolution of metabolic pathways in plants. We used publicly available sets of microarray data obtained in a wide range of different stress and developmental conditions to investigate the co-expression of genes encoding enzymes of secondary metabolism pathways, in particular indoles, phenylpropanoids, and flavonoids. We performed hierarchical clustering of gene expression profiles and found that major enzymes of each pathway display a clear and robust co-expression throughout all the conditions studied. Moreover, detailed analysis evidenced that some genes display co-regulation in particular physiological conditions only, certainly reflecting their modular recruitment into stress- or developmentally regulated biosynthetic pathways. The combination of these microarray data with sequence analysis allows to draw very precise hypotheses on the function of otherwise uncharacterized genes. To illustrate this approach, we focused our analysis on secondary metabolism glycosyltransferases (UGTs), a multigenic family involved in the conjugation of small molecules to sugars like glucose. We propose that UGT74B1 and UGT74C1 may be involved in aromatic and aliphatic glucosinolates synthesis, respectively. We also suggest that UGT75C1 may function as an anthocyanin-5-O-glucosyltransferase in planta. Therefore, this data-mining approach appears very powerful for the functional prediction of unknown genes, and could be transposed to virtually any other gene family. Finally, we suggest that analysis of expression pattern divergence of duplicated genes also provides some insight into the mechanisms of metabolic pathway evolution.

  12. Odorant-binding proteins and xenobiotic metabolizing enzymes: implications in olfactory perireceptor events.

    Heydel, Jean-Marie; Coelho, Alexandra; Thiebaud, Nicolas; Legendre, Arièle; Le Bon, Anne-Marie; Faure, Philippe; Neiers, Fabrice; Artur, Yves; Golebiowski, Jérôme; Briand, Loïc

    2013-09-01

    At the periphery of the olfactory system, the binding of odorants on olfactory receptors (ORs) is usually thought to be the first level of the perception of smell. However, at this stage, there is evidence that other molecular mechanisms also interfere with this chemoreception by ORs. These perireceptor events are mainly supported by two groups of proteins present in the olfactory nasal mucus or in the nasal epithelium. Odorant-binding proteins (OBPs), the first group of proteins have been investigated for many years. OBPs are small carrier proteins capable of binding odorants with affinities in the micromolar range. Although there is no absolute evidence to support their functional roles in vertebrates, OBPs are good candidates for the transport of inhaled odorants towards the ORs via the nasal mucus. The second group of proteins involves xenobiotic metabolizing enzymes, which are strongly expressed in the olfactory epithelium and supposed to be involved in odorant transformation, degradation, and/or olfactory signal termination. Following an overview of these proteins, this review explores their roles, which are still a matter of debate.

  13. County-Scale Spatial Distribution of Soil Enzyme Activities and Enzyme Activity Indices in Agricultural Land: Implications for Soil Quality Assessment

    Xiangping Tan

    2014-01-01

    Full Text Available Here the spatial distribution of soil enzymatic properties in agricultural land was evaluated on a county-wide (567 km2 scale in Changwu, Shaanxi Province, China. The spatial variations in activities of five hydrolytic enzymes were examined using geostatistical methods. The relationships between soil enzyme activities and other soil properties were evaluated using both an integrated total enzyme activity index (TEI and the geometric mean of enzyme activities (GME. At the county scale, soil invertase, phosphatase, and catalase activities were moderately spatially correlated, whereas urease and dehydrogenase activities were weakly spatially correlated. Correlation analysis showed that both TEI and GME were better correlated with selected soil physicochemical properties than single enzyme activities. Multivariate regression analysis showed that soil OM content had the strongest positive effect while soil pH had a negative effect on the two enzyme activity indices. In addition, total phosphorous content had a positive effect on TEI and GME in orchard soils, whereas alkali-hydrolyzable nitrogen and available potassium contents, respectively, had negative and positive effects on these two enzyme indices in cropland soils. The results indicate that land use changes strongly affect soil enzyme activities in agricultural land, where TEI provides a sensitive biological indicator for soil quality.

  14. Discovery of (R)-2-(6-Methoxynaphthalen-2-yl)butanoic Acid as a Potent and Selective Aldo-keto Reductase 1C3 Inhibitor.

    Adeniji, Adegoke; Uddin, Md Jashim; Zang, Tianzhu; Tamae, Daniel; Wangtrakuldee, Phumvadee; Marnett, Lawrence J; Penning, Trevor M

    2016-08-25

    Type 5 17β-hydroxysteroid dehydrogenase, aldo-keto reductase 1C3 (AKR1C3) converts Δ(4)-androstene-3,17-dione and 5α-androstane-3,17-dione to testosterone (T) and 5α-dihydrotestosterone, respectively, in castration resistant prostate cancer (CRPC). In CRPC, AKR1C3 is implicated in drug resistance, and enzalutamide drug resistance can be surmounted by indomethacin a potent inhibitor of AKR1C3. We examined a series of naproxen analogues and find that (R)-2-(6-methoxynaphthalen-2-yl)butanoic acid (in which the methyl group of R-naproxen was replaced by an ethyl group) acts as a potent AKR1C3 inhibitor that displays selectivity for AKR1C3 over other AKR1C enzymes. This compound was devoid of inhibitory activity on COX isozymes and blocked AKR1C3 mediated production of T and induction of PSA in LNCaP-AKR1C3 cells as a model of a CRPC cell line. R-Profens are substrate selective COX-2 inhibitors and block the oxygenation of endocannabinoids and in the context of advanced prostate cancer R-profens could inhibit intratumoral androgen synthesis and act as analgesics for metastatic disease.

  15. Outbreaks of highly pathogenic avian influenza H5N1 clade 2.3.2.1c in hunting falcons and kept wild birds in Dubai implicate intercontinental virus spread.

    Naguib, Mahmoud M; Kinne, Jörg; Chen, Honglin; Chan, Kwok-Hung; Joseph, Sunitha; Wong, Po-Chun; Woo, Patrick C Y; Wernery, Renate; Beer, Martin; Wernery, Ulrich; Harder, Timm C

    2015-11-01

    Highly pathogenic avian influenza viruses (HPAIVs) of subtype H5N1 have continued to perpetuate with divergent genetic variants in poultry within Asia since 2003. Further dissemination of Asian-derived H5 HPAIVs to Europe, Africa and, most recently, to the North American continent has occurred. We report an outbreak of HPAIV H5N1 among falcons kept for hunting and other wild bird species bred as falcon prey in Dubai, United Arab Emirates, during the autumn of 2014. The causative agent was identified as avian influenza virus subtype H5N1, clade 2.3.2.1c, by genetic and phylogenetic analyses. High mortality in infected birds was in accordance with systemic pathomorphological and histological alterations in affected falcons. Genetic analysis showed the HPAIV H5N1 of clade 2.3.2.1c is a reassortant in which the PB2 segment was derived from an Asian-origin H9N2 virus lineage. The Dubai H5N1 viruses were closely related to contemporary H5N1 HPAIVs from Nigeria, Burkina-Faso, Romania and Bulgaria. Median-joining network analysis of 2.3.2.1c viruses revealed that the Dubai outbreak was an episode of a westward spread of these viruses on a larger scale from unidentified Asian sources. The incursion into Dubai, possibly via infected captive hunting falcons returning from hunting trips to central Asian countries, preceded outbreaks in Nigeria and other West African countries. The alarmingly enhanced geographical mobility of clade 2.3.2.1.c and clade 2.3.4.4 viruses may represent another wave of transcontinental dissemination of Asian-origin HPAIV H5 viruses, such as the outbreak at Qinghai Lake caused by clade 2.2 (‘Qinghai’ lineage) in 2005.

  16. A1C Test and Diabetes

    ... Diagnosis The A1C Test & Diabetes The A1C Test & Diabetes What is the A1C test? The A1C test ... A1C test be used to diagnose type 2 diabetes and prediabetes? Yes. In 2009, an international expert ...

  17. Differential role of human choline kinase alpha and beta enzymes in lipid metabolism: implications in cancer onset and treatment.

    David Gallego-Ortega

    Full Text Available BACKGROUND: The Kennedy pathway generates phosphocoline and phosphoethanolamine through its two branches. Choline Kinase (ChoK is the first enzyme of the Kennedy branch of synthesis of phosphocholine, the major component of the plasma membrane. ChoK family of proteins is composed by ChoKalpha and ChoKbeta isoforms, the first one with two different variants of splicing. Recently ChoKalpha has been implicated in the carcinogenic process, since it is over-expressed in a variety of human cancers. However, no evidence for a role of ChoKbeta in carcinogenesis has been reported. METHODOLOGY/PRINCIPAL FINDINGS: Here we compare the in vitro and in vivo properties of ChoKalpha1 and ChoKbeta in lipid metabolism, and their potential role in carcinogenesis. Both ChoKalpha1 and ChoKbeta showed choline and ethanolamine kinase activities when assayed in cell extracts, though with different affinity for their substrates. However, they behave differentially when overexpressed in whole cells. Whereas ChoKbeta display an ethanolamine kinase role, ChoKalpha1 present a dual choline/ethanolamine kinase role, suggesting the involvement of each ChoK isoform in distinct biochemical pathways under in vivo conditions. In addition, while overexpression of ChoKalpha1 is oncogenic when overexpressed in HEK293T or MDCK cells, ChoKbeta overexpression is not sufficient to induce in vitro cell transformation nor in vivo tumor growth. Furthermore, a significant upregulation of ChoKalpha1 mRNA levels in a panel of breast and lung cancer cell lines was found, but no changes in ChoKbeta mRNA levels were observed. Finally, MN58b, a previously described potent inhibitor of ChoK with in vivo antitumoral activity, shows more than 20-fold higher efficiency towards ChoKalpha1 than ChoKbeta. CONCLUSION/SIGNIFICANCE: This study represents the first evidence of the distinct metabolic role of ChoKalpha and ChoKbeta isoforms, suggesting different physiological roles and implications in human

  18. Targeted mutagenesis of mitochondrial carbonic anhydrases VA and VB implicates both enzymes in ammonia detoxification and glucose metabolism.

    Shah, Gul N; Rubbelke, Timothy S; Hendin, Joshua; Nguyen, Hien; Waheed, Abdul; Shoemaker, James D; Sly, William S

    2013-04-30

    Prior studies with carbonic anhydrase (CA) inhibitors implicated mitochondrial CA in ureagenesis and gluconeogenesis. Subsequent studies identified two mitochondrial CAs. To distinguish the contribution of each enzyme, we studied the effects of targeted disruption of the murine CA genes, called Car5A and Car5B. The Car5A mutation had several deleterious consequences. Car5A null mice were smaller than wild-type littermates and bred poorly. However, on sodium-potassium citrate-supplemented water, they produced offspring in expected numbers. Their blood ammonia concentrations were markedly elevated, but their fasting blood sugars were normal. By contrast, Car5B null mice showed normal growth and normal blood ammonia levels. They too had normal fasting blood sugars. Car5A/B double-knockout (DKO) mice showed additional abnormalities. Impaired growth was more severe than for Car5A null mice. Hyperammonemia was even greater as well. Although fertile, DKO animals were produced in less-than-predicted numbers even when supplemented with sodium-potassium citrate in their drinking water. Survival after weaning was also reduced, especially for males. In addition, fasting blood glucose levels for DKO mice were significantly lower than for controls (153 ± 33 vs. 230 ± 24 mg/dL). The enhanced hyperammonemia and lower fasting blood sugar, which are both seen in the DKO mice, indicate that both Car5A and Car5B contribute to both ammonia detoxification (ureagenesis) and regulation of fasting blood sugar (gluconeogenesis). Car5A, which is expressed mainly in liver, clearly has the predominant role in ammonia detoxification. The contribution of Car5B to ureagenesis and gluconeogenesis was evident only on a Car5A null background.

  19. 7 CFR 1c.114 - Cooperative research.

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Cooperative research. 1c.114 Section 1c.114 Agriculture Office of the Secretary of Agriculture PROTECTION OF HUMAN SUBJECTS § 1c.114 Cooperative research. Cooperative research projects are those projects covered by this policy which involve more than...

  20. Proteinaceous inhibitors of carbohydrate-active enzymes in cereals - implication in agriculture, cereal-processing and nutrition

    Juge, Nathalie; Svensson, Birte

    2006-01-01

    Enzymes that degrade, modify, or create glycosidic bonds are involved in carbohydrate biosynthesis and remodelling. Microbial carbohydrate-active enzymes form the basis of current green technology in the food, feed, starch, paper and pulp industries and the revolution in genomics may offer long......-term gains on the quality and quantity of the raw materials. Proteinaceous inhibitors of carbohydrate-active enzymes (alpha-amylase, limit-dextrinase, polygalacturonase, pectin lyase, pectin methylesterase, invertase and xyloglucan endoglucanase) naturally occur in plants where they are involved in various...... roles from plant defence to metabolism. Xylanase inhibitors represent the latest addition to this growing family. In this review, we will focus on the inhibitors of carbohydrate-active enzymes present in cereals, mostly represented by et-amylase and xylanase inhibitors, and summarise the existing...

  1. Led Astray by Hemoglobin A1c

    Jean Chen MD

    2016-01-01

    Full Text Available Hemoglobin A1c (A1c is used frequently to diagnose and treat diabetes mellitus. Therefore, it is important be aware of factors that may interfere with the accuracy of A1c measurements. This is a case of a rare hemoglobin variant that falsely elevated a nondiabetic patient’s A1c level and led to a misdiagnosis of diabetes. A 67-year-old male presented to endocrine clinic for further management after he was diagnosed with diabetes based on an elevated A1c of 10.7%, which is approximately equivalent to an average blood glucose of 260 mg/dL. Multiple repeat A1c levels remained >10%, but his home fasting and random glucose monitoring ranged from 92 to 130 mg/dL. Hemoglobin electrophoresis and subsequent genetic analysis diagnosed the patient with hemoglobin Wayne, a rare hemoglobin variant. This variant falsely elevates A1c levels when A1c is measured using cation-exchange high-performance liquid chromatography. When the boronate affinity method was applied instead, the patient’s A1c level was actually 4.7%. Though hemoglobin Wayne is clinically silent, this patient was erroneously diagnosed with diabetes and started on an antiglycemic medication. Due to this misdiagnosis, the patient was at risk of escalation in his “diabetes management” and hypoglycemia. Therefore, it is important that providers are aware of factors that may result in hemoglobin A1c inaccuracy including hemoglobin variants.

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

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

    1997-01-01

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

  3. Implication for functions of the ectopic adipocyte copper amine oxidase (AOC3 from purified enzyme and cell-based kinetic studies.

    Sam H Shen

    Full Text Available AOC3 is highly expressed in adipocytes and smooth muscle cells, but its function in these cells is currently unknown. The in vivo substrate(s of AOC3 is/are also unknown, but could provide an invaluable clue to the enzyme's function. Expression of untagged, soluble human AOC3 in insect cells provides a relatively simple means of obtaining pure enzyme. Characterization of enzyme indicates a 6% titer for the active site 2,4,5-trihydroxyphenylalanine quinone (TPQ cofactor and corrected k(cat values as high as 7 s(-1. Substrate kinetic profiling shows that the enzyme accepts a variety of primary amines with different chemical features, including nonphysiological branched-chain and aliphatic amines, with measured k(cat/K(m values between 10(2 and 10(4 M(-1 s(-1. K(m(O(2 approximates the partial pressure of oxygen found in the interstitial space. Comparison of the properties of purified murine to human enzyme indicates k(cat/K(m values that are within 3 to 4-fold, with the exception of methylamine and aminoacetone that are ca. 10-fold more active with human AOC3. With drug development efforts investigating AOC3 as an anti-inflammatory target, these studies suggest that caution is called for when screening the efficacy of inhibitors designed against human enzymes in non-transgenic mouse models. Differentiated murine 3T3-L1 adipocytes show a uniform distribution of AOC3 on the cell surface and whole cell K(m values that are reasonably close to values measured using purified enzymes. The latter studies support a relevance of the kinetic parameters measured with isolated AOC3 variants to adipocyte function. From our studies, a number of possible substrates with relatively high k(cat/K(m have been discovered, including dopamine and cysteamine, which may implicate a role for adipocyte AOC3 in insulin-signaling and fatty acid metabolism, respectively. Finally, the demonstrated AOC3 turnover of primary amines that are non-native to human tissue suggests

  4. Human sulfotransferase SULT1C1: cDNA cloning, tissue-specific expression, and chromosomal localization

    Her, Chengtao; Weinshilboum, R.M. [Mayo Foundation, Rochester, MN (United States); Kaur, G.P. [Temple Univ. Medical School, Philadelphia, PA (United States)] [and others

    1997-05-01

    We have isolated and sequenced a cDNA that encodes an apparent human orthologue of a rat sulfotransferase (ST) cDNA that has been referred to as {open_quotes}ST1C1{close_quotes} - although it was recently recommended that sulfotransferase proteins and cDNAs be abbreviated {open_quotes}SULT.{close_quotes} The new human cDNA was cloned from a fetal liver-spleen cDNA library and had an 888-bp open reading frame. The amino acid sequence of the protein encoded by the cDNA was 62% identical with that encoded by the rat ST1C1 cDNA and included signature sequences that are conserved in all cytosolic SULT enzymes. Dot blot analysis of mRNA from 50 human tissues indicated that the cDNA was expressed in adult human stomach, kidney, and thyroid, as well as fetal kidney and liver. Northern blot analyses demonstrated that the major SULT1C1 mRNA in those same tissues was 1.4 kb in length. We next determined the partial human SULT1C1 gene sequence for a portion of the 5{prime}-terminus of one intron. That sequence was used to design SULT1C1 gene-specific primers that were used to perform the PCR with DNA from human/rodent somatic cell hybrids to demonstrate that the gene was located on chromosome 2. PCR amplifications performed with human chromosome 2/rodent hybrid cell DNA as template sublocalized SULT1C1 to a region between bands 2q11.1 and 2q11.2. 14 refs., 2 figs.

  5. High activity and low temperature optima of extracellular enzymes in Arctic sediments: implications for carbon cycling by heterotrophic microbial communities

    Arnosti, C.; Jørgensen, BB

    2003-01-01

    (chondroitin sulfate, fucoidan, xylan and pullulan) to determine the temperature-activity responses of hydrolysis of a related class of compounds. All 4 enzyme activities showed similarly low temperature optima in the range of 15 to 18degreesC. These temperature optima are considerably lower than most previous...

  6. A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis

    Siegel, Gabriele; Obernosterer, Gregor; Fiore, Roberto;

    2009-01-01

    The microRNA pathway has been implicated in the regulation of synaptic protein synthesis and ultimately in dendritic spine morphogenesis, a phenomenon associated with long-lasting forms of memory. However, the particular microRNAs (miRNAs) involved are largely unknown. Here we identify specific m...

  7. A Survey of Soil Enzyme Activities along Major Roads in Beijing: The Implications for Traffic Corridor Green Space Management.

    Li, Tianxin; Meng, Linglong; Herman, Uwizeyimana; Lu, Zhongming; Crittenden, John

    2015-10-08

    Soil quality is critical to the management of urban green space, in particular, along traffic corridors where traffic-related air pollution is significant. Soil quality can be evaluated by soil enzyme activities, which show quick responses to both natural and anthropogenic disturbances. In this study, we investigated three soil enzyme activities (i.e., dehydrogenase, catalase and urease) along the major roads in urban areas of Beijing. Results show the activities of dehydrogenase, catalase and urease in urban samples were 58.8%, 68.2% and 48.5% less than the rural sample, respectively. The content of fluorescent amino acids as indicators of microbial activities was also consistently lower in urban samples than the rural. We observed two times greater exposure of particulate material along the roadsides in urban areas than rural areas. Although traffic air pollutants provide some nutrient sources to stimulate the URE activity, the exposure to traffic-related air pollution leads to the substantial decrease in enzyme activities. There were significant negative correlations for exposure to PM10 with DHA (r = -0.8267, p = 0.0017) and CAT (r = -0.89, p = 0.0002) activities. For the urban soils URE activity increased with the increasing of PM. We conclude that the degraded soil quality can negatively affect the target of developing plants and green spaces along the traffic corridors to mitigate the traffic impact. This study suggests the investigation of integrated strategies to restore the soil quality, reinforce the ecological service functions of green spaces along the traffic corridors and reduce the traffic pollutants.

  8. Genes implicated in thiopurine-induced toxicity: Comparing TPMT enzyme activity with clinical phenotype and exome data in a paediatric IBD cohort

    Coelho, Tracy; Andreoletti, Gaia; Ashton, James J.; Batra, Akshay; Afzal, Nadeem Ahmad; Gao, Yifang; Williams, Anthony P.; Beattie, Robert M.; Ennis, Sarah

    2016-01-01

    The aim of our study was to assess the utility of next generation sequencing (NGS) for predicting toxicity and clinical response to thiopurine drugs in paediatric patients with inflammatory bowel disease. Exome data for 100 patients were assessed against biochemically measured TPMT enzyme activity, clinical response and adverse effects. The TPMT gene and a panel of 15 other genes implicated in thiopurine toxicity were analysed using a gene based statistical test (SKAT-O test). Nine patients out of 100 (Crohn’s disease- 67, ulcerative colitis- 23 and IBDU-10) had known TPMT mutations associated with deficient enzyme activity. A novel and a highly pathogenic TPMT variant not detectable through standard genotyping, was identified through NGS in an individual intolerant to thiopurines. Of the 14 patients intolerant to thiopurines, NGS identified deleterious TPMT variants in 5 individuals whereas the biochemical test identified 8 individuals as intolerant (sensitivity 35.7% and 57.14%; specificity 93.75% and 50% respectively). SKAT-O test identified a significant association between MOCOS gene and TPMT activity (p = 0.0015), not previously reported. Although NGS has the ability to detect rare or novel variants not otherwise identified through standard genotyping, it demonstrates no clear advantage over the biochemical test in predicting toxicity in our modest cohort. PMID:27703193

  9. Convergent evidences from human and animal studies implicate angiotensin I-converting enzyme activity in cognitive performance in schizophrenia

    Gadelha, A; Vendramini, A M; Yonamine, C M; Nering, M; Berberian, A; Suiama, M A; Oliveira, V; Lima-Landman, M T; Breen, G; Bressan, R A; Abílio, V; Hayashi, M A F

    2015-01-01

    In schizophrenia (SCZ), higher angiotensin I-converting enzyme (ACE) levels have been reported in patient's blood and cerebrospinal fluid (CSF). Hereby, we propose to explore whether the ACE activity levels are associated to cognitive performance in SCZ. Seventy-two patients with SCZ or schizoaffective disorder diagnosis, and 69 healthy controls (HCs) underwent a cognitive battery with parallel collection of peripheral blood samples to measure ACE activity. Significant higher ACE activity levels were confirmed in the plasma of SCZ patients compared with HCs (Student's t=−5.216; Pmodel was 0.343. This result was evident only comparing extreme groups for ACE activity, when splitting the sample in three groups with similar number of subjects. To clarify this finding, we performed an evaluation of the cognitive performance of transgenic mice with three copies of ACE gene in novel object recognition (NOR) test, which showed that such animals presented impairment in NOR (Pmodel suggest both the association of ACE to cognitive deficits in SCZ. This finding may support the evaluation of novel treatment protocols and/or of innovative drugs for specific intervention of cognitive deficits in SCZ envisioning concomitant ACE activity and behavior evaluations. PMID:26645626

  10. Blood Test: Hemoglobin A1C

    ... the hemoglobin A1c test to determine if your child's diabetes management plan needs to be adjusted. Typically the ... the risk of developing long-term complications of diabetes, which can include ... needed for this test. Having your child wear a T-shirt or short-sleeved shirt ...

  11. General false positive ELISA reactions in visceral leishmaniasis. Implications for the use of enzyme immunoassay analyses in tropical Africa.

    Elshafie, Amir I; Mullazehi, Mohammed; Rönnelid, Johan

    2016-04-01

    Leishmaniasis is a neglected disease in tropical countries. Clinical and laboratory features may mimic autoimmune diseases and this can complicate the Leishmania diagnosis. Due to our previous investigation for false anti-CCP2 reactivity in Leishmania-infected subjects and our interest in immunity against the joint-specific collagen type II (CII) in rheumatoid arthritis (RA) we investigated the same cohort for anti-CII antibodies. We found elevated anti-CII reactivity in Leishmania-infected patients as compared to controls. When anti-CII OD values were compared with BSA-blocked control plates we found higher reactivity against BSA than in CII-coated plates in many Leishmania-infected patients. The percentage of such false positive anti-CII reactions increased with inflammatory activity, and was found in almost all Leishmania patients with highly active inflammatory disease, but was as low in Sudanese healthy controls as well as among Swedish RA patients. The correlation coefficients between false positive anti-CII and anti-CCP2 measured with a commercial ELISA were highest for patients with the most inflammatory disease but non-significant for Sudanese controls and Swedish RA patients, arguing that our findings may have general implications for ELISA measurements in leishmaniasis. ELISA investigations in areas endemic for leishmaniasis might benefit from individual-specific control wells for each serum sample. This approach might also be applicable to other geographical areas or patient groups with high incidence of inflammatory and infectious diseases.

  12. Photoaffinity labeling of Ras converting enzyme using peptide substrates that incorporate benzoylphenylalanine (Bpa) residues: improved labeling and structural implications.

    Kyro, Kelly; Manandhar, Surya P; Mullen, Daniel; Schmidt, Walter K; Distefano, Mark D

    2011-12-15

    Rce1p catalyzes the proteolytic trimming of C-terminal tripeptides from isoprenylated proteins containing CAAX-box sequences. Because Rce1p processing is a necessary component in the Ras pathway of oncogenic signal transduction, Rce1p holds promise as a potential target for therapeutic intervention. However, its mechanism of proteolysis and active site have yet to be defined. Here, we describe synthetic peptide analogues that mimic the natural lipidated Rce1p substrate and incorporate photolabile groups for photoaffinity-labeling applications. These photoactive peptides are designed to crosslink to residues in or near the Rce1p active site. By incorporating the photoactive group via p-benzoyl-l-phenylalanine (Bpa) residues directly into the peptide substrate sequence, the labeling efficiency was substantially increased relative to a previously-synthesized compound. Incorporation of biotin on the N-terminus of the peptides permitted photolabeled Rce1p to be isolated via streptavidin affinity capture. Our findings further suggest that residues outside the CAAX-box sequence are in contact with Rce1p, which has implications for future inhibitor design.

  13. SREBP-1c Gene Silencing can Decrease Lipid Deposits in Bovine Hepatocytes Cultured in Vitro

    Qinghua Deng

    2014-05-01

    Full Text Available Background: Fatty liver is a major metabolic disorder that occurs during early lactation in high-producing dairy cows. Sterol regulatory element-binding protein-1c (SREBP-1c is an important transcription factor that regulates lipid synthesis by regulating the expression of lipid metabolism genes. Methods: In this study, we reduced the expression of SREBP-1c by adenovirus-mediated SREBP-1c with a low expression vector (AD-GFP-SREBP-1c to study the effects of SREBP-1c on lipid deposits in bovine hepatocytes. The expression levels and enzyme activities of SERBP-1c and its target genes were determined by real-time PCR, western blot, and ELISA. Results: These results showed that Ad-GFP-SREBP-1c could inhibit SREBP-1c expression. The expression of the lipid synthesis enzyme acetyl-CoA carboxylase (ACC was down-regulated. The expression levels of the lipid oxidation enzymes long-chain fatty acyl-COA synthetase (ACSL-1, carnitine palmitoyltransferase І (CPT-І, carnitine palmitoyltransferase II (CPT- II, and β-hydroxyacyl-CoA-DH (HADH were significantly elevated. Furthermore, the expression levels of factors involved in the assembly and transport of very low-density lipoproteins (VLDLs, such as apolipoprotein B100 (ApoB, apolipoprotein E (ApoE, and microsomal triglyceride transfer protein (MTTP were decreased comparison with the negative control and the blank control groups, but the low-density lipoprotein receptor (LDLR was elevated. The concentrations of TG (triglyceride and VLDL were also reduced. Conclusion: These data suggest that low SREBP-1c expression can decrease lipid synthesis, increase lipid oxidation, and decrease the TG and VLDL content in bovine hepatocytes.

  14. Modulation of γ-secretase activity by multiple enzyme-substrate interactions: implications in pathogenesis of Alzheimer's disease.

    Zeljko M Svedružić

    Full Text Available BACKGROUND: We describe molecular processes that can facilitate pathogenesis of Alzheimer's disease (AD by analyzing the catalytic cycle of a membrane-imbedded protease γ-secretase, from the initial interaction with its C99 substrate to the final release of toxic Aβ peptides. RESULTS: The C-terminal AICD fragment is cleaved first in a pre-steady-state burst. The lowest Aβ42/Aβ40 ratio is observed in pre-steady-state when Aβ40 is the dominant product. Aβ42 is produced after Aβ40, and therefore Aβ42 is not a precursor for Aβ40. The longer more hydrophobic Aβ products gradually accumulate with multiple catalytic turnovers as a result of interrupted catalytic cycles. Saturation of γ-secretase with its C99 substrate leads to 30% decrease in Aβ40 with concomitant increase in the longer Aβ products and Aβ42/Aβ40 ratio. To different degree the same changes in Aβ products can be observed with two mutations that lead to an early onset of AD, ΔE9 and G384A. Four different lines of evidence show that γ-secretase can bind and cleave multiple substrate molecules in one catalytic turnover. Consequently depending on its concentration, NotchΔE substrate can activate or inhibit γ-secretase activity on C99 substrate. Multiple C99 molecules bound to γ-secretase can affect processive cleavages of the nascent Aβ catalytic intermediates and facilitate their premature release as the toxic membrane-imbedded Aβ-bundles. CONCLUSIONS: Gradual saturation of γ-secretase with its substrate can be the pathogenic process in different alleged causes of AD. Thus, competitive inhibitors of γ-secretase offer the best chance for a successful therapy, while the noncompetitive inhibitors could even facilitate development of the disease by inducing enzyme saturation at otherwise sub-saturating substrate. Membrane-imbedded Aβ-bundles generated by γ-secretase could be neurotoxic and thus crucial for our understanding of the amyloid hypothesis and AD

  15. Implication of Xenobiotic Metabolizing Enzyme gene (CYP2E1, CYP2C19, CYP2D6, mEH and NAT2 Polymorphisms in Breast Carcinoma

    Gabbouj Sallouha

    2008-04-01

    Full Text Available Abstract Background Xenobiotic Metabolizing Enzymes (XMEs contribute to the detoxification of numerous cancer therapy-induced products. This study investigated the susceptibility and prognostic implications of the CYP2E1, CYP2C19, CYP2D6, mEH and NAT2 gene polymorphisms in breast carcinoma patients. Methods The authors used polymerase chain reaction and restriction enzyme digestion to characterize the variation of the CYP2E1, CYP2C19, CYP2D6, mEH and NAT2 gene in a total of 560 unrelated subjects (246 controls and 314 patients. Results The mEH (C/C mutant and the NAT2 slow acetylator genotypes were significantly associated with breast carcinoma risk (p = 0.02; p = 0.01, respectively. For NAT2 the association was more pronounced among postmenopausal patients (p = 0.006. A significant association was found between CYP2D6 (G/G wild type and breast carcinoma risk only in postmenopausal patients (p = 0.04. Association studies of genetic markers with the rates of breast carcinoma specific overall survival (OVS and the disease-free survival (DFS revealed among all breast carcinoma patients no association to DFS but significant differences in OVS only with the mEH gene polymorphisms (p = 0.02. In addition, the mEH wild genotype showed a significant association with decreased OVS in patients with axillary lymph node-negative patients (p = 0.03 and with decreasesd DFS in patients with axillary lymph node-positive patients (p = 0.001. However, the NAT2 intermediate acetylator genotype was associated with decreased DFS in axillary lymph node-negative patients. Conclusion The present study may prove that polymorphisms of some XME genes may predict the onset of breast carcinoma as well as survival after treatment.

  16. [Evaluation of HbA1c using different methods in haemoglobin variant, Hb J-Bangkok].

    Sawaragi, Wakana; Shibuya, Hitoshi; Yasuda, Keiko; Suzuki, Haruki; Shimizu, Chikara; Matsuno, Kazuhiko

    2009-05-01

    A 31-year-old Japanese man with haemoglobin variant, Hb J-Bangkok [beta56 (D7) Gly-->Asp], was found by discrepant values between HbA1c and glycated-albumin. We measured HbA1c using three different methods, HPLC, enzyme assay and turbidimetric immunoassay. HbA1c value measured by HPLC was much lower than those by others. Furthermore, we estimated calculated glyco-haemoglobin value measured by high-resolution HPLC, revealing that HbA1c values measured by enzyme assay and turbidimetric immunoassay were comparable with calculated value. When measuring HbA1c value in haemoglobin variant, Hb J Bangkok, enzyme assay and turbidimetric immunoassay are useful methods.

  17. Pectic enzymes

    Benen, J.A.E.; Voragen, A.G.J.; Visser, J.

    2003-01-01

    The pectic enzymes comprise a diverse group of enzymes. They consist of main-chain depolymerases and esterases active on methyl- and acetylesters of galacturonosyl uronic acid residues. The depolymerizing enzymes comprise hydrolases as wel as lyases

  18. Enzyme assays.

    Reymond, Jean-Louis; Fluxà, Viviana S; Maillard, Noélie

    2009-01-07

    Enzyme assays are analytical tools to visualize enzyme activities. In recent years a large variety of enzyme assays have been developed to assist the discovery and optimization of industrial enzymes, in particular for "white biotechnology" where selective enzymes are used with great success for economically viable, mild and environmentally benign production processes. The present article highlights the aspects of fluorogenic and chromogenic substrates, sensors, and enzyme fingerprinting, which are our particular areas of interest.

  19. Hemoglobin variants detected by hemoglobin A1c (HbA1c) analysis and the effects on HbA1c measurements

    Nasir, Nadzimah Mohd; Thevarajah, M; Yean, Chew Yee

    2010-01-01

    Background: Hemoglobin (Hb) A1c is a tool widely used to monitor long-term glycemic control in diabetic patients. The objective of our study is to compare the HbA1c values measured on high performance liquid chromatography (HPLC) and immunoassay in patients who were detected to have hemoglobin variant after HbA1c analysis. Materials and Methods: We compared the HbA1c values measured using the Arkray Adams A1c HA-8160 (HPLC method) and Roche Cobas Integra (immunoturbidimetric method) from diab...

  20. Analysis list: Jmjd1c [Chip-atlas[Archive

    Full Text Available Jmjd1c Pluripotent stem cell + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Jmjd1...c.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Jmjd1c.5.tsv http://dbarchive.biosc...iencedbc.jp/kyushu-u/mm9/target/Jmjd1c.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Jmjd1c.Plu

  1. CONFIGURATION DEVELOPMENT ON THE PLATFORM 1C FOR ENTERPRISE AUTOMATION

    О.L. LIAKHOV; T.A. DMYTRENKO; A.О. TVERDOKHLIB; T.M. DERKACH; A.O. DMYTRENKO

    2015-01-01

    In this paper, the results of configuration development on the platform 1C for limited liability companies were presented. The object of study is the development process configuration platform 1C. The purpose of the study is the technological platform “1C: Enterprise”. The tasks included analyzing the technological platform “1C: Enterprise”, comparing the most popular ERP-systems, configurator devel-opment on the platform 1C. Such research methods as structured programming techniques and meth...

  2. Analysis list: Myo1c [Chip-atlas[Archive

    Full Text Available Myo1c Embryonic fibroblast + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/My...o1c.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Myo1c.5.tsv http://dbarchive.bioscienc...edbc.jp/kyushu-u/mm9/target/Myo1c.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Myo1c.Embryonic

  3. Anthracycline resistance mediated by reductive metabolism in cancer cells: The role of aldo-keto reductase 1C3

    Hofman, Jakub; Malcekova, Beata; Skarka, Adam; Novotna, Eva; Wsol, Vladimir, E-mail: wsol@faf.cuni.cz

    2014-08-01

    Pharmacokinetic drug resistance is a serious obstacle that emerges during cancer chemotherapy. In this study, we investigated the possible role of aldo-keto reductase 1C3 (AKR1C3) in the resistance of cancer cells to anthracyclines. First, the reducing activity of AKR1C3 toward anthracyclines was tested using incubations with a purified recombinant enzyme. Furthermore, the intracellular reduction of daunorubicin and idarubicin was examined by employing the transfection of A549, HeLa, MCF7 and HCT 116 cancer cells with an AKR1C3 encoding vector. To investigate the participation of AKR1C3 in anthracycline resistance, we conducted MTT cytotoxicity assays with these cells, and observed that AKR1C3 significantly contributes to the resistance of cancer cells to daunorubicin and idarubicin, whereas this resistance was reversible by the simultaneous administration of 2′-hydroxyflavanone, a specific AKR1C3 inhibitor. In the final part of our work, we tracked the changes in AKR1C3 expression after anthracycline exposure. Interestingly, a reciprocal correlation between the extent of induction and endogenous levels of AKR1C3 was recorded in particular cell lines. Therefore, we suggest that the induction of AKR1C3 following exposure to daunorubicin and idarubicin, which seems to be dependent on endogenous AKR1C3 expression, eventually might potentiate an intrinsic resistance given by the normal expression of AKR1C3. In conclusion, our data suggest a substantial impact of AKR1C3 on the metabolism of daunorubicin and idarubicin, which affects their pharmacokinetic and pharmacodynamic behavior. In addition, we demonstrate that the reduction of daunorubicin and idarubicin, which is catalyzed by AKR1C3, contributes to the resistance of cancer cells to anthracycline treatment. - Highlights: • Metabolism of anthracyclines by AKR1C3 was studied at enzyme and cellular levels. • Anthracycline resistance mediated by AKR1C3 was demonstrated in cancer cells. • Induction of AKR1C3

  4. Particle-size fractions-dependent extracellular enzyme activity in sediments and implications for resource allocation in a subtropical mangrove ecosystem

    L. Luo

    2015-01-01

    Full Text Available The distribution of extracellular enzyme activities in particle-size fractions of sediments was investigated in a subtropical mangrove ecosystem. Five enzymes involved in carbon (C, nitrogen (N, and phosphorus (P cycling were analyzed in the sand, silt, and clay of sediments. Among these fractions, the highest activities of phenol oxidase (PHO, β-D glucosidase (GLU, and N-acetyl-glucosiminidase (NAG were found in sand, and greater than bulk sediments of both intertidal zone (IZ and mangrove forest (MG. This result implied that sand fractions might protect selective enzymes through the adsorption without affecting their activities. Additionally, the enzyme-based resource allocation in various particle-size fractions demonstrated that nutirents availability varied with different particle-size fractions and only sand fraction of MG with highest total C showed high N and P availability among fractions. Besides, the analysis between elemental contents and enzymes activities in particle-size fractions suggested that enzymes could monitor the changes of nutrients availability and be good indicators of ecosystem responses to environmental changes. Thus, these results provided a means to assess the availability of different nutrients (C, N, and P during decomposition of sediment organic matter (SOM, and thus helping to better manage the subtropical mangrove ecosystems to sequester C into SOM.

  5. Analysis list: JMJD1C [Chip-atlas[Archive

    Full Text Available JMJD1C Blood + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/JMJD1C.1....tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/JMJD1C.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/JM...JD1C.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/JMJD1C.Blood.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Blood.gml ...

  6. Measuring the Enzyme Activity of Arabidopsis Deubiquitylating Enzymes.

    Kalinowska, Kamila; Nagel, Marie-Kristin; Isono, Erika

    2016-01-01

    Deubiquitylating enzymes, or DUBs, are important regulators of ubiquitin homeostasis and substrate stability, though the molecular mechanisms of most of the DUBs in plants are not yet understood. As different ubiquitin chain types are implicated in different biological pathways, it is important to analyze the enzyme characteristic for studying a DUB. Quantitative analysis of DUB activity is also important to determine enzyme kinetics and the influence of DUB binding proteins on the enzyme activity. Here, we show methods to analyze DUB activity using immunodetection, Coomassie Brilliant Blue staining, and fluorescence measurement that can be useful for understanding the basic characteristic of DUBs.

  7. Using simple molecular orbital calculations to predict disease: fast DFT methods applied to enzymes implicated in PKU, Parkinson's disease and Obsessive Compulsive Disorder

    Hofto, Laura; Hofto, Meghan; Cross, Jessica; Cafiero, Mauricio

    2007-09-01

    Many diseases can be traced to point mutations in the DNA coding for specific enzymes. These point mutations result in the change of one amino acid residue in the enzyme. We have developed a model using simple molecular orbital calculations which can be used to quantitatively determine the change in interaction between the enzyme's active site and necessary ligands upon mutation. We have applied this model to three hydroxylase proteins: phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase, and we have obtained excellent correlation between our results and observed disease symptoms. Furthermore, we are able to use this agreement as a baseline to screen other mutations which may also cause onset of disease symptoms. Our focus is on systems where the binding is due largely to dispersion, which is much more difficult to model inexpensively than pure electrostatic interactions. Our calculations are run in parallel on a sixteen processor cluster of 64-bit Athlon processors.

  8. Deletion of psychiatric risk gene Cacna1c impairs hippocampal neurogenesis in cell-autonomous fashion.

    Völkening, Bianca; Schönig, Kai; Kronenberg, Golo; Bartsch, Dusan; Weber, Tillmann

    2017-05-01

    Ca(2+) is a universal signal transducer which fulfills essential functions in cell development and differentiation. CACNA1C, the gene encoding the alpha-1C subunit (i.e., Cav 1.2) of the voltage-dependent l-type calcium channel (LTCC), has been implicated as a risk gene in a variety of neuropsychiatric disorders. To parse the role of Cav 1.2 channels located on astrocyte-like stem cells and their descendants in the development of new granule neurons, we created Tg(GLAST-CreERT2) /Cacna1c(fl/fl) /RCE:loxP mice, a transgenic tool that allows cell-type-specific inducible deletion of Cacna1c. The EGFP reporter was used to trace the progeny of recombined type-1 cells. FACS-sorted Cacna1c-deficient neural precursor cells from the dentate gyrus showed reduced proliferative activity in neurosphere cultures. Moreover, under differentiation conditions, Cacna1c-deficient NPCs gave rise to fewer neurons and more astroglia. Similarly, under basal conditions in vivo, Cacna1c gene deletion in type-1 cells decreased type-1 cell proliferation and reduced the neuronal fate-choice decision of newly born cells, resulting in reduced net hippocampal neurogenesis. Unexpectedly, electroconvulsive seizures completely compensated for the proliferation deficit of Cacna1c deficient type-1 cells, indicating that there must be Cav 1.2-independent mechanisms of controlling proliferation related to excitation. In the aggregate, this is the first report demonstrating the presence of functional L-type 1.2 channels on type-1 cells. Cav 1.2 channels promote type-1 cell proliferation and push the glia-to-neuron ratio in the direction of a neuronal fate choice and subsequent neuronal differentiation. Cav 1.2 channels expressed on NPCs and their progeny possess the ability to shape neurogenesis in a cell-autonomous fashion.

  9. Structure of Type IIL Restriction-Modification Enzyme MmeI in Complex with DNA Has Implications for Engineering New Specificities.

    Callahan, Scott J; Luyten, Yvette A; Gupta, Yogesh K; Wilson, Geoffrey G; Roberts, Richard J; Morgan, Richard D; Aggarwal, Aneel K

    2016-04-01

    The creation of restriction enzymes with programmable DNA-binding and -cleavage specificities has long been a goal of modern biology. The recently discovered Type IIL MmeI family of restriction-and-modification (RM) enzymes that possess a shared target recognition domain provides a framework for engineering such new specificities. However, a lack of structural information on Type IIL enzymes has limited the repertoire that can be rationally engineered. We report here a crystal structure of MmeI in complex with its DNA substrate and an S-adenosylmethionine analog (Sinefungin). The structure uncovers for the first time the interactions that underlie MmeI-DNA recognition and methylation (5'-TCCRAC-3'; R = purine) and provides a molecular basis for changing specificity at four of the six base pairs of the recognition sequence (5'-TCCRAC-3'). Surprisingly, the enzyme is resilient to specificity changes at the first position of the recognition sequence (5'-TCCRAC-3'). Collectively, the structure provides a basis for engineering further derivatives of MmeI and delineates which base pairs of the recognition sequence are more amenable to alterations than others.

  10. Drugs affecting HbA1c levels

    Ranjit Unnikrishnan

    2012-01-01

    Full Text Available Glycated hemoglobin (HbA1c is an important indicator of glycemic control in diabetes mellitus, based on which important diagnostic and therapeutic decisions are routinely made. However, there are several situations in which the level of HbA1c may not faithfully reflect the glycemic control in a given patient. Important among these is the use of certain non-diabetic medications, which can affect the HbA1c levels in different ways. This review focuses on the non-diabetic medications which can inappropriately raise or lower the HbA1c levels, and the postulated mechanisms for the same.

  11. The zebrafish orthologue of the dyslexia candidate gene DYX1C1 is essential for cilia growth and function.

    Gayathri Chandrasekar

    Full Text Available DYX1C1, a susceptibility gene for dyslexia, encodes a tetratricopeptide repeat domain containing protein that has been implicated in neuronal migration in rodent models. The developmental role of this gene remains unexplored. To understand the biological function(s of zebrafish dyx1c1 during embryonic development, we cloned the zebrafish dyx1c1 and used morpholino-based knockdown strategy. Quantitative real-time PCR analysis revealed the presence of dyx1c1 transcripts in embryos, early larval stages and in a wide range of adult tissues. Using mRNA in situ hybridization, we show here that dyx1c1 is expressed in many ciliated tissues in zebrafish. Inhibition of dyx1c1 produced pleiotropic phenotypes characteristically associated with cilia defects such as body curvature, hydrocephalus, situs inversus and kidney cysts. We also demonstrate that in dyx1c1 morphants, cilia length is reduced in several organs including Kupffer's vesicle, pronephros, spinal canal and olfactory placode. Furthermore, electron microscopic analysis of cilia in dyx1c1 morphants revealed loss of both outer (ODA and inner dynein arms (IDA that have been shown to be required for cilia motility. Considering all these results, we propose an essential role for dyx1c1 in cilia growth and function.

  12. Exposure to leachate from municipal battery recycling site: implication as key inhibitor of steroidogenic enzymes and risk factor of prostate damage in rats.

    Akintunde, Jacob K; Oboh, G

    2013-01-01

    Few or no studies have measured the effect of short- and long-term exposure to industrial leachate. Mature male Wistar strain albino rats (175-220 g) underwent sub-chronic exposure to leachate from the Elewi Odo municipal battery recycling site (EOMABRL) via oral administration for a period of 60 days at different doses (20%, 40%, 60%, 80%, and 100%) per kilogram of body weight to evaluate the toxic effects of the leachate on male reproductive function using steroidogenic enzymes and biomarkers of prostate damage. Control groups were treated equally but were given distilled water instead of the leachate. After the treatment periods, results showed that the treatment induced systemic toxicity at the doses tested by causing a significant (precycling site induces sub-chronic testicular toxicity by inhibiting key steroidogenic enzymes and activating key markers linked with prostate damage/cancer in rats.

  13. CDKN1C/p57kip2 is a candidate tumor suppressor gene in human breast cancer

    Pistey Robert

    2008-03-01

    Full Text Available Abstract Background CDKN1C (also known as p57KIP2 is a cyclin-dependent kinase inhibitor previously implicated in several types of human cancer. Its family members (CDKN1A/p21CIP1 and B/p27KIP1 have been implicated in breast cancer, but information about CDKN1C's role is limited. We hypothesized that decreased CDKN1C may be involved in human breast carcinogenesis in vivo. Methods We determined rates of allele imbalance or loss of heterozygosity (AI/LOH in CDKN1C, using an intronic polymorphism, and in the surrounding 11p15.5 region in 82 breast cancers. We examined the CDKN1C mRNA level in 10 cancers using quantitative real-time PCR (qPCR, and the CDKN1C protein level in 20 cancers using immunohistochemistry (IHC. All samples were obtained using laser microdissection. Data were analyzed using standard statistical tests. Results AI/LOH at 11p15.5 occurred in 28/73 (38% informative cancers, but CDKN1C itself underwent AI/LOH in only 3/16 (19% cancers (p = ns. In contrast, CDKN1C mRNA levels were reduced in 9/10 (90% cancers (p Conclusion CDKN1C is expressed in normal epithelium of most breast cancer cases, mainly in the myothepithelial layer. This expression decreases, at both the mRNA and protein level, in the large majority of breast cancers, and does not appear to be mediated by AI/LOH at the gene. Thus, CDKN1C may be a breast cancer tumor suppressor.

  14. 7 CFR 1c.117 - Documentation of informed consent.

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Documentation of informed consent. 1c.117 Section 1c... Documentation of informed consent. (a) Except as provided in paragraph (c) of this section, informed consent... wants documentation linking the subject with the research, and the subject's wishes will govern; or...

  15. FY-1C BEING THE LONGEST SERVING METSAT IN CHINA

    SunQing

    2004-01-01

    FY-1C, with a designed lifetime of 2 years, has been working on orbit for more than 5 years and its working life is the longest among China's satellites operating on sunsynchronous polar orbit. FY-1C meteorological satellite, developed by Shanghai Academy of Spaceflight Technology (SAST), was launched from Taiyuan Satellite Launch Center by LM-4B launch vehicle on May 10,

  16. ROBOTIC SYNTHESIS OF L-[1-C-11]TYROSINE

    LUURTSEMA, G; MEDEMA, J; ELSINGA, PH; VISSER, GM; VAALBURG, W

    1994-01-01

    L-[1-C-11]tyrosine promises to become an important tracer for determination of the protein synthesis rate (PSR) in tumor tissue and brain. The commercially available Anatech RB-86 robotic system is utilized for the automation of the L-[1-C-11]tyrosine production via the isocyanide method as reported

  17. CDKN1C mutations: two sides of the same coin.

    Eggermann, Thomas; Binder, Gerhard; Brioude, Frédéric; Maher, Eamonn R; Lapunzina, Pablo; Cubellis, Maria Vittoria; Bergadá, Ignacio; Prawitt, Dirk; Begemann, Matthias

    2014-11-01

    Cyclin-dependent kinase (CDK)-inhibitor 1C (CDKN1C) negatively regulates cellular proliferation and it has been shown that loss-of-function mutations in the imprinted CDKN1C gene (11p15.5) are associated with the overgrowth disorder Beckwith-Wiedemann syndrome (BWS). With recent reports of gain-of-function mutations of the PCNA domain of CDKN1C in growth-retarded patients with IMAGe syndrome or Silver-Russell syndrome (SRS), its key role for growth has been confirmed. Thereby, the last gap in the spectrum of molecular alterations in 11p15.5 in growth-retardation and overgrowth syndromes could be closed. Recent functional studies explain the strict association of CDKN1C mutations with clinically opposite phenotypes and thereby contribute to our understanding of the function and regulation of the gene in particular and epigenetic regulation in general.

  18. Predicting tumor responses to mitomycin C on the basis of DT-diaphorase activity or drug metabolism by tumor homogenates: implications for enzyme-directed bioreductive drug development.

    Phillips, R M; Burger, A M; Loadman, P M; Jarrett, C M; Swaine, D J; Fiebig, H H

    2000-11-15

    Mitomycin C (MMC) is a clinically used anticancer drug that is reduced to cytotoxic metabolites by cellular reductases via a process known as bioreductive drug activation. The identification of key enzymes responsible for drug activation has been investigated extensively with the ultimate aim of tailoring drug administration to patients whose tumors possess the biochemical machinery required for drug activation. In the case of MMC, considerable interest has been centered upon the enzyme DT-diaphorase (DTD) although conflicting reports of good and poor correlations between enzyme activity and response in vitro and in vivo have been published. The principle aim of this study was to provide a definitive answer to the question of whether tumor response to MMC could be predicted on the basis of DTD activity in a large panel of human tumor xenografts. DTD levels were measured in 45 human tumor xenografts that had been characterized previously in terms of their sensitivity to MMC in vitro and in vivo (the in vivo response profile to MMC was taken from work published previously). A poor correlation between DTD activity and antitumor activity in vitro as well as in vivo was obtained. This study also assessed the predictive value of an alternative approach based upon the ability of tumor homogenates to metabolize MMC. This approach is based on the premise that the overall rate of MMC metabolism may provide a better indicator of response than single enzyme measurements. MMC metabolism was evaluated in tumor homogenates (clarified by centrifugation at 1000 x g for 1 min) by measuring the disappearance of the parent compound by HPLC. In responsive [T/C 50%) tumors, the mean half life of MMC was 75+/-48.3 and 280+/-129.6 min, respectively. The difference between the two groups was statistically significant (P < 0.005). In conclusion, these results unequivocally demonstrate that response to MMC in vivo cannot be predicted on the basis of DTD activity. Measurement of MMC

  19. Novel six-nucleotide deletion in the hepatic fructose-1,6-bisphosphate aldolase gene in a patient with hereditary fructose intolerance and enzyme structure-function implications.

    Santamaria, R; Vitagliano, L; Tamasi, S; Izzo, P; Zancan, L; Zagari, A; Salvatore, F

    1999-01-01

    Hereditary fructose intolerance (HFI) is an autosomal recessive human disease that results from the deficiency of the hepatic aldolase isoenzyme. Affected individuals will succumb to the disease unless it is readily diagnosed and fructose eliminated from the diet. Simple and non-invasive diagnosis is now possible by direct DNA analysis that scans for known and unknown mutations. Using a combination of several PCR-based methods (restriction enzyme digestion, allele specific oligonucleotide hybridisation, single strand conformation analysis and direct sequencing) we identified a novel six-nucleotide deletion in exon 6 of the aldolase B gene (delta 6ex6) that leads to the elimination of two amino acid residues (Leu182 and Val183) leaving the message inframe. The three-dimensional structural alterations induced in the enzyme by delta 6ex6 have been elucidated by molecular graphics analysis using the crystal structure of the rabbit muscle aldolase as reference model. These studies showed that the elimination of Leu182 and Val183 perturbs the correct orientation of adjacent catalytic residues such as Lys146 and Glu187.

  20. Potential interaction between the GARS-AIRS-GART Gene and CP2/LBP-1c/LSF transcription factor in Down syndrome-related Alzheimer disease.

    Banerjee, Disha; Nandagopal, Krishnadas

    2007-12-01

    (1) GARS-AIRS-GART is an important candidate gene in studies of Down syndrome (DS)-related Alzheimer's disease (AD), due to its chromosomal localization (21q22.1) in the Down syndrome critical region, involvement in de novo purine biosynthesis, and over-expression in DS brain. The aim of this study was to identify factor(s) likely to enhance transcription of GARS-AIRS-GART in DS-related AD. (2) Based on a bio-informatics approach, the PromoterInspector, Promoter Scan II, and EBI toolbox CpG plot software programs were used to identify GARS-AIRS-GART sequences important for gene transcription. Transcription factor binding motifs within these regions were mapped with the help of the MatInspector and TFSEARCH programs. Factors implicated in neurodevelopment or neurodegeneration were the focus of attention, and mining of human (T1Dbase) and murine (GNF) expression databases revealed information on the regional distribution of these factors and their relative abundance vis-a-vis GARS-AIRS-GART. (3) The Leader-binding protein 1-c (LBP-1c/CP2/LSF) emerged as a promising candidate from these studies, as MatInspector and TFSEARCH analyses revealed a total of four CP2 binding sites with potential for functional interaction(s) within the promoter and CpG islands of GARS-AIRS-GART. Furthermore, two of these sites harbor sequences for methylation-sensitive restriction enzymes, which suggest that methylation status may, in part, regulate CP2-mediated transcription of GARS-AIRS-GART. A search of T1Dbase and GNF expression databases reveals co-expression of CP2 and GARS-AIRS-GART in brain regions relevant to DS-related AD. (4) The virtual screen identified CP2/LBP-1c/LSF as a factor that likely mediates enhanced transcription of GARS-AIRS-GART in DS-related AD.

  1. Hemoglobin A1c: Standardizacija “zlatnog standarda”

    2006-01-01

    Hemoglobin A1c (HbA1c) je u proteklih 30 godina primjene postao "zlatnim standardom" u kliničkom praćenju šećerne bolesti. Dobra kontrola glikemije, izražena kroz koncentraciju HbA1c ≤7%, danas je klinički normativ kroz koji se procjenjuje djelotvornost terapije i rizik pojave komplikacija šećerne bolesti i glavna tema komunikacije između dijabetologa i pacijenata. Raznovrsna i nestandardizirana metodologija, varijabilnost kemijskih entiteta nastalih glikacijom molekule hemoglobina i nepos...

  2. RANTES In1.1C allele polymorphisms in 13 Chinese ethnic populations

    QIAN Yuan; SUN Hao; CHU Jia-you

    2009-01-01

    Background The In1.1C single nucleotide polymorphism (SNP) allele results in reduced RANTES transcription, which is associated with increased frequency of HIV-1 infection, and rapid progression to AIDS among HIV-1-infected individuals. This study aimed to study the mutant frequency and polymorphism of RANTES in Chinese populations.Methods The genotypes of RANTES In1.1C were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) with the digestion of restriction endonuclease Mbo Ⅱ.Results Of the 617 individuals, 290 (47%) were carriers of the RANTES In1.1C allele, 52 of whom were homozygotes,whereas 238 were heterozygotes. The frequency of the RANTES In1.1C allele in those tested individuals was 0.2840.The frequencies of Inl.lC allele vaded from 0.07-0.27 in most of the populations in South-west China except for the two Lisu populations, while the frequencies of In1.1C spans from 0.35 to 0.45 in North-west China. The prevalence of the allele varied substantially between the South-west groups and North-west groups (X2=7.838, P=0.006).Conclusions The prevalence of the RANTES In1.1C allele varies substantially between the South-west groups and North-west groups. There is no significant difference between the groups with different languages, which suggests that language relationship is not consistent with the genetic relationship. These results have important implications for the design, assessment, and implementation of HIV-1 vaccines.

  3. Hemoglobin A1c and arterial and ventricular stiffness in older adults.

    Susan J Zieman

    Full Text Available OBJECTIVE: Arterial and ventricular stiffening are characteristics of diabetes and aging which confer significant morbidity and mortality; advanced glycation endproducts (AGE are implicated in this stiffening pathophysiology. We examined the association between HbA(1c, an AGE, with arterial and ventricular stiffness measures in older individuals without diabetes. RESEARCH DESIGN & METHODS: Baseline HbA(1c was measured in 830 participants free of diabetes defined by fasting glucose or medication use in the Cardiovascular Health Study, a population-based cohort study of adults aged ≥ 65 years. We performed cross-sectional analyses using baseline exam data including echocardiography, ankle and brachial blood pressure measurement, and carotid ultrasonography. We examined the adjusted associations between HbA(1c and multiple arterial and ventricular stiffness measures by linear regression models and compared these results to the association of fasting glucose (FG with like measures. RESULTS: HbA(1c was correlated with fasting and 2-hour postload glucose levels (r = 0.21; p<0.001 for both and positively associated with greater body-mass index and black race. In adjusted models, HbA(1c was not associated with any measure of arterial or ventricular stiffness, including pulse pressure (PP, carotid intima-media thickness, ankle-brachial index, end-arterial elastance, or left ventricular mass (LVM. FG levels were positively associated with systolic, diastolic and PP and LVM. CONCLUSIONS: In this sample of older adults without diabetes, HbA(1c was not associated with arterial or ventricular stiffness measures, whereas FG levels were. The role of AGE in arterial and ventricular stiffness in older adults may be better assessed using alternate AGE markers.

  4. Non-enzymatic modifications of prostaglandin H synthase 1 affect bifunctional enzyme activity - Implications for the sensitivity of blood platelets to acetylsalicylic acid.

    Kassassir, Hassan; Siewiera, Karolina; Talar, Marcin; Stec-Martyna, Emilia; Pawlowska, Zofia; Watala, Cezary

    2016-06-25

    Due to its ability to inhibit the blood platelet PGHS-1, acetylsalicylic acid (ASA, Aspirin(®)) is widely used as a preventive agent in atherothrombotic diseases. However, its beneficial effects seem to be lower in diabetic patients, suggesting that protein glycation may impair effective ASA-mediated acetylation process. On the other hand, it is proposed that ASA can prevent some of the late complications of diabetes by lowering the extent of glycation at protein free amino groups. The aim of this work was to evaluate the extents of non-enzymatic N-glycosylation (glycation) and acetylation of blood platelet PGHS-1 (COX-1) and the competition between glycation and acetylation was investigated in order to demonstrate how these two reactions may compete against platelet PGHS-1. When PGHS-1 was incubated with glycating/acetylating agents (glucose, Glu; 1,6-bisphosphofructose, 1,6-BPF; methylglyoxal, MGO, acetylsalicylic acid, ASA), the enzyme was modified in 13.4 ± 1.6, 5.3 ± 0.5, 10.7 ± 1.2 and 6.4 ± 1.1 mol/mol protein, respectively, and its activity was significantly reduced. The prior glycation/carbonylation of PGHS-1 with Glu, 1,6-BPF or MGO decreased the extent of acetylation from 6.4 ± 1.1 down to 2.5 ± 0.2, 3.6 ± 0.3 and 5.2 ± 0.2 mol/mol protein, respectively, but the enzyme still remained susceptible to the subsequent inhibition of its activity with ASA. When PGHS-1 was first acetylated with ASA and then incubated with glycating/carbonylating agents, we observed the following reductions in the enzyme modifications: from 13.4 ± 1.6 to 8.7 ± 0.6 mol/mol protein for Glu, from 5.3 ± 0.5 to 3.9 ± 0.3 mol/mol protein for 1,6-BPF and from 10.7 ± 1.2 to 7.5 ± 0.5 mol/mol protein for MGO, however subsequent glycation/carbonylation did not significantly affect PGHS-1 function. Overall, our outcomes allow to better understand the structural aspects of the chemical competition between glycation and acetylation of PGHS-1.

  5. Immunochemical Determination of Hemoglobin-A1c Utilizing a Glycated Peptide as Hemoglobin-A1c Analogon

    Stöllner, Daniela; Warsinke, Axel; Stöcklein, Walter; Dölling, Rudolf; Scheller, Frieder

    2001-01-01

    We describe the development of a heterogeneous affinity-matrix based immunoassay for the determination of HbA1c which could in future be applicable to analytical devices. We developed an immunoenzymometric assay (IEMA) where the glycated pentapeptide Val-His-Leu-Thr-Pro (VHLTP) as HbA1c analogon is immobilized either to the surface of a microtiter plate by adsorption or to an amino-modified cellulose membrane by covalent linkage. The immobilized analogon competes together with the HbA1c in...

  6. Neue biosensorische Prinzipien für die Hämoglobin-A1c Bestimmung

    Stöllner, Daniela

    2002-06-01

    mellitus. It is measured as the percentage of total hemoglobin. Up to 5 % HbA1c are considered as normal whereas in diabetic subjects it could be elevated from 5-20 %. In addition to amperometric biosensors for glucose self monitoring which have been successfully applied in diabetes management, biosensors for HbA1c would be an useful supplement for a comprehensive diabetes control. Objective of this work was to develop and compare amperometric biosensors for determination of HbA1c based on enzymatic and immunochemical methods. For the enzyme based HbA1c assay a novel fructosamine oxidase (FAO) derived from marine yeast Pichia pastoris, strain N1-1 was utilized. It recognizes and oxidatively degrades fructosyl-valine (FV) which corresponds to the glycated N-terminus of the beta-chain of HbA1c and therefore is regarded as a model compound for HbA1c. Hydrogen peroxide which is liberated by the FAO during FV conversion was indicated optically in a horseradish peroxidase (POD) coupled reaction and electrochemically. For the biosensor the FAO was embedded in polyvinyl alcohol-stylbazole (PVA-SbQ) and fixed it in front of a Pt-electrode. So far, the measuring range of FV did not cover the clinically relevant range of HbA1c. Low specificity was assumed since enzyme activity also was obtained with glycated peptides, e.g. fructosyl-valine-glycine, not corresponding to the glycated N-terminus of the hemoglobin-beta-chain. For the immunosensor two immunoassays formats - heterogeneous sandwich and heterogeneous competitive - were tested. The assays were designed as follows: The competitive immunoassay was based on the immobilized synthetic glycated pentapeptide fructosyl-valine-histidine-leucine-threonine-proline (glkPP) utilized as HbA1c analogue. The peptide has an amino acid sequence corresponding to the N-terminus of the hemoglobin beta-chains and is capable for competition together with the HbA1c of the sample for the amount of a glucose oxidase (GOD)-labelled anti-HbA1c antibody

  7. Food Enzymes

    McBroom, Rachel; Oliver-Hoyo, Maria T.

    2007-01-01

    Many students view biology and chemistry as two unrelated, separate sciences; how these courses are generally taught in high schools may do little to change that impression. The study of enzymes provide a great opportunity for both biology and chemistry teachers to share with students the interdisciplinary nature of science. This article describes…

  8. Enzyme immunoassay

    Feldt-Rasmussen, B; Dinesen, B; Deckert, M

    1985-01-01

    An enzyme linked immunoadsorbent assay for urinary albumin using commercially available reagents is described. The assay range is 2.5-120 micrograms/l. When samples are analysed in two standard dilutions, the assayable albumin concentration range is 2.5-240 mg/l, covering the clinical range from...

  9. Trimester-specific reference intervals for haemoglobin A(1c) (HbA(1c)) in pregnancy.

    O'Connor, Catherine

    2011-11-26

    Abstract Background: Diabetes in pregnancy imposes additional risks to both mother and infant. These increased risks are considered to be primarily related to glycaemic control which is monitored by means of glycated haemoglobin (HbA(1c)). The correlation of HbA(1c) with clinical outcomes emphasises the need to measure HbA(1c) accurately, precisely and for correct interpretation, comparison to appropriately defined reference intervals. Since July 2010, the HbA(1c) assay in Irish laboratories is fully metrologically traceable to the IFCC standard. The objective was to establish trimester-specific reference intervals in pregnancy for IFCC standardised HbA(1c) in non-diabetic Caucasian women. Methods: The authors recruited 311 non-diabetic Caucasian pregnant (n=246) and non-pregnant women (n=65). A selective screening based on risk factors for gestational diabetes was employed. All subjects had a random plasma glucose <7.7 mmol\\/L and normal haemoglobin level. Pregnancy trimester was defined as trimester 1 (T1, n=40) up to 12 weeks +6 days, trimester 2 (T2, n=106) 13-27 weeks +6 days, trimester 3 (T3, n=100) >28 weeks to term. Results: The normal HbA(1c) reference interval for Caucasian non-pregnant women was 29-37 mmol\\/mol (Diabetes Control and Complications Trial; DCCT: 4.8%-5.5%), T1: 24-36 mmol\\/mol (DCCT: 4.3%-5.4%), T2: 25-35 mmol\\/mol (DCCT: 4.4%-5.4%) and T3: 28-39 mmol\\/mol (DCCT: 4.7%-5.7%). HbA(1c) was significantly decreased in trimesters 1 and 2 compared to non-pregnant women. Conclusions: HbA(1c) trimester-specific reference intervals are required to better inform the management of pregnancies complicated by diabetes.

  10. Immunodiagnosis of bovine trypanosomiasis in Anambra and Imo states, Nigeria, using enzyme-linked immunosorbent assay: zoonotic implications to human health

    M.C. Ezeani

    2008-11-01

    Full Text Available Background & objectives: The prevalence of trypanosomiasis was studied in cattle, being a major source of animal protein in Nigeria, thus, a very likely means of spread of Human African Trypano-somosis (HAT. Methods: Enzyme-linked immunosorbent assay (ELISA was used to diagnose bovine trypanosomiasis in 264 samples collected from adult cattle of mixed breeds, age and sex, in Anambra and Imo states, Nigeria. Results: Out of 264 samples analysed, 21 (7.96% were seropositive for Trypanosoma congolense while 20 (7.58% were seropositive for T. vivax and 8 (3.03% were seropositive for T. brucei infections in both the states. Interpretation & conclusion: The predominant species was found to be T. congolense. Mixed infection of three species, T. vivax, T. congolense and T. brucei was found to dominate other mixed infections in both the states. ELISA detected the infection of the three species of trypanosomes in the same group of animals. The usefulness of antigen capture ELISA in the diagnosis of human or animal trypanosomiasis was established, and the possibility of the spread of HAT caused by T. brucei gambiense and T.b. rhodesiense through cattle was expressed.

  11. Ecological recovery of vegetation on a coke-factory soil: role of plant antioxidant enzymes and possible implications in site restoration.

    Dazy, Marc; Jung, Vincent; Férard, Jean-François; Masfaraud, Jean-François

    2008-12-01

    The present paper investigated the short-term colonization by plants of a highly degraded soil in field conditions. The objectives were to identify, through phytosociological analysis, the plant species able to grow on such polluted areas and to characterize pollutant effects at different biological levels through analyses of plant oxidative status, plant growth or community indexes of richness and biodiversity. Our results showed that among the plants present in the uncontaminated surrounding area, only few species were able to colonize the polluted soil. These species were typical of the first years of grassland successions. Ecological indexes proved that the polluted soil vegetation presented a lower degree of species richness and biodiversity than the control area. These discrepancies were partly explained by pollutant phytotoxicity. Indeed, for several species including Erigeron canadensis and Oenothera biennis, we observed toxic effects of the polluted soil on plant height and biomass. Moreover, at the cellular level, changes in antioxidant enzyme activities (SOD, CAT, APX, GPX and GRD) and lipid peroxidation level (MDA) were observed. Such biochemical changes seemed to play an important role on plant sensitivity/tolerance to pollutants and thus to render them more or less competitive for colonization of such disturbed areas.

  12. The high-affinity maltose switch MBP317-347 has low affinity for glucose: implications for targeting tumors with metabolically directed enzyme prodrug therapy.

    Valdes, Gilmer; Schulte, Reinhard W; Ostermeier, Marc; Iwamoto, Keisuke S

    2014-03-01

    Development of agents with high affinity and specificity for tumor-specific markers is an important goal of molecular-targeted therapy. Here, we propose a shift in paradigm using a strategy that relies on low affinity for fundamental metabolites found in different concentrations in cancerous and non-cancerous tissues: glucose and lactate. A molecular switch, MBP317-347, originally designed to be a high-affinity switch for maltose and maltose-like polysaccharides, was demonstrated to be a low-affinity switch for glucose, that is, able to be activated by high concentrations (tens of millimolar) of glucose. We propose that such a low-affinity glucose switch could be used as a proof of concept for a new prodrug therapy strategy denominated metabolically directed enzyme prodrug therapy (MDEPT) where glucose or, preferably, lactate serves as the activator. Accordingly, considering the typical differential concentrations of lactate found in tumors and in healthy tissues, a low-affinity lactate-binding switch analogous to the low-affinity glucose-binding switch MBP317-347 would be an order of magnitude more active in tumors than in normal tissues and therefore can work as a differential activator of anticancer drugs in tumors.

  13. Imbalance between pulmonary angiotensin-converting enzyme and angiotensin-converting enzyme 2 activity in acute respiratory distress syndrome

    Wosten-van Asperen, Roelie M.; Bos, Albert; Bem, Reinout A.; Dierdorp, Barbara S.; Dekker, Tamara; van Goor, Harry; Kamilic, Jelena; van der Loos, Chris M.; van den Berg, Elske; Bruijn, Martijn; van Woensel, Job B.; Lutter, Rene

    2013-01-01

    Objective: Angiotensin-converting enzyme and its effector peptide angiotensin II have been implicated in the pathogenesis of acute respiratory distress syndrome. Recently, angiotensin-converting enzyme 2 was identified as the counter-regulatory enzyme of angiotensin-converting enzyme that converts a

  14. Mutagenic scan of the H-N-H motif of colicin E9: implications for the mechanistic enzymology of colicins, homing enzymes and apoptotic endonucleases

    Walker, David C.; Georgiou, Theonie; Pommer, Ansgar J.; Walker, Daniel; Moore, Geoffrey R.; Kleanthous, Colin; James, Richard

    2002-01-01

    Colicin E9 is a microbial toxin that kills bacteria through random degradation of chromosomal DNA. Within the active site of the cytotoxic endonuclease domain of colicin E9 (the E9 DNase) is a 32 amino acid motif found in the H-N-H group of homing endonucleases. Crystal structures of the E9 DNase have implicated several conserved residues of the H-N-H motif in the mechanism of DNA hydrolysis. We have used mutagenesis to test the involvement of these key residues in colicin toxicity, metal ion binding and catalysis. Our data show, for the first time, that the H-N-H motif is the site of DNA binding and that Mg2+-dependent cleavage of double-stranded DNA is responsible for bacterial cell death. We demonstrate that more active site residues are required for catalysis in the presence of Mg2+ ions than transition metals, consistent with the recent hypothesis that the E9 DNase hydrolyses DNA by two distinct, cation-dependent catalytic mechanisms. The roles of individual amino acids within the H-N-H motif are discussed in the context of the available structural information on this and related DNases and we address the possible mechanistic similarities between caspase-activated DNases, responsible for the degradation of chromatin in eukaryotic apoptosis, and H-N-H DNases. PMID:12136104

  15. Commentary: improving persistently elevated HbA1c in diabetes mellitus patients in Nigeria.

    Oghagbon, Efosa K

    2014-01-01

    Glycated hemoglobin (HbA1c) level in patients with diabetes reflects quality of disease control and propensity to develop hyperglycemic complications. During more than 12 years of using HbA1c for monitoring of glycemic control among patients at Nigerian hospitals, the mean glycated hemoglobin ranged from 7.9% ± 2.4 to 8.3% ± 2.2. Most of these patients (63% to 68%) had poor glycemic controls with mean HbA1c greater than 7%. Factors that are implicated in this scenario are: 1) high cost of HbA1c testing, 2) ineffective management of risk factors, 3) poor patient compliance, 4) improperly managed diabetes education program, and 5) health care system defect. Central to improving diabetes glycemia is education of doctors, other health workers and patients, within the confines of an overhauled national health system. Physicians need to increase adherence to diabetes mellitus management guidelines and patients must be enrolled into a well-structured education program at health centers. Doctors, as leader of the health team, should drive such education schemes, which must be based on standard training curriculum, sufficient number of trained diabetes educators, and effective monitoring of patients. The most appropriate diabetes education model features small-to-moderate sized participant groups and makes use of motivational interviewing rather than a traditional advice-giving format. Improved health care funding is mandatory given the issue of cost and this can be helped by increased participation of patients in Nigeria's National Health Insurance Scheme. Failure to address the persistently elevated HbA1c will affect long-term quality of life, longevity and health care services in Nigeria.

  16. Catalytic properties of Phr family members of cell wall glucan remodeling enzymes: implications for the adaptation of Candida albicans to ambient pH.

    Kováčová, Kristína; Degani, Genny; Stratilová, Eva; Farkaš, Vladimír; Popolo, Laura

    2015-03-01

    Fungal wall formation is a dynamic process involving several categories of enzymes. The GH72 family of β(1,3)-glucanosyltransferases is essential for the determination of cell shape, for cell integrity and for virulence in pathogenic fungi. Candida albicans has five GH72 genes: PHR1 and PHR2 are pH dependent, the first being expressed at pH ≥ 6 and repressed at lower pH and the second regulated in the opposite manner, PGA4 is transcribed independently of pH whereas PHR3 and PGA5 have low expression levels. To characterize the catalytic properties of Phr1p-2p and probe the activity of Pga4p, we heterologously expressed these proteins and used a fluorescent assay based on the transfer of oligosaccharyl units from a donor to a sulforhodamine-labeled acceptor. Phr1p-2p used exclusively β-1,3-glucan or cell wall glucan as donor and laminarin-derived oligosaccharides as acceptor. The acceptor efficiency increased with the length of the oligosaccharide. The temperature optimum was 30°C. The pH optimum was 5.8 for Phr1p and 3 for Phr2p. Overall, adaptation to pH of C. albicans appears to involve a fine interplay among the pH-dependent activity of Phr1p and Phr2p, the pH-regulated expression of their genes and protein stability. Unexpectedly, Pga4p was inactive suggesting that it turned into a structural mannoprotein.

  17. Alkylating enzymes.

    Wessjohann, Ludger A; Keim, Jeanette; Weigel, Benjamin; Dippe, Martin

    2013-04-01

    Chemospecific and regiospecific modifications of natural products by methyl, prenyl, or C-glycosyl moieties are a challenging and cumbersome task in organic synthesis. Because of the availability of an increasing number of stable and selective transferases and cofactor regeneration processes, enzyme-assisted strategies turn out to be promising alternatives to classical synthesis. Two categories of alkylating enzymes become increasingly relevant for applications: firstly prenyltransferases and terpene synthases (including terpene cyclases), which are used in the production of terpenoids such as artemisinin, or meroterpenoids like alkylated phenolics and indoles, and secondly methyltransferases, which modify flavonoids and alkaloids to yield products with a specific methylation pattern such as 7-O-methylaromadendrin and scopolamine.

  18. Postoperative Trunk Shift in Lenke 1C Scoliosis

    Wang, Yu; Bünger, Cody Eric; Wu, Chunsen;

    2012-01-01

    STUDY DESIGN: A risk factor analysis study. OBJECTIVE: To identify the causative factors for postoperative trunk shift in Lenke 1C scoliosis and investigate how to prevent it. SUMMARY OF BACKGROUND DATA: When selective thoracic fusion is performed, postoperative trunk shift is a significant problem...... in the management of Lenke 1C scoliosis. It is often accompanied by unsatisfactory clinical outcomes and a risk of reoperation. METHODS: We reviewed all the patients with adolescent idiopathic scoliosis (AIS) surgically treated in our institution from 2002 through 2008. Inclusion criteria were as follows: (1......) patients with Lenke 1C curves who were treated with selective thoracic fusion using posterior pedicle screw-only constructs; (2) the lowest instrumented vertebra (LIV) ending at L1 level or above; and (3) 2-year radiographical follow-up. Eighteen radiographical parameters were chosen as potential risk...

  19. Main: 1C2A [RPSD[Archive

    Full Text Available 1C2A 大麦 Barley Hordeum vulgare l. Bowman-Birk Type Trypsin Inhibitor. Hordeum Vulgare Molecule: Bowma..., J.Y.Lee, S.W.Suh H.K.Song, Y.S.Kim, J.K.Yang, J.Moon, J.Y.Lee, S.W.Suh Crystal Structure Of A 16 Kda Double-Headed Bowma...B; 1C2A; X-ray; A=4-122.|InterPro; IPR000877; Prot_inh_BBI.|Pfam; PF00228; Bowman-Birk_leg; 4.|SMART; SM0026

  20. Genetic and bibliographic information: CACNA1C [GenLibi

    Full Text Available CACNA1C calcium channel, voltage-dependent, L type, alpha 1C subunit human Long QT Syndrome... (MeSH) Cardiovascular Diseases (C14) > Heart Diseases (C14.280) > Arrhythmias, Cardiac (C14.280.067) > Long QT Syndrome...) > Heart Defects, Congenital (C16.131.240.400) > Long QT Syndrome (C16.131.240.400.715) Pathological Condit...ions, Signs and Symptoms (C23) > Pathologic Processes (C23.550) > Arrhythmias, Cardiac (C23.550.073) > Long QT Syndrome (C23.550.073.547) 02A0514005 ...

  1. Dynamics and phase transitions in A 1C 60 compounds

    Schober, H.; Renker, B.; Heid, R.; Tölle, A.

    1997-02-01

    We present an overview of extensive inelastic neutron scattering experiments carried out on powders of A 1C 60. The various phases leave strong fingerprints in the microscopic dynamics confirming the solid-state chemical reactions. The strong kinetic phase transitions can be followed in real time and turn out to be highly complex.

  2. SREBP-1c regulates glucose-stimulated hepatic clusterin expression

    Kim, Gukhan [Department of Pharmacology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Kim, Geun Hyang; Oh, Gyun-Sik; Yoon, Jin [Department of Pharmacology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Bio-Medical Institute of Technology, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Kim, Hae Won [Department of Pharmacology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Kim, Min-Seon [Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Kim, Seung-Whan, E-mail: swkim7@amc.seoul.kr [Department of Pharmacology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Bio-Medical Institute of Technology, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of)

    2011-05-20

    Highlights: {yields} This is the first report to show nutrient-regulated clusterin expression. {yields} Clusterin expression in hepatocytes was increased by high glucose concentration. {yields} SREBP-1c is directly involved in the transcriptional activation of clusterin by glucose. {yields} This glucose-stimulated activation process is mediated through tandem E-box motifs. -- Abstract: Clusterin is a stress-response protein that is involved in diverse biological processes, including cell proliferation, apoptosis, tissue differentiation, inflammation, and lipid transport. Its expression is upregulated in a broad spectrum of diverse pathological states. Clusterin was recently reported to be associated with diabetes, metabolic syndrome, and their sequelae. However, the regulation of clusterin expression by metabolic signals was not addressed. In this study we evaluated the effects of glucose on hepatic clusterin expression. Interestingly, high glucose concentrations significantly increased clusterin expression in primary hepatocytes and hepatoma cell lines, but the conventional promoter region of the clusterin gene did not respond to glucose stimulation. In contrast, the first intronic region was transcriptionally activated by high glucose concentrations. We then defined a glucose response element (GlRE) of the clusterin gene, showing that it consists of two E-box motifs separated by five nucleotides and resembles carbohydrate response element (ChoRE). Unexpectedly, however, these E-box motifs were not activated by ChoRE binding protein (ChREBP), but were activated by sterol regulatory element binding protein-1c (SREBP-1c). Furthermore, we found that glucose induced recruitment of SREBP-1c to the E-box of the clusterin gene intronic region. Taken together, these results suggest that clusterin expression is increased by glucose stimulation, and SREBP-1c plays a crucial role in the metabolic regulation of clusterin.

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

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

    2013-03-01

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

  4. Data of evolutionary structure change: 1C4XA-2OG1B [Confc[Archive

    Full Text Available 1C4XA-2OG1B 1C4X 2OG1 A B ---TVEIIEKRFPSGT---LASHALVAGDPQSPAVVLLH...EEEEEEE HHHHHHHHHHHHH 0 1C4X... A 1C4XA FPSGT---LASHA ...645107269287 4.700198173522949 1 1C4X... A 1C4XA

  5. Transcriptional Regulation of Cytosolic Sulfotransferase 1C2 by Intermediates of the Cholesterol Biosynthetic Pathway in Primary Cultured Rat Hepatocytes.

    Rondini, Elizabeth A; Pant, Asmita; Kocarek, Thomas A

    2015-12-01

    Cytosolic sulfotransferase 1C2 (SULT1C2) is expressed in the kidney, stomach, and liver of rats; however, the mechanisms regulating expression of this enzyme are not known. We evaluated transcriptional regulation of SULT1C2 by mevalonate (MVA)-derived intermediates in primary cultured rat hepatocytes using several cholesterol synthesis inhibitors. Blocking production of mevalonate with the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor pravastatin (30 μM), reduced SULT1C2 mRNA content by ∼40% whereas the squalene synthase inhibitor squalestatin (SQ1, 0.1 μM), which causes accumulation of nonsterol isoprenoids, increased mRNA content by 4-fold. Treatment with MVA (10 mM) strongly induced SULT1C2 mRNA by 12-fold, and this effect was blocked by inhibiting squalene epoxidase but not by more distal cholesterol inhibitors, indicating the effects of MVA are mediated by postsqualene metabolites. Using rapid amplification of cDNA ends (RACE), we characterized the 5' end of SULT1C2 mRNA and used this information to generate constructs for promoter analysis. SQ1 and MVA increased reporter activity by ∼1.6- and 3-fold, respectively, from a construct beginning 49 base pairs (bp) upstream from the longest 5'-RACE product (-3140:-49). Sequence deletions from this construct revealed a hepatocyte nuclear factor 1 (HNF1) element (-2558), and mutation of this element reduced basal (75%) and MVA-induced (30%) reporter activity and attenuated promoter activation following overexpression of HNF1α or 1β. However, the effects of SQ1 were localized to a more proximal promoter region (-281:-49). Collectively, our findings demonstrate that cholesterol biosynthetic intermediates influence SULT1C2 expression in rat primary hepatocytes. Further, HNF1 appears to play an important role in mediating basal and MVA-induced SULT1C2 transcription.

  6. Design and Analysis of HJ-1-C Satellite SAR Antenna

    Zheng Shi-kun

    2014-06-01

    Full Text Available With truss deployable mesh parabolic reflector, the HJ-1-C SAR antenna has complex structure and multiple steps during the deployed processing. The design of the antenna is difficult in terms of deployed reliability and electrical performance. This paper makes intensive research on system, structure and electrical design, and the analysis of mechanical and thermal performance in the actual space conditions is also presented. The successful deploying in orbit and high image quality of the HJ-1-C satellite indicate that the mechanical, electronic, thermal and reliability design of the antenna satisfy the project requirement, and these research provides valuable experience for the design of the centralized mesh parabolic SAR antenna.

  7. MMP-2 inhibits PCSK9-induced degradation of the LDL receptor in Hepa1-c1c7 cells.

    Wang, Xiang; Berry, Evan; Hernandez-Anzaldo, Samuel; Sun, Difei; Adijiang, Ayinuer; Li, Liang; Zhang, Dawei; Fernandez-Patron, Carlos

    2015-02-13

    Low-density lipoprotein receptor (LDLR) catalyzes the uptake of LDL-cholesterol by liver and peripheral organs. The function of the LDLR is antagonized by pro-protein convertase subtilisin/kexin type 9 (PCSK9), which binds to LDLR at the plasma membrane inducing LDLR degradation. Here, we report that matrix metalloproteinase-2 (MMP-2) interacts with and cleaves PCSK9, as evidenced by proteomic, chemical cross-linkage, blue native-PAGE and domain-specific antibodies Western blot analyses. Furthermore, MMP-2 overexpression renders Hepa1-c1c7 cells resistant to PCSK9-induced LDLR degradation. The data suggest that pathological MMP-2 overexpression may protect the LDLR from PCSK-9-induced degradation.

  8. Aldo-keto reductase 1C1 induced by interleukin-1β mediates the invasive potential and drug resistance of metastatic bladder cancer cells

    Matsumoto, Ryuji; Tsuda, Masumi; Yoshida, Kazuhiko; Tanino, Mishie; Kimura, Taichi; Nishihara, Hiroshi; Abe, Takashige; Shinohara, Nobuo; Nonomura, Katsuya; Tanaka, Shinya

    2016-01-01

    In treating bladder cancer, determining the molecular mechanisms of tumor invasion, metastasis, and drug resistance are urgent to improving long-term patient survival. One of the metabolic enzymes, aldo-keto reductase 1C1 (AKR1C1), plays an essential role in cancer invasion/metastasis and chemoresistance. In orthotopic xenograft models of a human bladder cancer cell line, UM-UC-3, metastatic sublines were established from tumors in the liver, lung, and bone. These cells possessed elevated levels of EMT-associated markers, such as Snail, Slug, or CD44, and exhibited enhanced invasion. By microarray analysis, AKR1C1 was found to be up-regulated in metastatic lesions, which was verified in metastatic human bladder cancer specimens. Decreased invasion caused by AKR1C1 knockdown suggests a novel role of AKR1C1 in cancer invasion, which is probably due to the regulation of Rac1, Src, or Akt. An inflammatory cytokine, interleukin-1β, was found to increase AKR1C1 in bladder cancer cell lines. One particular non-steroidal anti-inflammatory drug, flufenamic acid, antagonized AKR1C1 and decreased the cisplatin-resistance and invasion potential of metastatic sublines. These data uncover the crucial role of AKR1C1 in regulating both metastasis and drug resistance; as a result, AKR1C1 should be a potent molecular target in invasive bladder cancer treatment. PMID:27698389

  9. Technicians prepare the inflatable wing on Paresev 1-C

    1963-01-01

    This photo shows the Paresev (Paraglider Research Vehicle) space frame receiving a new wing. Frank Fedor and a technician helper are attaching a half-scale version of an inflatable wing in a hangar at NASA Flight Research Center at Edwards, California. The Paresev in this configuration was called the 1-C and was expected to closely approximate the aerodynamic characteristics that would be encountered with the Gemini space capsule with a parawing extended. The whole wing was not inflatable; the three chambers that acted as spars and supported the wing inflated.

  10. Internal Calibration of HJ-1-C Satellite SAR System

    Yang Zhen

    2014-06-01

    Full Text Available The HJ-1-C satellite is a Synthetic Aperture Radar (SAR satellite of a small constellation for environmental and disaster monitoring. At present, it is in orbit and working well. The SAR system uses a mesh reflector antenna and centralized power amplifier, and has an internal calibration function in orbit. This study introduces the internal calibration modes and signal paths. The design and realization of the internal calibrator are discussed in detail. Finally, the internal calibration data acquired in orbit are also analyzed.

  11. Data of evolutionary structure change: 1C5QA-3BSQA [Confc[Archive

    Full Text Available 1C5QA-3BSQA 1C5Q 3BSQ A A IVGGYTCGANTVPYQVSLNSG-YHFCGGSLINSQWVVSA...ALLSGNQLHCGGVLVNERWVLTAAHCKMNEYTVHLGSDTLGDRRA--QRIKASKSFRHPGYSTQTHVNDLMLVKLNSQARL...el> 0 1C5Q A 1C5QA...A 3BSQA ALLSGNQLHCGA 1C5QA VSWGS-GCAQK<

  12. Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III

    Thiffault, Isabelle; Wolf, Nicole I.; Forget, Diane; Guerrero, Kether; Tran, Luan T.; Choquet, Karine; Lavallée-Adam, Mathieu; Poitras, Christian; Brais, Bernard; Yoon, Grace; Sztriha, Laszlo; Webster, Richard I.; Timmann, Dagmar; van de Warrenburg, Bart P.; Seeger, Jürgen; Zimmermann, Alíz; Máté, Adrienn; Goizet, Cyril; Fung, Eva; van der Knaap, Marjo S.; Fribourg, Sébastien; Vanderver, Adeline; Simons, Cas; Taft, Ryan J.; Yates III, John R.; Coulombe, Benoit; Bernard, Geneviève

    2015-01-01

    A small proportion of 4H (Hypomyelination, Hypodontia and Hypogonadotropic Hypogonadism) or RNA polymerase III (POLR3)-related leukodystrophy cases are negative for mutations in the previously identified causative genes POLR3A and POLR3B. Here we report eight of these cases carrying recessive mutations in POLR1C, a gene encoding a shared POLR1 and POLR3 subunit, also mutated in some Treacher Collins syndrome (TCS) cases. Using shotgun proteomics and ChIP sequencing, we demonstrate that leukodystrophy-causative mutations, but not TCS mutations, in POLR1C impair assembly and nuclear import of POLR3, but not POLR1, leading to decreased binding to POLR3 target genes. This study is the first to show that distinct mutations in a gene coding for a shared subunit of two RNA polymerases lead to selective modification of the enzymes' availability leading to two different clinical conditions and to shed some light on the pathophysiological mechanism of one of the most common hypomyelinating leukodystrophies, POLR3-related leukodystrophy. PMID:26151409

  13. CD1c+ blood dendritic cells have Langerhans cell potential.

    Milne, Paul; Bigley, Venetia; Gunawan, Merry; Haniffa, Muzlifah; Collin, Matthew

    2015-01-15

    Langerhans cells (LCs) are self-renewing in the steady state but repopulated by myeloid precursors after injury. Human monocytes give rise to langerin-positive cells in vitro, suggesting a potential precursor role. However, differentiation experiments with human lineage-negative cells and CD34(+) progenitors suggest that there is an alternative monocyte-independent pathway of LC differentiation. Recent data in mice also show long-term repopulation of the LC compartment with alternative myeloid precursors. Here we show that, although monocytes are able to express langerin, when cultured with soluble ligands granulocyte macrophage colony-stimulating factor (GM-CSF), transforming growth factor β (TGFβ), and bone morphogenetic protein 7 (BMP7), CD1c(+) dendritic cells (DCs) become much more LC-like with high langerin, Birbeck granules, EpCAM, and E-cadherin expression under the same conditions. These data highlight a new potential precursor function of CD1c(+) DCs and demonstrate an alternative pathway of LC differentiation that may have relevance in vivo.

  14. GPM Level 1C R Common Calibrated Brightness Temperatures Collocated VV03B

    National Aeronautics and Space Administration — All 1C products have a common L1C data structure, simple and generic. Each L1C swath includes scan time, latitude and longitude, scan status, quality, incidence...

  15. GPM, SSMI F16 Level 1C Common Calibrated Brightness Temperatures VV02A

    National Aeronautics and Space Administration — All 1C products have a common L1C data structure, simple and generic. Each L1C swath includes scan time, latitude and longitude, scan status, quality, incidence...

  16. GPM, TRMM TMI Level 1C Common Calibrated Brightness Temperatures VV02A

    National Aeronautics and Space Administration — All 1C products have a common L1C data structure, simple and generic. Each L1C swath includes scan time, latitude and longitude, scan status, quality, incidence...

  17. GPM, MT1 SAPHIR Level 1C Common Calibrated Brightness Temperatures VV02A

    National Aeronautics and Space Administration — All 1C products have a common L1C data structure, simple and generic. Each L1C swath includes scan time, latitude and longitude, scan status, quality, incidence...

  18. GPM Level 1C R Common Calibrated Brightness Temperatures Collocated VV03A

    National Aeronautics and Space Administration — All 1C products have a common L1C data structure, simple and generic. Each L1C swath includes scan time, latitude and longitude, scan status, quality, incidence...

  19. GPM, NOAA-18 MHS Level 1C Common Calibrated Brightness Temperatures VV02A

    National Aeronautics and Space Administration — All 1C products have a common L1C data structure, simple and generic. Each L1C swath includes scan time, latitude and longitude, scan status, quality, incidence...

  20. GPM GMI Level 1C Common Calibrated Brightness Temperatures Collocated VV03B

    National Aeronautics and Space Administration — All 1C products have a common L1C data structure, simple and generic. Each L1C swath includes scan time, latitude and longitude, scan status, quality, incidence...

  1. GPM, SSMI F17 Level 1C Common Calibrated Brightness Temperatures VV02A

    National Aeronautics and Space Administration — All 1C products have a common L1C data structure, simple and generic. Each L1C swath includes scan time, latitude and longitude, scan status, quality, incidence...

  2. GPM, SSMI F18 Level 1C Common Calibrated Brightness Temperatures VV02A

    National Aeronautics and Space Administration — All 1C products have a common L1C data structure, simple and generic. Each L1C swath includes scan time, latitude and longitude, scan status, quality, incidence...

  3. GPM GMI Level 1C Common Calibrated Brightness Temperatures Collocated VV03A

    National Aeronautics and Space Administration — All 1C products have a common L1C data structure, simple and generic. Each L1C swath includes scan time, latitude and longitude, scan status, quality, incidence...

  4. GPM, NOAA-19 MHS Level 1C Common Calibrated Brightness Temperatures VV02A

    National Aeronautics and Space Administration — All 1C products have a common L1C data structure, simple and generic. Each L1C swath includes scan time, latitude and longitude, scan status, quality, incidence...

  5. GPM, METOPA MHS Level 1C Common Calibrated Brightness Temperatures VV02A

    National Aeronautics and Space Administration — All 1C products have a common L1C data structure, simple and generic. Each L1C swath includes scan time, latitude and longitude, scan status, quality, incidence...

  6. GPM, METOPB MHS Level 1C Common Calibrated Brightness Temperatures VV02A

    National Aeronautics and Space Administration — All 1C products have a common L1C data structure, simple and generic. Each L1C swath includes scan time, latitude and longitude, scan status, quality, incidence...

  7. Enzyme detection by microfluidics

    2013-01-01

    Microfluidic-implemented methods of detecting an enzyme, in particular a DNA-modifying enzyme, are provided, as well as methods for detecting a cell, or a microorganism expressing said enzyme. The enzyme is detected by providing a nucleic acid substrate, which is specifically targeted...... by that enzyme...

  8. The Kinetics of Enzyme Mixtures

    Simon Brown

    2014-03-01

    Full Text Available Even purified enzyme preparations are often heterogeneous. For example, preparations of aspartate aminotransferase or cytochrome oxidase can consist of several different forms of the enzyme. For this reason we consider how different the kinetics of the reactions catalysed by a mixture of forms of an enzyme must be to provide some indication of the characteristics of the species present. Based on the standard Michaelis-Menten model, we show that if the Michaelis constants (Km of two isoforms differ by a factor of at least 20 the steady-state kinetics can be used to characterise the mixture. However, even if heterogeneity is reflected in the kinetic data, the proportions of the different forms of the enzyme cannot be estimated from the kinetic data alone. Consequently, the heterogeneity of enzyme preparations is rarely reflected in measurements of their steady-state kinetics unless the species present have significantly different kinetic properties. This has two implications: (1 it is difficult, but not impossible, to detect molecular heterogeneity using kinetic data and (2 even when it is possible, a considerable quantity of high quality data is required.

  9. Elevated Liver Enzymes

    Symptoms Elevated liver enzymes By Mayo Clinic Staff Elevated liver enzymes may indicate inflammation or damage to cells in the liver. Inflamed or ... than normal amounts of certain chemicals, including liver enzymes, into the bloodstream, which can result in elevated ...

  10. Toxicological and biochemical analyses demonstrate no toxic effect of Cry1C and Cry2A to Folsomia candida

    Yang, Yan; Chen, Xiuping; Cheng, Lisheng; Cao, Fengqin; Romeis, Jörg; Li, Yunhe; Peng, Yufa

    2015-01-01

    Collembolans are common soil arthropods that may be exposed to insecticidal proteins produced in genetically engineered (GE) plants by ingestion of crop residues or root exudates. In the present study, a dietary exposure assay was validated and used to assess the lethal and sublethal effects of two Bacillus thuringiensis (Bt) insecticidal proteins, Cry1C and Cry2A, on Folsomia candida. Using the insecticidal compounds potassium arsenate (PA), protease inhibitor (E-64), and Galanthus nivalis agglutinin (GNA) mixed into Baker’s yeast, we show that the assay used can detect adverse effects on F. candida. Survival and development were significantly reduced when F. candida was fed a diet containing PA, E-64, and GNA at 9, 75, and 100 μg/g diet, respectively, but not when fed a diet containing 300 μg/g Cry1C or 600 μg/g Cry2A. The activities of test antioxidant-, detoxification-, and digestion-related enzymes in F. candida were unaltered by a diet containing 300 μg/g Cry1C or 600 μg/g Cry2A, but were significantly increased by a diet containing 75 μg/g E-64. The results confirm that Cry1C and Cry2A are not toxic to F. candida at concentrations that are much higher than those encountered under field conditions. PMID:26494315

  11. Toxicological and biochemical analyses demonstrate no toxic effect of Cry1C and Cry2A to Folsomia candida.

    Yang, Yan; Chen, Xiuping; Cheng, Lisheng; Cao, Fengqin; Romeis, Jörg; Li, Yunhe; Peng, Yufa

    2015-10-23

    Collembolans are common soil arthropods that may be exposed to insecticidal proteins produced in genetically engineered (GE) plants by ingestion of crop residues or root exudates. In the present study, a dietary exposure assay was validated and used to assess the lethal and sublethal effects of two Bacillus thuringiensis (Bt) insecticidal proteins, Cry1C and Cry2A, on Folsomia candida. Using the insecticidal compounds potassium arsenate (PA), protease inhibitor (E-64), and Galanthus nivalis agglutinin (GNA) mixed into Baker's yeast, we show that the assay used can detect adverse effects on F. candida. Survival and development were significantly reduced when F. candida was fed a diet containing PA, E-64, and GNA at 9, 75, and 100 μg/g diet, respectively, but not when fed a diet containing 300 μg/g Cry1C or 600 μg/g Cry2A. The activities of test antioxidant-, detoxification-, and digestion-related enzymes in F. candida were unaltered by a diet containing 300 μg/g Cry1C or 600 μg/g Cry2A, but were significantly increased by a diet containing 75 μg/g E-64. The results confirm that Cry1C and Cry2A are not toxic to F. candida at concentrations that are much higher than those encountered under field conditions.

  12. Crystal structures of three classes of non-steroidal anti-inflammatory drugs in complex with aldo-keto reductase 1C3.

    Jack U Flanagan

    Full Text Available Aldo-keto reductase 1C3 (AKR1C3 catalyses the NADPH dependent reduction of carbonyl groups in a number of important steroid and prostanoid molecules. The enzyme is also over-expressed in prostate and breast cancer and its expression is correlated with the aggressiveness of the disease. The steroid products of AKR1C3 catalysis are important in proliferative signalling of hormone-responsive cells, while the prostanoid products promote prostaglandin-dependent proliferative pathways. In these ways, AKR1C3 contributes to tumour development and maintenance, and suggest that inhibition of AKR1C3 activity is an attractive target for the development of new anti-cancer therapies. Non-steroidal anti-inflammatory drugs (NSAIDs are one well-known class of compounds that inhibits AKR1C3, yet crystal structures have only been determined for this enzyme with flufenamic acid, indomethacin, and closely related analogues bound. While the flufenamic acid and indomethacin structures have been used to design novel inhibitors, they provide only limited coverage of the NSAIDs that inhibit AKR1C3 and that may be used for the development of new AKR1C3 targeted drugs. To understand how other NSAIDs bind to AKR1C3, we have determined ten crystal structures of AKR1C3 complexes that cover three different classes of NSAID, N-phenylanthranilic acids (meclofenamic acid, mefenamic acid, arylpropionic acids (flurbiprofen, ibuprofen, naproxen, and indomethacin analogues (indomethacin, sulindac, zomepirac. The N-phenylanthranilic and arylpropionic acids bind to common sites including the enzyme catalytic centre and a constitutive active site pocket, with the arylpropionic acids probing the constitutive pocket more effectively. By contrast, indomethacin and the indomethacin analogues sulindac and zomepirac, display three distinctly different binding modes that explain their relative inhibition of the AKR1C family members. This new data from ten crystal structures greatly broadens

  13. Black Hole Collapse in the 1/c Expansion

    Anous, Tarek; Rovai, Antonin; Sonner, Julian

    2016-01-01

    We present a first-principles CFT calculation corresponding to the spherical collapse of a shell of matter in three dimensional quantum gravity. In field theory terms, we describe the equilibration process, from early times to thermalization, of a CFT following a sudden injection of energy at time t=0. By formulating a continuum version of Zamolodchikov's monodromy method to calculate conformal blocks at large central charge c, we give a framework to compute a general class of probe observables in the collapse state, incorporating the full backreaction of matter fields on the dual geometry. This is illustrated by calculating a scalar field two-point function at time-like separation and the time-dependent entanglement entropy of an interval, both showing thermalization at late times. The results are in perfect agreement with previous gravity calculations in the AdS$_3$-Vaidya geometry. Information loss appears in the CFT as an explicit violation of unitarity in the 1/c expansion, restored by nonperturbative co...

  14. The biomechanical properties of F1C pili

    Castelain, Mickaël; Klinth, Jeanna; Lindberg, Stina; Andersson, Magnus; Uhlin, Bernt Eric; Axner, Ove

    2014-01-01

    Uropathogenic Escherichia coli (UPEC) express various kinds of organelles, so-called pili or fimbriae, that mediate adhesion to host tissue in the urinary tract through specific receptor-adhesin interactions. The biomechanical properties of these pili have been considered important for the ability of bacteria to withstand shear forces from rinsing urine flows. Force measuring optical tweezers have been used to characterize individual organelles of F1C type expressed by UPEC bacteria with respect to such properties. Qualitatively, the force-vs.-elongation response was found to be similar to that of other types of helix-like pili expressed by UPEC, i.e. type 1, P, and S, with force-induced elongation in three regions of which one represents the important uncoiling mechanism of the helix-like quaternary structure. Quantitatively, the steady-state uncoiling force was assessed to 26.4(1.4) pN, which is similar to those of other pili (which range from 21 pN for SI to 30 pN for type 1). The corner velocity for dynam...

  15. Data of evolutionary structure change: 1C7IA-1QIIA [Confc[Archive

    Full Text Available 1C7IA-1QIIA 1C7I 1QII A A THQIVTTQYGKVKGTTE----NGVHKWKGIPYAKPPVGQ...GPFGFMHLSSFDEAYSDNLGLLDQAAALKWVRENISAFGGDPDNVTVFGESAGGMSIAALLAMPAAKGLFQKAIMESGAS----RTMTKEQAASTAAAFLQVLGINES...QLDRLHTVAAEDLLKAAD----QLRIAEKE------NIFQLFFQPALDPKTLPEEPEKSIAEGAASGIPLLIGTTRDEGYF...ndex> 1C7I A 1C7IA...1QII A 1QIIA MGTRVPVLSSHISA <

  16. Variables involved in the discordance between HbA1c and fructosamine: the glycation gap revisited.

    Carles Zafon

    Full Text Available AIMS: Glycation gap (GG is defined as the difference between the measured level of HbA1c and the level that would be predicted from its regression on the fructosamine level. The aims of the study were: 1 To determine the reproducibility and consistency of GC; 2 To discover factors related to GG value. Given that metformin might increase glucose transport through the erythrocyte membrane, this treatment was also considered in the analyses of the results. METHODS: GG was calculated in two blood samples separated 30.6 (SD 7.3 weeks, obtained in 508 type 2 diabetic patients. The following variables were considered: HbA1c, fructosamine, glucose, creatinine, hematological parameters and treatment with metformin. Multivariate and logistic regression analyses were performed to explore the variables independently related to CG. RESULTS: GG was reproducible and consistent over time. Creatinine, mean corpuscular hemoglobin concentration (MCHC, and glycemia (inverse relationship; and HbA1c and treatment with metformin (direct relationship were independently related to GG. Patients treated with metformin showed higher HbA1c values, despite similar fructosamine concentrations, than patients not treated with the drug. CONCLUSIONS: GG is independently related to serum levels of creatinine, MCHC and treatment with metformin. The spurious effect of metformin on Hb glycation could have serious clinical implications and should be considered when interpreting the results of clinical trials.

  17. Progesterone stimulates adipocyte determination and differentiation 1/sterol regulatory element-binding protein 1c gene expression. potential mechanism for the lipogenic effect of progesterone in adipose tissue.

    Lacasa, D; Le Liepvre, X; Ferre, P; Dugail, I

    2001-04-13

    Fatty acid synthase (FAS), a nutritionally regulated lipogenic enzyme, is transcriptionally controlled by ADD1/SREBP1c (adipocyte determination and differentiation 1/sterol regulatory element-binding protein 1c), through insulin-mediated stimulation of ADD1/SREBP1c expression. Progesterone exerts lipogenic effects on adipocytes, and FAS is highly induced in breast tumor cell lines upon progesterone treatment. We show here that progesterone up-regulates ADD1/SREBP1c expression in the MCF7 breast cancer cell line and the primary cultured preadipocyte from rat parametrial adipose tissue. In MCF7, progesterone induced ADD1/SREBP1c and Metallothionein II (a well known progesterone-regulated gene) mRNAs, with comparable potency. In preadipocytes, progesterone increased ADD1/SREBP1c mRNA dose-dependently, but not SREBP1a or SREBP2. Run-on experiments demonstrated that progesterone action on ADD1/SREBP1c was primarily at the transcriptional level. The membrane-bound and mature nuclear forms of ADD1/SREBP1 protein accumulated in preadipocytes cultured with progesterone, and FAS induction could be abolished by adenovirus-mediated overexpression of a dominant negative form of ADD1/SREBP1 in these cells. Finally, in the presence of insulin, progesterone was unable to up-regulate ADD1/SREBP1c mRNA in preadipocytes, whereas its effect was restored after 24 h of insulin deprivation. Together these results demonstrate that ADD1/SREBP1c is controlled by progesterone, which, like insulin, acts by increasing ADD1/SREBP1c gene transcription. This provides a potential mechanism for the lipogenic actions of progesterone on adipose tissue.

  18. Detection of total and A1c-glycosylated hemoglobin in human whole blood using sandwich immunoassays on polydimethylsiloxane-based antibody microarrays.

    Chen, Huang-Han; Wu, Chih-Hsing; Tsai, Mei-Ling; Huang, Yi-Jing; Chen, Shu-Hui

    2012-10-16

    The percentage of glycosylated hemoglobin A1c (%GHbA1c) in human whole blood indicates the average plasma glucose concentration over a prolonged period of time and is used to diagnose diabetes. However, detecting GHbA1c in the whole blood using immunoassays has limited detection sensitivity due to its low percentage in total hemoglobin (tHb) and interference from various glycan moieties in the sample. We have developed a sandwich immunoassay using an antibody microarray on a polydimethylsiloxane (PDMS) substrate modified with fluorinated compounds to detect tHb and glycosylated hemoglobin A1c (GHbA1c) in human whole blood without sample pretreatment. A polyclonal antibody against hemoglobin (Hb) immobilized on PDMS is used as a common capture probe to enrich all forms of Hb followed by detection via monoclonal anti-Hb and specific monoclonal anti-GHbA1c antibodies for tHb and GHbA1c detection, respectively. This method prevents the use of glycan binding molecules and dramatically reduces the background interference, yielding a detection limit of 3.58 ng/mL for tHb and 0.20 ng/mL for GHbA1c. The fluorinated modification on PDMS is superior to the glass substrate and eliminates the need for the blocking step which is required in commercial enzyme linked immunosorbent assay (ELISA) kits. Moreover, the detection sensitivity for GHbA1c is 4-5 orders of magnitude higher, but the required sample amount is 25 times less than the commercial method. On the basis of patient sample data, a good linear correlation between %GHbA1c values determined by our method and the certified high performance liquid chromatography (HPLC) standard method is shown with R(2) > 0.98, indicating the great promise of the developed method for clinical applications.

  19. STUDY OF HBA1C LEVELS IN ACUTE CORONARY SYNDROME

    Ramesh Naidu

    2015-09-01

    Full Text Available Diabetes mellitus is a disease of Antiquity known to mankind since the past 3500 years. It is a big concern because of devastating effects of its complications. Diabetes is considered a highly vascular disease with both microvascular and macrovascular complications . Macrovascular complications start taking place long before the patient has over diabetes . 1 Hyperglycemia accelerates the process of atherosclerosis by the formation of glycated proteins and advanced glycation end products, which act by increasing the end othelial dysfunction . 2 High admission blood glucose levels after acute Myocardial Infarction are common and are associated with an increased risk of death in subjects with and without diabetes . 3 Glycometabolic state at hospital admission is an important ri sk Marker for long - term mortality in patients with AMI. Glycosylated hemoglobin provides a measure of average blood glucose levels during the period of 8 to 12 weeks . 4 So it could prove useful for the diagnosis of diabetes mellitus in ACS when stress induc ed hyperglycemia is a confounding factor as it is unlikely to rise with acute hyperglycemia. This study has been carried out in Medicine department of Rangaraya medical college GGH Kakinada, Sraddha Hospital, Visakhapatnam, Andhra medical college, KGH, Vis akhapatnam, GEMS hospital Srikakulam with an aim to estimate glycosylated Hemoglobin in ACS which is a prognostic factor for ACS. Among various variables and clinical details during course of disease, the estimation of glycosylated hemoglobin (HbA1c gives useful estimation for ACS in prognosis, outcome and sequelae of complications. Patients with higher levels of glycosylated hemoglobin have higher risk factors like hypertension, obesity, dyslipidemia and hence predisposed to ACS in early age.

  20. Peptides-Derived from Thai Rice Bran Improves Endothelial Function in 2K-1C Renovascular Hypertensive Rats

    Orachorn Boonla

    2015-07-01

    Full Text Available In recent years, a number of studies have investigated complementary medical approaches to the treatment of hypertension using dietary supplements. Rice bran protein hydrolysates extracted from rice is a rich source of bioactive peptides. The present study aimed to investigate the vasorelaxation and antihypertensive effects of peptides-derived from rice bran protein hydrolysates (RBP in a rat model of two kidney-one clip (2K-1C renovascular hypertension. 2K-1C hypertension was induced in male Sprague-Dawley rats by placing a silver clip around the left renal artery, whereas sham-operated rats were served as controls. 2K-1C and sham-operated rats were intragastrically administered with RBP (50 mg kg−1 or 100 mg kg−1 or distilled water continuously for six weeks. We observed that RBP augmented endothelium-dependent vasorelaxation in all animals. Administration of RBP to 2K-1C rats significantly reduced blood pressure and decreased peripheral vascular resistance compared to the sham operated controls (p < 0.05. Restoration of normal endothelial function and blood pressure was associated with reduced plasma angiotensin converting enzyme (ACE, decreased superoxide formation, reduced plasma malondialdehyde and increased plasma nitrate/nitrite (p < 0.05. Up-regulation of eNOS protein and down-regulation of p47phox protein were found in 2K-1C hypertensive rats-treated with RBP. Our results suggest that RBP possesses antihypertensive properties which are mainly due to the inhibition of ACE, and its vasodilatory and antioxidant activity.

  1. CDKN1C/P57 is regulated by the Notch target gene Hes1 and induces senescence in human hepatocellular carcinoma.

    Giovannini, Catia; Gramantieri, Laura; Minguzzi, Manuela; Fornari, Francesca; Chieco, Pasquale; Grazi, Gian Luca; Bolondi, Luigi

    2012-08-01

    CDKN1C/P57 is a cyclin-dependent kinase inhibitor implicated in different human cancers, including hepatocellular carcinoma (HCC); however, little is known regarding the role of CDKN1C/P57 and its regulation in HCC. In this study, we show that the down-regulation of Notch1 and Notch3 in two HCC cell lines resulted in Hes1 down-regulation, CDKN1C/P57 up-regulation, and reduced cell growth. In line with these data, we report that CDKN1C/P57 is a target of transcriptional repression by the Notch effector, Hes1. We found that the up-regulation of CDKN1C/P57 by cDNA transfection decreased tumor growth, as determined by growth curve, flow cytometry analysis, and cyclin D1 down-regulation, without affecting the apoptosis machinery. Indeed, the expression of Bax, Noxa, PUMA, BNIP(3), and cleaved caspase-3 was not affected by CDKN1C/P57 induction. Morphologically CDKN1C/p57-induced HCC cells became flat and lengthened in shape, accumulated the senescence-associated β-galactosidase marker, and increased P16 protein expression. Evaluation of senescence in cells depleted both for Hes1 and CDKN1C/P57 revealed that the senescent state really depends on the accumulation of CDKN1C/p57. Finally, we validated our in vitro results in primary HCCs, showing that Hes1 protein expression inversely correlates with CDKN1C/P57 mRNA levels. In addition, reduced Hes1 protein expression is accompanied by a shorter time to recurrence after curative resection, suggesting that Hes1 may represent a biomarker for prediction of patients with poor prognosis.

  2. Deubiquitylating enzymes and disease

    Baker Rohan T

    2008-10-01

    Full Text Available Abstract Deubiquitylating enzymes (DUBs can hydrolyze a peptide, amide, ester or thiolester bond at the C-terminus of UBIQ (ubiquitin, including the post-translationally formed branched peptide bonds in mono- or multi-ubiquitylated conjugates. DUBs thus have the potential to regulate any UBIQ-mediated cellular process, the two best characterized being proteolysis and protein trafficking. Mammals contain some 80–90 DUBs in five different subfamilies, only a handful of which have been characterized with respect to the proteins that they interact with and deubiquitylate. Several other DUBs have been implicated in various disease processes in which they are changed by mutation, have altered expression levels, and/or form part of regulatory complexes. Specific examples of DUB involvement in various diseases are presented. While no specific drugs targeting DUBs have yet been described, sufficient functional and structural information has accumulated in some cases to allow their rapid development. Publication history Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com.

  3. Phase 1 trial of AMA1-C1/Alhydrogel plus CPG 7909: an asexual blood-stage vaccine for Plasmodium falciparum malaria.

    Gregory E D Mullen

    Full Text Available BACKGROUND: Apical Membrane Antigen 1 (AMA1, a polymorphic merozoite surface protein, is a leading blood-stage malaria vaccine candidate. This is the first reported use in humans of an investigational vaccine, AMA1-C1/Alhydrogel, with the novel adjuvant CPG 7909. METHODS: A phase 1 trial was conducted at the University of Rochester with 75 malaria-naive volunteers to assess the safety and immunogenicity of the AMA1-C1/Alhydrogel+CPG 7909 malaria vaccine. Participants were sequentially enrolled and randomized within dose escalating cohorts to receive three vaccinations on days 0, 28 and 56 of either 20 microg of AMA1-C1/Alhydrogel+564 microg CPG 7909 (n = 15, 80 microg of AMA1-C1/Alhydrogel (n = 30, or 80 microg of AMA1-C1/Alhydrogel+564 microg CPG 7909 (n = 30. RESULTS: Local and systemic adverse events were significantly more likely to be of higher severity with the addition of CPG 7909. Anti-AMA1 immunoglobulin G (IgG were detected by enzyme-linked immunosorbent assay (ELISA, and the immune sera of volunteers that received 20 microg or 80 microg of AMA1-C1/Alhydrogel+CPG 7909 had up to 14 fold significant increases in anti-AMA1 antibody concentration compared to 80 microg of AMA1-C1/Alhydrogel alone. The addition of CPG 7909 to the AMA1-C1/Alhydrogel vaccine in humans also elicited AMA1 specific immune IgG that significantly and dramatically increased the in vitro growth inhibition of homologous parasites to levels as high as 96% inhibition. CONCLUSION/SIGNIFICANCE: The safety profile of the AMA1-C1/Alhydrogel+CPG 7909 malaria vaccine is acceptable, given the significant increase in immunogenicity observed. Further clinical development is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov NCT00344539.

  4. Relationship of HbA1c variability, absolute changes in HbA1c, and all-cause mortality in type 2 diabetes

    Skriver, Mette Vinther; Sandbæk, Annelli; Kristensen, Jette Kolding;

    2015-01-01

    OBJECTIVE: We assessed the relationship of mortality with glycated hemoglobin (HbA1c) variability and with absolute change in HbA1c. DESIGN: A population-based prospective observational study with a median follow-up time of 6 years. METHODS: Based on a validated algorithm, 11 205 Danish individuals...

  5. Development of an HbA1c-based conversion equation for estimating glycated albumin in a Korean population with a wide range of glucose intolerance.

    Chang Hee Jung

    Full Text Available BACKGROUND: Compared to the golden standard glycation index of HbA1c, glycated albumin (GA has potentials for assessing insulin secretory dysfunction and glycemic fluctuation as well as predicting diabetic vascular complications. However, the reference ranges of GA and a conversion equation need to be clearly defined. We designed this study to determine the reference ranges in patients with normal glucose tolerance (NGT based on conventional measures of glycemic status and to devise a conversion equation for calculating HbA1c and GA in a Korean population. METHODOLOGY/PRINCIPAL FINDINGS: In this multicenter, retrospective, cross-sectional study, we recruited antidiabetic drug-naïve patients with available glycemic variables including HbA1c, GA, and fasting plasma glucose regardless of glucose status. For the reference interval of serum GA, 5th to 95th percentile value of GA in subjects with NGT was adopted. The conversion equation between HbA1c and GA was devised using an estimating regression model with unknown break-points method. The reference range for GA was 9.0-14.0% in 2043 subjects. The 95th percentile responding values for FPG, and HbA1c were approximately 5.49 mmol/l, and 5.6%, respectively. The significant glycemic turning points were 5.868% HbA1c and 12.2% GA. The proposed conversion equation for below and above the turning point were GA (% = 6.960+0.8963 × HbA1c (% and GA (% = -9.609+3.720 × HbA1c (%, respectively. CONCLUSIONS/SIGNIFICANCE: These results should be helpful in future studies on the clinical implications of high GA relative to HbA1c and the clinical implementation of diabetes management.

  6. Antibody-Mediated Inhibition of the FGFR1c Isoform Induces a Catabolic Lean State in Siberian Hamsters.

    Samms, Ricardo J; Lewis, Jo E; Lory, Alex; Fowler, Maxine J; Cooper, Scott; Warner, Amy; Emmerson, Paul; Adams, Andrew C; Luckett, Jeni C; Perkins, Alan C; Wilson, Dana; Barrett, Perry; Tsintzas, Kostas; Ebling, Francis J P

    2015-11-16

    Hypothalamic tanycytes are considered to function as sensors of peripheral metabolism. To facilitate this role, they express a wide range of receptors, including fibroblast growth factor receptor 1 (FGFR1). Using a monoclonal antibody (IMC-H7) that selectively antagonizes the FGFR1c isoform, we investigated possible actions of FGFR1c in a natural animal model of adiposity, the Siberian hamster. Infusion of IMC-H7 into the third ventricle suppressed appetite and increased energy expenditure. Likewise, peripheral treatment with IMC-H7 decreased appetite and body weight and increased energy expenditure and fat oxidation. A greater reduction in body weight and caloric intake was observed in response to IMC-H7 during the long-day fat state as compared to the short-day lean state. This enhanced response to IMC-H7 was also observed in calorically restricted hamsters maintained in long days, suggesting that it is the central photoperiodic state rather than the peripheral adiposity that determines the response to FGFR1c antagonism. Hypothalamic thyroid hormone availability is controlled by deiodinase enzymes (DIO2 and DIO3) expressed in tanycytes and is the key regulator of seasonal cycles of energy balance. Therefore, we determined the effect of IMC-H7 on hypothalamic expression of these deiodinase enzymes. The reductions in food intake and body weight were always associated with decreased expression of DIO2 in the hypothalamic ependymal cell layer containing tanycytes. These data provide further support for the notion the tanycytes are an important component of the mechanism by which the hypothalamus integrates central and peripheral signals to regulate energy intake and expenditure.

  7. Data of evolutionary structure change: 1C7IA-1P0IA [Confc[Archive

    Full Text Available 1C7IA-1P0IA 1C7I 1P0I A A THQIVTTQYGKVKGT--TE--NGVHKWKGIPYAKPPVGQ...GPFGFMHLSSFDEAYSDNLGLLDQAAALKWVRENISAFGGDPDNVTVFGESAGGMSIAALLAMPAAKGLFQKAIMESGAS----RTMTKEQAASTAAAFLQVLGINES...QLDRLHTVAAEDLLKA-----ADQLRIAE-----KENIFQLFFQPALDPKTLPEEPEKSIAEGAASGIPLLIGTTRDEGYF...TLELPFVFGNLDELERMAKAEITDEVKQLSHTIQSAWTTFAKTGNPST---EAVNWPAYHEESRETVILDS-EITIENDPESEKRQKLF------ --IIIA...WNPNTDLSEDCLYLNVWIPAPKPKNATVLIWIYGGGFQTGTSSLHVYDGKFLARVERVIVVSMNYRVGALGFLALPG-NPEAPGNMGLFDQQLALQWVQKNIAAFGGN

  8. Engineering cytochrome p450 enzymes.

    Gillam, Elizabeth M J

    2008-01-01

    The last 20 years have seen the widespread and routine application of methods in molecular biology such as molecular cloning, recombinant protein expression, and the polymerase chain reaction. This has had implications not only for the study of toxicological mechanisms but also for the exploitation of enzymes involved in xenobiotic clearance. The engineering of P450s has been performed with several purposes. The first and most fundamental has been to enable successful recombinant expression in host systems such as bacteria. This in turn has led to efforts to solubilize the proteins as a prerequisite to crystallization and structure determination. Lagging behind has been the engineering of enzyme activity, hampered in part by our still-meager comprehension of fundamental structure-function relationships in P450s. However, the emerging technique of directed evolution holds promise in delivering both engineered enzymes for use in biocatalysis and incidental improvements in our understanding of sequence-structure and sequence-function relationships, provided that data mining can extract the fundamental correlations underpinning the data. From the very first studies on recombinant P450s, efforts were directed toward constructing fusions between P450s and redox partners in the hope of generating more efficient enzymes. While this aim has been allowed to lie fallow for some time, this area merits further investigation as does the development of surface-displayed P450 systems for biocatalytic and biosensor applications. The final application of engineered P450s will require other aspects of their biology to be addressed, such as tolerance to heat, solvents, and high substrate and product concentrations. The most important application of these enzymes in toxicology in the near future is likely to be the biocatalytic generation of drug metabolites for the pharmaceutical industry. Further tailoring will be necessary for specific toxicological applications, such as in

  9. Involvement of metals in enzymatic and nonenzymatic decomposition of C-terminal alpha-hydroxyglycine to amide: an implication for the catalytic role of enzyme-bound zinc in the peptidylamidoglycolate lyase reaction.

    Takahashi, Kenichi; Harada, Saori; Higashimoto, Yuichiro; Shimokawa, Chizu; Sato, Hideaki; Sugishima, Masakazu; Kaida, Yasuhiko; Noguchi, Masato

    2009-02-24

    The peptide C-terminal amide group essential for the full biological activity of many peptide hormones is produced by consecutive actions of peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidylamidoglycolate lyase (PAL); PHM catalyzes the hydroxylation of C-terminal glycine, and PAL decomposes the peptidyl-alpha-hydroxyglycine to an amidated peptide and glyoxylate. PAL contains 1 mol of zinc, but its role, catalytic or structural, has not yet been clarified. In this study, we found that a series of transition metals, Mn(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+), and Cd(2+), catalyze the nonenzymatic decomposition of the hydroxyglycine intermediate in a concentration-dependent manner. The second-order rate constant of the metal catalysis increased with elevation of pH, indicating that the hydrated metal acts as a general base. Extensive removal of the enzyme-bound metals remarkably diminished the PAL activity; k(cat) of the metal-depleted enzyme retaining 0.1 mol of zinc decreased to 3.2 s(-1) from 25.7 s(-1) of the wild-type enzyme. Among a series of divalent metals tested, Zn(2+), Co(2+), and Cd(2+) could fully restore the PAL activity of the metal-depleted enzyme. Especially, Zn substitution reproduced the steady-state parameters of the wild-type enzyme. On the other hand, Co and Cd substitution largely altered the kinetic parameters; the k(cat) increased 3- and 5-fold and the K(m) for the substrate increased 2.5- and 4-fold, respectively. These observations support that the enzyme-bound zinc plays a catalytic role, rather than a structural role, in the PAL reaction through the action of zinc-bound water as a general base.

  10. File list: Oth.Bld.05.JMJD1C.AllCell [Chip-atlas[Archive

    Full Text Available Oth.Bld.05.JMJD1C.AllCell hg19 TFs and others JMJD1C Blood SRX1304576,SRX1304581,SR...X1304579,SRX763970 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Bld.05.JMJD1C.AllCell.bed ...

  11. File list: Oth.ALL.50.JMJD1C.AllCell [Chip-atlas[Archive

    Full Text Available Oth.ALL.50.JMJD1C.AllCell hg19 TFs and others JMJD1C All cell types SRX1304576,SRX1...304581,SRX1304579,SRX763970 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.ALL.50.JMJD1C.AllCell.bed ...

  12. File list: Oth.ALL.20.JMJD1C.AllCell [Chip-atlas[Archive

    Full Text Available Oth.ALL.20.JMJD1C.AllCell hg19 TFs and others JMJD1C All cell types SRX1304576,SRX1...304581,SRX1304579,SRX763970 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.ALL.20.JMJD1C.AllCell.bed ...

  13. File list: Oth.Bld.10.JMJD1C.AllCell [Chip-atlas[Archive

    Full Text Available Oth.Bld.10.JMJD1C.AllCell hg19 TFs and others JMJD1C Blood SRX1304576,SRX1304581,SR...X1304579,SRX763970 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Bld.10.JMJD1C.AllCell.bed ...

  14. 7 CFR 1c.123 - Early termination of research support: Evaluation of applications and proposals.

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Early termination of research support: Evaluation of applications and proposals. 1c.123 Section 1c.123 Agriculture Office of the Secretary of Agriculture PROTECTION OF HUMAN SUBJECTS § 1c.123 Early termination of research support: Evaluation of applications...

  15. Data of evolutionary structure change: 1C75A-1CTJA [Confc[Archive

    Full Text Available 1C75A-1CTJA 1C75 1CTJ A A -VD---AEAVVQQKCISCHGGDLTGASA--PAID-KAGA... A 1C75A AGANY-----SEEEI ...ure> HHHH----- HHHHure> ATOM 398 C... 481 GLU CA 425 GLU CA 452 ILE CA 652 1CT...J A 1CTJA AIEQFLDGGF

  16. HbA1c measurements from dried blood spots : validation and patient satisfaction

    Fokkema, Margaretha; Bakker, Andries J; de Boer, Fokje; Kooistra, Jeltsje; de Vries, Sifra; Wolthuis, Albert

    2009-01-01

    Background: This study evaluates HbA1c measurements from dried blood spots collected on filter paper and compares HbA1c from filter paper (capillary blood) with HbA1c measured in venous blood. Methods: Patient satisfaction was evaluated using a questionnaire. The performance with the filter paper me

  17. Changing from glucose to HbA1c for diabetes diagnosis

    Nielsen, Aneta Aleksandra; Petersen, Per Hyltoft; Green, Anders;

    2014-01-01

    BACKGROUND: In Denmark, the use of HbA1c in the diagnosis of diabetes was adopted from March 2012. We evaluated the change in the number of diabetes cases diagnosed by haemoglobin A1c (HbA1c) versus fasting venous plasma glucose (FPG), and estimated the influence of analytical variation and bias ...

  18. To Your Health: NLM update transcript - Beyond A1C for diabetes treatment

    ... the 'resources' section of MedlinePlus.gov's A1C health topic page . The National Diabetes Education Program provides additional information ... the 'resources' section of MedlinePlus.gov's A1C health topic page. MedlinePlus.gov's A1C health topic page additionally provides ...

  19. Data of evolutionary structure change: 1C7MA-1CTYA [Confc[Archive

    Full Text Available 1C7MA-1CTYA 1C7M 1CTY A A MADPAAGEKVFGK-CKACHKLDG--NDGVGPHLNGVVGR...ID> A 1C7MA HKLDG--NDGVG ...ure> EE -- ure> ATOM 234 CA HIS A ...hain> 1CTY A 1CTYA H...TVEKGGPHKVG ure> ure>

  20. Data of evolutionary structure change: 1C5DA-3FCTA [Confc[Archive

    Full Text Available 1C5DA-3FCTA 1C5D 3FCT A A DIQMTQSPPSLSASLGDKVTITCQASQDINKYIAWYQQK...>A 1C5DA LQYGN-LYTFG ...ure>EE - ure> ATOM 3925 CA LEU A 89 -8.668 18.46...ne> 3FCT A 3FCT...A QQYSSYPLTFG ure>EE EE

  1. 7 CFR 1c.118 - Applications and proposals lacking definite plans for involvement of human subjects.

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Applications and proposals lacking definite plans for involvement of human subjects. 1c.118 Section 1c.118 Agriculture Office of the Secretary of Agriculture PROTECTION OF HUMAN SUBJECTS § 1c.118 Applications and proposals lacking definite plans for involvement...

  2. Enzyme inhibition by iminosugars

    López, Óscar; Qing, Feng-Ling; Pedersen, Christian Marcus

    2013-01-01

    Imino- and azasugar glycosidase inhibitors display pH dependant inhibition reflecting that both the inhibitor and the enzyme active site have groups that change protonation state with pH. With the enzyme having two acidic groups and the inhibitor one basic group, enzyme-inhibitor complexes...

  3. Mutations of the Imprinted CDKN1C Gene as a Cause of the Overgrowth Beckwith-Wiedemann Syndrome: Clinical Spectrum and Functional Characterization.

    Brioude, Frederic; Netchine, Irène; Praz, Francoise; Le Jule, Marilyne; Calmel, Claire; Lacombe, Didier; Edery, Patrick; Catala, Martin; Odent, Sylvie; Isidor, Bertrand; Lyonnet, Stanislas; Sigaudy, Sabine; Leheup, Bruno; Audebert-Bellanger, Séverine; Burglen, Lydie; Giuliano, Fabienne; Alessandri, Jean-Luc; Cormier-Daire, Valérie; Laffargue, Fanny; Blesson, Sophie; Coupier, Isabelle; Lespinasse, James; Blanchet, Patricia; Boute, Odile; Baumann, Clarisse; Polak, Michel; Doray, Berenice; Verloes, Alain; Viot, Géraldine; Le Bouc, Yves; Rossignol, Sylvie

    2015-09-01

    Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder associating macroglossia, abdominal wall defects, visceromegaly, and a high risk of childhood tumor. Molecular anomalies are mostly epigenetic; however, mutations of CDKN1C are implicated in 8% of cases, including both sporadic and familial forms. We aimed to describe the phenotype of BWS patients with CDKN1C mutations and develop a functional test for CDKN1C mutations. For each propositus, we sequenced the three exons and intron-exon boundaries of CDKN1C in patients presenting a BWS phenotype, including abdominal wall defects, without 11p15 methylation defects. We developed a functional test based on flow cytometry. We identified 37 mutations in 38 pedigrees (50 patients and seven fetuses). Analysis of parental samples when available showed that all mutations tested but one was inherited from the mother. The four missense mutations led to a less severe phenotype (lower frequency of exomphalos) than the other 33 mutations. The following four tumors occurred: one neuroblastoma, one ganglioneuroblastoma, one melanoma, and one acute lymphoid leukemia. Cases of BWS caused by CDKN1C mutations are not rare. CDKN1C sequencing should be performed for BWS patients presenting with abdominal wall defects or cleft palate without 11p15 methylation defects or body asymmetry, or in familial cases of BWS.

  4. Haemoglobin J-Baltimore can be detected by HbA1c electropherogram but with underestimated HbA1c value.

    Brunel, Valéry; Lahary, Agnčs; Chagraoui, Abdeslam; Thuillez, Christian

    2016-01-01

    Glycated haemoglobin (HbA(1c)) is considered the gold standard for assessing diabetes compensation and treatment. In addition, fortuitous detection of haemoglobin variants during HbA1c measurement is not rare. Recently, two publications reported different conclusions on accuracy of HbA(1c) value using capillary electrophoresis method in presence of haemoglobin J-Baltimore (HbJ).
Here we describe the fortuitous detection of unknown HbJ using capillary electrophoresis for measurement of HbA(1c). A patient followed for gestational diabetes in our laboratory presented unknown haemoglobin on Capillarys 2 Flex Piercing analyser which was identified as HbJ. HbJ is not associated with haematological abnormalities. High Performance Liquid Chromatography methods are known to possibly underestimate HbA(1c) value in the presence of this variant. This variant and its glycated form are clearly distinguished on electropherogram but HbJ was responsible for underestimating the true area of HbA(1c).
 Capillary electrophoresis is a good method for detecting HbJ but does not seem suitable for evaluation of HbA(1C) value in patients in presence of HbJ variant.

  5. Role of positron emission tomography and bone scintigraphy in the evaluation of bone involvement in metastatic pheochromocytoma and paraganglioma: specific implications for succinate dehydrogenase enzyme subunit B gene mutations.

    Zelinka, T.; Timmers, H.J.L.M.; Kozupa, A.; Chen, C.C.; Carrasquillo, J.A.; Reynolds, J.C.; Ling, A.; Eisenhofer, G.; Lazurova, I.; Adams, K.T.; Whatley, M.A.; Widimsky, J.Jr.; Pacak, K.

    2008-01-01

    We performed a retrospective analysis of 71 subjects with metastatic pheochromocytoma and paraganglioma (30 subjects with mutation of succinate dehydrogenase enzyme subunit B (SDHB) gene and 41 subjects without SDHB mutation). Sixty-nine percent presented with bone metastases (SDHB +/-: 77% vs 63%),

  6. Use of fructosyl peptide oxidase for HbA1c assay.

    Yonehara, Satoshi; Inamura, Norio; Fukuda, Miho; Sugiyama, Koji

    2015-03-01

    ARKRAY, Inc developed the world's first automatic glycohemoglobin analyzer based on HPLC (1981). After that, ARKRAY developed enzymatic HbA1c assay "CinQ HbA1c" with the spread and diversification of HbA1c measurement (2007). CinQ HbA1c is the kit of Clinical Chemistry Analyzer, which uses fructosyl peptide oxidase (FPOX) for a measurement reaction. This report mainly indicates the developmental background, measurement principle, and future of the enzymatic method HbA1c reagent.

  7. The synthetic retinoid AGN 193109 but not retinoic acid elevates CYP1A1 levels in mouse embryos and Hepa-1c1c7 cells.

    Soprano, D R; Gambone, C J; Sheikh, S N; Gabriel, J L; Chandraratna, R A; Soprano, K J; Kochhar, D M

    2001-07-15

    The synthetic retinoid AGN 193109 is a potent pan retinoic acid receptor (RAR) antagonist. Treatment of pregnant mice with a single oral 1 mg/kg dose of this antagonist on day 8 postcoitum results in severe craniofacial (median cleft face or frontonasal deficiency) and eye malformations in virtually all exposed fetuses. Using differential display analysis, we have determined that CYP1A1 mRNA levels are elevated in mouse embryos 6 h following treatment with AGN 193109. Similarly, an elevation in CYP1A1 mRNA levels, protein levels, and aryl hydrocarbon hydoxylase activity occurs in Hepa-1c1c7 cells, with the maximal elevation observed when the cells were treated with 10(-5) M AGN 193109 for 4 to 8 h. Elevation in CYP1A1 mRNA levels in mouse embryos and Hepa-1c1c7 cells does not occur upon treatment with the natural retinoid, all-trans-retinoic acid. Finally, elevation in CYP1A1 mRNA levels was not observed when mutant Hepa-1c1c7 cells, which are defective in either the aryl hydrocarbon receptor (AhR) or aryl hydrocarbon receptor nuclear translocator (ARNT), were treated with AGN 193109. This suggests that the AhR/ARNT pathway and not the RAR/RXR pathway is mediating the elevation of CYP1A1 mRNA levels by AGN 193109, at least in the Hepa-1c1c7 cells. This is the first example of a retinoid that displays the abililty to regulate both the RAR/RXR and AhR/ARNT transcriptional regulatory pathways.

  8. Enzyme kinetics of conjugating enzymes: PAPS sulfotransferase.

    James, Margaret O

    2014-01-01

    The sulfotransferase (SULT) enzymes catalyze the formation of sulfate esters or sulfamates from substrates that contain hydroxy or amine groups, utilizing 3'-phosphoadenosyl-5'-phosphosulfate (PAPS) as the donor of the sulfonic group. The rate of product formation depends on the concentrations of PAPS and substrate as well as the sulfotransferase enzyme; thus, if PAPS is held constant while varying substrate concentration (or vice versa), the kinetic constants derived are apparent constants. When studied over a narrow range of substrate concentrations, classic Michaelis-Menten kinetics can be observed with many SULT enzymes and most substrates. Some SULT enzymes exhibit positive or negative cooperativity during conversion of substrate to product, and the kinetics fit the Hill plot. A characteristic feature of most sulfotransferase-catalyzed reactions is that, when studied over a wide range of substrate concentrations, the rate of product formation initially increases as substrate concentration increases, then decreases at high substrate concentrations, i.e., they exhibit substrate inhibition or partial substrate inhibition. This chapter gives an introduction to sulfotransferases, including a historical note, the nomenclature, a description of the function of SULTs with different types of substrates, presentation of examples of enzyme kinetics with SULTs, and a discussion of what is known about mechanisms of substrate inhibition in the sulfotransferases.

  9. Transgenic restorer rice line T1c-19 with stackedcry1C*/bargenes has low weediness potential without selection pressure

    HUANG Yao; LI Ji-kun; QIANG Sheng; DAI Wei-min; SONG Xiao-ling

    2016-01-01

    Stacked (insect and herbicide resistant) transgenic rice T1c-19 withcry1C*/bargenes, its receptor rice Minghui 63 (herein MH63) and a local two-line hybridindica rice Fengliangyou Xiang 1 (used as a control) were compared for agronomic performance under ifeld conditions without the relevant selection pressures. Agronomic traits (plant height, tiler number, and aboveground dry biomass), reproductive ability (polen viability, panicle length, and ifled grain number of main pani-cles, seed set, and grain yield), and weediness characteristics (seed shattering, seed overwintering ability, and volunteer seedling recruitment) were used to assess the potential weediness without selection pressure of stacked transgene rice T1c-19. In wet direct-seeded and transplanted rice ifelds, T1c-19 and its receptor MH63 performed similarly regarding vegetative growth and reproductive ability, but both of them were signiifcantly inferior to the control. T1c-19 did not display weed characteristics; it had weak overwintering ability, low seed shattering and failed to establish volunteers. Exogenous insect and herbicide resistance genes did not confer competitive advantage to transgenic rice T1c-19 grown in the ifeld without the relevant selection pressures.

  10. Identification of a novel polyfluorinated compound as a lead to inhibit the human enzymes aldose reductase and AKR1B10: structure determination of both ternary complexes and implications for drug design.

    Cousido-Siah, Alexandra; Ruiz, Francesc X; Mitschler, André; Porté, Sergio; de Lera, Ángel R; Martín, María J; Manzanaro, Sonia; de la Fuente, Jesús A; Terwesten, Felix; Betz, Michael; Klebe, Gerhard; Farrés, Jaume; Parés, Xavier; Podjarny, Alberto

    2014-03-01

    Aldo-keto reductases (AKRs) are mostly monomeric enzymes which fold into a highly conserved (α/β)8 barrel, while their substrate specificity and inhibitor selectivity are determined by interaction with residues located in three highly variable external loops. The closely related human enzymes aldose reductase (AR or AKR1B1) and AKR1B10 are of biomedical interest because of their involvement in secondary diabetic complications (AR) and in cancer, e.g. hepatocellular carcinoma and smoking-related lung cancer (AKR1B10). After characterization of the IC50 values of both AKRs with a series of polyhalogenated compounds, 2,2',3,3',5,5',6,6'-octafluoro-4,4'-biphenyldiol (JF0064) was identified as a lead inhibitor of both enzymes with a new scaffold (a 1,1'-biphenyl-4,4'-diol). An ultrahigh-resolution X-ray structure of the AR-NADP(+)-JF0064 complex has been determined at 0.85 Å resolution, allowing it to be observed that JF0064 interacts with the catalytic residue Tyr48 through a negatively charged hydroxyl group (i.e. the acidic phenol). The non-competitive inhibition pattern observed for JF0064 with both enzymes suggests that this acidic hydroxyl group is also present in the case of AKR1B10. Moreover, the combination of surface lysine methylation and the introduction of K125R and V301L mutations enabled the determination of the X-ray crystallographic structure of the corresponding AKR1B10-NADP(+)-JF0064 complex. Comparison of the two structures has unveiled some important hints for subsequent structure-based drug-design efforts.

  11. Synthesis of New Pyrazolo[5,1-c]triazine, Triazolo[5,1-c]triazine, Triazino[4,3-b]indazole and Benzimidazo[2,1-c]triazine Derivatives Incorporating Chromen-2-one Moiety

    Khalil, Mohamed A.; Sayed, Samia M.; Raslan, Mohamed A. [Aswan Univ., Aswan (Egypt)

    2013-10-15

    The versatile, hitherto unreported 3-(4-(2-phenyldiazenyl)-2-oxo-2H-chromen-3-yl)-3-oxopropanenitrile 3 was prepared by two convenient routes: either by the reaction of ethyl 4-(2-phenyldiazenyl)-2-oxo-2H-chromen-3-carboxylate 2 with acetonitrile in the presence of sodium hydride or by treatment of 4-(2-phenyldiazenyl)-3-(2-bromoacetyl)-2H-chromen-2-one 5 with potassium cyanide. Reaction of 3 with heterocyclic diazonium salts 6, 7, 14 and 17 furnished the corresponding hydrazones 8, 9, 15 and 18. The latter hydrazones underwent intramolecular cyclization into the corresponding pyrazolo[5,1-c]-1,2,4-triazine 10, 1,2,4-triazolo[5,1-c]-1,2,4-triazine 11, 1,2,4-triazino[4,3-b]indazole 16 and imidazo[2,1-c]-1,2,4-triazine 19 derivatives, respectively upon refluxing in pyridine.

  12. Residual glycosaminoglycan accumulation in mitral and aortic valves of a patient with attenuated MPS I (Scheie syndrome after 6 years of enzyme replacement therapy: Implications for early diagnosis and therapy

    Yohei Sato

    2015-12-01

    Full Text Available Mucopolysaccharidosis (MPS is an inherited metabolic disease caused by deficiency of the enzymes needed for glycosaminoglycan (GAG degradation. MPS type I is caused by the deficiency of the lysosomal enzyme alpha-l-iduronidase and is classified into Hurler syndrome, Scheie syndrome, and Hurler–Scheie syndrome based on disease severity and onset. Cardiac complications such as left ventricular hypertrophy, cardiac valve disease, and coronary artery disease are often observed in MPS type I. Enzyme replacement therapy (ERT has been available for MPS type I, but the efficacy of this treatment for cardiac valve disease is unknown. We report on a 56-year-old female patient with attenuated MPS I (Scheie syndrome who developed aortic and mitral stenosis and coronary artery narrowing. The cardiac valve disease progressed despite ERT and she finally underwent double valve replacement and coronary artery bypass grafting. The pathology of the cardiac valves revealed GAG accumulation and lysosomal enlargement in both the mitral and aortic valves. Zebra body formation was also confirmed using electron microscopy. Our results suggest that ERT had limited efficacy in previously established cardiac valve disease. Early diagnosis and initiation of ERT is crucial to avoid further cardiac complications in MPS type I.

  13. Glycated Hemoglobin (HbA1c): Clinical Applications of a Mathematical Concept

    Leow, Melvin Khee Shing

    2016-01-01

    Background and purpose: Glycated hemoglobin (HbA1c) reflects the cumulative glucose exposure of erythrocytes over a preceding time frame proportional to erythrocyte survival. HbA1c is thus an areal function of the glucose-time curve, an educationally useful concept to aid teaching and clinical judgment. Methods: An ordinary differential equation is formulated as a parsimonious model of HbA1c. The integrated form yields HbA1c as an area-under-the-curve (AUC) of a glucose-time profile. The rate constant of the HbA1c model is then derived using the validated regression equation in the ADAG study that links mean blood glucose and HbA1c with a very high degree of goodness-of-fit. Results: This model has didactic utility to enable patients, biomedical students and clinicians to appreciate how HbA1c may be conceptually inferred from discrete blood glucose values using continuous glucose monitoring system (CGMS) or self-monitored blood glucose (SMBG) glucometer readings as shown in the examples. It can be appreciated how hypoglycemia can occur with rapid HbA1c decline despite poor glycemic control. Conclusions: Being independent of laboratory assay pitfalls, computed ‘virtual’ HbA1c serves as an invaluable internal consistency cross-check against laboratory-measured HbA1c discordant with SMBG readings suggestive of inaccurate/fraudulent glucometer records or hematologic disorders including thalassemia and hemoglobinopathy. This model could be implemented within portable glucometers, CGMS devices and even smartphone apps for deriving tentative ‘virtual’ HbA1c from serial glucose readings as an adjunct to measured HbA1c. Such predicted ‘virtual’ HbA1c readily accessible via glucometers may serve as feedback to modify behavior and empower diabetic patients to achieve better glycemic control. PMID:27708483

  14. The transcriptional factor LBP-1c/CP2/LSF gene on chromosome 12 is a genetic determinant of Alzheimer's disease.

    Lambert, J C; Goumidi, L; Vrièze, F W; Frigard, B; Harris, J M; Cummings, A; Coates, J; Pasquier, F; Cottel, D; Gaillac, M; St Clair, D; Mann, D M; Hardy, J; Lendon, C L; Amouyel, P; Chartier-Harlin, M C

    2000-09-22

    Although the varepsilon4 allele of the apolipoprotein E gene appears as an important biological marker for Alzheimer's disease (AD) susceptibility, other genetic determinants are clearly implicated in the AD process. Here, we propose that a genetic variation in the transcriptional factor LBP-1c/CP2/LSF gene, located close to the LRP locus, is a genetic susceptibility factor for AD. We report an association between a non-coding polymorphism (G-->A) in the 3'-untranslated region of this gene and sporadic AD in French and British populations and a similar trend in a North American population. The combined analysis of these three independent populations provides evidence of a protective effect of the A allele (OR = 0.58, 95% CI 0.44-0.75). We describe a potential biologically relevant role for the A allele whereby it reduces binding to nuclear protein(s). The absence of the A allele was associated with a lower LBP-1c/CP2/LSF gene expression in lymphocytes from AD cases compared with controls. Our data suggest that polymorphic variation in the implication of the LBP-1c/CP2/LSF gene may be important for the pathogenesis of AD, particularly since LBP-1c/CP2/LSF interacts with proteins such as GSKbeta, Fe65 and certain factors involved in the inflammatory response.

  15. Enzymes for improved biomass conversion

    Brunecky, Roman; Himmel, Michael E.

    2016-02-02

    Disclosed herein are enzymes and combinations of the enzymes useful for the hydrolysis of cellulose and the conversion of biomass. Methods of degrading cellulose and biomass using enzymes and cocktails of enzymes are also disclosed.

  16. Occurrence of S and F1C/S-related fimbrial determinants and their expression in Escherichia coli strains isolated from extraintestinal infections.

    Sokolowska-Köhler, W; Schönian, G; Bollmann, R; Schubert, A; Parschau, J; Seeberg, A; Presber, W

    1997-05-01

    The presence of S and F1C/S-related fimbrial determinants was determined in 462 E. coli strains obtained from different extraintestinal infections and in 162 control isolates of E. coli by using two different DNA probes: an oligonucleotide probe consisting of three oligonucleotides that bind specifically to the S adhesin gene and a polynucleotide probe which is not able to distinguish between S, F1C, and S-related sequences. The expression of S and F1C phenotypes was tested by dot enzyme immunoassay with the corresponding monoclonal antibodies. S fimbriae genotypes were observed more frequently in septic (25%) and urinary (12%) isolates of E. coli than in faecal and water isolates (1%) and often occurred together with O2, O6, O18 and O83 antigens. F1C/S-related fimbrial DNA was detected with a higher frequency in UTI isolates (26%) than in septic (16%) and faecal (10%) isolates and was most frequently associated with O4, O6, and O75 serotypes. Since the production of S and F1C fimbriae was comparatively rare in all clinical and control isolates of E. coli, DNA hybridization assays which allow the sensitive and specific detection of fimbrial determinants even in the absence of their expression are preferable to phenotypic assays.

  17. Unhairing with enzymes

    Crispim, A.; Mota, M.

    2003-01-01

    The use of enzymes in the leather industry is increasing and their application is being widened to include operations such as de-greasing, unhairing and other wet-end operations. Enzymes can also be used to assist with recycling leather wastes as well as to avoid pollution. The present work is devoted to illustrate the potential application of enzymes in unhairing without hair destruction. Enzymatic unhairing is based upon the weakening of the epidermis basal layer to which the hair is at...

  18. Reduced Combustion Mechanism for C1-C4 Hydrocarbons and its Application in CFD Flare Modeling.

    Damodara, Vijaya; Chen, Daniel H; Lou, Helen H; Rasel, Kader M A; Richmond, Peyton; Wang, Anan; Li, Xianchang

    2016-12-20

    Emissions from flares constitute unburned hydrocarbons, CO, soot, and other partially burned and altered hydrocarbons along with CO2 and water. Soot or visible smoke is of particular concern for flare operators /regulatory agencies. The goal of the study is to develop a computational fluid dynamics (CFD) model capable of predicting flare combustion efficiency (CE) and soot emission. Since detailed combustion mechanisms are too complicated for (CFD) application, a 50-species reduced mechanism, LU 3.0.1, was developed. LU 3.0.1 is capable of handling C4 hydrocarbons and soot precursor species (C2H2, C2H4, C6H6). The new reduced mechanism LU 3.0.1 was first validated against experimental performance indicators: laminar flame speed, adiabatic flame temperature, and ignition delay. Further, CFD simulations using LU 3.0.1 were run to predict soot emission and CE of air-assisted flare tests conducted in 2010 in Tulsa, Oklahoma using ANSYS FLUENT software. Non-premixed Probability Density Function (PDF) model and Eddy Dissipation Concept (EDC) model results are discussed. It is also noteworthy that, when used in conjunction with the EDC turbulence-chemistry model, LU 3.0.1 can reasonably predict volatile organic compound (VOC) emissions as well. Implication statement A reduced combustion mechanism containing 50 C1-C4 species and soot precursors has been developed and validated against experimental data. The combustion mechanism is then employed in the computational fluid dynamics (CFD) of modeling of soot emission and combustion efficiency (CE) of controlled flares for which experimental soot and CE data are available. The validated CFD modeling tools are useful for oil, gas, and chemical industries to comply with EPA's mandate to achieve smokeless flaring with a high CE.

  19. Lipid and liver abnormalities in haemoglobin A1c-defined prediabetes and type 2 diabetes

    Calanna, S; Scicali, R; Di Pino, A;

    2014-01-01

    BACKGROUND AND AIMS: We aimed to investigate lipid abnormalities and liver steatosis in patients with HbA1c-defined prediabetes and type 2 diabetes compared to individuals with HbA1c-defined normoglycaemia. METHODS AND RESULTS: Ninety-one subjects with prediabetes according to HbA1c, i.e. from 5.......7 to 6.4% (39-46 mmol/mol), 50 newly diagnosed patients with HbA1c-defined type 2 diabetes (HbA1c ≥6.5% [≥48 mmol/mol]), and 67 controls with HbA1c lower than 5.7% (... of the liver, and BARD (body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes) score for evaluation of liver fibrosis, were performed in all subjects. In comparison to controls, subjects with prediabetes were characterised by: lower apolipoprotein AI and HDL cholesterol levels...

  20. Microbial amylolytic enzymes.

    Vihinen, M; Mäntsälä, P

    1989-01-01

    Starch-degrading, amylolytic enzymes are widely distributed among microbes. Several activities are required to hydrolyze starch to its glucose units. These enzymes include alpha-amylase, beta-amylase, glucoamylase, alpha-glucosidase, pullulan-degrading enzymes, exoacting enzymes yielding alpha-type endproducts, and cyclodextrin glycosyltransferase. Properties of these enzymes vary and are somewhat linked to the environmental circumstances of the producing organisms. Features of the enzymes, their action patterns, physicochemical properties, occurrence, genetics, and results obtained from cloning of the genes are described. Among all the amylolytic enzymes, the genetics of alpha-amylase in Bacillus subtilis are best known. Alpha-Amylase production in B. subtilis is regulated by several genetic elements, many of which have synergistic effects. Genes encoding enzymes from all the amylolytic enzyme groups dealt with here have been cloned, and the sequences have been found to contain some highly conserved regions thought to be essential for their action and/or structure. Glucoamylase appears usually in several forms, which seem to be the results of a variety of mechanisms, including heterogeneous glycosylation, limited proteolysis, multiple modes of mRNA splicing, and the presence of several structural genes.

  1. Adenylate-forming enzymes

    Schmelz, Stefan; Naismith, James H.

    2012-01-01

    Thioesters, amides and esters are common chemical building blocks in a wide array of natural products. The formation of these bonds can be catalyzed in a variety of ways. For chemists, the use of an activating group is a common strategy and adenylate enzymes are exemplars of this approach. Adenylating enzymes activate the otherwise unreactive carboxylic acid by transforming the normal hydroxyl leaving group into adenosine monophosphate. Recently there have been a number of studies of such enzymes and in this review we suggest a new classification scheme. The review highlights the diversity in enzyme fold, active site architecture and metal coordination that has evolved to catalyze this particular reaction. PMID:19836944

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

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

    2015-05-17

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

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

    Sezgin Vatansever

    2015-05-01

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

  4. Hemoglobin A1c Versus Oral Glucose Tolerance Test in Postpartum Diabetes Screening

    Picón, María José; Murri, Mora; Muñoz, Araceli; Fernández-García, José Carlos; Gomez-Huelgas, Ricardo; Francisco J Tinahones

    2012-01-01

    OBJECTIVE To determine the usefulness of measuring hemoglobin A1c (A1C), alone or combined with the fasting glucose test, compared with the oral glucose tolerance test (OGTT) for the reassessment of the carbohydrate metabolism status in postpartum women with a history of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS We evaluated the status of carbohydrate metabolism by performing the OGTT and fasting glucose and A1C tests in 231 postpartum women with prior GDM 1 year after ...

  5. Hemoglobin A1c May Be an Inadequate Diagnostic Tool for Diabetes Mellitus in Anemic Subjects

    Jung Il Son

    2013-10-01

    Full Text Available BackgroundRecently, a hemoglobin A1c (HbA1c level of 6.5% has been determined to be a criterion for diabetes mellitus (DM, and it is a widely used marker for the diagnosis of DM. However, HbA1c may be influenced by a number of factors. Anemia is one of the most prevalent diseases with an influence on HbA1c; however, its effect on HbA1c varies based on the variable pathophysiology of anemia. The aim of this study was to determine the effect of anemia on HbA1c levels.MethodsAnemic subjects (n=112 and age- and sex-matched controls (n=217 who were drug naive and suspected of having DM were enrolled. The subjects underwent an oral glucose tolerance test and HbA1c simultaneously. We compared mean HbA1c and its sensitivity and specificity for diagnosing DM between each subgroup.ResultsClinical characteristics were found to be similar between each subgroup. Also, when glucose levels were within the normal range, the difference in mean HbA1c was not significant (P=0.580. However, when plasma glucose levels were above the diagnostic cutoff for prediabetes and DM, the mean HbA1c of the anemic subgroup was modestly higher than in the nonanemic group. The specificity of HbA1c for diagnosis of DM was significantly lower in the anemic subgroup (P<0.05.ConclusionThese results suggest that the diagnostic significance of HbA1c might be limited in anemic patients.

  6. Targeting the MUC1-C oncoprotein inhibits self-renewal capacity of breast cancer cells.

    Alam, Maroof; Rajabi, Hasan; Ahmad, Rehan; Jin, Caining; Kufe, Donald

    2014-05-15

    The capacity of breast cancer cells to form mammospheres in non-adherent serum-free culture is used as a functional characteristic of the self-renewing stem-like cell population. The present studies demonstrate that silencing expression of the MUC1-C oncoprotein inhibits growth of luminal MCF-7 and HER2-overexpressing SKBR3 breast cancer cells as mammospheres. We also show that triple-negative MDA-MB-468 breast cancer cells are dependent on MUC1-C for growth as mammospheres and tumor xenografts. Similar results were obtained when MUC1-C function was inhibited by expression of a MUC1-C(CQCAQA) mutant. Moreover, treatment with the MUC1-C inhibitor GO-203, a cell penetrating peptide that binds to the MUC1-C cytoplasmic domain and blocks MUC1-C function, confirmed the importance of this target for self-renewal. The mechanistic basis for these findings is supported by the demonstration that MUC1-C activates NF-κB, occupies the IL-8 promoter with NF-κB, and induces IL-8 transcription. MUC1-C also induces NF-κB-dependent expression of the IL-8 receptor, CXCR1. In concert with these results, targeting MUC1-C with GO-203 suppresses IL-8/CXCR1 expression and disrupts the formation of established mammospheres. Our findings indicate that MUC1-C contributes to the self-renewal of breast cancer cells by activating the NF-κBIL-8/CXCR1 pathway and that targeting MUC1-C represents a potential approach for the treatment of this population.

  7. Should Studies of Diabetes Treatment Stratification Correct for Baseline HbA1c?

    Angus G Jones

    Full Text Available Baseline HbA1c is a major predictor of response to glucose lowering therapy and therefore a potential confounder in studies aiming to identify other predictors. However, baseline adjustment may introduce error if the association between baseline HbA1c and response is substantially due to measurement error and regression to the mean. We aimed to determine whether studies of predictors of response should adjust for baseline HbA1c.We assessed the relationship between baseline HbA1c and glycaemic response in 257 participants treated with GLP-1R agonists and assessed whether it reflected measurement error and regression to the mean using duplicate 'pre-baseline' HbA1c measurements not included in the response variable. In this cohort and an additional 2659 participants treated with sulfonylureas we assessed the relationship between covariates associated with baseline HbA1c and treatment response with and without baseline adjustment, and with a bias correction using pre-baseline HbA1c to adjust for the effects of error in baseline HbA1c.Baseline HbA1c was a major predictor of response (R2 = 0.19,β = -0.44,p<0.001.The association between pre-baseline and response was similar suggesting the greater response at higher baseline HbA1cs is not mainly due to measurement error and subsequent regression to the mean. In unadjusted analysis in both cohorts, factors associated with baseline HbA1c were associated with response, however these associations were weak or absent after adjustment for baseline HbA1c. Bias correction did not substantially alter associations.Adjustment for the baseline HbA1c measurement is a simple and effective way to reduce bias in studies of predictors of response to glucose lowering therapy.

  8. ADD1/SREBP1c activates the PGC1-alpha promoter in brown adipocytes

    Hao, Qin; Hansen, Jacob B; Petersen, Rasmus K

    2010-01-01

    regulatory element-binding protein-1c (SREBP1c) and peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC1alpha) in brown and inguinal white adipose tissues, but not in epididymal white adipose tissue. Using in vitro models of white and brown adipocytes we demonstrate that beta......-adrenergic stimulation induced expression of LXRalpha, ADD1/SREBP1c and PGC1alpha in cells with a brown-like adipose phenotype. We demonstrate that ADD1/SREBP1c is a powerful inducer of PGC1alpha expression via a conserved E box in the proximal promoter and that beta-adrenergic stimulation led to recruitment of ADD1...

  9. Thyroid hormone transport and metabolism by OATP1C1 and consequences of genetic variation

    van der Deure, Wendy M; Hansen, Pia Skov; Peeters, Robin P

    2008-01-01

    OATP1C1 has been characterized as a specific thyroid hormone transporter. Based on its expression in capillaries in different brain regions, OATP1C1 is thought to play a key-role in transporting thyroid hormone across the blood-brain barrier. For this reason, we studied the specificity of iodothy......OATP1C1 has been characterized as a specific thyroid hormone transporter. Based on its expression in capillaries in different brain regions, OATP1C1 is thought to play a key-role in transporting thyroid hormone across the blood-brain barrier. For this reason, we studied the specificity...... of iodothyronine transport by OATP1C1 in detail by analysis of thyroid hormone uptake in OATP1C1-transfected COS1 cells. Furthermore, we examined whether OATP1C1 is rate-limiting in subsequent thyroid hormone metabolism in cells co-transfected with deiodinases. We also studied the effect of genetic variation...... (T4S), little transport of rT3 and no transport of T3 or T3S compared to mock transfected cells. Metabolism of T4, T4S and rT3 by co-transfected deiodinases was greatly augmented in the presence of OATP1C1. The OATP1C1-intron3C>T, Pro143Thr and C3035T polymorphisms were not consistently associated...

  10. MUC1-C oncoprotein regulates glycolysis and pyruvate kinase M2 activity in cancer cells.

    Michio Kosugi

    Full Text Available Aerobic glycolysis in cancer cells is regulated by multiple effectors that include Akt and pyruvate kinase M2 (PKM2. Mucin 1 (MUC1 is a heterodimeric glycoprotein that is aberrantly overexpressed by human breast and other carcinomas. Here we show that transformation of rat fibroblasts by the oncogenic MUC1-C subunit is associated with Akt-mediated increases in glucose uptake and lactate production, consistent with the stimulation of glycolysis. The results also demonstrate that the MUC1-C cytoplasmic domain binds directly to PKM2 at the B- and C-domains. Interaction between the MUC1-C cytoplasmic domain Cys-3 and the PKM2 C-domain Cys-474 was found to stimulate PKM2 activity. Conversely, epidermal growth factor receptor (EGFR-mediated phosphorylation of the MUC1-C cytoplasmic domain on Tyr-46 conferred binding to PKM2 Lys-433 and inhibited PKM2 activity. In human breast cancer cells, silencing MUC1-C was associated with decreases in glucose uptake and lactate production, confirming involvement of MUC1-C in the regulation of glycolysis. In addition, EGFR-mediated phosphorylation of MUC1-C in breast cancer cells was associated with decreases in PKM2 activity. These findings indicate that the MUC1-C subunit regulates glycolysis and that this response is conferred in part by PKM2. Thus, the overexpression of MUC1-C oncoprotein in diverse human carcinomas could be of importance to the Warburg effect of aerobic glycolysis.

  11. Selective Coactivator Interactions in Gene Activation by SREBP-1a and -1c

    Toth, Julia I.; Datta, Shrimati; Athanikar, Jyoti N.; Freedman, Leonard P.; Osborne, Timothy F.

    2004-01-01

    Requisite levels of intracellular cholesterol and fatty acids are maintained in part by the sterol regulatory element binding proteins (SREBPs). Three major SREBP isoforms exist; SREBP-1a and SREBP-1c are expressed from overlapping mRNAs, whereas SREBP-2 is encoded by a separate gene. The active forms of SREBP-1a and SREBP-1c differ only at their extreme N termini; SREBP-1c lacks 28 aa present in SREBP-1a and instead contains 4 unique aa of its own. While the SREBP-1a and -1c isoforms differe...

  12. Effect of Long-Term Periodontal Care on Hemoglobin A1c in Type 2 Diabetes.

    Merchant, A T; Georgantopoulos, P; Howe, C J; Virani, S S; Morales, D A; Haddock, K S

    2016-04-01

    This was a prospective cohort study evaluating 126,805 individuals with diabetes and periodontal disease receiving care at all Veterans Administration medical centers and clinics in the United States from 2005 through 2012. The exposures were periodontal treatment at baseline (PT0) and at follow-up (PT2). The outcomes were change in HbA1c following initial treatment (ΔHbA1c1) and follow-up treatment (ΔHbA1c2), and diabetes control was defined as HbA1c at periodontal disease on glycemic control among individuals with type 2 diabetes. Participants were 64 y old on average, 97% were men, and 71% were white. At baseline, the average diabetes duration was 4 y, 12% of participants were receiving insulin, and 60% had HbA1c periodontal maintenance visit following baseline. Periodontal treatment at baseline and follow-up reduced HbA1c by -0.02% and -0.074%, respectively. Treatment at follow-up increased the likelihood of individuals achieving diabetes control by 5% and 3% at the HbA1c periodontal treatment at follow-up was greater (ΔHbA1c2 = -0.25%) among individuals with higher baseline HbA1c. Long-term periodontal care provided in a clinical setting improved long-term glycemic control among individuals with type 2 diabetes and periodontal disease.

  13. Use of Fructosyl Peptide Oxidase for HbA1c Assay

    Yonehara, Satoshi; Inamura, Norio; Fukuda, Miho; Sugiyama, Koji

    2015-01-01

    ARKRAY, Inc developed the world’s first automatic glycohemoglobin analyzer based on HPLC (1981). After that, ARKRAY developed enzymatic HbA1c assay “CinQ HbA1c” with the spread and diversification of HbA1c measurement (2007). CinQ HbA1c is the kit of Clinical Chemistry Analyzer, which uses fructosyl peptide oxidase (FPOX) for a measurement reaction. This report mainly indicates the developmental background, measurement principle, and future of the enzymatic method HbA1c reagent.

  14. Characterization of the aldo-keto reductase 1C gene cluster on pig chromosome 10: possible associations with reproductive traits

    Nonneman Dan J

    2006-09-01

    Full Text Available Abstract Background The rate of pubertal development and weaning to estrus interval are correlated and affect reproductive efficiency of swine. Quantitative trait loci (QTL for age of puberty, nipple number and ovulation rate have been identified in Meishan crosses on pig chromosome 10q (SSC10 near the telomere, which is homologous to human chromosome 10p15 and contains an aldo-keto reductase (AKR gene cluster with at least six family members. AKRs are tissue-specific hydroxysteroid dehydrogenases that interconvert weak steroid hormones to their more potent counterparts and regulate processes involved in development, homeostasis and reproduction. Because of their location in the swine genome and their implication in reproductive physiology, this gene cluster was characterized and evaluated for effects on reproductive traits in swine. Results Screening the porcine CHORI-242 BAC library with a full-length AKR1C4 cDNA identified 7 positive clones and sample sequencing of 5 BAC clones revealed 5 distinct AKR1C genes (AKR1CL2 and AKR1C1 through 4, which mapped to 126–128 cM on SSC10. Using the IMpRH7000rad and IMNpRH212000rad radiation hybrid panels, these 5 genes mapped between microsatellite markers SWR67 and SW2067. Comparison of sequence data with the porcine BAC fingerprint map show that the cluster of genes resides in a 300 kb region. Twelve SNPs were genotyped in gilts observed for age at first estrus and ovulation rate from the F8 and F10 generations of one-quarter Meishan descendants of the USMARC resource population. Age at puberty, nipple number and ovulation rate data were analyzed for association with genotypes by MTDFREML using an animal model. One SNP, a phenylalanine to isoleucine substitution in AKR1C2, was associated with age of puberty (p = 0.07 and possibly ovulation rate (p = 0.102. Two SNP in AKR1C4 were significantly associated with nipple number (p ≤ 0.03 and another possibly associated with age at puberty (p = 0

  15. CYP1B1 C4326G polymorphism and susceptibility to cervical cancer in Chinese Han women.

    Li, Ya; Tan, Shi-Qiao; Ma, Qian-Hong; Li, Lei; Huang, Zhong-Ying; Wang, Yan; Li, Shang-Wei

    2013-12-01

    Cytochrome P450 1B1 (CYP1B1) is a key P450 enzyme, which could catalyze the formation of 4-hydroxy estrogen metabolites and play a role in estrogen-dependent cancers. We hypothesized that genetic variant in CYP1B1 may modify individual susceptibility to cervical cancer. The aim of this study was to evaluate the association between CYP1B1 C4326G polymorphism and cervical cancer risk in Chinese women. We extracted the peripheral blood samples in 250 patients with cervical cancer and 250 female controls. The matrix-assisted laser desorption ionization time-of-flight mass spectrometry method and direct DNA sequencing were performed to detect the polymorphism. The frequencies of CC, CG, and GG genotypes of CYP1B1 C4326G in cases and controls were 66.0, 26.8, 7.2% and 75.2, 21.6, and 3.2%, respectively, and there was a significant difference between the two groups (P = 0.034). Compared with the wild-type CC genotype, the variant GG genotype was associated with a significantly increased risk of cervical cancer (adjusted OR = 2.30; 95% CI = 1.02, 5.50). Moreover, stratification analysis by age, smoking, drinking, human papillomaviruses (HPV) 16 or 18 carrier status, and family history of cervical cancer, we found that the variant genotypes containing the G allele were associated with a significantly increased risk of cervical cancer among HPV 16 or 18-positive individuals (adjusted OR = 2.85; 95% CI = 1.45, 5.62) and among women younger than 45 years old (adjusted OR = 1.87; 95% CI = 1.03, 3.37). These results suggest that CYP1B1 C4326G polymorphism may increase risk of cervical cancer in Chinese women, especially among young individuals with high-risk HPV infection.

  16. CELLULOSE DEGRADATION BY OXIDATIVE ENZYMES

    Maria Dimarogona

    2012-09-01

    Full Text Available Enzymatic degradation of plant biomass has attracted intensive research interest for the production of economically viable biofuels. Here we present an overview of the recent findings on biocatalysts implicated in the oxidative cleavage of cellulose, including polysaccharide monooxygenases (PMOs or LPMOs which stands for lytic PMOs, cellobiose dehydrogenases (CDHs and members of carbohydrate-binding module family 33 (CBM33. PMOs, a novel class of enzymes previously termed GH61s, boost the efficiency of common cellulases resulting in increased hydrolysis yields while lowering the protein loading needed. They act on the crystalline part of cellulose by generating oxidized and non-oxidized chain ends. An external electron donor is required for boosting the activity of PMOs. We discuss recent findings concerning their mechanism of action and identify issues and questions to be addressed in the future.

  17. Restriction enzyme mining for SNPs in genomes.

    Chuang, Li-Yeh; Yang, Cheng-Hong; Tsui, Ke-Hung; Cheng, Yu-Huei; Chang, Phei-Lang; Wen, Cheng-Hao; Chang, Hsueh-Wei

    2008-01-01

    Many different single nucleotide polymorphisms (SNPs) genotyping methods have been developed recently. However, most of them are expensive. Using restriction enzymes for SNP genotyping is a cost-effective method. However, restriction enzyme mining for SNPs in a genome sequence is still challenging for researchers who do not have a background in genomics and bioinformatics. In this review, the basic bioinformatics tools used for restriction enzyme mining for SNP genotyping are summarized and described. The objectives of this paper include: i) the introduction of SNPs, genotyping and PCR-restriction fragment length polymorphism (RFLP); ii) a review of components for genotyping software, including tools for primer design only or restriction enzyme mining only; iii) a review of software providing the flanking sequence for primer design; iv) recent advances in PCR-RFLP tools and natural and mutagenic PCR-RFLP; v) highlighting the strategy for restriction enzyme mining for SNP genotyping; vi) a discussion of potential problems for multiple PCR-RFLP. The different implications for restriction enzymes on sense and antisense strands are also discussed. Our PCR-RFLP freeware, SNP-RFLPing, is included in this review to illustrate many characteristics of PCR-RFLP software design. Future developments will include further sophistication of PCR-RFLP software in order to provide better visualization and a more interactive environment for SNP genotyping and to integrate the software with other tools used in association studies.

  18. Magnetically responsive enzyme powders

    Pospiskova, Kristyna, E-mail: kristyna.pospiskova@upol.cz [Regional Centre of Advanced Technologies and Materials, Palacky University, Slechtitelu 11, 783 71 Olomouc (Czech Republic); Safarik, Ivo, E-mail: ivosaf@yahoo.com [Regional Centre of Advanced Technologies and Materials, Palacky University, Slechtitelu 11, 783 71 Olomouc (Czech Republic); Department of Nanobiotechnology, Institute of Nanobiology and Structural Biology of GCRC, Na Sadkach 7, 370 05 Ceske Budejovice (Czech Republic)

    2015-04-15

    Powdered enzymes were transformed into their insoluble magnetic derivatives retaining their catalytic activity. Enzyme powders (e.g., trypsin and lipase) were suspended in various liquid media not allowing their solubilization (e.g., saturated ammonium sulfate and highly concentrated polyethylene glycol solutions, ethanol, methanol, 2-propanol) and subsequently cross-linked with glutaraldehyde. Magnetic modification was successfully performed at low temperature in a freezer (−20 °C) using magnetic iron oxides nano- and microparticles prepared by microwave-assisted synthesis from ferrous sulfate. Magnetized cross-linked enzyme powders were stable at least for two months in water suspension without leakage of fixed magnetic particles. Operational stability of magnetically responsive enzymes during eight repeated reaction cycles was generally without loss of enzyme activity. Separation of magnetically modified cross-linked powdered enzymes from reaction mixtures was significantly simplified due to their magnetic properties. - Highlights: • Cross-linked enzyme powders were prepared in various liquid media. • Insoluble enzymes were magnetized using iron oxides particles. • Magnetic iron oxides particles were prepared by microwave-assisted synthesis. • Magnetic modification was performed under low (freezing) temperature. • Cross-linked powdered trypsin and lipase can be used repeatedly for reaction.

  19. Artificial Enzymes, "Chemzymes"

    Bjerre, Jeannette; Rousseau, Cyril Andre Raphaël; Pedersen, Lavinia Georgeta M;

    2008-01-01

    Enzymes have fascinated scientists since their discovery and, over some decades, one aim in organic chemistry has been the creation of molecules that mimic the active sites of enzymes and promote catalysis. Nevertheless, even today, there are relatively few examples of enzyme models...... that successfully perform Michaelis-Menten catalysis under enzymatic conditions (i.e., aqueous medium, neutral pH, ambient temperature) and for those that do, very high rate accelerations are seldomly seen. This review will provide a brief summary of the recent developments in artificial enzymes, so called...... "Chemzymes", based on cyclodextrins and other molecules. Only the chemzymes that have shown enzyme-like activity that has been quantified by different methods will be mentioned. This review will summarize the work done in the field of artificial glycosidases, oxidases, epoxidases, and esterases, as well...

  20. Bioinformatic analysis of an unusual gene-enzyme relationship in the arginine biosynthetic pathway among marine gamma proteobacteria: implications concerning the formation of N-acetylated intermediates in prokaryotes

    Labedan Bernard

    2006-01-01

    Full Text Available Abstract Background The N-acetylation of L-glutamate is regarded as a universal metabolic strategy to commit glutamate towards arginine biosynthesis. Until recently, this reaction was thought to be catalyzed by either of two enzymes: (i the classical N-acetylglutamate synthase (NAGS, gene argA first characterized in Escherichia coli and Pseudomonas aeruginosa several decades ago and also present in vertebrates, or (ii the bifunctional version of ornithine acetyltransferase (OAT, gene argJ present in Bacteria, Archaea and many Eukaryotes. This paper focuses on a new and surprising aspect of glutamate acetylation. We recently showed that in Moritella abyssi and M. profunda, two marine gamma proteobacteria, the gene for the last enzyme in arginine biosynthesis (argH is fused to a short sequence that corresponds to the C-terminal, N-acetyltransferase-encoding domain of NAGS and is able to complement an argA mutant of E. coli. Very recently, other authors identified in Mycobacterium tuberculosis an independent gene corresponding to this short C-terminal domain and coding for a new type of NAGS. We have investigated the two prokaryotic Domains for patterns of gene-enzyme relationships in the first committed step of arginine biosynthesis. Results The argH-A fusion, designated argH(A, and discovered in Moritella was found to be present in (and confined to marine gamma proteobacteria of the Alteromonas- and Vibrio-like group. Most of them have a classical NAGS with the exception of Idiomarina loihiensis and Pseudoalteromonas haloplanktis which nevertheless can grow in the absence of arginine and therefore appear to rely on the arg(A sequence for arginine biosynthesis. Screening prokaryotic genomes for virtual argH-X 'fusions' where X stands for a homologue of arg(A, we retrieved a large number of Bacteria and several Archaea, all of them devoid of a classical NAGS. In the case of Thermus thermophilus and Deinococcus radiodurans, the arg(A-like sequence

  1. Hb A1c Separation by High Performance Liquid Chromatography in Hemoglobinopathies

    Chandrashekar, Vani

    2016-01-01

    Hb A1c measurement is subject to interference by hemoglobin traits and this is dependent on the method used for determination. In this paper we studied the difference between Hb A1c measured by HPLC in hemoglobin traits and normal chromatograms. We also studied the correlation of Hb A1c with age. Hemoglobin analysis was carried out by high performance liquid chromatography. Spearman's rank correlation was used to study correlation between A1c levels and age. Mann-Whitney U test was used to study the difference in Hb A1c between patients with normal hemoglobin and hemoglobin traits. A total of 431 patients were studied. There was positive correlation with age in patients with normal chromatograms only. No correlation was seen in Hb E trait or beta thalassemia trait. No significant difference in Hb A1c of patients with normal chromatograms and patients with hemoglobin traits was seen. There is no interference by abnormal hemoglobin in the detection of A1c by high performance liquid chromatography. This method cannot be used for detection of A1c in compound heterozygous and homozygous disorders. PMID:26989559

  2. CALCINEURIN INHIBITS DESENSITIZATION OF CLONED RAT 5-HT(1C)RECEPTORS

    BODDEKE, HWGM; HOFFMAN, BJ; PALACIOS, JM; HOYER, D

    1993-01-01

    Functional responses to stimulation of rat 5-HT1C receptors expressed in A9 cells were studied using whole cell voltage clamp recording technique. Stimulation of 5-HT1C receptors with serotonin (5-HT) evoked calcium-dependent outward currents of 109 pA in cells clamped at -50 mV. Pretreatment with t

  3. Data of evolutionary structure change: 1C4TC-1DPCA [Confc[Archive

    Full Text Available 1C4TC-1DPCA 1C4T 1DPC C A -----------ARSEKRVP----RKRVAERLLEAKNSTA...> ARG CA 109 VAL CA 154 ALA CA 140 1DPC... A 1DPCA IEEVPMTRLMQIGA GLU CA 181 1DPC A 1DPC... TYR CA 237 HIS CA 284 ASN CA 217 1DPC

  4. Soil pH regulates the abundance and diversity of Group 1.1c Crenarchaeota.

    Lehtovirta, Laura E; Prosser, James I; Nicol, Graeme W

    2009-12-01

    Archaeal communities in many acidic forest soil systems are dominated by a distinct crenarchaeal lineage Group 1.1c. In addition, they are found consistently in other acidic soils including grassland pasture, moorland and alpine soils. To determine whether soil pH is a major factor in determining their presence and abundance, Group 1.1c community size and composition were investigated across a pH gradient from 4.5 to 7.5 that has been maintained for > 40 years. The abundances of Group 1.1c Crenarchaeota, total Crenarchaeota and total bacteria were assessed by quantitative PCR (qPCR) targeting 16S rRNA genes and the diversity of Group 1.1c crenarchaeal community was investigated by denaturing gradient gel electrophoresis (DGGE) and phylogenetic analysis. The abundance of Group 1.1c Crenarchaeota declined as the pH increased, whereas total Crenarchaeota and Bacteria showed no clear trend. Community diversity of Group 1.1c Crenarchaeota was also influenced with different DGGE bands dominating at different pH. Group 1.1c Crenarchaeota were also quantified in 13 other soils representing a range of habitats, soil types and pH. These results exhibited the same trend as that shown across the pH gradient with Group 1.1c Crenarchaeota representing a greater proportion of total Crenarchaeota in the most acidic soils.

  5. Hb A1c Separation by High Performance Liquid Chromatography in Hemoglobinopathies

    Vani Chandrashekar

    2016-01-01

    Full Text Available Hb A1c measurement is subject to interference by hemoglobin traits and this is dependent on the method used for determination. In this paper we studied the difference between Hb A1c measured by HPLC in hemoglobin traits and normal chromatograms. We also studied the correlation of Hb A1c with age. Hemoglobin analysis was carried out by high performance liquid chromatography. Spearman’s rank correlation was used to study correlation between A1c levels and age. Mann-Whitney U test was used to study the difference in Hb A1c between patients with normal hemoglobin and hemoglobin traits. A total of 431 patients were studied. There was positive correlation with age in patients with normal chromatograms only. No correlation was seen in Hb E trait or beta thalassemia trait. No significant difference in Hb A1c of patients with normal chromatograms and patients with hemoglobin traits was seen. There is no interference by abnormal hemoglobin in the detection of A1c by high performance liquid chromatography. This method cannot be used for detection of A1c in compound heterozygous and homozygous disorders.

  6. Elevated third-trimester haemoglobin A 1c predicts preterm delivery in type 1 diabetes

    Ekbom, Pia; Damm, Peter; Feldt-Rasmussen, Bo;

    2008-01-01

    The prevalence of preterm delivery is considerably elevated in women with type 1 diabetes. The aim of the study was to evaluate haemoglobin A(1c) (HbA(1c)) as a predictor of preterm delivery. Two hundred thirteen consecutive pregnant women with type 1 diabetes and normal urinary albumin excretion...

  7. Information Management System training in the conditions of application configurations "1C: Enterprise"

    Sergei Bogatenkov

    2014-04-01

    Full Text Available Introduction of information technology increases the efficiency of solving professional problems and to increase the role of information training. The article describes a system of information training in the conditions of application configurations "1C: Enterprise" based on the classification of staff according to their level of training and quality requirements, including the availability of appropriate certificates of 1C.

  8. Data of evolutionary structure change: 1C12A-1MCEA [Confc[Archive

    Full Text Available 1C12A-1MCEA 1C12 1MCE A A DIELTQSPSSMSVSLGDTVSITCHASQ---GISSNIGWL...DINVKWKIDGSERQNGVLNSWTDQDSKDSTYSMSSTLTLTKDEYERHNSYTCEATHKTSTSPIVKSFNRNEA- PSALTQ-PPSASGSLGQSVTI.../line> 1MCE A 1MCEA...ne> 1MCE A 1MCEA 2 1MCE A 1MCEA

  9. Data of evolutionary structure change: 1C7JA-2ACEA [Confc[Archive

    Full Text Available 1C7JA-2ACEA 1C7J 2ACE A A THQIVTTQYGKVKGTTE----NGVHKWKGIPYAKPPVGQ...A 2ACEA MGTRVPVLSSHISA EEE...A 341 GLU CA 425 2ACE A 2ACEA...ne> ALA CA 282 2ACE A 2ACEA...ain> 2ACE A 2ACEA

  10. Data of evolutionary structure change: 1C2RA-1COTA [Confc[Archive

    Full Text Available 1C2RA-1COTA 1C2R 1COT A A -GDAAKGEKEFNKCKTCHSIIAPDGTEIVKGAKTGPNLY... THR CA 278 1COT A 1COTA...9563 20.21500015258789 -19.988000869750977 tion> 0.286000013351440430.7390000224113464 tion> 1.702983021736145 3.216418981552124 ...

  11. Data of evolutionary structure change: 1C2RB-1COTA [Confc[Archive

    Full Text Available 1C2RB-1COTA 1C2R 1COT B A -GDAAKGEKEFNKCKTCHSIIAPDGTEIVKGAKTGPNLY...CA 337 THR CA 277 1COT A 37.21200180053711 -25.844999313354492 tion> -0.03099999949336...3 0.597000002861023 tion> 1.6881250143051147 3.115614891052246 ...

  12. High maternal HbA1c is associated with overweight in neonates

    Mikkelsen, Maria R.; Nielsen, Sigrid Bruun; Stage, E;

    2011-01-01

    The aims of this study were to determine the prevalence of women with gestational diabetes mellitus (GDM) not obtaining HbA1c within the normal range (≤ 5.6%) before delivery and to examine whether elevated HbA1c values are associated with an increased risk of large for gestational age (LGA) infa...

  13. High maternal HbA1c is associated with overweight in neonates

    Mikkelsen, Maria R.; Nielsen, Sigrid Bruun; Stage, E;

    2011-01-01

    The aims of this study were to determine the prevalence of women with gestational diabetes mellitus (GDM) not obtaining HbA1c within the normal range (= 5.6%) before delivery and to examine whether elevated HbA1c values are associated with an increased risk of large for gestational age (LGA) infa...

  14. 18 CFR 1c.1 - Prohibition of natural gas market manipulation.

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Prohibition of natural gas market manipulation. 1c.1 Section 1c.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES PROHIBITION OF ENERGY MARKET MANIPULATION §...

  15. 18 CFR 2.1c - Policy statement on consultation with Indian tribes in Commission proceedings.

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Policy statement on consultation with Indian tribes in Commission proceedings. 2.1c Section 2.1c Conservation of Power and Water... (3) Is filed with the Secretary of the Commission. See generally 18 CFR 2.19. Statements of...

  16. Cotton cellulose: enzyme adsorption and enzymic hydrolysis

    Beltrame, P.L.; Carniti, P.; Focher, B.; Marzetti, A.; Cattaneo, M.

    1982-01-01

    The adsorption of a crude cellulase complex from Trichoderma viride on variously pretreated cotton cellulose samples was studied in the framework of the Langmuir approach at 2-8 degrees. The saturation amount of adsorbed enzyme was related to the susceptibility of the substrates to hydrolysis. In every case the adsorption process was faster by 2-3 orders of magnitude than the hydrolysis step to give end products. For ZnCl/sub 2/-treated cotton cellulose the Langmuir parameters correlated fairly well with the value of the Michaelis constant, measured for its enzymic hydrolysis, and the adsorptive complex was indistinguishable from the complex of the Michaelis-Menten model for the hydrolysis.

  17. An enzymatic method for the determination of hemoglobinA(1C).

    Hirokawa, Kozo; Shimoji, Kazuhiko; Kajiyama, Naoki

    2005-07-01

    Fructosyl peptide oxidase is a flavoenzyme that catalyzes the oxidative deglycation of N-(1-deoxyfructosyl)-Val-His, a model compound of hemoglobin (Hb)A(1C). To develop an enzymatic method for the measurement of HbA(1C), we screened for a proper protease using N-(1-deoxyfructosyl)-hexapeptide as a substrate. Several proteases, including Neutral protease from Bacillus polymyxa, were found to release N-(1-deoxyfructosyl)-Val-His efficiently, however no protease was found to release N-(1-deoxyfructosyl)-Val. Neutral protease also digested HbA(1C) to release N-(1-deoxyfructosyl)-Val-His, and then the fructosyl peptide was detected using fructosyl peptide oxidase. The linear relationship was observed between the concentration of HbA(1C) and the absorbancy of fructosyl peptide oxidase reaction, hence this new method is a practical means for measuring HbA(1C.).

  18. Trajectories of HbA1c levels in children and youth with type 1 diabetes.

    Orit Pinhas-Hamiel

    Full Text Available To illustrate the distribution of Hemoglobin A1c (HbA1c levels according to age and gender among children, adolescents and youth with type 1 diabetes (T1DM.Consecutive HbA1c measurements of 349 patients, aged 2 to 30 years with T1DM were obtained from 1995 through 2010. Measurement from patients diagnosed with celiac disease (n = 20, eating disorders (n = 41 and hemoglobinopathy (n = 1 were excluded. The study sample comprised 4815 measurements of HbA1c from 287 patients. Regression percentiles of HbA1c were calculated as a function of age and gender by the quantile regression method using the SAS procedure QUANTREG.Crude percentiles of HbA1c as a function of age and gender, and the modeled curves produced using quantile regression showed good concordance. The curves show a decline in HbA1c levels from age 2 to 4 years at each percentile. Thereafter, there is a gradual increase during the prepubertal years with a peak at ages 12 to 14 years. HbA1c levels subsequently decline to the lowest values in the third decade. Curves of females and males followed closely, with females having HbA1c levels about 0.1% (1.1 mmol/mol higher in the 25th 50th and 75th percentiles.We constructed age-specific distribution curves for HbA1c levels for patients with T1DM. These percentiles may be used to demonstrate the individual patient's measurements longitudinally compared with age-matched patients.

  19. Kr-pok increases FASN expression by modulating the DNA binding of SREBP-1c and Sp1 at the proximal promoter.

    Jeon, Bu-Nam; Kim, Yeon-Sook; Choi, Won-Il; Koh, Dong-In; Kim, Min-Kyeong; Yoon, Jae-Hyeon; Kim, Min-Young; Hur, Benjamin; Paik, Philip Dong-Hyun; Hur, Man-Wook

    2012-04-01

    Kr-pok (kidney cancer-related POZ domain and Krüppel-like protein) is a new proto-oncogenic POZ-domain transcription factor. Fatty acid synthase gene (FASN) encodes one of the key enzymes in fatty acids synthesis and is the only enzyme that synthesizes fatty acids in cancer cells. Sp1 and SREBP-1c are the two major transcription activators of FASN. We investigated whether Kr-pok modulates transcription of the FASN. FASN expression is significantly decreased in Kr-pok knockout murine embryonic fibroblasts. Coimmunoprecipitation, GST fusion protein pull-down, and immunocytochemistry assays show that the zinc-finger domain of Kr-pok interacts directly with the bZIP DNA binding domain of SREBP-1. Electrophoretic mobility shift assay, oligonucleotide pull-down, and chromatin immunoprecipitation assays showed that Kr-pok changes the transcription factor binding dynamics of Sp1 and SREBP-1c to the SRE/E-box elements of the proximal promoter. We found that Kr-pok expression increased during 3T3-L1 preadipocyte differentiation and that FASN expression is decreased by the knockdown of Kr-pok. Kr-pok facilitates the SREBP-1c-mediated preadipocyte differentiation and/or fatty acid synthesis. Kr-pok may act as an important regulator of fatty acid synthesis and may induce rapid cancer cell proliferation by increasing palmitate synthesis.

  20. Separation and conductimetric detection of C1-C7 aliphatic monocarboxylic acids and C1-C7 aliphatic monoamines on unfunctionized polymethacrylate resin columns.

    Ohta, Kazutoku; Towata, Atsuya; Ohashi, Masayoshi; Takeuchi, Toyohide

    2004-06-11

    The application of unfunctionized polymethacrylate resin (TSKgel G3000PWXL) as a stationary phase in liquid chromatography with conductimetric detection for C1-C7 aliphatic monocarboxylic acids (formic acid, acetic acid, propionic acid, butyric acid, isovaleric acid, valeric acid, 3,3-dimethylbutyric acid, 4-methylvaleric acid, hexanoic acid, 2-methylhexanoic acid, 5-methylhexanoic acid and heptanoic acid) and C1-C7 aliphatic monoamines (methylamine, ethylamine, propylamine, isobutylamine, butylamine, isoamylamine, amylamine, 1,3-dimethylbutylamine, hexylamine, 2-heptylamine and heptylamine) was attempted with C8 aliphatic monocarboxylic acids (2-propylvaleric acid, 2-ethylhexanoic acid, 2-methylheptanoic acid and octanoic acid) and C8 aliphatic monoamines (1,5-dimethylhexylamine, 2-ethylhexylamine, 1-methylheptylamine and octylamine) as eluents, respectively. Using 1 mM 2-methylheptanoic acid at pH 4.0 as the eluent, excellent separation and relatively high sensitive detection for these C1-C7 carboxylic acids were achieved on a TSKgel G3000PWXL column (150 mm x 6 mm i.d.) in 60 min. Using 2 mM octylamine at pH 11.0 as the eluent, excellent separation and relatively high sensitive detection for these C1-C7 amines were also achieved on the TSKgel G3000PWXL column in 60 min.

  1. Differences in TCDD-elicited gene expression profiles in human HepG2, mouse Hepa1c1c7 and rat H4IIE hepatoma cells

    Burgoon Lyle D

    2011-04-01

    Full Text Available Abstract Background 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD is an environmental contaminant that elicits a broad spectrum of toxic effects in a species-specific manner. Current risk assessment practices routinely extrapolate results from in vivo and in vitro rodent models to assess human risk. In order to further investigate the species-specific responses elicited by TCDD, temporal gene expression responses in human HepG2, mouse Hepa1c1c7 and rat H4IIE cells were compared. Results Microarray analysis identified a core set of conserved gene expression responses across species consistent with the role of AhR in mediating adaptive metabolic responses. However, significant species-specific as well as species-divergent responses were identified. Computational analysis of the regulatory regions of species-specific and -divergent responses suggests that dioxin response elements (DREs are involved. These results are consistent with in vivo rat vs. mouse species-specific differential gene expression, and more comprehensive comparative DRE searches. Conclusions Comparative analysis of human HepG2, mouse Hepa1c1c7 and rat H4IIE TCDD-elicited gene expression responses is consistent with in vivo rat-mouse comparative gene expression studies, and more comprehensive comparative DRE searches, suggesting that AhR-mediated gene expression is species-specific.

  2. Enzyme molecules as nanomotors.

    Sengupta, Samudra; Dey, Krishna K; Muddana, Hari S; Tabouillot, Tristan; Ibele, Michael E; Butler, Peter J; Sen, Ayusman

    2013-01-30

    Using fluorescence correlation spectroscopy, we show that the diffusive movements of catalase enzyme molecules increase in the presence of the substrate, hydrogen peroxide, in a concentration-dependent manner. Employing a microfluidic device to generate a substrate concentration gradient, we show that both catalase and urease enzyme molecules spread toward areas of higher substrate concentration, a form of chemotaxis at the molecular scale. Using glucose oxidase and glucose to generate a hydrogen peroxide gradient, we induce the migration of catalase toward glucose oxidase, thereby showing that chemically interconnected enzymes can be drawn together.

  3. Ras-association domain family 1C protein promotes breast cancer cell migration and attenuates apoptosis

    Aragon Robert J

    2010-10-01

    Full Text Available Abstract Background The Ras association domain family 1 (RASSF1 gene is a Ras effector encoding two major mRNA forms, RASSF1A and RASSF1C, derived by alternative promoter selection and alternative mRNA splicing. RASSF1A is a tumor suppressor gene. However, very little is known about the function of RASSF1C both in normal and transformed cells. Methods Gene silencing and over-expression techniques were used to modulate RASSF1C expression in human breast cancer cells. Affymetrix-microarray analysis was performed using T47D cells over-expressing RASSF1C to identify RASSF1C target genes. RT-PCR and western blot techniques were used to validate target gene expression. Cell invasion and apoptosis assays were also performed. Results In this article, we report the effects of altering RASSF1C expression in human breast cancer cells. We found that silencing RASSF1C mRNA in breast cancer cell lines (MDA-MB231 and T47D caused a small but significant decrease in cell proliferation. Conversely, inducible over-expression of RASSF1C in breast cancer cells (MDA-MB231 and T47D resulted in a small increase in cell proliferation. We also report on the identification of novel RASSF1C target genes. RASSF1C down-regulates several pro-apoptotic and tumor suppressor genes and up-regulates several growth promoting genes in breast cancer cells. We further show that down-regulation of caspase 3 via overexpression of RASSF1C reduces breast cancer cells' sensitivity to the apoptosis inducing agent, etoposide. Furthermore, we found that RASSF1C over-expression enhances T47D cell invasion/migration in vitro. Conclusion Together, our findings suggest that RASSF1C, unlike RASSF1A, is not a tumor suppressor, but instead may play a role in stimulating metastasis and survival in breast cancer cells.

  4. Molecular Motor MYO1C, Acetyltransferase KAT6B and Osteogenetic Transcription Factor RUNX2 Expression in Human Masseter Muscle Contributes to Development of Malocclusion

    Desh, Heather; Gray, S Lauren; Horton, Michael J; Raoul, Gwenael; Rowlerson, Anthea M; Ferri, Joel; Vieira, Alexandre R; Sciote, James J

    2014-01-01

    Objective Type I myosins are molecular motors necessary for glucose transport in the cytoplasm and initiation of transcription in the nucleus. Two of these, MYO1H and MYO1C, are paralogs which may be important in the development of malocclusion. The objective of this study was to investigate their gene expression in the masseter muscle of malocclusion subjects. Two functionally related proteins known to contribute to malocclusion were also investigated: KAT6B (a chromatin remodeling epigenetic enzyme which is activated by MYO1C) and RUNX2 (a transcription factor regulating osteogenesis which is activated by KAT6B). Design Masseter muscle samples and malocclusion classifications were obtained from orthognathic surgery subjects. Muscle was sectioned and immunostained to determine fiber type properties. RNA was isolated from the remaining sample to determine expression levels for the four genes by TaqMan® RT-PCR. Fiber type properties, gene expression quantities and malocclusion classification were compared. Results There were very significant associations (P<0.0000001) between MYO1C and KAT6B expressions. There were also significant associations (P<0.005) between RUNX2 expression and masseter muscle type II fiber properties. Very few significant associations were identified between MYO1C and masseter muscle fiber type properties. Conclusions The relationship between MYO1C and KAT6B suggests that the two are interacting in chromatin remodeling for gene expression. This is the nuclear myosin1 (NM1) function of MYO1C. A surprising finding is the relationship between RUNX2 and type II masseter muscle fibers, since RUNX2 expression in mature muscle was previously unknown. Further investigations are necessary to elucidate the role of RUNX2 in adult masseter muscle. PMID:24698832

  5. A Phytophthora infestans RXLR effector targets plant PP1c isoforms that promote late blight disease.

    Boevink, Petra C; Wang, Xiaodan; McLellan, Hazel; He, Qin; Naqvi, Shaista; Armstrong, Miles R; Zhang, Wei; Hein, Ingo; Gilroy, Eleanor M; Tian, Zhendong; Birch, Paul R J

    2016-01-29

    Plant pathogens deliver effectors to alter host processes. Knowledge of how effectors target and manipulate host proteins is critical to understand crop disease. Here, we show that in planta expression of the RXLR effector Pi04314 enhances leaf colonization by Phytophthora infestans via activity in the host nucleus and attenuates induction of jasmonic and salicylic acid-responsive genes. Pi04314 interacts with three host protein phosphatase 1 catalytic (PP1c) isoforms, causing their re-localization from the nucleolus to the nucleoplasm. Re-localization of PP1c-1 also occurs during infection and is dependent on an R/KVxF motif in the effector. Silencing the PP1c isoforms or overexpression of a phosphatase-dead PP1c-1 mutant attenuates infection, demonstrating that host PP1c activity is required for disease. Moreover, expression of PP1c-1mut abolishes enhanced leaf colonization mediated by in planta Pi04314 expression. We argue that PP1c isoforms are susceptibility factors forming holoenzymes with Pi04314 to promote late blight disease.

  6. Hemoglobin A1c levels and aortic arterial stiffness: the Cardiometabolic Risk in Chinese (CRC study.

    Jun Liang

    Full Text Available OBJECTIVE: The American Diabetes Association (ADA recently published new clinical guidelines in which hemoglobin A1c (HbA1c was recommended as a diagnostic test for diabetes. The present study was to investigate the association between HbA1c and cardiovascular risk, and compare the associations with fasting glucose and 2-hour oral glucose tolerance test (2 h OGTT. RESEARCH DESIGN AND METHODS: The study samples are from a community-based health examination survey in central China. Carotid-to-femoral pulse wave velocity (cfPWV and HbA1c were measured in 5,098 men and women. RESULTS: After adjustment for age, sex, and BMI, the levels of HbA1c were significantly associated with an increasing trend of cfPWV in a dose-dependent fashion (P for trend 0.05. CONCLUSIONS: HbA1c was related to high cfPWV, independent of conventional cardiovascular risk factors. Senior age and high blood pressure might amplify the adverse effects of HbA1c on cardiovascular risk.

  7. Interference of the Hope Hemoglobin With Hemoglobin A1c Results.

    Chakraborty, Sutirtha; Chanda, Dalia; Gain, Mithun; Krishnan, Prasad

    2015-01-01

    Hemoglobin A1c (HbA1c) is now considered to be the marker of choice in diagnosis and management of diabetes mellitus, based on the results of certain landmark clinical trials. Herein, we report the case of a 52-year-old ethnic Southeast Asian Indian man with impaired glucose tolerance whose glycated hemoglobin (ie, HbA1c) levels, as measured via Bio-Rad D10 high-performance liquid chromatography (HPLC) and Roche Tina-quant immunoassay were 47.8% and 44.0%, respectively. No variant hemoglobin (Hb) peak was observed via the D10 chromatogram. We assayed the patient specimen on the Sebia MINICAP capillary electrophoresis platform; the HbA1c level was 6.8%, with a large variant Hb peak of 42.0%. This finding suggested the possible presence of the heterozygous Hb Hope, which can result in spuriously elevated HbA1c results on HPLC and turbidimetric immunoassays. Although the capillary electrophoresis system was able to identify the variant, the A1c results should not be considered accurate due to overlapping of the variant and adult Hb peaks on the electrophoretogram reading. Hb Hope is usually clinically silent but can present such analytical challenges. Through this case study, we critically discuss the limitations of various HbA1c assay methods, highlighting the fact that laboratory professionals need to be aware of occurrences of Hb Hope, to help ensure patient safety.

  8. Myo1c binding to submembrane actin mediates insulin-induced tethering of GLUT4 vesicles.

    Boguslavsky, Shlomit; Chiu, Tim; Foley, Kevin P; Osorio-Fuentealba, Cesar; Antonescu, Costin N; Bayer, K Ulrich; Bilan, Philip J; Klip, Amira

    2012-10-01

    GLUT4-containing vesicles cycle between the plasma membrane and intracellular compartments. Insulin promotes GLUT4 exocytosis by regulating GLUT4 vesicle arrival at the cell periphery and its subsequent tethering, docking, and fusion with the plasma membrane. The molecular machinery involved in GLUT4 vesicle tethering is unknown. We show here that Myo1c, an actin-based motor protein that associates with membranes and actin filaments, is required for insulin-induced vesicle tethering in muscle cells. Myo1c was found to associate with both mobile and tethered GLUT4 vesicles and to be required for vesicle capture in the total internal reflection fluorescence (TIRF) zone beneath the plasma membrane. Myo1c knockdown or overexpression of an actin binding-deficient Myo1c mutant abolished insulin-induced vesicle immobilization, increased GLUT4 vesicle velocity in the TIRF zone, and prevented their externalization. Conversely, Myo1c overexpression immobilized GLUT4 vesicles in the TIRF zone and promoted insulin-induced GLUT4 exposure to the extracellular milieu. Myo1c also contributed to insulin-dependent actin filament remodeling. Thus we propose that interaction of vesicular Myo1c with cortical actin filaments is required for insulin-mediated tethering of GLUT4 vesicles and for efficient GLUT4 surface delivery in muscle cells.

  9. Enzymic lactose hydrolysis

    Miller, J.J.; Brand, J.C.

    1980-01-01

    Acid or enzymic hydrolysis can be used to hydrolyze lactose. Advantages of both are compared and details of enzymic hydrolysis using yeast or fungal enzymes given. The new scheme outlined involves recycling lactase. Because lactose and lactase react to ultrafiltration (UF) membranes differently separation is possible. Milk or milk products are ultrafiltered to separate a concentrate from a lactose-rich permeate which is treated with lactase in a reactor until hydrolysis reaches a required level. The lactase can be removed by UF as it does not permeate the membrane, and it is recycled back to the reactor. Permeate from the second UF stage may or may not be recombined with the concentrate from the first stage to produce a low lactose product (analysis of a typical low-lactose dried whole milk is given). Batch or continuous processes are explained and a batch process without enzyme recovery is discussed. (Refs. 4).

  10. Enzymes in Analytical Chemistry.

    Fishman, Myer M.

    1980-01-01

    Presents tabular information concerning recent research in the field of enzymes in analytic chemistry, with methods, substrate or reaction catalyzed, assay, comments and references listed. The table refers to 128 references. Also listed are 13 general citations. (CS)

  11. Membrane Assisted Enzyme Fractionation

    Yuan, Linfeng

    . In this thesis, separations using crossflow elecro-membrane filtration (EMF) of amino acids, bovine serum albumin (BSA) and industrial enzymes from Novozymes were performed. The main objective of this study was to investigate the technological feasibility of EMF in the application of industrial enzyme...... fractionation, such as removal of a side activity from the main enzyme activity. As a proof-of-concept, amino acids were used as model solution to test the feasibility of EMF in the application of amphoteric molecule separation. A single amino acid was used to illustrate the effect of an electric field...... on the separation performance were very small in the investigated range. The mass transport of each enzyme can be well explained by the Extended-Nernst-Planck equation. Better separation was observed at lower feed concentration, higher solution pH in the investigated range and with a polysulfone (PS) MF membrane...

  12. Antepartum A1C, maternal diabetes outcomes, and selected offspring outcomes: an epidemiological review.

    Katon, Jodie; Williams, Michelle A; Reiber, Gayle; Miller, Edith

    2011-05-01

    Between 1989 and 2004, the prevalence of gestational diabetes mellitus (GDM) in the United States increased by 122%. Glycated haemoglobin, as measured by haemoglobin A1C (A1C), can potentially identify pregnant women at high risk for adverse outcomes associated with GDM including macrosomia and post-partum glucose intolerance. Our objective was to systematically review the literature with respect to A1C levels during pregnancy and associated maternal and offspring outcomes. We used MEDLINE to identify relevant publications from 1975 to 2009. We included articles if they met the following criteria: original full text articles in English; primary exposure of antepartum A1C; women with GDM at baseline or who developed GDM during the study; primary outcome of GDM, insulin use, post-partum abnormal glucose or type 2 diabetes (T2DM), birthweight, macrosomia or large for gestational age. Case series and case reports were excluded. Twenty studies met our criteria. A1C at GDM diagnosis was positively associated with post-partum abnormal glucose. Women with post-partum T2DM or impaired glucose tolerance had mean A1C at GDM diagnosis higher than those with normal post-partum glucose (P ≤ 0.002) and a 1% increase in A1C at GDM diagnosis was associated with 2.36 times higher odds of post-partum abnormal glucose 6 weeks after delivery [95% confidence interval 1.19, 4.68]. The association of A1C and birthweight varied substantially between studies, with correlation coefficients ranging from 0.11 to 0.51. A1C, a less burdensome and costly measure than an oral glucose tolerance test, appears to be an attractive measure for identifying women at high risk of adverse outcomes associated with GDM.

  13. Utility of hemoglobin A1c to screen for impaired glucose tolerance

    Edy K. Ginting

    2014-07-01

    Full Text Available Background Childhood obesity is associated with an increased likelihood for having impaired glucose tolerance, dyslipidemia, and diabetes. Hemoglobin A1c (HbA1c has emerged as a recommended diagnostic tool for identifying diabetes and persons at risk for the disease. This recommendation was based on data in adults, showing the relationship between HbA1C and the future development of diabetes. However, studies in the pediatric population have been limited and no standard values of HbA1c levels in children have been established. Objective To evaluate HbA1c as a test for impaired glucose tolerance in obese children and adolescents and to identify the optimal HbA1c threshold level (cut off point. Methods We studied 65 obese and 4 overweight children (BMI ≥ +2 SD for age and gender aged 10-15 years in Palembang. All subjects underwent HbA1c and oral glucose tolerance tests. Results Nineteen out of 69 subjects (28% had impaired glucose tolerance. Based on the receiver operating characteristic curve, the optimal cut off point of HbA1c related to impaired glucose tolerance as diagnosed by oral glucose tolerance test was found to be 5.25%, with 63% sensitivity and 64% specificity, 40% positive predictive value, and 82% negative predictive value. The area under the receiver operating characteristic curve was 0.687 (95%CI 0.541–0.833; P < 0.001. Conclusion A HbA1c cut off value of 5.25% may be used as a screening tool to identify children and adolescents with impaired glucose tolerance. [Paediatr Indones. 2014;54:223-6.].

  14. Evaluation and interference study of hemoglobin A1c measured by turbidimetric inhibition immunoassay.

    Chang, J; Hoke, C; Ettinger, B; Penerian, G

    1998-03-01

    The technical performance of the turbidimetric immunoinhibition (TI) assay for hemoglobin (Hb) A1c (Tina-quant Hb A1c, Boehringer Mannheim, Indianapolis, Ind) was evaluated by using the BM/Hitachi 911 analyzer. Intra-assay imprecision was less than 2.7%, and interassay imprecision was less than 2.8% as measured by coefficient of variation. In 93 subjects with diabetes who did not have hemoglobin variants, results of the TI assay for Hb A1c correlated strongly with those obtained by using a high-performance liquid chromatography analyzer (Diamat, BioRad Laboratories, Hercules, Calif). Among 241 subjects who had or did not have hemoglobin variants, the TI assay for Hb A1c correlated strongly with results of affinity chromatography for total glycated hemoglobin (Glyc-Affin GHb, IsoLab, Akron, Ohio). We also studied the effect of various percentages of hemoglobin S, C, E, and F on the accuracy of the TI Hb A1c assay. Only high hemoglobin F percentages caused interference. More than 14 times as many samples can be analyzed per hour by using the TI Hb A1c assay than can be analyzed by using the HPLC assay. For high-volume reference laboratories, using the fully automated TI Hb A1c assay to monitor glycemic control in patients with diabetes may be preferable to using the conventional ion-exchange high-performance liquid chromatography Hb A1c assay because the TI assay measures Hb A1c more accurately in patients with diabetes who have hemoglobin variants, and it requires less time.

  15. Challenges in HbA1c Analysis and Reporting in Patients with Variant Hemoglobins.

    Sultana, T A; Sheme, Z A; Sultana, G S; Sultana, B; Mishu, F A; Khan, N Z; Sarkar, B C; Muttalib, M A; Khan, S A; Choudhury, S; Mahtab, H

    2016-04-01

    Hemoglobin A1c (HbA(1)c) is a well-established indicator of mean glycemia. The presence of genetic variants of hemoglobin can profoundly affect the accuracy of HbA(1)c measurements. Variants of hemoglobin especially Hemoglobin E (HbE) is prevalent in South East Asia including Bangladesh. The objective of our study is to compare the HbA(1)c values measured on high performance liquid chromatography (HPLC) and Turbidimetric Inhibition Immunoassay (TINIA) in diabetic patients with variant hemoglobins including HbE. A total of 7595 diabetic patients receiving treatment at BIRDEM General Hospital were analyzed for HbA(1)c results within a period of two months from December 2013 to January 2014. Seventy two cases out of 7595 (0.95%) had either undetectable or below normal HbA(1)c levels (males-33 and females-39; ratio = 0.82:1) by HPLC method. In 34(0.45%) cases, HbA(1)c value was undetectable by HPLC method but was in the reportable range by TINIA method. In the other 38 (0.55%) cases, HbA(1)c levels were below the reportable range (Hb variant, proper knowledge of hemoglobin variants which affect the measurements HbA(1)c level is essential. MCV of 80fl or below may serve as a rough guide to select samples that require analysis by TINIA method. Moreover, HPLC may be a convenient and inexpensive tool for screening of hemoglobinopathies especially among diabetic population in Bangladesh. It may therefore be helpful in improving management of complications related to both anaemia and iron overload.

  16. Overproduction of ligninolytic enzymes

    Elisashvili, Vladimir; Kachlishvili, Eva; Torok, Tamas

    2014-06-17

    Methods, compositions, and systems for overproducing ligninolytic enzymes from the basidiomycetous fungus are described herein. As described, the method can include incubating a fungal strain of Cerrena unicolor IBB 303 in a fermentation system having growth medium which includes lignocellulosic material and then cultivating the fungal strain in the fermentation system under conditions wherein the fungus expresses the ligninolytic enzymes. In some cases, the lignocellulosic material is mandarin peel, ethanol production residue, walnut pericarp, wheat bran, wheat straw, or banana peel.

  17. RNA-modifying enzymes.

    Ferré-D'Amaré, Adrian R

    2003-02-01

    A bewildering number of post-transcriptional modifications are introduced into cellular RNAs by enzymes that are often conserved among archaea, bacteria and eukaryotes. The modifications range from those with well-understood functions, such as tRNA aminoacylation, to widespread but more mysterious ones, such as pseudouridylation. Recent structure determinations have included two types of RNA nucleobase modifying enzyme: pseudouridine synthases and tRNA guanine transglycosylases.

  18. Pengaruh Level HBA1C Terhadap Fungsi Fagositosis Neutrofil (PMN pada Penderita Periodontitis Diabetika

    Ahmad Syaify

    2016-08-01

    Full Text Available Latar belakang. Diabetes Melitus (DM merupakan penyakit sistemik yang sangat terkait dengan meningkatnya keparahan penyakit periodontal. Pada penderita DM diduga kuat bahwa keparahan periodontitis disebabkan oleh gangguan fungsi leukosit. Sel neutrofil (PMN diketahui berperan besar di dalam system pertahanan jaringan periodontal. Kontrol glikemik pada penderita DM dapat diketahui dengan pemeriksaan level HbA1c. Tujuan. Penelitian ini untuk mengetahui pengaruh level HbA1c pada penderita periodontitis diabetika terhadap fungsi fagositosis sel PMN. Bahan dan Cara. Sel PMN dari darah tepi 15 pasien periodontitis terdiri 5 periodontitis tana DM, 5 periodontitis diabetika terkontrol (HbA1c7 diuji aktivitas fagositosinya dengan partikel lateks. Fungsi fagositosis dihitung dengan rumus indeks fagositosis (IF. Hasil. Terdapat perbedaan significant IF sel PMN subyek periodontitis diabetika tidak terkontrol (HbA1c>7 dengan periodontitis non DM. IF tertinggi pada subyek periodontitis non DM dan tertinggi pada periodontitis diabetika tidak terkontrol (HbA1c>7. Kesimpulan. Level HbA1c berpengaruh terhadap fungsi fagositosis sel PMN yang dilihat dari indeks fagositosis (IF.    Background. Diabetes mellitus is a systemic condition that has long been associated with an increased and severity of periodontal disease. The severity of periodontitis in diabetic patients was thought caused by decreation of leukocytes function. Polymorphonuclear leukocytes (PMN play a key role in the maintenance of gingival (HbA1c level. Aims. The objective of this study was to analyse the influence of HbA1C level to fagositosis index on diabetic periodontitis patients. Material and Methods. PMN were taken from peripheral blood of 15 periodontitis patients consisted of 5 subject with uncontrolled DM (HbA1c>7, 5 subject with controlled DM (HbA1c7 and periodontitis non diabetic subjects. The higest PI was on diabetic periodontitis with HbA1c level >7 and the lowest PI was on non

  19. Neue biosensorische Prinzipien für die Hämoglobin-A1c Bestimmung

    Stöllner, Daniela

    2005-01-01

    Hämoglobin-A1c (HbA1c) ist ein Hämoglobin (Hb)-Subtypus, der durch nicht-enzymatische Glykierung des N-terminalen Valinrestes der Hämoglobin-beta-Kette entsteht. Das gemessene Verhältnis von HbA1c zum Gesamt-Hämoglobin (5-20 % bei Diabetikern) repräsentiert den Mittelwert der Blutglucosekonzentration über einen zweimonatigen Zeitraum und stellt zur Beurteilung der diabetischen Stoffwechsellage eine Ergänzung zur Akutkontrolle der Glukosekonzentration dar. Ziel der vorliegenden Arbeit war es, ...

  20. NOAA Climate Data Record (CDR) of MSU Level 1c Brightness Temperature, Version 1.0

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset contains Level 1c inter-calibrated brightness temperatures from the Microwave Sounding Unit (MSU) sensors onboard nine polar orbiting satellites...

  1. Comparison of Hemoglobin A1c assay performance on two different commercial systems

    Jozo Ćorić

    2015-04-01

    Full Text Available Introduction: Glycated hemoglobin (HbA1c is formed by non-enzymatic binding of glucose to the free amino group of the N-terminal end of the ß-chain of hemoglobin A. HbA1c is representative of the mean blood glucose level over three months. The aim of the study was to evaluate the Hemoglobin A1c immunoturbidimetric assay performance on two different commercial systems.Methods: We evaluated the precision and trueness for determination of HbA1c in whole blood. Concentrations of total hemoglobin and HbA1c were evaluated on Dimension Xpand (Siemens and Cobas 501 (Roche analyzers. HbA1c was measured in a latex agglutination inhibition test. Commercial controls Liquichek Diabetes Control Level 1 and Liquichek Diabetes Control Level 2 (Bio Rad at two levels were used for quality control. Analytical validation of HbA1c included: within-run imprecision, between-day imprecision, inaccuracy and comparison determination on the human samples on 2 systems: Dimension Xpand and Cobas 501 analyzers. Results: Within-run imprecision on the commercially controls for Level 1 is 4.5% and Level 2 is 3.2% between-day imprecision on commercially controls is 6.1% Level 1 and 5.1% Level 2 for respectively inac- curacy on commercially controls for Level 1 is 1.8% and Level 2 is 4.8%. Method comparison on human samples shows the correlation coefficient of 0.99.Conclusion: The presented results of the analytical evaluation methods for the determination of HbA1c showed an acceptable accuracy and precision.

  2. Maternal and offspring genetic variants of AKR1C3 and the risk of childhood leukemia

    Liu, Chen-Yu; Hsu, Yi-Hsiang; Pan, Pi-Chen; Wu, Ming-Tsang; Ho, Chi-Kung; Su, Li; Xu, Xin; Li, Yi; Christiani, David C.

    2008-01-01

    The aldo-keto reductase 1C3 (AKR1C3) gene located on chromosome 10p15-p14, a regulator of myeloid cell proliferation and differentiation, represents an important candidate gene for studying human carcinogenesis. In a prospectively enrolled population-based case–control study of Han Chinese conducted in Kaohsiung in southern Taiwan, a total of 114 leukemia cases and 221 controls

  3. Pengaruh Level HBA1C Terhadap Fungsi Fagositosis Neutrofil (PMN) pada Penderita Periodontitis Diabetika

    Ahmad Syaify

    2016-01-01

    Latar belakang. Diabetes Melitus (DM) merupakan penyakit sistemik yang sangat terkait dengan meningkatnya keparahan penyakit periodontal. Pada penderita DM diduga kuat bahwa keparahan periodontitis disebabkan oleh gangguan fungsi leukosit. Sel neutrofil (PMN) diketahui berperan besar di dalam system pertahanan jaringan periodontal. Kontrol glikemik pada penderita DM dapat diketahui dengan pemeriksaan level HbA1c. Tujuan. Penelitian ini untuk mengetahui pengaruh level HbA1c pada penderita peri...

  4. Comparing risk profiles of individuals diagnosed with diabetes by OGTT and HbA1c

    Borg, R; Vistisen, D; Witte, Daniel Rinse;

    2010-01-01

    Glycated haemoglobin (HbA(1c)) has been proposed as an alternative to the oral glucose tolerance test for diagnosing diabetes. We compared the cardiovascular risk profile of individuals identified by these two alternative methods.......Glycated haemoglobin (HbA(1c)) has been proposed as an alternative to the oral glucose tolerance test for diagnosing diabetes. We compared the cardiovascular risk profile of individuals identified by these two alternative methods....

  5. Epigenetic Characterization of CDKN1C in Placenta Samples from Non-syndromic Intrauterine Growth Restriction

    López-Abad, Miriam; Iglesias-Platas, Isabel; Monk, David

    2016-01-01

    The cyclin-dependent kinase (CDK)-inhibitor 1C (CDKN1C) gene is expressed from the maternal allele and is located within the centromeric imprinted domain at chromosome 11p15. It is a negative regulator of proliferation, with loss-of-function mutations associated with the overgrowth disorder Beckwith–Wiedemann syndrome. Recently, gain-of-function mutations within the PCNA domain have been described in two disorders characterized by growth failure, namely IMAGe (intra-uterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita and genital abnormalities) syndrome and Silver–Russell syndrome (SRS). Over-expression of CDKN1C by maternally inherited microduplications also results in SRS, suggesting that in addition to activating mutations this gene may regulate growth by changes in dosage. To determine if CDKN1C is involved in non-syndromic IUGR we compared the expression and DNA methylation levels in a large cohort of placental biopsies from IUGR and uneventful pregnancies. We observe higher levels of expression of CDKN1C in IUGR placentas compared to those of controls. All placenta biopsies heterozygous for the PAPA repeat sequence in exon 2 showed appropriate monoallelic expression and no mutations in the PCNA domain were observed. The expression profile was independent of both genetic or methylation variation in the minimal CDKN1C promoter interval and of methylation of the cis-acting maternally methylated region associated with the neighboring KCNQ1OT1 non-coding RNA. Chromatin immunoprecipitation revealed binding sites for CTCF within the unmethylated CDKN1C gene body CpG island and putative enhancer regions, associated with the canonical enhancer histone signature, H3K4me1 and H3K27ac, located ∼58 and 360 kb away. Using 3C-PCR we identify constitutive higher-order chromatin loops that occur between one of these putative enhancer regions and CDKN1C in human placenta tissues, which we propose facilitates expression. PMID:27200075

  6. Epigenetic characterization of CDKN1C in placenta samples from non-syndromic intrauterine growth restriction

    David eMonk

    2016-04-01

    Full Text Available The Cyclin-dependent kinase (CDK-inhibitor 1C (CDKN1C gene is expressed from the maternal allele and is located within the centromeric imprinted domain at chromosome 11p15. It is a negative regulator of proliferation, with loss-of-function mutations associated with the overgrowth disorder Beckwith-Wiedemann syndrome. Recently, gain-of-function mutations within the PCNA domain have been described in two disorders characterized by growth failure, namely IMAGe (intra-uterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita and genital abnormalities syndrome and Silver-Russell syndrome (SRS. Over-expression of CDKN1C by maternally inherited microduplications also results in SRS, suggesting that in addition to activating mutations this gene may regulate growth by changes in dosage. To determine if CDKN1C is involved in non-syndromic IUGR we compared the expression and DNA methylation levels in a large cohort of placental biopsies from IUGR and uneventful pregnancies. We observe higher levels of expression of CDKN1C in IUGR placentas compared to those of controls. All placenta biopsies heterozygous for the PAPA repeat sequence in exon 2 showed appropriate monoallelic expression and no mutations in the PCNA domain were observed. The expression profile was independent of both genetic or methylation variation in the minimal CDKN1C promoter interval and of methylation of the cis-acting maternally methylated region associated with the neighboring KCNQ1OT1 non-coding RNA. Chromatin immunoprecipitation revealed binding sites for CTCF within the unmethylated CDKN1C gene body CpG island and putative enhancer regions, associated with the canonical enhancer histone signature, H3K4me1 and H3K27ac, located ~58 and 360 kb away. Using 3C-PCR we identify constitutive higher-order chromatin loops that occur between one of these putative enhancer regions and CDKN1C in human placenta tissues, which we propose facilitates expression.

  7. Applications of Environmental Remote Sensing by HJ-1C SAR Imageries

    Tian Wei; Xu Xu; Bian Xiao-lin; Chai Xun; Wang Shi-ang; Gong Hua-ze; Xiong Wen-cheng; Shao Yun

    2014-01-01

    The HJ-1C satellite was successfully launched in November 19, 2012. The HJ-1C and HJ-1A/1B satellites, which were launched in September 06, 2008, constitute the “2+1” small satellite constellation for environmental and disaster monitoring. This study focuses on the analysis and evaluation of the satellite performance with respect to environmental remote sensing, including land use interpretation, land cover classification, oil spill identification, retrieval of sea waves, and monitoring of...

  8. Detection of HbA(1c) by boronate affinity immunoassay using bacterial magnetic particles.

    Tanaka, T; Matsunaga, T

    2001-12-01

    We have developed a boronate affinity immunoassay system using m-aminophenylboronic acid (mAPB) coupling to bacterial magnetic particles (BMPs). Homobifunctional crosslinker, Bis-(succcimidyl)suberate (BS3), was employed for preparation of mAPB-BMPs conjugates (mAPB-BMPs). Quantities of HbA(1c) on mAPB-BMPs were evaluated based on luminescence from alkaline phosphatase-conjugated anti-Hb antibody (ALP-antibody) binding to HbA(1c) on the BMP surface. The binding of HbA(1c) to mAPB-BMPs occurred gradually and was almost completed within 10 mm. The coupling reaction is enhanced due to static electric interaction between the positive charges on HbA(1c) and negative charges on BMPs. The amount of HbA(1c) binding to mAPB-BMPs increased with increasing sodium chloride concentrations in the range of 0-100 mM. However, the amount of Hb binding to mAPB-BMPs also increased in high concentration of sodium chloride. The Hb binding to mAPB-BMPs was detached from mAPB-BMPs when Hb-mAPB-BMPs were washed with low salt buffer. This indicates that Hb is nonspecifically adsorbed onto the surface of mAPB-BMPs in high concentration of sodium chloride. These results suggest that selective separation of HbA(1c) using mAPB-BMPs can be achieved with these conditions. A dose-response curve was obtained between luminescence intensity and HbA(1c) concentration using a fully automated boronate affinity immunoassay. A linear relationship between luminescence intensity and HbA(1c) concentration was obtained in the range of 10-10(4) ng/ml.

  9. Adjoint representation of the graded Lie algebra osp(2/1; C) and its exponentiation

    Ilyenko, K

    2003-01-01

    We construct explicitly the grade star Hermitian adjoint representation of osp(2/1; C) graded Lie algebra. Its proper Lie subalgebra, the even part of the graded Lie algebra osp(2/1; C), is given by su(2) compact Lie algebra. The Baker-Campbell-Hausdorff formula is considered and reality conditions for the Grassman-odd transformation parameters, which multiply the pair of odd generators of the graded Lie algebra, are clarified.

  10. Conformational and membrane interaction studies of the antimicrobial peptide alyteserin-1c and its analogue [E4K]alyteserin-1c.

    Subasinghage, Anusha P; O'Flynn, Donal; Conlon, J Michael; Hewage, Chandralal M

    2011-08-01

    Alyteserin-1c (GLKEIFKAGLGSLVKGIAAHVAS.NH(2)), first isolated from skin secretions of the midwife toad Alytes obstetricans, shows selective growth-inhibitory activity against Gram-negative bacteria. The structures of alyteserin-1c and its more potent and less haemolytic analogue [E4K]alyteserin-1c were investigated in various solution and membrane mimicking environments by proton NMR spectroscopy and molecular modelling. In aqueous solution, the peptide displays a lack of secondary structure but, in a 2,2,2-trifluoroethanol (TFE-d(3))-H(2)O solvent mixture, the structure is characterised by an extended alpha helix between residues Leu(2) and Val(21). Solution structural studies in the membrane mimicking environments, sodium dodecyl sulphate (SDS), dodecylphosphocholine (DPC), and 1,2-dihexanoyl-sn-glycero-3-phosphatidylcholine (DHPC) micelles, indicate that these peptides display an alpha helical structure between residues Lys(3) and Val(21). Positional studies of the peptides in SDS, DPC and DHPC media show that the N-terminal and central residues lie inside the micelle while C-terminal residues beyond Ala(19) do not interact with the micelles.

  11. Corrected Hemoglobin A1c as an Index of Glycemic Control in the Preceding One Month

    2002-01-01

    The corrected hemoglobin A1c(cHbA1c) value was calculated on the basis of HbA1c data obtained over 4 months in 19 patients with type 2 diabetes. The usefulness of cHbA1c as a short-term glycemic control index was compared with that of glycated albumin. Both the HbA1c value (measured by immunoassay) and the calculated cHbA1c value showed significant positive correlations with glycated albumin. However, cHbA1c showed a stronger correlation with glycated albumin. In each patient,the variation of...

  12. The angiotensin converting enzyme inhibitor, captopril, prevents the hyperactivity and impulsivity of neurokinin-1 receptor gene 'knockout' mice: sex differences and implications for the treatment of attention deficit hyperactivity disorder.

    Porter, Ashley J; Pillidge, Katharine; Grabowska, Ewelina M; Stanford, S Clare

    2015-04-01

    Mice lacking functional neurokinin-1 receptors (NK1R-/-) display behavioural abnormalities resembling attention deficit hyperactivity disorder (ADHD): locomotor hyperactivity, impulsivity and inattentiveness. The preferred ligand for NK1R, substance P, is metabolised by angiotensin converting enzyme (ACE), which forms part of the brain renin angiotensin system (BRAS). In view of evidence that the BRAS modulates locomotor activity and cognitive performance, we tested the effects of drugs that target the BRAS on these behaviours in NK1R-/- and wildtype mice. We first tested the effects of the ACE inhibitor, captopril, on locomotor activity. Because there are well-established sex differences in both ADHD and ACE activity, we compared the effects of captopril in both male and female mice. Locomotor hyperactivity was evident in male NK1R-/- mice, only, and this was abolished by treatment with captopril. By contrast, male wildtypes and females of both genotypes were unaffected by ACE inhibition. We then investigated the effects of angiotensin AT1 (losartan) and AT2 (PD 123319) receptor antagonists on the locomotor activity of male NK1R-/- and wildtype mice. Both antagonists increased the locomotor activity of NK1R-/- mice, but neither affected the wildtypes. Finally, we tested the effects of captopril on the performance of male NK1R-/- and wildtype mice in the 5-choice serial reaction-time task (5-CSRTT) and found that ACE inhibition prevented the impulsivity of NK1R-/- mice. These results indicate that certain behaviours, disrupted in ADHD, are influenced by an interaction between the BRAS and NK1R, and suggest that ACE inhibitors could provide a novel treatment for this disorder.

  13. Role of positron emission tomography and bone scintigraphy in the evaluation of bone involvement in metastatic pheochromocytoma and paraganglioma: specific implications for succinate dehydrogenase enzyme subunit B gene mutations.

    Zelinka, Tomás; Timmers, Henri J L M; Kozupa, Anna; Chen, Clara C; Carrasquillo, Jorge A; Reynolds, James C; Ling, Alexander; Eisenhofer, Graeme; Lazúrová, Ivica; Adams, Karen T; Whatley, Millie A; Widimsky, Jirí; Pacak, Karel

    2008-03-01

    We performed a retrospective analysis of 71 subjects with metastatic pheochromocytoma and paraganglioma (30 subjects with mutation of succinate dehydrogenase enzyme subunit B (SDHB) gene and 41 subjects without SDHB mutation). Sixty-nine percent presented with bone metastases (SDHB +/-: 77% vs 63%), 39% with liver metastases (SDHB +/-: 27% vs 47%), and 32% with lung metastases (SDHB +/-: 37% vs 29%). The most common sites of bone involvement were thoracic spine (80%; SDHB+/-: 83% vs 77%), lumbar spine (78%; SDHB +/-: 78% vs 75%), and pelvic and sacral bones (78%; SDHB +/-: 91% vs 65%, P=0.04). Subjects with SDHB mutation also showed significantly higher involvement of long bones (SDHB +/-: 78% vs 30%, P=0.007) than those without the mutation. The best overall sensitivity in detecting bone metastases demonstrated positron emission tomography (PET) with 6-[(18)F]-fluorodopamine ([(18)F]-FDA; 90%), followed by bone scintigraphy (82%), computed tomography or magnetic resonance imaging (CT/MRI; 78%), 2-[(18)F]-fluoro-2-deoxy-d-glucose ([(18)F]-FDG) PET (76%), and scintigraphy with [(123/131)I]-metaiodobenzylguanidine (71%). In subjects with SDHB mutation, imaging modalities with best sensitivities for detecting bone metastases were CT/MRI (96%), bone scintigraphy (95%), and [(18)F]-FDG PET (92%). In subjects without SDHB mutations, the modality with the best sensitivity for bone metastases was [(18)F]-FDA PET (100%). In conclusion, bone scintigraphy should be used in the staging of patients with malignant pheochromocytoma and paraganglioma, particularly in patients with SDHB mutations. As for PET imaging, [(18)F]-FDG PET is highly recommended in SDHB mutation patients, whereas [(18)F]-FDA PET is recommended in patients without the mutation.

  14. An experimental double-blind irradiation study of a novel topical product (TPF 50) compared to other topical products with DNA repair enzymes, antioxidants, and growth factors with sunscreens: implications for preventing skin aging and cancer.

    Emanuele, Enzo; Spencer, James M; Braun, Martin

    2014-03-01

    The exposure to ultraviolet radiation (UVR) is a major risk factor for skin aging and the development of non-melanoma skin cancer (NMSC). Although traditional sunscreens remain the mainstay for the prevention of UVR-induced skin damage, they cannot ensure a complete protection against the whole spectrum of molecular lesions associated with UVR exposure. The formation of helix-distorting photoproducts such as cyclobutane pyrimidine dimers (CPD), as well as oxidative damage to DNA bases, including the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8OHdG) are among the key DNA lesions associated with photoaging and tumorigenesis. Besides DNA lesions, UVR-induced formation of free radicals can result in protein carbonylation (PC), a major form of irreversible protein damage that inactivates their biological function. This study compares a complex novel topical product (TPF50) consisting of three actives, ie, 1) traditional physical sunscreens (SPF 50), 2) a liposome-encapsulated DNA repair enzymes complex (photolyase, endonuclease, and 8-oxoguanine glycosylase [OGG1]), and 3) a potent antioxidant complex (carnosine, arazine, ergothionine) to existing products. Specifically, we assessed the ability of TFP50 vs those of DNA repair and antioxidant and growth factor topical products used with SPF 50 sunscreens in preventing CPD, 8OHdG, and PC formation in human skin biopsies after experimental irradiations. In head-to-head comparison studies, TPF50 showed the best efficacy in reducing all of the three molecular markers. The results indicated that the three TPF50 components had a synergistic effect in reducing CPD and PC, but not 8OHdG. Taken together, our results indicate that TPF50 improves the genomic and proteomic integrity of skin cells after repeated exposure to UVR, ultimately reducing the risk of skin aging and NMSC.

  15. What is the Role of HbA1c in Diabetic Hemodialysis Patients?

    Coelho, Silvia

    2016-01-01

    The definition of a good glycemic control in patients with diabetes mellitus on hemodialysis is far from settled. In the general population, hemoglobin A1c is highly correlated with the average glycemia of the last 8-12 weeks. However, in hemodialysis patients, the correlation of hbA1c with glycemia is weaker as it also reflects changes in hemoglobin characteristics and red blood cells half-life. As expected, studies show that the association between HbA1c and outcomes in these patients differ from the general population. Therefore, the value of HbA1c in the treatment of hemodialysis patients has been questioned. Guidelines are generally cautious in their recommendations about possible targets of HbA1c in this population. Indeed, the risk of not treating hyperglycemia should be weighed against the particularly high risk of precipitating hypoglycemia in dialysis patients. In this review, a critical analysis of the current role of HbA1c in the care of hemodialysis patients is presented.

  16. Development of hemoglobin A1c certified reference material by liquid chromatography isotope dilution mass spectrometry.

    Bi, Jiaming; Wu, Liqing; Yang, Bin; Yang, Yi; Wang, Jing

    2012-04-01

    We report the development of a National Institute of Metrology (NIM) hemoglobin A(1c) (HbA(1c)) certified reference material (CRM). Each CRM unit contains about 10 μL of hemoglobin. Both hemoglobin and glycated hemoglobin were quantitatively determined by high-performance liquid chromatography (HPLC)-isotope dilution mass spectrometry (IDMS) with synthesized VHLTPE and glycated VHLTPE as standards. The mass fraction of synthesized VHLTPE or glycated VHLTPE was also quantitatively determined by HPLC-IDMS with NIM amino acid CRMs as standards. The homogeneity and stability of the CRMs were examined with a commercial HbA(1c) analyzer based on the HPLC principle. Fifteen units were randomly selected for homogeneity examination, and statistical analysis showed there was no inhomogeneity. Examination of the stability showed that the CRM was stable for at least 6 months at -80 °C. Uncertainty components of the balance, amino acid purity, hydrolysis and proteolysis efficiency, method reproducibility, homogeneity, and stability were taken into consideration for uncertainty evaluation. The certified value of NIM HbA(1c) CRM was expressed as the ratio of HbA(1c) to total hemoglobin in moles, and was (9.6 ± 1.9)%. The CRM can be used as a calibration or validation standard for clinical diagnostics. It is expected to improve the comparability for HbA(1c) measurement in China.

  17. Applications of Environmental Remote Sensing by HJ-1C SAR Imageries

    Tian Wei

    2014-06-01

    Full Text Available The HJ-1C satellite was successfully launched in November 19, 2012. The HJ-1C and HJ-1A/1B satellites, which were launched in September 06, 2008, constitute the “2+1” small satellite constellation for environmental and disaster monitoring. This study focuses on the analysis and evaluation of the satellite performance with respect to environmental remote sensing, including land use interpretation, land cover classification, oil spill identification, retrieval of sea waves, and monitoring of coastal mariculture. The data used in this study cover the city of Beijing and the sea of the Fujian Province. Nine HJ-1C satellite images (level-2, S band, VV Pol, strip mode, 5 m resolution from December 2012 to January 2013 are used. The conclusions are as follows: (1 the HJ-1C SAR images can be used to manually identify farmland, woodland, roads, rivers, urban construction, and rural residential areas; (2 the accuracy of the automatic land cover classification increased significantly when the HJ-1C SAR and HJ-1B CCD fusion images are used; (3 the HJ-1C satellite can be used to identify oil spills, to invert wave parameters, and to extract information regarding inshore aquaculture.

  18. A hemoglobin A1C immunoassay method not affected by carbamylated hemoglobin.

    Rose, A M; Tongate, C; Valdes, R

    1995-01-01

    Hemoglobin A1C (HbA1C) methods based on charge separation of Hb species are subject to interference from carbamylated Hb (carb Hb). Carb Hb adducts are formed via interaction of terminal amino groups of HbA with isocyanic acid, after the spontaneous dissociation of urea to cyanate. It is hypothesized that a new immunoassay method, using a monoclonal antibody that recognizes the N-terminus of the Hb beta-chain and its sugar moiety, should be refractory to cross-reactive interference from carb Hb. To test this hypothesis, Hb was carbamylated in vitro and co-migration of carb Hb assessed with HbA1C using an electrophoretic method. Densitometric scans - post sodium cyanate incubation and electrophoretic separation - showed a 5 to 7 fold elevation of the HbA1C peak only, while HbA1C values obtained using immunoassay were unaffected. Also assessed was carbamylation interference in vivo, and a positive proportional bias with the electrophoretic system (Y) was observed compared to the immunoassay system (X) (y = 1.2x - 0.21 percent). Others have shown that carb Hb may cause a clinically significant false elevation in patient HbA1C values, when methods based on charge separation of Hb species are used. It is our conclusion, however, that while carb Hb may play a role, the differences observed in this study are largely due to calibration.

  19. Stability study for magnetic reagent assaying Hb and HbA1c

    Hsieh, Wen-Pin [Actherm Inc., Hsinchu 200, Taiwan (China); Chieh, J.J.; Yang, C.C. [Institute of Electro-optical Science and Technology, National Taiwan Normal University, Taipei 116, Taiwan (China); Yang, S.Y. [Institute of Electro-optical Science and Technology, National Taiwan Normal University, Taipei 116, Taiwan (China); MagQu Co., Ltd., Sindian Dist., New Taipei City 231, Taiwan (China); Chen, Po-Yu; Huang, Yu-Hao [Actherm Inc., Hsinchu 200, Taiwan (China); Hong, Y.W. [Institute of Electro-optical Science and Technology, National Taiwan Normal University, Taipei 116, Taiwan (China); Horng, H.E., E-mail: phyfv001@ntnu.edu.tw [Institute of Electro-optical Science and Technology, National Taiwan Normal University, Taipei 116, Taiwan (China)

    2013-01-15

    Reagents for magnetically labeled immunoassay on human Hb and human HbA1c have been synthesized. The reagents consist of Fe{sub 3}O{sub 4} magnetic particles biofunctionalized with antibodies against Hb and HbA1c. It has been demonstrated that the reagents can be applied to quantitatively detect Hb and HbA1c by using immunomagnetic reduction assay. In addition to characterizing the assay properties, such as the standard curve and the low-detection limit, the stability of reagents is investigated. To do this, the temporal dependence of particle sizes and the bio-activity of reagents are monitored. The results show that the reagents are highly stable when stored at 2-8 Degree-Sign C. This means that the reagents synthesized in this work are promising for practical applications. - Highlights: Black-Right-Pointing-Pointer The properties of assaying Hb and HbA1c using immunomagnetic reduction are studied. Black-Right-Pointing-Pointer The magnetic nanoparticles with antibodies are highly stable in solutions. Black-Right-Pointing-Pointer No significant mutual interference between Hb and HbA1c in assays is observed. Black-Right-Pointing-Pointer High-sensitivity assays on Hb and HbA1c using immunomagnetic reduction are achieved.

  20. Red cell enzymes.

    Paniker, N V

    1975-03-01

    As compared to other cells of the body, the mammalian red cell has one of the simplest structural organizations. As a result, this cell has been extensively used in studies involving the structure, function, and integrity of cell membranes as well as cytoplasmic events. Additionally, the metabolic activities of the red blood cell are also relatively simple. During the past quarter century or so, an ocean of knowledge has been gathered on various aspects of red cell metabolism and function. The fields of enzymes, hemoglobin, membrane, and metabolic products comprise the major portion of this knowledge. These advances have made valuable contributions to biochemistry and medicine. Despite these favorable aspects of this simple, anucleated cell, it must be conceded that our knowledge about the red cell is far from complete. We are still in the dark concerning the mechanism involved in several aspects of its membrane, hemoglobin, enzymes, and a large number of other constituents. For example, a large number of enzymes with known catalytic activity but with unknown function have eluded investigators despite active pursuit. This review will be a consolidation of our present knowledge of human red cell enzymes, with particular reference to their usefulness in the diagnosis and therapy of disease. Owing to the multitude of publications by prominent investigators on each of the approximately 50 enzymes discussed in this review, it was impossible to cite a majority of them.

  1. Random-walk enzymes

    Mak, Chi H.; Pham, Phuong; Afif, Samir A.; Goodman, Myron F.

    2015-01-01

    Enzymes that rely on random walk to search for substrate targets in a heterogeneously dispersed medium can leave behind complex spatial profiles of their catalyzed conversions. The catalytic signatures of these random-walk enzymes are the result of two coupled stochastic processes: scanning and catalysis. Here we develop analytical models to understand the conversion profiles produced by these enzymes, comparing an intrusive model, in which scanning and catalysis are tightly coupled, against a loosely coupled passive model. Diagrammatic theory and path-integral solutions of these models revealed clearly distinct predictions. Comparison to experimental data from catalyzed deaminations deposited on single-stranded DNA by the enzyme activation-induced deoxycytidine deaminase (AID) demonstrates that catalysis and diffusion are strongly intertwined, where the chemical conversions give rise to new stochastic trajectories that were absent if the substrate DNA was homogeneous. The C → U deamination profiles in both analytical predictions and experiments exhibit a strong contextual dependence, where the conversion rate of each target site is strongly contingent on the identities of other surrounding targets, with the intrusive model showing an excellent fit to the data. These methods can be applied to deduce sequence-dependent catalytic signatures of other DNA modification enzymes, with potential applications to cancer, gene regulation, and epigenetics. PMID:26465508

  2. Random-walk enzymes

    Mak, Chi H.; Pham, Phuong; Afif, Samir A.; Goodman, Myron F.

    2015-09-01

    Enzymes that rely on random walk to search for substrate targets in a heterogeneously dispersed medium can leave behind complex spatial profiles of their catalyzed conversions. The catalytic signatures of these random-walk enzymes are the result of two coupled stochastic processes: scanning and catalysis. Here we develop analytical models to understand the conversion profiles produced by these enzymes, comparing an intrusive model, in which scanning and catalysis are tightly coupled, against a loosely coupled passive model. Diagrammatic theory and path-integral solutions of these models revealed clearly distinct predictions. Comparison to experimental data from catalyzed deaminations deposited on single-stranded DNA by the enzyme activation-induced deoxycytidine deaminase (AID) demonstrates that catalysis and diffusion are strongly intertwined, where the chemical conversions give rise to new stochastic trajectories that were absent if the substrate DNA was homogeneous. The C →U deamination profiles in both analytical predictions and experiments exhibit a strong contextual dependence, where the conversion rate of each target site is strongly contingent on the identities of other surrounding targets, with the intrusive model showing an excellent fit to the data. These methods can be applied to deduce sequence-dependent catalytic signatures of other DNA modification enzymes, with potential applications to cancer, gene regulation, and epigenetics.

  3. Random-walk enzymes.

    Mak, Chi H; Pham, Phuong; Afif, Samir A; Goodman, Myron F

    2015-09-01

    Enzymes that rely on random walk to search for substrate targets in a heterogeneously dispersed medium can leave behind complex spatial profiles of their catalyzed conversions. The catalytic signatures of these random-walk enzymes are the result of two coupled stochastic processes: scanning and catalysis. Here we develop analytical models to understand the conversion profiles produced by these enzymes, comparing an intrusive model, in which scanning and catalysis are tightly coupled, against a loosely coupled passive model. Diagrammatic theory and path-integral solutions of these models revealed clearly distinct predictions. Comparison to experimental data from catalyzed deaminations deposited on single-stranded DNA by the enzyme activation-induced deoxycytidine deaminase (AID) demonstrates that catalysis and diffusion are strongly intertwined, where the chemical conversions give rise to new stochastic trajectories that were absent if the substrate DNA was homogeneous. The C→U deamination profiles in both analytical predictions and experiments exhibit a strong contextual dependence, where the conversion rate of each target site is strongly contingent on the identities of other surrounding targets, with the intrusive model showing an excellent fit to the data. These methods can be applied to deduce sequence-dependent catalytic signatures of other DNA modification enzymes, with potential applications to cancer, gene regulation, and epigenetics.

  4. Enzyme recycling in lignocellulosic biorefineries

    Jørgensen, Henning; Pinelo, Manuel

    2017-01-01

    platform. Cellulases are the most important enzymes required in this process, but the complex nature of lignocellulose requires several other enzymes (hemicellulases and auxiliary enzymes) for efficient hydrolysis. Enzyme recycling increases the catalytic productivity of the enzymes by reusing them...... upscaled and tested in industrial settings, mainly because of many difficulties with recycling of enzymes from the complex lignocellulose hydrolyzate at industrially relevant conditions, i.e., high solids loadings. The challenges are associated with the large number of different enzymes required...... for efficient hydrolysis, enzyme stability, and the detrimental interaction between enzyme and lignin. This review provides a comprehensive overview of the various methods for enzyme recovery and recycling, for example recycling of free enzymes, readsorption to fresh material, recycling of solids, membrane...

  5. HbA1c Test as a Tool in the Diagnosis of Gestational Diabetes Mellitus.

    Paula Breitenbach Renz

    Full Text Available Gestational diabetes mellitus (GDM is a prevalent and potentially serious condition which may put both mothers and neonates at risk. The current recommendation for diagnosis is the oral glucose tolerance test (OGTT. This study aimed to determine the usefulness of HbA1c test as a diagnostic tool for GDM as compared to the traditional criteria based on the OGTT.This was a diagnostic test accuracy study. We performed OGTT and HbA1c test in women attending prenatal visits at a tertiary hospital. GDM was defined according to WHO1999 or ADA/WHO 2013 criteria. ROC curve was used to evaluate the diagnostic performance of HbA1c. Sensitivity, specificity and likelihood ratios for different HbA1c cut-off points were calculated.Of the 262 women in the third trimester of gestation enrolled in the study, 86 (33% were diagnosed with GDM. Only five of these women presented HbA1c ≥48 mmol/mol (6.5%. This cut-off point presented 100% specificity but very low sensitivity (7%. Based on ROC curve, and considering OGTT as the reference criterion, HbA1c ≥40 mmol/mol (5.8% showed adequate specificity in diagnosing GDM (94.9% but low sensitivity (26.4%. Unlike, HbA1c values of 31 mmol/mol (5.0% presented adequate sensitivity (89.7% but low specificity (32.6% to detect GDM. For women with HbA1c ≥40 mmol/mol (5.8%, the positive and negative likelihood ratios were 5.14 (95%CI 2.49-10.63 and 0.78 (0.68-0.88, respectively. The post-test probability of GDM was about 40%, representing a 4.0-fold increase in the mean pre-test probability. This cut-off point could eliminate the need for the unpleasant and laborious OGTT tests in almost one third of cases, as 38% of patients with GDM may be diagnosable by HbA1c test alone.Our results show that combined HbA1c and OGTT measurements may be useful in diagnosing GDM.

  6. Fasting Plasma Glucose and Hemoglobin A1c in Identifying and Predicting Diabetes

    Wang, Wenyu; Lee, Elisa T.; Howard, Barbara V.; Fabsitz, Richard R.; Devereux, Richard B.; Welty, Thomas K.

    2011-01-01

    OBJECTIVE To compare fasting plasma glucose (FPG) and HbA1c in identifying and predicting type 2 diabetes in a population with high rates of diabetes. RESEARCH DESIGN AND METHODS Diabetes was defined as an FPG level ≥126 mg/dL or an HbA1c level ≥6.5%. Data collected from the baseline and second exams (1989–1995) of the Strong Heart Study were used. RESULTS For cases of diabetes identified by FPG ≥126 mg/dL, using HbA1c ≥6.5% at the initial and 4-year follow-up diabetes screenings (or in identifying incident cases in 4 years) among undiagnosed participants left 46% and 59% of cases of diabetes undetected, respectively, whereas for cases identified by HbA1c ≥6.5%, using FPG ≥126 mg/dL left 11% and 59% unidentified, respectively. Age, waist circumference, urinary albumin-to-creatinine ratio, and baseline FPG and HbA1c levels were common significant risk factors for incident diabetes defined by either FPG or HbA1c; triglyceride levels were significant for diabetes defined by HbA1c alone, and blood pressure and sibling history of diabetes were significant for diabetes defined by FPG alone. Using both the baseline FPG and HbA1c in diabetes prediction identified more people at risk than using either measure alone. CONCLUSIONS Among undiagnosed participants, using HbA1c alone in initial diabetes screening identifies fewer cases of diabetes than FPG, and using either FPG or HbA1c alone cannot effectively identify diabetes in a 4-year periodic successive diabetes screening or incident cases of diabetes in 4 years. Using both criteria may identify more people at risk. The proposed models using the commonly available clinical measures can be applied to assessing the risk of incident diabetes using either criterion. PMID:21270194

  7. Entropy and Enzyme Catalysis.

    Åqvist, Johan; Kazemi, Masoud; Isaksen, Geir Villy; Brandsdal, Bjørn Olav

    2017-02-21

    The role played by entropy for the enormous rate enhancement achieved by enzymes has been debated for many decades. There are, for example, several confirmed cases where the activation free energy is reduced by around 10 kcal/mol due to entropic effects, corresponding to a rate enhancement of ∼10(7) compared to the uncatalyzed reaction. However, despite substantial efforts from both the experimental and theoretical side, no real consensus has been reached regarding the origin of such large entropic contributions to enzyme catalysis. Another remarkable instance of entropic effects is found in enzymes that are adapted by evolution to work at low temperatures, near the freezing point of water. These cold-adapted enzymes invariably show a more negative entropy and a lower enthalpy of activation than their mesophilic orthologs, which counteracts the exponential damping of reaction rates at lower temperature. The structural origin of this universal phenomenon has, however, remained elusive. The basic problem with connecting macroscopic thermodynamic quantities, such as activation entropy and enthalpy derived from Arrhenius plots, to the 3D protein structure is that the underlying detailed (microscopic) energetics is essentially inaccessible to experiment. Moreover, attempts to calculate entropy contributions by computer simulations have mostly focused only on substrate entropies, which do not provide the full picture. We have recently devised a new approach for accessing thermodynamic activation parameters of both enzyme and solution reactions from computer simulations, which turns out to be very successful. This method is analogous to the experimental Arrhenius plots and directly evaluates the temperature dependence of calculated reaction free energy profiles. Hence, by extensive molecular dynamics simulations and calculations of up to thousands of independent free energy profiles, we are able to extract activation parameters with sufficient precision for making

  8. Angiotensin-converting enzyme

    Sørensen, P G; Rømer, F K; Cortes, D

    1984-01-01

    In order to evaluate bleomycin-associated lung damage in humans, lung function parameters and serum levels of the endothelial-bound angiotensin-converting enzyme (ACE) were determined by serial measurements in 11 patients who were treated for testicular cancer. None developed clinical or radiolog......In order to evaluate bleomycin-associated lung damage in humans, lung function parameters and serum levels of the endothelial-bound angiotensin-converting enzyme (ACE) were determined by serial measurements in 11 patients who were treated for testicular cancer. None developed clinical...

  9. Flax lignan concentrate attenuate hypertension and abnormal left ventricular contractility via modulation of endogenous biomarkers in two-kidney-one-clip (2K1C hypertensive rats

    Sameer Hanmantrao Sawant

    Full Text Available ABSTRACT The present investigation was designed to study the effect of flax lignan concentrate obtained from Linum usitatissimum L., Linaceae, in two-kidney, one clip (2K1C hypertension model in Wistar rats. 2K1C Goldblatt model rats were divided randomly into six groups: sham, 2K1C control, captopril (30 mg/kg, flax lignan concentrate (200, 400 and 800 mg/kg. Flax lignan concentrate and captopril were administered daily for eight consecutive weeks. Sham-operated, and 2K1C control rats received the vehicle. Treatment with flax lignan concentrate (400 and 800 mg/kg significantly and dose-dependently restored the hemodynamic parameters systolic blood pressure, diastolic blood pressure, mean arterial blood pressure and left ventricular functions. The flax lignan concentrate significantly restored the elevated hepatic, renal and cardiac marker enzymes in the serum. It also restored the organs weights (kidney and heart, serum electrolyte level and histological abnormalities. Furthermore, flax lignan concentrate significantly elevated the level of biochemical markers that is enzymatic antioxidants superoxide dismutase, glutathione and decreased malondialdehyde in the heart and kidney tissues. Meanwhile, we found that plasma nitric oxide and plasma nitric oxide synthase contents were significantly increased in the flax lignan concentrate-treated group, and plasma endothelin-1 and renal angiotensin-II levels were significantly lower than 2K1C hypertensive group. In conclusion, the antihypertensive and antioxidant effect of flax lignan concentrate were dose-dependent and at the highest dose (i.e. 800 mg/kg similar to those of captopril (30 mg/kg. It is suggested that flax lignan concentrate reduced blood pressure by reduction of renal angiotensin-II level, inhibition of plasma endothelin-1 production, induction of the nitric oxide, nitric oxide synthase and in vivo antioxidant defense system.

  10. Genic and global functions for Paf1C in chromatin modification and gene expression in Arabidopsis.

    Sookyung Oh

    Full Text Available In budding yeast, intragenic histone modification is linked with transcriptional elongation through the conserved regulator Paf1C. To investigate Paf1C-related function in higher eukaryotes, we analyzed the effects of loss of Paf1C on histone H3 density and patterns of H3 methylated at K4, K27, and K36 in Arabidopsis genes, and integrated this with existing gene expression data. Loss of Paf1C did not change global abundance of H3K4me3 or H3K36me2 within chromatin, but instead led to a 3' shift in the distribution of H3K4me3 and a 5' shift in the distribution of H3K36me2 within genes. We found that genes regulated by plant Paf1C showed strong enrichment for both H3K4me3 and H3K27me3 and also showed a high degree of tissue-specific expression. At the Paf1C- and PcG-regulated gene FLC, transcriptional silencing and loss of H3K4me3 and H3K36me2 were accompanied by expansion of H3K27me3 into the promoter and transcriptional start regions and further enrichment of H3K27me3 within the transcribed region. These results highlight both genic and global functions for plant Paf1C in histone modification and gene expression, and link transcriptional activity with cellular memory.

  11. Overexpression of AtBMI1C, a polycomb group protein gene, accelerates flowering in Arabidopsis.

    Wei Li

    Full Text Available Polycomb group protein (PcG-mediated gene silencing is emerging as an essential developmental regulatory mechanism in eukaryotic organisms. PcGs inactivate or maintain the silenced state of their target chromatin by forming complexes, including Polycomb Repressive Complex 1 (PRC1 and 2 (PRC2. Three PRC2 complexes have been identified and characterized in Arabidopsis; of these, the EMF and VRN complexes suppress flowering by catalyzing the trimethylation of lysine 27 on histone H3 of FLOWER LOCUS T (FT and FLOWER LOCUS C (FLC. However, little is known about the role of PRC1 in regulating the floral transition, although AtRING1A, AtRING1B, AtBMI1A, and AtBMI1B are believed to regulate shoot apical meristem and embryonic development as components of PRC1. Moreover, among the five RING finger PcGs in the Arabidopsis genome, four have been characterized. Here, we report that the fifth, AtBMI1C, is a novel, ubiquitously expressed nuclear PcG protein and part of PRC1, which is evolutionarily conserved with Psc and BMI1. Overexpression of AtBMI1C caused increased H2A monoubiquitination and flowering defects in Arabidopsis. Both the suppression of FLC and activation of FT were observed in AtBMI1C-overexpressing lines, resulting in early flowering. No change in the H3K27me3 level in FLC chromatin was detected in an AtBMI1C-overexpressing line. Our results suggest that AtBMI1C participates in flowering time control by regulating the expression of FLC; moreover, the repression of FLC by AtBMI1C is not due to the activity of PRC2. Instead, it is likely the result of PRC1 activity, into which AtBMI1C is integrated.

  12. On the Temperature Dependence of Enzyme-Catalyzed Rates.

    Arcus, Vickery L; Prentice, Erica J; Hobbs, Joanne K; Mulholland, Adrian J; Van der Kamp, Marc W; Pudney, Christopher R; Parker, Emily J; Schipper, Louis A

    2016-03-29

    One of the critical variables that determine the rate of any reaction is temperature. For biological systems, the effects of temperature are convoluted with myriad (and often opposing) contributions from enzyme catalysis, protein stability, and temperature-dependent regulation, for example. We have coined the phrase "macromolecular rate theory (MMRT)" to describe the temperature dependence of enzyme-catalyzed rates independent of stability or regulatory processes. Central to MMRT is the observation that enzyme-catalyzed reactions occur with significant values of ΔCp(‡) that are in general negative. That is, the heat capacity (Cp) for the enzyme-substrate complex is generally larger than the Cp for the enzyme-transition state complex. Consistent with a classical description of enzyme catalysis, a negative value for ΔCp(‡) is the result of the enzyme binding relatively weakly to the substrate and very tightly to the transition state. This observation of negative ΔCp(‡) has important implications for the temperature dependence of enzyme-catalyzed rates. Here, we lay out the fundamentals of MMRT. We present a number of hypotheses that arise directly from MMRT including a theoretical justification for the large size of enzymes and the basis for their optimum temperatures. We rationalize the behavior of psychrophilic enzymes and describe a "psychrophilic trap" which places limits on the evolution of enzymes in low temperature environments. One of the defining characteristics of biology is catalysis of chemical reactions by enzymes, and enzymes drive much of metabolism. Therefore, we also expect to see characteristics of MMRT at the level of cells, whole organisms, and even ecosystems.

  13. Genes Encoding Enzymes Involved in Ethanol Metabolism

    Hurley, Thomas D.; Edenberg, Howard J.

    2012-01-01

    The effects of beverage alcohol (ethanol) on the body are determined largely by the rate at which it and its main breakdown product, acetaldehyde, are metabolized after consumption. The main metabolic pathway for ethanol involves the enzymes alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Seven different ADHs and three different ALDHs that metabolize ethanol have been identified. The genes encoding these enzymes exist in different variants (i.e., alleles), many of which differ by a single DNA building block (i.e., single nucleotide polymorphisms [SNPs]). Some of these SNPs result in enzymes with altered kinetic properties. For example, certain ADH1B and ADH1C variants that are commonly found in East Asian populations lead to more rapid ethanol breakdown and acetaldehyde accumulation in the body. Because acetaldehyde has harmful effects on the body, people carrying these alleles are less likely to drink and have a lower risk of alcohol dependence. Likewise, an ALDH2 variant with reduced activity results in acetaldehyde buildup and also has a protective effect against alcoholism. In addition to affecting drinking behaviors and risk for alcoholism, ADH and ALDH alleles impact the risk for esophageal cancer. PMID:23134050

  14. Survey of Air Pollution Effect on Variation of Glycosylated Hemoglobin A1C (HbA1C level in Diabetic Patients in Tehran

    Fatemeh Mousavi

    2013-05-01

    Materials and Methods: During November-January 2010-11, Tehran, capital of Iran, was exposed with high levels of air pollution. A retrospective cohort study was carried out on 330 patients diagnosed with diabetes mellitus for at least 12 months referring to 3 endocrinal care clinics. A questionnaire in two demographic and diabetic related sections was prepared. The patients' HbA1C level recorded on November-January 2009-10 was compared with November-January 2010-11. Descriptive analysis and paired t-test were carried out using SPSS 18 software. Results: The patients investigated were divided into two groups. The first group was composed of 108 patients (53.7% female and 46.3% male with diabetes mellitus type I (Insulin Dependent, age mean of 17.22, and SD of 11.57. The second group was composed of 222 patients (58.6% female and 41.4% male with diabetes mellitus type II (Noninsulin Dependent, age mean of 53.91, and SD of 12.12. The change of HbAIC level in both groups wa not statistically significant; in first group, HbA1C level increased from 7.71 to 7.75 mg / 100 ml (P =0.828 and in second group, it increased from 7.06 to 7.08 mg / 100 ml (P = 0.798. Conclusion: According to the results obtained, it can be concluded that relation of air pollution and HbA1C mean variation in diabetic patients was insignificant.

  15. The surface science of enzymes

    Rod, Thomas Holm; Nørskov, Jens Kehlet

    2002-01-01

    One of the largest challenges to science in the coming years is to find the relation between enzyme structure and function. Can we predict which reactions an enzyme catalyzes from knowledge of its structure-or from its amino acid sequence? Can we use that knowledge to modify enzyme function......? To solve these problems we must understand in some detail how enzymes interact with reactants from its surroundings. These interactions take place at the surface of the enzyme and the question of enzyme function can be viewed as the surface science of enzymes. In this article we discuss how to describe...... catalysis by enzymes, and in particular the analogies between enzyme catalyzed reactions and surface catalyzed reactions. We do this by discussing two concrete examples of reactions catalyzed both in nature (by enzymes) and in industrial reactors (by inorganic materials), and show that although analogies...

  16. Amperometric Enzyme Electrodes

    1989-12-01

    form of carbon (glascy carbon, graphite, reticulated vitreous carbon, carbon paste, fiber or foil). Carbon is favored for enzyme immoblization...interference from spurious electroactive species in blood, t proprietary multilayer membranie that includes a cellulose acetate memirane and a Nucleopore

  17. Computational enzyme design

    Bolon, Daniel N.

    2002-08-01

    The long-term objective of computational enzyme design is the ability to generate efficient protein catalysts for any chemical reaction. This thesis develops and experimentally validates a general computational approach for the design of enzymes with novel function. In order to include catalytic mechanism in protein design, a high-energy state (HES) rotamer (side chain representation) was constructed. In this rotamer, substrate atoms are in a HES. In addition, at least one amino acid side chain is positioned to interact favorably with substrate atoms in their HES and facilitate the reaction. Including an amino acid side chain in the HES rotamer automatically positions substrate relative to a protein scaffold and allows protein design algorithms to search for sequences capable of interacting favorably with the substrate. Because chemical similarity exists between the transition state and the high-energy state, optimizing the protein sequence to interact favorably with the HES rotamer should lead to transition state stabilization. In addition, the HES rotamer model focuses the subsequent computational active site design on a relevant phase space where an amino acid is capable of interacting in a catalytically active geometry with substrate. Using a HES rotamer model of the histidine mediated nucleophilic hydrolysis of p-nitrophenyl acetate, the catalytically inert 108 residue E. coli thioredoxin as a scaffold, and the ORBIT protein design software to compute sequences, an active site scan identified two promising active site designs. Experimentally, both candidate ?protozymes? demonstrated catalytic activity significantly above background. In addition, the rate enhancement of one of these ?protozymes? was the same order of magnitude as the first catalytic antibodies. Because polar groups are frequently buried at enzyme-substrate interfaces, improved modeling of buried polar interactions may benefit enzyme design. By studying native protein structures, rules have been

  18. Ciliary dyslexia candidate genes DYX1C1 and DCDC2 are regulated by Regulatory Factor X (RFX) transcription factors through X-box promoter motifs

    Tammimies, Kristiina; Bieder, Andrea; Lauter, Gilbert; Sugiaman-Trapman, Debora; Torchet, Rachel; Hokkanen, Marie-Estelle; Burghoorn, Jan; Castrén, Eero; Kere, Juha; Tapia-Páez, Isabel; Swoboda, Peter

    2016-01-01

    DYX1C1, DCDC2, and KIAA0319 are three of the most replicated dyslexia candidate genes (DCGs). Recently, these DCGs were implicated in functions at the cilium. Here, we investigate the regulation of these DCGs by Regulatory Factor X transcription factors (RFX TFs), a gene family known for transcriptionally regulating ciliary genes. We identify conserved X-box motifs in the promoter regions of DYX1C1, DCDC2, and KIAA0319 and demonstrate their functionality, as well as the ability to recruit RFX TFs using reporter gene and electrophoretic mobility shift assays. Furthermore, we uncover a complex regulation pattern between RFX1, RFX2, and RFX3 and their significant effect on modifying the endogenous expression of DYX1C1 and DCDC2 in a human retinal pigmented epithelial cell line immortalized with hTERT (hTERT-RPE1). In addition, induction of ciliogenesis increases the expression of RFX TFs and DCGs. At the protein level, we show that endogenous DYX1C1 localizes to the base of the cilium, whereas DCDC2 localizes along the entire axoneme of the cilium, thereby validating earlier localization studies using overexpression models. Our results corroborate the emerging role of DCGs in ciliary function and characterize functional noncoding elements, X-box promoter motifs, in DCG promoter regions, which thus can be targeted for mutation screening in dyslexia and ciliopathies associated with these genes.—Tammimies, K., Bieder, A., Lauter, G., Sugiaman-Trapman, D., Torchet, R., Hokkanen, M.-E., Burghoorn, J., Castrén, E., Kere, J., Tapia-Páez, I., Swoboda, P. Ciliary dyslexia candidate genes DYX1C1 and DCDC2 are regulated by Regulatory Factor (RF) X transcription factors through X-box promoter motifs. PMID:27451412

  19. Integration of HPV6 and downregulation of AKR1C3 expression mark malignant transformation in a patient with juvenile-onset laryngeal papillomatosis.

    Christian Ulrich Huebbers

    Full Text Available Juvenile-onset recurrent respiratory papillomatosis (RRP is associated with low risk human papillomavirus (HPV types 6 and 11. Malignant transformation has been reported solely for HPV11-associated RRP in 2-4% of all RRP-cases, but not for HPV6. The molecular mechanisms in the carcinogenesis of low risk HPV-associated cancers are to date unknown. We report of a female patient, who presented with a laryngeal carcinoma at the age of 24 years. She had a history of juvenile-onset RRP with an onset at the age of three and subsequently several hundred surgical interventions due to multiple recurrences of RRP. Polymerase chain reaction (PCR or bead-based hybridization followed by direct sequencing identified HPV6 in tissue sections of previous papilloma and the carcinoma. P16(INK4A, p53 and pRb immunostainings were negative in all lesions. HPV6 specific fluorescence in situ hybridization (FISH revealed nuclear staining suggesting episomal virus in the papilloma and a single integration site in the carcinoma. Integration-specific amplification of papillomavirus oncogene transcripts PCR (APOT-PCR showed integration in the aldo-keto reductase 1C3 gene (AKR1C3 on chromosome 10p15.1. ArrayCGH detected loss of the other gene copy as part of a deletion at 10p14-p15.2. Western blot analysis and immunohistochemistry of the protein AKR1C3 showed a marked reduction of its expression in the carcinoma. In conclusion, we identified a novel molecular mechanism underlying a first case of HPV6-associated laryngeal carcinoma in juvenile-onset RRP, i.e. that HPV6 integration in the AKR1C3 gene resulted in loss of its expression. Alterations of AKR1C gene expression have previously been implicated in the tumorigenesis of other (HPV-related malignancies.

  20. Ciliary dyslexia candidate genes DYX1C1 and DCDC2 are regulated by Regulatory Factor X (RFX) transcription factors through X-box promoter motifs.

    Tammimies, Kristiina; Bieder, Andrea; Lauter, Gilbert; Sugiaman-Trapman, Debora; Torchet, Rachel; Hokkanen, Marie-Estelle; Burghoorn, Jan; Castrén, Eero; Kere, Juha; Tapia-Páez, Isabel; Swoboda, Peter

    2016-10-01

    DYX1C1, DCDC2, and KIAA0319 are three of the most replicated dyslexia candidate genes (DCGs). Recently, these DCGs were implicated in functions at the cilium. Here, we investigate the regulation of these DCGs by Regulatory Factor X transcription factors (RFX TFs), a gene family known for transcriptionally regulating ciliary genes. We identify conserved X-box motifs in the promoter regions of DYX1C1, DCDC2, and KIAA0319 and demonstrate their functionality, as well as the ability to recruit RFX TFs using reporter gene and electrophoretic mobility shift assays. Furthermore, we uncover a complex regulation pattern between RFX1, RFX2, and RFX3 and their significant effect on modifying the endogenous expression of DYX1C1 and DCDC2 in a human retinal pigmented epithelial cell line immortalized with hTERT (hTERT-RPE1). In addition, induction of ciliogenesis increases the expression of RFX TFs and DCGs. At the protein level, we show that endogenous DYX1C1 localizes to the base of the cilium, whereas DCDC2 localizes along the entire axoneme of the cilium, thereby validating earlier localization studies using overexpression models. Our results corroborate the emerging role of DCGs in ciliary function and characterize functional noncoding elements, X-box promoter motifs, in DCG promoter regions, which thus can be targeted for mutation screening in dyslexia and ciliopathies associated with these genes.-Tammimies, K., Bieder, A., Lauter, G., Sugiaman-Trapman, D., Torchet, R., Hokkanen, M.-E., Burghoorn, J., Castrén, E., Kere, J., Tapia-Páez, I., Swoboda, P. Ciliary dyslexia candidate genes DYX1C1 and DCDC2 are regulated by Regulatory Factor (RF) X transcription factors through X-box promoter motifs.

  1. The Moderately Efficient Enzyme: Futile Encounters and Enzyme Floppiness.

    Bar-Even, Arren; Milo, Ron; Noor, Elad; Tawfik, Dan S

    2015-08-18

    The pioneering model of Henri, Michaelis, and Menten was based on the fast equilibrium assumption: the substrate binds its enzyme reversibly, and substrate dissociation is much faster than product formation. Here, we examine this assumption from a somewhat different point of view, asking what fraction of enzyme-substrate complexes are futile, i.e., result in dissociation rather than product formation. In Knowles' notion of a "perfect" enzyme, all encounters of the enzyme with its substrate result in conversion to product. Thus, the perfect enzyme's catalytic efficiency, kcat/KM, is constrained by only the diffusion on-rate, and the fraction of futile encounters (defined as φ) approaches zero. The available data on >1000 different enzymes suggest that for ≥90% of enzymes φ > 0.99 and for the "average enzyme" φ ≥ 0.9999; namely, <1 of 10(4) encounters is productive. Thus, the "fast equilibrium" assumption holds for the vast majority of enzymes. We discuss possible molecular origins for the dominance of futile encounters, including the coexistence of multiple sub-states of an enzyme's active site (enzyme floppiness) and/or its substrate. Floppiness relates to the inherent flexibility of proteins, but also to conflicting demands, or trade-offs, between rate acceleration (the rate-determining chemical step) and catalytic turnover, or between turnover rate and accuracy. The study of futile encounters and active-site floppiness may contribute to a better understanding of enzyme catalysis, enzyme evolution, and improved enzyme design.

  2. Alpha- and beta-cell abnormalities in haemoglobin A1c-defined prediabetes and type 2 diabetes

    Calanna, Salvatore; Scicali, Roberto; Di Pino, Antonino;

    2014-01-01

    New recommendations for the use of glycated haemoglobin A1c (HbA1c) to diagnose prediabetes and type 2 diabetes have changed the constitution of the two populations. We aimed to investigate the pathophysiological characteristics of individuals with HbA1c-defined prediabetes and type 2 diabetes...... compared to subjects with HbA1c-defined prediabetes and controls. Plasma levels of incretin hormones were similar across the three groups. HbA1c associated negatively with insulinogenic index, disposition index, and incretin effect. Our findings show clear alpha- and beta-cell dysfunction in HbA1c...

  3. Allelic variants of DYX1C1 are not associated with dyslexia in India

    Saviour Pushpa

    2008-01-01

    Full Text Available Dyslexia is a hereditary neurological disorder that manifests as an unexpected difficulty in learning to read despite adequate intelligence, education, and normal senses. The prevalence of dyslexia ranges from 3 to 15% of the school aged children. Many genetic studies indicated that loci on 6p21.3, 15q15-21, and 18p11.2 have been identified as promising candidate gene regions for dyslexia. Recently, it has been suggested that allelic variants of gene, DYX1C1 influence dyslexia. In the present study, exon 2 and 10 of DYX1C1 has been analyzed to verify whether these single nucleotide polymorphisms (SNPs influence dyslexia, in our population. Our study identified 4 SNPs however, none of these SNPS were found to be significantly associated with dyslexia suggesting DYX1C1 allelic variants are not associated with dyslexia.

  4. Postoperative spinal alignment remodeling in Lenke 1C scoliosis treated with selective thoracic fusion

    Wang, Yu; Bünger, Cody; Zhang, Yanqun;

    2012-01-01

    and how spinal alignment remodeling affects spinal balance. METHODS: All adolescent idiopathic scoliosis (AIS) cases surgically treated in our institution between 2002 and 2008 were reviewed. Inclusion criteria were as follows: Lenke 1C scoliosis patients treated with posterior pedicle screw...... after surgery. Although some patients regained spinal balance through postoperative spinal alignment remodeling, 11 patients remained imbalanced at 2-year follow-up. CONCLUSIONS: Selective thoracic fusion is prone to cause leftward spinal imbalance in Lenke 1C scoliosis patients. Postoperative spinal...... alignment remodeling can facilitate recovery of spinal balance in some patients. Postoperative spinal imbalance in Lenke 1C scoliosis patients could be prevented by selecting stable vertebra or the vertebrae above as LIV, checking the balance condition during surgery, or considering ratio criteria when...

  5. Association Between the Presence of Iron Deficiency Anemia and Hemoglobin A1c in Korean Adults

    Hong, Jae W.; Ku, Cheol R.; Noh, Jung H.; Ko, Kyung S.; Rhee, Byoung D.; Kim, Dong-Jun

    2015-01-01

    Abstract Few studies have investigated the clinical effect of iron deficiency anemia (IDA) on the use of the Hemoglobin A1c (HbA1c) as a screening parameter for diabetes or prediabetes. We investigated the association between IDA and HbA1c levels in Korean adults. Among the 11,472 adults (≥19 years of age) who participated in the 2011–2012 Korea National Health and Nutrition Examination Survey (a cross-sectional and nationally representative survey conducted by the Korean Center for Disease Control for Health Statistics), 807 patients with diabetes currently taking anti-diabetes medications were excluded from this study. We compared the weighted HbA1c levels and weighted proportion (%) of HbA1c levels of ≥5.7%, ≥6.1%, and ≥6.5% according to the range of fasting plasma glucose (FPG) levels and the presence of IDA. Among 10,665 participants (weighted n = 35,229,108), the prevalence of anemia and IDA was 7.3% and 4.3%, respectively. The HbA1c levels were higher in participants with IDA (5.70% ± 0.02%) than in normal participants (5.59% ± 0.01%; P < 0.001), whereas there was no significant difference in FPG levels. In participants with an FPG level of <100 mg/dL and 100 to 125 mg/dL, the weighted HbA1c level was higher in those with IDA (5.59% ± 0.02% and 6.00% ± 0.05%) than in normal participants (5.44% ± 0.01% and 5.82% ± 0.01%) after adjusting for confounders such as age, sex, FPG level, heavy alcohol drinking, waist circumference, and smoking status as well as after exclusion of an estimated glomerular filtration rate of <60 mL/min/1.73 m2 (P < 0.001, <0.01). The weighted proportions (%) of an HbA1c level of ≥5.7% and ≥6.1% were also higher in participants with IDA than in normal participants (P < 0.001, <0.05). However, the weighted HbA1c levels in individuals with an FPG level ≥126 mg/dL and a weighted proportion (%) of an HbA1c level of ≥6.5% showed no significant differences according to

  6. Stability study for magnetic reagent assaying Hb and HbA1c

    Hsieh, Wen-Pin; Chieh, J. J.; Yang, C. C.; Yang, S. Y.; Chen, Po-Yu; Huang, Yu-Hao; Hong, Y. W.; Horng, H. E.

    2013-01-01

    Reagents for magnetically labeled immunoassay on human Hb and human HbA1c have been synthesized. The reagents consist of Fe3O4 magnetic particles biofunctionalized with antibodies against Hb and HbA1c. It has been demonstrated that the reagents can be applied to quantitatively detect Hb and HbA1c by using immunomagnetic reduction assay. In addition to characterizing the assay properties, such as the standard curve and the low-detection limit, the stability of reagents is investigated. To do this, the temporal dependence of particle sizes and the bio-activity of reagents are monitored. The results show that the reagents are highly stable when stored at 2-8 °C. This means that the reagents synthesized in this work are promising for practical applications.

  7. Sanger Sequencing for BRCA1 c.68_69del, BRCA1 c.5266dup and BRCA2 c.5946del Mutation Screen on Pap Smear Cytology Samples.

    Lee, Sin Hang; Zhou, Shaoxia; Zhou, Tianjun; Hong, Guofan

    2016-02-08

    Three sets of polymerase chain reaction (PCR) primers were designed for heminested PCR amplification of the target DNA fragments in the human genome which include the site of BRCA1 c.68_69del, BRCA1 c.5266dup and BRCA2 c.5946del respectively, to prepare the templates for direct Sanger sequencing screen of these three founder mutations. With a robust PCR mixture, crude proteinase K digestate of the fixed cervicovaginal cells in the liquid-based Papanicolaou (Pap) cytology specimens can be used as the sample for target DNA amplification without pre-PCR DNA extraction, purification and quantitation. The post-PCR products can be used directly as the sequencing templates without further purification or quantitation. By simplifying the frontend procedures for template preparation, the cost for screening these three founder mutations can be reduced to about US $200 per test when performed in conjunction with human papillomavirus (HPV) assays now routinely ordered for cervical cancer prevention. With this projected price structure, selective patients in a high-risk population can be tested and each provided with a set of DNA sequencing electropherograms to document the absence or presence of these founder mutations in her genome to help assess inherited susceptibility to breast and ovarian cancer in this era of precision molecular personalized medicine.

  8. The Effect of Aromatic Hydrocarbon Receptor on the Phenotype of the Hepa 1c1c7 Murine Hepatoma Cells in the Absence of Dioxin

    Feng Wang

    2007-01-01

    Full Text Available The aromatic hydrocarbon receptor (AhR mediates biological responses to certain exogenous ligands, such as the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, and has also been demonstrated to modulate the cell cycle and differentiated state of several cell lines independently of exogenous ligands. In this study, we used DNA micorarray analysis to elucidate the profile of genes responsive to the expression of unliganded AhR by re-introducing AhR into an AhR-deficient mouse derivative (c19 of the mouse hepatoma cell line Hepa1c1c7. 22 gene products were up-regulated and 8 were down-regulated two-fold or more in c19 cells infected with a retroviral vector expressing mouse AhR. Surprisingly, expression of genes involved in cell proliferation or differentiation were not affected by introduction of AhR. AhR also did not restore expression of the albumin gene in c19 cells. Introduction of AhR into c12, a similar AhRdefective mouse hepatoma cell line, also did not restore albumin expression, and furthermore, did not lead to changes in cellular morphology or cell cycle parameters. These observations fail to support the notion that unliganded AhR regulates proliferation and differentiation of liver-derived cells.

  9. Sanger Sequencing for BRCA1 c.68_69del, BRCA1 c.5266dup and BRCA2 c.5946del Mutation Screen on Pap Smear Cytology Samples

    Sin Hang Lee

    2016-02-01

    Full Text Available Three sets of polymerase chain reaction (PCR primers were designed for heminested PCR amplification of the target DNA fragments in the human genome which include the site of BRCA1 c.68_69del, BRCA1 c.5266dup and BRCA2 c.5946del respectively, to prepare the templates for direct Sanger sequencing screen of these three founder mutations. With a robust PCR mixture, crude proteinase K digestate of the fixed cervicovaginal cells in the liquid-based Papanicolaou (Pap cytology specimens can be used as the sample for target DNA amplification without pre-PCR DNA extraction, purification and quantitation. The post-PCR products can be used directly as the sequencing templates without further purification or quantitation. By simplifying the frontend procedures for template preparation, the cost for screening these three founder mutations can be reduced to about US $200 per test when performed in conjunction with human papillomavirus (HPV assays now routinely ordered for cervical cancer prevention. With this projected price structure, selective patients in a high-risk population can be tested and each provided with a set of DNA sequencing electropherograms to document the absence or presence of these founder mutations in her genome to help assess inherited susceptibility to breast and ovarian cancer in this era of precision molecular personalized medicine.

  10. HIGH MATERNAL HbA1c IS ASSOCIATED WITH NEONATAL HYPOCALCEMIA

    Abdul Tawab

    2014-10-01

    Full Text Available INTRODUCTION: Hypocalcemia occurs within the first 72 hours of birth in up to 50% of IDMs. The objective of the study was to compare the incidence of hypocalcemia in Infants of Pre-Gestational Diabetic & Gestational Diabetic mothers and to find the association of hypocalcemia and maternal diabetic control. MATERIAL AND METHODS: A tertiary care teaching hospital based prospective study over a period of 2 years. 40 Cases were included in the study 20 breast fed full term infants of Gestational diabetic mothers and 20 breastfed full term infants of Pre-Gestational diabetic mothers were enrolled in the study. Serum calcium of neonates in both groups was sent at 48 hours of life. Mean maternal HbA1c level was used to access maternal diabetic control. OBSERVATION AND RESULTS: Neonates of GDM showed statistically significant change in the serum calcium levels (Mean calcium level 9.055 mg/dl and maternal HBA1c levels (mean HbA1c level 5.85% an compared to neonates of PGDM (Mean calcium level 8.015 mg/dl, mean HbA1c level 6.75% (p=0.0001. 7 out of 20 neonates (35 % of Pre Gestational Diabetic mothers had hypocalcemia at 48 hour postnatal age and 3 out of 20 neonates (15% of Gestational Diabetic mothers had hypocalcemia at 48 hour postnatal age. Incidence of hypocalcemia is more when diabetes is poorly controlled [HbA1C>6%] in both groups and it was statistically significant. CONCLUSION: Infants born to Pre-Gestational diabetic mothers are at a higher risk of developing hypocalcemia than infants of gestational diabetic mothers. Incidence of hypocalcemia can be predicted with diabetic control [maternal HbA1c levels]. Studies with larger sample size will give more definitive results on this issue.

  11. Conformational Changes in the Orai1 C-Terminus Evoked by STIM1 Binding.

    Leidamarie Tirado-Lee

    Full Text Available Store-operated CRAC channels regulate a wide range of cellular functions including gene expression, chemotaxis, and proliferation. CRAC channels consist of two components: the Orai proteins (Orai1-3, which form the ion-selective pore, and STIM proteins (STIM1-2, which form the endoplasmic reticulum (ER Ca2+ sensors. Activation of CRAC channels is initiated by the migration of STIM1 to the ER-plasma membrane (PM junctions, where it directly interacts with Orai1 to open the Ca2+-selective pores of the CRAC channels. The recent elucidation of the Drosophila Orai structure revealed a hexameric channel wherein the C-terminal helices of adjacent Orai subunits associate in an anti-parallel orientation. This association is maintained by hydrophobic interactions between the Drosophila equivalents of human Orai1 residues L273 and L276. Here, we used mutagenesis and chemical cross-linking to assess the nature and extent of conformational changes in the self-associated Orai1 C-termini during STIM1 binding. We find that linking the anti-parallel coiled-coils of the adjacent Orai1 C-termini through disulfide cross-links diminishes STIM1-Orai1 interaction, as assessed by FRET. Conversely, prior binding of STIM1 to the Orai1 C-terminus impairs cross-linking of the Orai1 C-termini. Mutational analysis indicated that a bend of the Orai1 helix located upstream of the self-associated coils (formed by the amino acid sequence SHK establishes an appropriate orientation of the Orai1 C-termini that is required for STIM1 binding. Together, our results support a model wherein the self-associated Orai1 C-termini rearrange modestly to accommodate STIM1 binding.

  12. HbA1c, fasting plasma glucose and the prediction of diabetes

    Soulimane, Soraya; Simon, Dominique; Shaw, Jonathan

    2012-01-01

    With diabetes defined by HbA1c≥6.5% and/or FPG≥7.0mmol/l and/or diabetes treatment, we investigated HbA1c and fasting plasma glucose (FPG) thresholds/change-points above which the incidence of diabetes increases.......With diabetes defined by HbA1c≥6.5% and/or FPG≥7.0mmol/l and/or diabetes treatment, we investigated HbA1c and fasting plasma glucose (FPG) thresholds/change-points above which the incidence of diabetes increases....

  13. Design and Implementation of the HJ-1-C Satellite SAR Full-power Radiation Test

    Zhang Hua-chun; Tao Xin; Ni Jiang; Yu Wei-dong

    2014-01-01

    In this paper, the HJ-1-C SAR full-power radiation test design is presented. For the new problems caused by SAR high-power concentrated emissions, the radar-receiving channel-leakage power test is proposed to ensure the safety of the radar-receiving path, and the transceiver channel closed-loop radar system test is discussed. The experimental results show that the proposed HJ-1-C SAR full-power radiation test scheme is reasonable and feasible, with the desired outcome.

  14. The Load Design and Implementation of HJ-1-C Space-borne SAR

    Yu Wei-dong; Yang Ru-liang; Deng Yun-kai; Zhao Feng-jun; Lei Hong

    2014-01-01

    HJ-1-C is a Synthetic Aperture Radar (SAR) satellite in the Constellation of “2+1” for China environment and disaster monitoring. It works at S-band with a resolution of 5 m. SAR payload uses a reflector antenna and a high-power concentrated transmitter. Its light weight and high efficiency is very suitable for a small satellite platform. Now HJ-1-C satellite has been launched into orbit and has acquired Chinese first S-band SAR images from space, which demonstrate excellent quality and rich ...

  15. Design and Implementation of the HJ-1-C Satellite SAR Full-power Radiation Test

    Zhang Hua-chun

    2014-06-01

    Full Text Available In this paper, the HJ-1-C SAR full-power radiation test design is presented. For the new problems caused by SAR high-power concentrated emissions, the radar-receiving channel-leakage power test is proposed to ensure the safety of the radar-receiving path, and the transceiver channel closed-loop radar system test is discussed. The experimental results show that the proposed HJ-1-C SAR full-power radiation test scheme is reasonable and feasible, with the desired outcome.

  16. Feature Fusion Based Road Extraction for HJ-1-C SAR Image

    Lu Ping-ping; Du Kang-ning; Yu Wei-dong; Wang Yu; Deng Yun-kai

    2014-01-01

    Road network extraction in SAR images is one of the key tasks of military and civilian technologies. To solve the issues of road extraction of HJ-1-C SAR images, a road extraction algorithm is proposed based on the integration of ratio and directional information. Due to the characteristic narrow dynamic range and low signal to noise ratio of HJ-1-C SAR images, a nonlinear quantization and an image filtering method based on a multi-scale autoregressive model are proposed here. A road extracti...

  17. Research and Realization of the HJ-1C Real-time Software Frame Synchronization Algorithm

    Hou Yang-shuan

    2014-06-01

    Full Text Available Conventional software frame synchronization methods are inefficient in processing huge continuous data without synchronization words. To improve the processing speed, a real-time synchronization algorithm is proposed based on reverse searching. Satellite data are grouped and searched in the reverse direction to avoid searching for synchronization words in huge continuous invalid data; thus, the frame synchronization speed is improved enormously. The fastest processing speed is up to 15445.9 Mbps when HJ-1C data are tested. This method is presently applied to the HJ-1C quick-look system in remote sensing satellite ground stations.

  18. Halophilic adaptation of enzymes.

    Madern, D; Ebel, C; Zaccai, G

    2000-04-01

    It is now clear that the understanding of halophilic adaptation at a molecular level requires a strategy of complementary experiments, combining molecular biology, biochemistry, and cellular approaches with physical chemistry and thermodynamics. In this review, after a discussion of the definition and composition of halophilic enzymes, the effects of salt on their activity, solubility, and stability are reviewed. We then describe how thermodynamic observations, such as parameters pertaining to solvent-protein interactions or enzyme-unfolding kinetics, depend strongly on solvent composition and reveal the important role played by water and ion binding to halophilic proteins. The three high-resolution crystal structures now available for halophilic proteins are analyzed in terms of haloadaptation, and finally cellular response to salt stress is discussed briefly.

  19. Associations of NQO1 C609T and NQO1 C465T polymorphisms with acute leukemia risk: a PRISMA-compliant meta-analysis

    He, Hairong; Zhai, Xiaoyu; Liu, Xiaomin; Zheng, Jie; Zhai, Yajing; Gao, Fan; Chen, Yonghua; Lu, Jun

    2017-01-01

    Objective The NAD(P)H:quinone oxidoreductase (NQO1) C609T and C465T polymorphisms have been widely thought to be associated with the risk of acute leukemia (AL) in recent years, but the correlations are still unclear. A meta-analysis is generally acknowledged as one of the best methods for secondary research, and so it was applied in this study with the aim of elucidating how the NQO1 C609T and C465T polymorphisms are related to the risk of AL. Methods Relevant studies were searched in the PubMed, EMBASE, CNKI, and Wanfang databases, and the obtained data were analyzed using Stata (version 12.1). The allele-contrast model was applied, and odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate relationship strengths. Meta-regression was used to identify sources of heterogeneity, and subgroup analyses were conducted. Publication bias was analyzed using funnel plots, with the trim-and-fill method used to analyze the effect of publication bias on pooled results. In addition, sensitivity analysis, the fail-safe number method, and cumulative analysis by publication year were performed to measure the stability of the obtained results. Results This meta-analysis included 28 relevant studies involving 5,953 patients and 8,667 controls. Overall, the C609T polymorphism was associated with the risk of acute lymphoblastic leukemia (ALL; OR =1.18, 95% CI =1.00–1.39, P=0.05). Meanwhile, race was found to be a potential source of heterogeneity for the relationship between the C609T polymorphism and acute myeloid leukemia (AML) risk, and the subgroup analysis identified the C609T polymorphism as a risk factor for AML in Asians (OR =1.34, 95% CI =1.03–1.74, P=0.03). The number of studies about C465T polymorphism was too small to pool the data. Conclusion There are increased risks of ALL in all subjects and of AML in Asians for carriers of the NQO1 C609T polymorphism. Further studies are needed to verify the associations of the C465T polymorphism with the

  20. C1-C2 rotary subluxation following posterior stabilization for congenital atlantoaxial dislocation.

    Behari S

    2000-04-01

    Full Text Available The authors report a rare complication of C1-C2 rotary subluxation in two children following posterior stabilization for congenital atlantoaxial dislocation (AAD. A patient, with mobile AAD, underwent Brook′s C1-C2 fusion while the other, with fixed AAD, underwent transoral decompression followed by Jain′s occipitocervical fusion. A pre-existing ligamentous laxity associated with an asymmetrical wire tightening or slippage of the wires due to rotation of the neck in the former, and the drilling of the C1-C2 lateral joints during the transoral procedure in the latter, could have contributed to the rotary subluxation. Both patients presented with persistent torticollis due to fusion in an asymmetrical position with dislocated facet joints. Rotary C1-C2 subluxation, when coexisting with anterior dislocation, has the potential to cause severe and occasionally fatal cord compression. Well defined criteria to diagnose this entity by conventional radiology exist, however, due to the overlap of anatomy, the condition is often overlooked. In the present study, three dimensional reconstruction images using helical computerized tomography were very useful in delineating the subluxation and in planning its surgical reduction and arthrodesis.

  1. Efficient Synthesis of the C1- C7 Fragment of Didemnaketal A

    Xue Qiang LI; Xue Zhi ZHAO; Pei Nian LIU; Yong Qiang TU

    2004-01-01

    The stereoselective synthesis of the C1-C7 fragment (3R,4S,6R)-3,4-di[(tert-butyl- dimethylsilyl)oxy]-7-hydroxy-6-methylheptan-2-one, which is the crucial intermediate for synthesis of the HIV-1 protease inhibitive didemnaketals, was developed via 12 steps from the natural (+)-pulegone.

  2. Stereoselective synthesis of C1-C24 fragment of antanapeptin-A

    Srinivas Avula

    2016-03-01

    Full Text Available The stereoselective synthesis of the (C1-C24 fragment of Antanapeptin–A is described. The required stereochemistry of b -hydroxy- a -methyl acid unit was accomplished through Aldol reaction using Evans’ chiral auxiliary followed by the installation of terminal alkyne with Ohira–Bestmann reagent.

  3. Hemoglobin A1c measurement for the diagnosis of Type 2 diabetes in children

    Kapadia Chirag

    2012-12-01

    Full Text Available Abstract Laboratory measurements of hemoglobin A1c above 6.5% were approved as an additional diagnostic criteria for diabetes mellitus by the American Diabetes Association in 2010. Several recent pediatric studies have cast HbA1c measurement in children in an unfavorable light in the pediatric population, by comparing HbA1c measurements to results on oral glucose tolerance test (OGTT or fasting plasma glucose (FPG. However, many of these studies do not recognize that diabetes diagnostic criteria are based upon long-term health outcomes. In this sense, OGTT and FPG have themselves never been validated in the pediatric population. Studies to validate diagnostic tests for diabetes in pediatric populations may take a substantial period of time, and may prove unfeasible. However, studies that tie diagnostic results as a child to diagnostic results as an adult may be more feasible and may provide the data needed to determine which pediatric diagnostic criteria to use. Thus, for the time being, except for cases of hemoglobinopathy, cystic fibrosis, and a few other exceptions, describing HbA1c as ‘lacking in sensitivity or specificity’ in the pediatric population because of lack of correlation with OGTT is not scientifically sound.

  4. Data of evolutionary structure change: 1DSUA-1C1MA [Confc[Archive

    Full Text Available n>1DSUA SVQLN----GAHLC >EEEE ---- Eucture... A 1C1MA SLQYRSGSSWAHTC ...>EEEEEE EEE E> ATOM 123 CA SER A 32 -2.328 59.41...CAESN-RRDSC e>EE - EEEture...ence>CAGGDGVRSGC >EE EEE> ATOM 1

  5. Stereoselective synthesis of the C1-C13 fragment of (+)-discodermolide using asymmetric allyltitanations.

    BouzBouz, Samir; Cossy, Janine

    2003-08-21

    [reaction: see text] The synthesis of the C1-C13 fragment of (+)-discodermolide has been achieved. The configurations of the stereogenic centers have been controlled by enantioselective allyl- and crotyltitanations of aldehydes, and the Z configuration of the olefin at C8-C9 was controlled by a ring-closing metathesis.

  6. On the causes of compositional order in the Ni sub c Pt sub (1-c) alloys

    Gyorffy, B.L. (Bristol Univ. (United Kingdom). H.H. Wills Physics Lab.); Pinski, F.J. (Cincinnati Univ., OH (United States). Dept. of Physics); Ginatempo, B. (Messina Univ. (Italy). Ist. di Fisica Teorica); Johnson, D.D. (Sandia National Labs., Albuquerque, NM (United States)); Staunton, J.B. (Warwick Univ., Coventry (United Kingdom). Dept. of Physics); Shelton, W.A.; Stocks, G.M.; Nicholson, D.M.

    1991-01-01

    We review, briefly, the arguments which gave rise to the current controversy concerning the origin of compositional order in Ni{sub c}Pt{sub 1-c} alloys. We note that strain fluctuations play an important role in determining the state of compositional order in this system and outline a theoretical framework that takes account of them. 29 refs., 4 figs.

  7. Residual endotoxin contaminations in recombinant proteins are sufficient to activate human CD1c+ dendritic cells.

    Schwarz, Harald; Schmittner, Maria; Duschl, Albert; Horejs-Hoeck, Jutta

    2014-01-01

    Many commercially available recombinant proteins are produced in Escherichia coli, and most suppliers guarantee contamination levels of less than 1 endotoxin unit (EU). When we analysed commercially available proteins for their endotoxin content, we found contamination levels in the same range as generally stated in the data sheets, but also some that were higher. To analyse whether these low levels of contamination have an effect on immune cells, we stimulated the monocytic cell line THP-1, primary human monocytes, in vitro differentiated human monocyte-derived dendritic cells, and primary human CD1c+ dendritic cells (DCs) with very low concentrations of lipopolysaccharide (LPS; ranging from 0.002-2 ng/ml). We show that CD1c+ DCs especially can be activated by minimal amounts of LPS, equivalent to the levels of endotoxin contamination we detected in some commercially available proteins. Notably, the enhanced endotoxin sensitivity of CD1c+ DCs was closely correlated with high CD14 expression levels observed in CD1c+ DCs that had been maintained in cell culture medium for 24 hours. When working with cells that are particularly sensitive to LPS, even low endotoxin contamination may generate erroneous data. We therefore recommend that recombinant proteins be thoroughly screened for endotoxin contamination using the limulus amebocyte lysate test, fluorescence-based assays, or a luciferase based NF-κB reporter assay involving highly LPS-sensitive cells overexpressing TLR4, MD-2 and CD14.

  8. Hemoglobin A1c measurement for the diagnosis of Type 2 diabetes in children.

    Kapadia, Chirag; Zeitler, Philip

    2012-12-20

    Laboratory measurements of hemoglobin A1c above 6.5% were approved as an additional diagnostic criteria for diabetes mellitus by the American Diabetes Association in 2010. Several recent pediatric studies have cast HbA1c measurement in children in an unfavorable light in the pediatric population, by comparing HbA1c measurements to results on oral glucose tolerance test (OGTT) or fasting plasma glucose (FPG). However, many of these studies do not recognize that diabetes diagnostic criteria are based upon long-term health outcomes. In this sense, OGTT and FPG have themselves never been validated in the pediatric population. Studies to validate diagnostic tests for diabetes in pediatric populations may take a substantial period of time, and may prove unfeasible. However, studies that tie diagnostic results as a child to diagnostic results as an adult may be more feasible and may provide the data needed to determine which pediatric diagnostic criteria to use. Thus, for the time being, except for cases of hemoglobinopathy, cystic fibrosis, and a few other exceptions, describing HbA1c as 'lacking in sensitivity or specificity' in the pediatric population because of lack of correlation with OGTT is not scientifically sound.

  9. Association of the rs3743205 variant of DYX1C1 with dyslexia in Chinese children

    Waye Mary MY

    2011-05-01

    Full Text Available Abstract Background Dyslexia is a learning disability that is characterized by difficulties in the acquisition of reading and spelling skills independent of intelligence, motivation or schooling. Studies of western populations have suggested that DYX1C1 is a candidate gene for dyslexia. In view of the different languages used in Caucasian and Chinese populations, it is therefore worthwhile to investigate whether there is an association of DYX1C1 in Chinese children with dyslexia. Method and Results Eight single nucleotide polymorphisms (SNPs were genotyped from three hundred and ninety three individuals from 131 Chinese families with two which have been reported in the literature and six tag SNPs at DYX1C1. Analysis for allelic and haplotypic associations was performed with the UNPHASED program and multiple testing was corrected using false discovery rates. We replicated the previously reported association of rs3743205 in Chinese children with dyslexia (pcorrected = 0.0072. This SNP was also associated with rapid naming, phonological memory and orthographic skills in quantitative trait analysis. Conclusion Our findings suggest that DYX1C1 is associated with dyslexia in people of Chinese ethnicity in Hong Kong.

  10. Data of evolutionary structure change: 1BU1C-1OOTA [Confc[Archive

    Full Text Available 1BU1C-1OOTA 1BU1 1OOT C A -IIVVALYDYEAIHHEDLSFQKGDQMVVLEES---GEWW...> 1OOT A 1OOTA -34.0260009765625 9.805000305175781 9.982999801635742 ti...x> -0.800000011920929 -0.42399999499320984 tion> 2.0220730304718018 4...bID> A 1OOTA WTGRV--NGREG

  11. C1-c2 pedicle screw fixation for treatment of old odontoid fractures.

    Qi, Lei; Li, Mu; Zhang, Shuai; Si, Haipeng; Xue, Jingsong

    2015-02-01

    Nonunion and C1-C2 instability of odontoid fractures usually result from delayed diagnosis and inappropriate treatment. However, the available treatment options for odontoid fractures remain controversial. The authors evaluated the effectiveness of internal screw fixation via the C1 and C2 pedicle in cases of old odontoid fractures. This retrospective study included 21 patients with old odontoid fractures (13 men and 8 women; mean age, 46.5 years; range, 24-69 years). Internal screw fixation via the C1 and C2 pedicle was performed in all patients. Fracture reduction and C1-C2 fusion were assessed with imaging. The neck pain visual analog scale score and cervical spinal cord functional Japanese Orthopaedic Association score (for those who had cervical spinal cord injury) were used to evaluate the effectiveness of treatment. Postoperative complications were recorded. Postoperative imaging showed that the C1-C2 dislocation was satisfactorily repositioned in all patients. Bone fusion was observed 1 year after surgery in all patients. No loosening or breaking of internal fixation occurred. The preoperative neck pain visual analog scale score was 5.9±1.5 and improved significantly to 1.8±0.8 after surgery (PC2 pedicle was found to be an effective and safe surgical approach for the treatment of old odontoid fractures with C1-C2 dislocation or instability.

  12. Data of evolutionary structure change: 1LA6B-1C7BA [Confc[Archive

    Full Text Available -YDDIG >GGG --HHHHH> ATOM 1233 C...pdbChain> 1C7BA WGKVGAHAGEYG >HHHHGGGHHHHH...pdbChain> 1LA6B QRYFI-----MSNAN >GGG ----- HH.../entryIDChain> KTYFPHFDLSHGSAQ >GGG HH> > ATOM 1430 CA GLN B 39 8.656 -4.420 -18.548 1.00 34.33

  13. The Load Design and Implementation of HJ-1-C Space-borne SAR

    Yu Wei-dong

    2014-06-01

    Full Text Available HJ-1-C is a Synthetic Aperture Radar (SAR satellite in the Constellation of “2+1” for China environment and disaster monitoring. It works at S-band with a resolution of 5 m. SAR payload uses a reflector antenna and a high-power concentrated transmitter. Its light weight and high efficiency is very suitable for a small satellite platform. Now HJ-1-C satellite has been launched into orbit and has acquired Chinese first S-band SAR images from space, which demonstrate excellent quality and rich information about scenes imaged. This success verifies our design, testing and experiment work on the payload. With its following operation, HJ-1-C satellite is expected to make a great contribution to the applications of environment protection and disaster monitoring in China. This paper introduces the design and development of HJ-1-C SAR payload, present its main parameters and performance, describes its device details and its manufacture, testing and experiment process. Some images acquired in the orbit are showed.

  14. Predictors of HbA1c levels in patients initiating metformin

    Martono, Doti P.; Hak, Eelko; Heerspink, Hiddo Lambers; Wilffert, Bob; Denig, Petra

    2016-01-01

    Objective: The aim was to assess demographic and clinical factors as predictors of short (6 months) and long term (18 months) HbA1c levels in diabetes patients initiating metformin treatment. Research design and methods: We conducted a cohort study including type 2 diabetes patients who received the

  15. Periodontal treatment and HbA1c levels in subjects with diabetes mellitus.

    Altamash, M; Klinge, B; Engström, P-E

    2016-01-01

    It has earlier been reported that individuals with poorly controlled diabetes have severe periodontal disease (PD) compared to well-controlled diabetes. This longitudinal interventional study compared periodontal treatment outcomes with HbA1c level changes in four groups of diabetic and non-diabetic patients with or without PD, respectively. HbA1c, bleeding on probing (BOP), plaque index and periodontal pocket depth (PPD) 4 Diabetics with PD and without PD showed reductions in HbA1c levels with a mean value of 0·3% after 3 months and mean values of 1% and 0·8%, respectively, after 6 months. Diabetics with PD showed higher levels of BOP versus non-diabetics without PD (P diabetics without PD (P diabetics with PD showed higher number of PPD 4 diabetics without PD (P diabetics with PD (P Diabetics without PD showed higher levels of PPD 4 diabetics without PD (P periodontal treatment in all groups improved periodontal inflammatory conditions with a decrease in HbA1c levels in a period of three and 6 months. No change was seen in the number of pockets PPD 4 diabetic subjects with PD after non-surgical and surgical treatment.

  16. Dynamics and phase transitions in A{sub 1}C{sub 60} compounds

    Schober, H.; Toelle, A. [Institut Max von Laue - Paul Langevin, 38 -Grenoble (France); Renker, B.; Heid, R. [INFP, Forschungszentrum Karlsruhe, D-76021, Karlsruhe (Germany)

    1997-06-01

    We present an overview of extensive inelastic neutron scattering experiments carried out on powders of A{sub 1}C{sub 60}. The various phases leave strong fingerprints in the microscopic dynamics confirming the solid-state chemical reactions. The strong kinetic phase transitions can be followed in real time and turn to be highly complex. (orig.).

  17. Targeting of the MUC1-C Oncoprotein in Colitis-Associated Colorectal Cancer

    2014-11-01

    14 APPENDICES None. 2 Targeting of the MUC1-C Oncoprotein in Colitis ...xenografts in nude mice and to develop a MUC1+/IL-10-/- model of colitis to determine whether MUC1 function affects the inflammatory response and colon...function affects the inflammatory response and colon tumorigenesis in a MUC1+/IL-10-/- mouse model of colitis . Intestinal inflammation increases

  18. 75 FR 10395 - Attestation Applications by Facilities Temporarily Employing H-1C Nonimmigrant Foreign Workers as...

    2010-03-05

    ...-1A registered nurse temporary visa program created by the Immigration Nursing Relief Act of 1989... NRDAA, and that of the Nursing Relief Act establishing the H-1A program, support an interpretation that... Administration 20 CFR Part 655 Attestation Applications by Facilities Temporarily Employing H-1C...

  19. Regulation of Trib2 by an E2F1-C/EBPα feedback loop in AML cell proliferation.

    Rishi, Loveena

    2014-04-10

    The loss of regulation of cell proliferation is a key event in leukemic transformation, and the oncogene tribbles (Trib)2 is emerging as a pivotal target of transcription factors in acute leukemias. Deregulation of the transcription factor E2F1, normally repressed by CCAAT enhancer-binding protein α (C\\/EBPα)-p42, occurs in acute myeloid leukemia (AML), resulting in the perturbation of cell cycle and apoptosis, emphasizing its importance in the molecular pathogenesis of AML. Here we show that E2F family members directly regulate Trib2 in leukemic cells and identify a feedback regulatory loop for E2F1, C\\/EBPα, and Trib2 in AML cell proliferation and survival. Further analyses revealed that E2F1-mediated Trib2 expression was repressed by C\\/EBPα-p42, and in normal granulocyte\\/macrophage progenitor cells, we detect C\\/EBPα bound to the Trib2 promoter. Pharmacological inhibition of the cell cycle or Trib2 knockdown resulted in a block in AML cell proliferation. Our work proposes a novel paradigm whereby E2F1 plays a key role in the regulation of Trib2 expression important for AML cell proliferation control. Importantly, we identify the contribution of dysregulated C\\/EBPα and E2F1 to elevated Trib2 expression and leukemic cell survival, which likely contributes to the initiation and maintenance of AML and may have significant implications for normal and malignant hematopoiesis.

  20. Peri-conceptional A1C and risk of serious adverse pregnancy outcome in 933 women with type 1 diabetes

    Jensen, Dorte M; Korsholm, Lars; Ovesen, Per;

    2009-01-01

    OBJECTIVE: To study the association between peri-conceptional A1C and serious adverse pregnancy outcome (congenital malformations and perinatal mortality). RESEARCH DESIGN AND METHODS: Prospective data were collected in 933 singleton pregnancies complicated by type 1 diabetes. RESULTS: The risk...... malformation rate increased significantly at A1C above 10.4%, whereas perinatal mortality was increased even at A1C below 6.9%. CONCLUSIONS: These results support recent guidelines of preconceptional A1C levels diabetes....

  1. Schizophrenia Related Variants in CACNA1C also Confer Risk of Autism.

    Jun Li

    Full Text Available Autism spectrum disorder (ASD is a group of neurodevelopmental disorders with a strong genetic component. Many lines of evidence indicated that ASD shares common genetic variants with other psychiatric disorders (for example, schizophrenia. Previous studies detected that calcium channels are involved in the etiology of many psychiatric disorders including schizophrenia and autism. Significant association between CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit and schizophrenia was detected. Furthermore, rare mutation in CACNA1C is suggested to cause Timothy syndrome, a multisystem disorder including autism-associated phenotype. However, there is no evidence for association between CACNA1C and autism in Chinese Han population. To investigate the association between single nucleotide polymorphisms (SNP in CACNA1C and autism, we first performed a family-based association study between eighteen SNPs in CACNA1C and autism in 239 trios. All SNPs were genotyped by using Sequenom genotyping platform. Two SNPs (rs1006737 and rs4765905 have a trend of association with autism. To further confirm the association between these two SNPs with autism, we expanded the sample size to 553 trios by adding 314 trios. Association analyses for SNPs and haplotype were performed by using family-based association test (FBAT and Haploview software. Permutation tests were used for multiple testing corrections of the haplotype analyses (n=10,000. The significance level for all statistical tests was two-tailed (p<0.05. The results demonstrated that G allele of rs1006737 and G allele of rs4765905 showed a preferential transmission to affected offspring in 553 trios (p=0.035. Haplotype analyses showed that two haplotypes constructed from rs1006737 and rs4765905 were significantly associated with autism (p=0.030, 0.023, respectively; Global p=0.046. These results were still significant after permutation correction (n=10,000, p=0.027. Our research suggests

  2. HBx truncation mutants differentially modulate SREBP-1a and -1c transcription and HBV replication.

    Wu, Qi; Liu, Qiang

    2015-12-01

    As master transcription factors for lipogenesis, sterol regulatory element-binding protein-1 (SREBP-1) has two isoforms, SREBP-1a and SREBP-1c. Hepatitis B virus X (HBx) can up-regulate the transcription of both SREBP-1a and SREBP-1c. HBx is a small protein consisting of 154 amino acids. Truncated forms of HBx, often found in the tissues after HBV infection, may have a role in the pathogenesis associated with HBV infection. In this study, we examined the effects of two HBx truncation mutants, HBx aa. 1-127 and HBx aa. 43-154, on the transcription of SREBP-1a and SREBP-1c. HBx 1-127 can up-regulate SREBP-1c, but not SREBP-1a transcription, whereas HBx 43-154 can activate SREBP-1a, but not SREBP-1c transcription. We further determined the activities of two HBV enhancers after the expression of the truncated HBx proteins. HBx 1-127 and HBx 43-154 can only up-regulate HBV enhancer I or HBV enhancer II, respectively. Knocking down SREBP-1 abrogates enhancer activation by HBx proteins, suggesting a role of SREBP-1. In addition, using HBV enhancer mutants, we found that the binding sequence for AP-1 on enhancer I is essential for its activation by HBx 1-127, whereas C/EBP and Sp1 sites are required for enhancer II activation by HBx 43-154. Finally, we showed that both HBx 1-127 and HBx 43-154 can increase HBV transcription and HBV replication dependent upon SREBP-1 because knocking down SREBP-1 abrogates the up-regulation. Furthermore, upon ectopic expression of either SREBP-1a or SREBP-1c, we showed that SREBP-1a is involved in HBV transcription and replication up-regulation by HBx 43-154, whereas SREBP-1c is involved in HBV transcription and replication up-regulation by HBx 1-127. Our results should help understand the interactions between HBV and the SREBP-1-mediated lipogenic pathway.

  3. MicroRNA-221 inhibits CDKN1C/p57 expression in human colorectal carcinoma

    Kai SUN; Wei WANG; Jun-jie ZENG; Cheng-tang WU; Shang-tong LEI; Guo-xin LI

    2011-01-01

    Aim: To investigate the regulatory effect of microRNA-221 (miR-221) on CDKN1C/p57 expression in colorectal carcinoma (CRC).Methods: Thirty four CRC and adjacent non-tumorous tissue samples were collected individually. Total RNA and protein were isolatedand from these samples and four human CRC-derived cell lines (including HT-29, Lovo, SW-480 and Caco2). MiR-221 expression was examined using real-time RT-PCR. CRC cells were treated with or without anti-p57-siRNA prior to the addition of premiR-221 or anti-miR-221. The mRNA and protein levels of CDKN1C/p57 were examined using semi-quantitative RT-PCR and Western blot, respectively. CRC cell proliferation and apoptosis were assessed using MTT assay and flow cytometry, respectively.The CDKN1C/p57 3'-UTR fragment was amplified using PCR from the genomic DNA of human colon cells and inserted into a luciferase reporter construct. The reporter construct was then transfected into CRC cells together with pre-miR-221 or anti-miR-221, and the luciferase activity in the transfected cells was examined.Results: MiR-221 expression was significantly up-regulated in 90% of CRC samples compared to that in the adjacent non-tumorous tissue, and the expression level was positively correlated to an advanced TNM stage and local invasion. There was no significant difference in CDKN1C/p57 mRNA expression between CRC and corresponding non-tumorous tissues, whereas CDKN1C/p57 protein expression was markedly decreased in the CRC samples. A significant inverse correlation between miR-221 and CDKN1C/p57expression was found in CRC cells. Moreover, a miR-221-specific inhibitor significantly increased CDKN1C/p57 protein expression in CRC cells. Anti-miR-221 markedly inhibited CRC cell proliferation and induced apoptosis. This inhibitory effect was abolished by pretreatment with a nti-p57-siRNA, suggesting that the inhibition was mediated by CDKN1C/p57. A significant increase of the luciferase activity was observed in CRC cells co-transfected with

  4. Effects of Sleep Disorders on Hemoglobin A1c Levels in Type 2 Diabetic Patients

    Keskin, Ahmet; Ünalacak, Murat; Bilge, Uğur; Yildiz, Pinar; Güler, Seda; Selçuk, Engin Burak; Bilgin, Muzaffer

    2015-01-01

    Background: Studies have reported the presence of sleep disorders in approximately 50–70% of diabetic patients, and these may contribute to poor glycemic control, diabetic neuropathy, and overnight hypoglycemia. The aim of this study was to determine the frequency of sleep disorders in diabetic patients, and to investigate possible relationships between scores of these sleep disorders and obstructive sleep apnea syndrome (OSAS) and diabetic parameters (fasting blood glucose, glycated hemoglobin A1c [HbA1c], and lipid levels). Methods: We used the Berlin questionnaire (BQ) for OSAS, the Epworth Sleepiness Scale (ESS), and the Pittsburgh Sleep Quality Index (PSQI) to determine the frequency of sleep disorders and their possible relationships with fasting blood glucose, HbA1c, and lipid levels. Results: The study included 585 type 2 diabetic patients admitted to family medicine clinics between October and December 2014. Sleep, sleep quality, and sleep scores were used as the dependent variables in the analysis. The ESS scores showed that 54.40% of patients experienced excessive daytime sleepiness, and according to the PSQI, 64.30% experienced poor-quality sleep. The BQ results indicated that 50.20% of patients were at high-risk of OSAS. HbA1c levels correlated significantly with the ESS and PSQI results (r = 0.23, P < 0.001 and r = 0.14, P = 0.001, respectively), and were significantly higher in those with high-risk of OSAS as defined by the BQ (P < 0.001). These results showed that HbA1c levels were related to sleep disorders. Conclusions: Sleep disorders are common in diabetic patients and negatively affect the control of diabetes. Conversely, poor diabetes control is an important factor disturbing sleep quality. Addressing sleep disturbances in patients who have difficulty controlling their blood glucose has dual benefits: Preventing diabetic complications caused by sleep disturbance and improving diabetes control. PMID:26668142

  5. Regulation of GLUT4 gene expression by SREBP-1c in adipocytes.

    Im, Seung-Soon; Kwon, Sool-Ki; Kang, Seung-Youn; Kim, Tae-Hyun; Kim, Ha-Il; Hur, Man-Wook; Kim, Kyung-Sup; Ahn, Yong-Ho

    2006-10-01

    Expression of the GLUT4 (glucose transporter type 4 isoform) gene in adipocytes is subject to hormonal or metabolic control. In the present study, we have characterized an adipose tissue transcription factor that is influenced by fasting/refeeding regimens and insulin. Northern blotting showed that refeeding increased GLUT4 mRNA levels for 24 h in adipose tissue. Consistent with an increased GLUT4 gene expression, the mRNA levels of SREBP (sterol-regulatory-element-binding protein)-1c in adipose tissue were also increased by refeeding. In streptozotocin-induced diabetic rats, insulin treatment increased the mRNA levels of GLUT4 in adipose tissue. Serial deletion, luciferase reporter assays and electrophoretic mobility-shift assay studies indicated that the putative sterol response element is located in the region between bases -109 and -100 of the human GLUT4 promoter. Transduction of the SREBP-1c dominant negative form to differentiated 3T3-L1 adipocytes caused a reduction in the mRNA levels of GLUT4, suggesting that SREBP-1c mediates the transcription of GLUT4. In vivo chromatin immunoprecipitation revealed that refeeding increased the binding of SREBP-1 to the putative sterol-response element in the GLUT4. Furthermore, treating streptozotocin-induced diabetic rats with insulin restored SREBP-1 binding. In addition, we have identified an Sp1 binding site adjacent to the functional sterol-response element in the GLUT4 promoter. The Sp1 site appears to play an additive role in SREBP-1c mediated GLUT4 gene upregulation. These results suggest that upregulation of GLUT4 gene transcription might be directly mediated by SREBP-1c in adipose tissue.

  6. New diagnostic criteria for diabetes: is the change from glucose to HbA1c possible in all populations?

    Jørgensen, Marit Eika; Bjerregaard, Peter; Borch-Johnsen, Knut;

    2010-01-01

    Recently, a change of the diagnostic tool for diabetes from an oral glucose tolerance test (OGTT) to hemoglobin A1c (HbA1c) has been suggested. The aim of the study was to assess whether ethnicity modified the association between glucose levels and HbA1c and to compare diabetes prevalence according...

  7. Unrecognized glycometabolic disturbance as measured by hemoglobin A1c is associated with a poor outcome after acute myocardial infarction

    Gustafsson, Ida; Kistorp, Caroline N; James, Margaret K;

    2007-01-01

    BACKGROUND: Glycated hemoglobin A1c (HbA1c) is a measure of the average blood glucose levels over 2 months and is minimally affected by acute hyperglycemia often observed in myocardial infarction (MI). In a large population of high-risk patients with MI, we examined the prognostic impact of HbA1c...

  8. Shiga toxin 1c-producing Escherichia coli strains : phenotypic and genetic characterization and association with human disease

    Friedrich, Alexander W; Borell, Julia; Bielaszewska, Martina; Fruth, Angelika; Tschäpe, Helmut; Karch, Helge

    2003-01-01

    The distribution of the stx(1c) allele among Shiga toxin (Stx)-producing Escherichia coli (STEC) and the virulence characteristics of stx(1c)-harboring STEC are unknown. In this study, we identified stx(1c) in 76 (54.3%) of 140 eae-negative, but in none of 155 eae-positive, human STEC isolates (P <

  9. Aqueous extracts of selenium-fertilized broccoli increase selenoprotein activity and inhibit DNA single-strand breaks, but decrease the activity of quinone reductase in Hepa 1c1c7 cells.

    Keck, Anna-Sigrid; Finley, John W

    2006-05-01

    Depending on growth conditions, broccoli may be enriched in the isothiocyanate sulforaphane and/or the mineral selenium (Se); both compounds may play an important role in the reduction of intracellular oxidative stress and chronic disease prevention. Sulforaphane up-regulates transcription of Phase II detoxification proteins (e.g. quinone reductase [QR]), whereas Se is needed for the production of thioredoxin reductase (TR) and glutathione peroxidase-1 (GPx1), both of which exhibit antioxidant activity. The objective of the present study was to determine whether the fertilization of broccoli with Se increases the antioxidant ability of broccoli. Hydrogen peroxide-induced DNA single-strand breaks (measured by single cell electrophoresis, Comet assay) and activity of antioxidant enzymes (GPx, TR and QR) were measured in mouse hepatoma cells (Hepa 1c1c7 cells) treated with purified sulforaphane, sodium selenite or extracts of selenized broccoli. When supplied separately as chemically pure substances, sodium selenite was more effective than sulforaphane for reduction of single-strand breaks. Se-fertilized broccoli extracts were the most effective for reduction of DNA single-strand breaks, and extracts that contained 0.71 microM Se and 0.08 microM sulforaphane inhibited 94% of DNA single-strand breaks. A significant positive association (r = 0.81, p = 0.009) between GPx1 activity and inhibition of DNA single-strand breaks as well as a 24h lag time between addition of Se, sulforaphane or broccoli extract and inhibition of single-strand breaks suggests that some of the antioxidant protection is mediated through selenoproteins. Conversely, fertilization of broccoli with Se decreased the ability of broccoli extract to induce QR activity. These results demonstrate that Se and sulforaphane, alone or as a component of broccoli, may help decrease oxidative stress. They further suggest that Se is the most important for decreasing oxidative stress, but maximizing the Se content

  10. Treating Wastewater With Immobilized Enzymes

    Jolly, Clifford D.

    1991-01-01

    Experiments show enzymes are immobilized on supporting materials to make biocatalyst beds for treatment of wastewater. With suitable combination of enzymes, concentrations of various inorganic and organic contaminants, including ammonia and urea, reduced significantly.

  11. A STUDY TO CORRELATE HBA1C LEVELS AND LEFT VENTRICULAR DIASTOLIC DYSFUNCTION IN NEWLY DIAGNOSED TYPE II DIABETES MELLITUS

    Vasanthi

    2016-06-01

    Full Text Available AIM To assess the correlation of HBA1C levels with left ventricular diastolic dysfunction in newly diagnosed Type 2 diabetic patient. This prospective study was done at Department of General Medicine, OPD, Medical Wards, Stanley Medical College and Hospital, Chennai. RESULT The mean HBA1C levels were meaningfully more in Left Ventricular Diastolic Dysfunction (LVDD positive group compared to the LVDD negative group by 1.33%. This significant difference of 15% increase in mean HBA1C levels in LVDD positive group compared to the LVDD negative group is true and has not occurred by chance. CONCLUSION One-fifth to one-third of diabetic patients will develop LVDD. Patients with HBA1C (8 to 10 have double the chances to develop LVDD than with HbA1c 6.5 to 8. Patients with HBA1C more than 10 have five times the chances to develop LVDD than with HbA1C 6.5 to 8. Patients with HBA1C more than 10 have three times the chances to develop LVDD than with HBA1C 8 to 10. One-fourth to one-half of diabetic patients will develop LVDD grade 1. Patients with HBA1C 8 to 10 have double the chances to develop LVDD grade 1 than with HBA1C 6.5 to 8. Patients with HBA1C more than 10 have four times the chances to develop LVDD grade 1 than with HBA1C 6.5 to 8. Patients with HBA1C more than 10 have two times the chances to develop LVDD than with HBA1C 8 to 10

  12. Talk about hemoglobin A1c%再谈糖化血红蛋白

    居漪

    2015-01-01

    Hemoglobin A1c ( HbA1c ) is confirmed by the 2 epidemiological surveys , the UK Prospective Diabetes Study(UKPDS)and the Diabetes Control and Complications Trial Research (DCCT), as an important marker which is closely related to diabetes and its complications .HbA1c has been used more and more widely in clinical laboratories . Due to the diversity of HbA1c detection technologies , there is large difference among results , and thus it is unable to meet the demand of clinical diagnosis and treatment .Along with the International Federation of Clinical Chemistry and Laboratory Medicine ( IFCC ) and American Association for Clinical Chemistry ( AACC ) to carry out the HbA1c standardization, testing quality in laboratories has been significantly improved .Since 2010, HbA1c has been included in the diagnostic criteria for diabetes by American Diabetes Association ( ADA ) , the International Diabetes Federation (IDF) and World Health Organization(WHO).In China, HbA1c detection begins relatively late in clinical application , quality management and standardization , but the rate of progress of work and performance are very obvious .Although HbA1c has temporarily not been included in the Chinese diabetes diagnosis guide , we believe that as long as we keep the unity and cooperation , we will create standardization in our own way and serve the clinicians and patients with diabetes mellitus better .%糖化血红蛋白( HbA1c )作为被英国前瞻性糖尿病研究( UKPDS)、美国糖尿病控制和并发症试验(DCCT)两大流行病学调查结果证实的与糖尿病及其并发症密切相关的重要标志物,在临床上得到了越来越广泛的应用。但是,HbA1c实验室检测技术的多样性导致其检测结果差异较大,无法满足临床诊治的需求。随着国际临床化学与医学实验室联盟(IFCC)和美国临床化学协会(AACC)HbA1c标准化工作的开展,实验室HbA1c的检测质量得到了显著提升。2010

  13. The Catalytic Function of Enzymes.

    Splittgerber, Allan G.

    1985-01-01

    Discusses: structure of the enzyme molecule; active site; reaction mechanism; transition state; factors affecting enzyme reaction rates, concentration of enzyme; concentration of substrate; product concentration; temperature effects and pH effects; factors causing a lowering of activation energy; proximity and orientation effects; substrate strain…

  14. The ratio of glycated albumin to hemoglobin A1c measured in IFCC units accurately represents the glycation gap.

    Akatsuka, Junya; Mochizuki, Mie; Musha, Ikuma; Ohtake, Akira; Kobayashi, Kisho; Kikuchi, Toru; Kikuchi, Nobuyuki; Kawamura, Tomoyuki; Urakami, Tatsuhiko; Sugihara, Shigetaka; Hoshino, Tadao; Amemiya, Shin

    2015-01-01

    The glycation gap (G-gap: difference between measured hemoglobin A1c [A1C] and the value predicted by its regression on the fructosamine level) is stable and associated with diabetic complications. Measuring A1C level in International Federation of Clinical Chemistry (IFCC) units (A1C-SI; mmol/mol) and National Glycohemoglobin Standardization Program units (A1C-NGSP; %) and using glycated albumin (GA) level instead of fructosamine level for calculating the G-gap, we investigated whether the G-gap is better represented by GA/A1C ratio if expressed in SI units (GA/A1C-SI ratio) rather than in NGSP units (GA/A1C-% ratio). We examined 749 Japanese children with type 1 diabetes using simultaneous GA and A1C measurements. Of these, 369 patients were examined more than five times to assess the consistency of the G-gap and the GA/A1C ratio within individuals. The relationship of GA/A1C-% ratio to the corresponding A1C-NGSP was stronger than that of GA/A1C-SI ratio to A1C-IFCC. At enrollment, the inverse relationship between the GA/A1C-SI ratio and G-gap was highly significant (R(2) = 0.95) compared with that between the GA/A1C-% ratio and G-gap (R(2) = 0.69). A highly significant inverse relationship was also observed between the mean GA/A1C-SI ratio and the mean G-gaps obtained individually over time (R(2) = 0.95) compared with that using the corresponding A1C-NGSP (R(2) = 0.67). We conclude that the G-gap is better represented by the GA/A1C-SI ratio. We propose the use of mean GA/A1C-SI ratios easily obtained individually over time as reference values in Japanese children with type 1 diabetes (6.75 ± 0.60 [means ± SD]).

  15. An Analysis of the FY-1C, Iridium 33, and Cosmos 2251 Fragments

    Liou, J.-C.

    2014-01-01

    The beginning of the year 2013 marks the sixth anniversary of the destruction of the Fengyun-1C (FY-1C) weather satellite as the result of an anti-satellite test conducted by China in January 2007 and the fourth anniversary of the accidental collision between Cosmos 2251 and the operational Iridium 33 in February 2009. These two events represent the worst satellite breakups in history. A total of 5579 fragments have been cataloged by the U.S. Space Surveillance Network (SSN), and almost 5000 of them were still in orbit in January 2013. In addition to these cataloged objects, hundreds of thousands (or more) of fragments down to the millimeter size regime were also generated during the breakups. These fragments are too small to be tracked by the SSN, but are large enough to be a safety concern for human space activities and robotic missions in low Earth orbit (LEO, the region below 2000 km altitude). Like their cataloged siblings, many of them remain in orbit today. These two breakup events dramatically changed the landscape of the orbital debris environment in LEO. The spatial density of the cataloged population in January 2013 is shown as the top blue curve. The combined FY-1C, Iridium 33, and Cosmos 2251 fragments (black curve) account for about 50 percent of the cataloged population below an altitude of 1000 km. They are also responsible for the concentrations at 770 km and 850 km, altitudes at which the collisions occurred. The effects of the FY-1C, Iridium 33, and Cosmos 2251 fragments will continue to be felt for decades to come. For example, approximately half of the generated FY-1C fragments will remain in orbit 20 years from now. In general, the Iridium 33 and Cosmos 2251 fragments will decay faster than the FY-1C fragments because of their lower altitudes. Of the Iridium 33 and Cosmos 2251 fragments, the former have much shorter orbital lifetimes than the latter, because lightweight composite materials were heavily used in the construction of the Iridium

  16. Kinetic Measurements for Enzyme Immobilization.

    Cooney, Michael J

    2017-01-01

    Enzyme kinetics is the study of the chemical reactions that are catalyzed by enzymes, with a focus on their reaction rates. The study of an enzyme's kinetics considers the various stages of activity, reveals the catalytic mechanism of this enzyme, correlates its value to assay conditions, and describes how a drug or a poison might inhibit the enzyme. Victor Henri initially reported that enzyme reactions were initiated by a bond between the enzyme and the substrate. By 1910, Michaelis and Menten were advancing their work by studying the kinetics of an enzyme saccharase which catalyzes the hydrolysis of sucrose into glucose and fructose. They published their analysis and ever since the Michaelis-Menten equation has been used as the standard to describe the kinetics of many enzymes. Unfortunately, soluble enzymes must generally be immobilized to be reused for long times in industrial reactors. In addition, other critical enzyme properties have to be improved like stability, activity, inhibition by reaction products, and selectivity towards nonnatural substrates. Immobilization is by far the chosen process to achieve these goals.Although the Michaelis-Menten approach has been regularly adapted to the analysis of immobilized enzyme activity, its applicability to the immobilized state is limited by the barriers the immobilization matrix places upon the measurement of compounds that are used to model enzyme kinetics. That being said, the estimated value of the Michaelis-Menten coefficients (e.g., V max, K M) can be used to evaluate effects of immobilization on enzyme activity in the immobilized state when applied in a controlled manner. In this review enzyme activity and kinetics are discussed in the context of the immobilized state, and a few novel protocols are presented that address some of the unique constraints imposed by the immobilization barrier.

  17. Electrochemical detection of HbA1c, a marker [correction of maker] for diabetes, using a flow immunoassay system.

    Tanaka, Tsuyoshi; Tsukube, Shoko; Izawa, Kojiro; Okochi, Mina; Lim, Tae-Kyu; Watanabe, Shugo; Harada, Manabu; Matsunaga, Tadashi

    2007-04-15

    An on-chip electrochemical flow immunoassay system for the detection of hemoglobin A1c (HbA1c) was developed using anti-human hemoglobin (Hb) IgG labeled with ferrocene monocarboxylic acid (Fc-COOH) and boronate-affinity chromatography. An on-chip column packed with boronate-activated agarose beads was used for the separation of HbA1c from both non-glycated Hb and free antibody. Anti-human Hb IgG conjugated to Fc-COOH (Fc-IgG) was used for the electrochemical detection of HbA1c. The assay procedure included immunoreactions with Fc-IgG and HbA1c, separation of immunocomplexes by boronate affinity, and electrochemical detection of Fc-IgG-HbA1c immunocomplexes. The immunoreaction mixtures were injected onto a boronate-affinity column. HbA1c-antibody complexes were then trapped onto the column by the affinity of HbA1c to boronic acid. Subsequently, elution buffer containing sorbitol was applied to elute HbA1c-antibody complexes and a current was detected by applying 600 mV versus Ag/AgCl. The elution signal was an estimation of the HbA1c amount. A linear correlation between the increase of current and HbA1c concentration was obtained up to an HbA1c concentration of 500 microg/ml. The HbA1c flow immunoassay was successfully achieved using hemolysates. This electrochemical flow immunoassay system enabled us to construct a novel point-of-care testing device for the monitoring of glycated proteins including HbA1c.

  18. Molecular modeling of human BAD and its interaction with PKAc or PP1c.

    Yang, Jie

    2009-03-01

    To build up the structure of human BAD (Bcl-2 antagonist of cell death), subsequently combined with PKAc or PP1c (protein phosphatase 1), to investigate the interaction relationship between BAD and its kinase/PTPese at the molecular level. Additionally, it is concerned with the search for all optimal positions and orientations of a set of amino acid residues of BAD, while its binding sites include N-termini (Glu19, Ala27, and Ser34-Lys35), BH3-located helical domain (Arg98-Lys126), and C-termini (Trp154-Ser163 and Ser167-Gln168). The related sites of PKAc are mainly assembled in C-terminal alpha/beta-domain of PKAc, which comprises the KTL motif (47-49), Glu203 residue, a helical region (Asp241-Arg256), and the span from 328 to 333; while the interaction sites with BAD converge at C-terminal beta-domain of PP1c, which includes the DEK motif (166-168), the stretch from 179 to 197 including a helix (Glu184-Arg188), Glu230-Asp242 segment containing Val232-His237 helix, and Glu287-Leu289 loop. In conclusion, analysis of the complex between BAD and PKAc or PP1c provides a novel viewpoint on the structural origins of molecular recognition. And the complex models suggest that BH3 domain of BAD interact with PKAc or PP1c by electrostatic, van der Waals contacts, hydrogen bond and salt bridge. This is helpful for our development and research of some new drugs, especially mimetic BH3 peptides and inspires scientists with BAD complex and molecular mechanism of its integrating glycolysis and apoptosis.

  19. Relationship between level of HbA1C and breast cancer

    Fariba Jousheghany

    2016-12-01

    Conclusion: While there was a statistically significant association between HbA1C and obesity, there were no significant associations found with this analysis. However, there are clinically meaningful relationships based on observed trends. Future directions for research may involve exploring a larger sample of patients and the role of therapeutic regimens on blood sugar control and BMI of breast cancer patients and influence on cancer prognosis.

  20. Synthetic studies on hemicalide: development of a convergent approach toward the C1-C25 fragment.

    Sorin, Geoffroy; Fleury, Etienne; Tran, Christine; Prost, Elise; Molinier, Nicolas; Sautel, François; Massiot, Georges; Specklin, Simon; Meyer, Christophe; Cossy, Janine; Lannou, Marie-Isabelle; Ardisson, Janick

    2013-09-20

    Synthetic studies on hemicalide, a recently isolated marine natural product displaying highly potent antiproliferative activity and a unique mode of action, have highlighted a reliable Horner-Wadsworth-Emmons olefination to create the C6-C7 alkene and a remarkable efficient Suzuki-Miyaura coupling to form the C15-C16 bond, resulting in the development of a convergent approach toward the C1-C25 fragment.

  1. Measurement of the figure of merit M for 1-C3F6/SF6 mixtures

    Christensen, Jørn Erik Berril; McAllister, Iain Wilson

    1997-01-01

    High precision measurements of the linear part of the Paschen curve are reported for 1-C3F6/SF6 mixtures. From these measurements, values for the pressure-reduced limiting electric field strength (E/p)lim and the associated figure of merit M are derived. These two parameters can be used...... to characterise the insulating properties of a strongly electronegative gas or gas mixture. The present measurements confirm the existence of positive synergism....

  2. System Design and In-orbit Verification of the HJ-1-C SAR Satellite

    Zhang Run-ning; Jiang Xiu-peng

    2014-01-01

    HJ-1-C is a SAR satellite owned by the Chinese Environment and Natural Disaster Monitoring constellation, and works together with the optical satellites HJ-1-A/B for monitoring environment and natural disasters. In this paper, the system design and characteristics of the first Chinese civil SAR satellite are described. In addition, the interface relation between SAR payload and platform is studied. Meanwhile, the data transmission capability, attitude, power, and temperature control that supp...

  3. A review of variant hemoglobins interfering with hemoglobin A1c measurement.

    Little, Randie R; Roberts, William L

    2009-05-01

    Hemoglobin A1c (HbA1c) is used routinely to monitor long-term glycemic control in people with diabetes mellitus, as HbA1c is related directly to risks for diabetic complications. The accuracy of HbA1c methods can be affected adversely by the presence of hemoglobin (Hb) variants or elevated levels of fetal hemoglobin (HbF). The effect of each variant or elevated HbF must be examined with each specific method. The most common Hb variants worldwide are HbS, HbE, HbC, and HbD. All of these Hb variants have single amino acid substitutions in the Hb beta chain. HbF is the major hemoglobin during intrauterine life; by the end of the first year, HbF falls to values close to adult levels of approximately 1%. However, elevated HbF levels can occur in certain pathologic conditions or with hereditary persistence of fetal hemoglobin. In a series of publications over the past several years, the effects of these four most common Hb variants and elevated HbF have been described. There are clinically significant interferences with some methods for each of these variants. A summary is given showing which methods are affected by the presence of the heterozygous variants S, E, C, and D and elevated HbF. Methods are divided by type (immunoassay, ion-exchange high-performance liquid chromatography, boronate affinity, other) with an indication of whether the result is artificially increased or decreased by the presence of a Hb variant. Laboratorians should be aware of the limitations of their method with respect to these interferences.

  4. Major enzymes controlling the androgenic pressure in the developing lung.

    Tremblay, Yves; Provost, Pierre R

    2013-09-01

    A sex difference is observed in the incidence and morbidity of respiratory distress syndrome (RDS) of the neonate and in bronchopulmonary dysplasia (BPD). The involvement of androgens is well evidenced in RDS and it is suspected in BPD. Interestingly, the developing lung is not an inert tissue just exposed to circulating androgens, but is rather an active androgen metabolizing tissue, expressing enzymes involved in both androgen synthesis and inactivation. The present review focuses on the major enzymes involved in androgen metabolism within the developing lung. Testosterone synthesis and inactivation by AKR1C3/Akr1c6 (human/mouse 17β-hydroxysteroid dehydrogenases (HSDs) type 5) and HSD17B2 (17β-HSD type 2), respectively, play an important role in the developing lung. Akr1c14 (3α-HSD) shows a strong increase in expression according to developmental time. The canalicular stage of lung development corresponding to the surge of surfactant lipid synthesis, which is linked to RDS, as well as saccularization/alveolarization, which are linked to BPD, are covered by this review for the mouse and human species. The androgen metabolizing enzymes expressed within the developing lung can become potential pharmaceutical targets in the objective of accelerating lung maturation by specific treatments. The classic deleterious effects of androgens on lung maturation and the surge of surfactant synthesis in males are well known. Conversely, androgens also have positive impacts on the development of both male and female lungs. Steroidogenic enzymes are key regulators of these positive effects. This article is part of a Special Issue entitled 'CSR 2013'.

  5. Engineering human interferon α1c/86D with phage display technology

    马学军; 胡荣; 吕海; 魏开坤; 张丽兰; 薛水星; 侯云德

    1999-01-01

    Human interferon-α1c/86D (IFNα1c/86D) was functionally displayed on the surface of the filamentous bacteriophage using a phagemid vector system (pCANTAB5E). The key amino acid residues involved in the receptor binding were further defined with phage displayed 6-mer peptide library and two neutralizing antibodies against linear epitopes on the IFN-α1b, indicating that residues 30, 33, 34, (AB-loop) and residues 124, 126, 127 (D helix, DE-loop) were more critical than the adjacent residues for recognition of receptor. In addition, a cassette mutagenesis library was generated by fully randomizing the sequence of the four positions 29, 31, 32 and 35 in AB-loop, and used to select phage-IFN variants with WISH-hased panning method. Three phage-IFN variants were isolated to possess more antiviral activity in the range of 4—16-fold than parental phage-IFN after IPTG-induced soluble expression. The results suggest that phage displayed phage-IFN α1c/86D variants with increased specific activity might be obta

  6. Proper motion and Photometric Variability of the Candidate Propotoplanet TMR-1C

    Riaz, B

    2010-01-01

    Aims: In their HST/NICMOS observations, Terebey et al. 1998 (T98) detected a candidate protoplanet, TMR-1C, that lies at a separation of about 10" (~1000 AU) from the Class I protostar TMR-1 (IRAS 04361+2547). A narrow filament-like structure was observed extending south-east from the central proto-binary system towards TMR-1C, suggesting a morphology in which the candidate protoplanet may have been ejected from the TMR-1 system. Follow-up low-resolution spectroscopy by Terebey et al. 2000 however could not confirm if this object is a protoplanet or a low-luminosity background star. Methods: We present two epochs of near-infrared photometric observations obtained at the CFHT of the TMR-1 system. The time span of ~7 years between the two sets of observations provides an opportunity to study the proper motion of the components, as well as to check for any photometric variability that would indicate the youth of this source. Results: Our study shows TMR-1C to be co-moving with the protobinary TMR-1AB, based on a...

  7. Coherent Performance Analysis of the HJ-1-C Synthetic Aperture Radar

    Li Hai-ying

    2014-06-01

    Full Text Available Synthetic Aperture Radar (SAR is a coherent imaging radar. Hence, coherence is critical in SAR imaging. In a coherent system, several sources can degrade performance. Based on the HJ-1-C SAR system implementation and sensor characteristics, this study evaluates the effect of frequency stability and pulse-to-pulse timing jitter on the SAR coherent performance. A stable crystal oscillator with short-term stability of 10×1.0−10 / 5 ms is used to generate the reference frequency by using a direct multiplier and divider. Azimuth ISLR degradation owing to the crystal oscillator phase noise is negligible. The standard deviation of the pulse-to-pulse timing jitter of HJ-1-C SAR is lower than 2ns (rms and the azimuth random phase error in the synthetic aperture time slightly degrades the side lobe of the azimuth impulse response. The mathematical expressions and simulation results are presented and suggest that the coherent performance of the HJ-1-C SAR system meets the requirements of synthetic aperture radar imaging.

  8. Feature Fusion Based Road Extraction for HJ-1-C SAR Image

    Lu Ping-ping

    2014-06-01

    Full Text Available Road network extraction in SAR images is one of the key tasks of military and civilian technologies. To solve the issues of road extraction of HJ-1-C SAR images, a road extraction algorithm is proposed based on the integration of ratio and directional information. Due to the characteristic narrow dynamic range and low signal to noise ratio of HJ-1-C SAR images, a nonlinear quantization and an image filtering method based on a multi-scale autoregressive model are proposed here. A road extraction algorithm based on information fusion, which considers ratio and direction information, is also proposed. By processing Radon transformation, main road directions can be extracted. Cross interferences can be suppressed, and the road continuity can then be improved by the main direction alignment and secondary road extraction. The HJ-1-C SAR image acquired in Wuhan, China was used to evaluate the proposed method. The experimental results show good performance with correctness (80.5% and quality (70.1% when applied to a SAR image with complex content.

  9. Deletion of the Mouse Homolog of CACNA1C Disrupts Discrete Forms of Hippocampal-Dependent Memory and Neurogenesis within the Dentate Gyrus

    Bell, Ryan Z.; Fisher, Grace L.

    2016-01-01

    Abstract L-type voltage-gated calcium channels (LVGCCs) have been implicated in various forms of learning, memory, and synaptic plasticity. Within the hippocampus, the LVGCC subtype, CaV1.2 is prominently expressed throughout the dentate gyrus. Despite the apparent high levels of CaV1.2 expression in the dentate gyrus, the role of CaV1.2 in hippocampal- and dentate gyrus-associated forms of learning remain unknown. To address this question, we examined alternate forms of hippocampal-dependent associative and spatial memory in mice lacking the mouse ortholog of CACNA1C (Cacna1c), which encodes CaV1.2, with dentate gyrus function implicated in difficult forms of each task. We found that while the deletion of CaV1.2 did not impair the acquisition of fear of a conditioned context, mice lacking CaV1.2 exhibited deficits in the ability to discriminate between two contexts, one in which the mice were conditioned and one in which they were not. Similarly, CaV1.2 knock-out mice exhibited normal acquisition and recall of the location of the hidden platform in a standard Morris water maze, but were unable to form a memory of the platform location when the task was made more difficult by restricting the number of available spatial cues. Within the dentate gyrus, pan-neuronal deletion of CaV1.2 resulted in decreased cell proliferation and the numbers of doublecortin-positive adult-born neurons, implicating CaV1.2 in adult neurogenesis. These results suggest that CaV1.2 is important for dentate gyrus-associated tasks and may mediate these forms of learning via a role in adult neurogenesis and cell proliferation within the dentate gyrus. PMID:27957527

  10. Targeting amyloid-degrading enzymes as therapeutic strategies in neurodegeneration.

    Turner, Anthony J; Fisk, Lilia; Nalivaeva, Natalia N

    2004-12-01

    The levels of amyloid beta-peptides (Abeta) in the brain represent a dynamic equilibrium state as a result of their biosynthesis from the amyloid precursor protein (APP) by beta- and gamma-secretases, their degradation by a team of amyloid-degrading enzymes, their subsequent oligomerization, and deposition into senile plaques. While most therapeutic attention has focused on developing inhibitors of secretases to prevent Abeta formation, enhancing the rate of Abeta degradation represents an alternative and viable strategy. Current evidence both in vivo and in vitro suggests that there are three major players in amyloid turnover: neprilysin, endothelin converting enzyme(s), and insulin-degrading enzyme, all of which are zinc metallopeptidases. Other proteases have also been implicated in amyloid metabolism, including angiotensin-converting enzyme, and plasmin but for these the evidence is less compelling. Neprilysin and endothelin converting enzyme(s) are homologous membrane proteins of the M13 peptidase family, which normally play roles in the biosynthesis and/or metabolism of regulatory peptides. Insulin-degrading enzyme is structurally and mechanistically distinct. The regional, cellular, and subcellular localizations of these enzymes differ, providing an efficient and diverse mechanism for protecting the brain against the normal accumulation of toxic Abeta peptides. Reduction in expression levels of some of these proteases following insults (e.g., hypoxia and ischemia) or aging might predispose to the development of Alzheimer's disease. Conversely, enhancement of their levels by gene delivery or pharmacological means could be neuroprotective. Even a relatively small enhancement of Abeta metabolism could slow the inexorable progression of the disease. The relative merits of targeting these enzymes for the treatment of Alzheimer's disease will be reviewed and possible side-effects of enhancing their activity evaluated.

  11. Effects of Sleep Disorders on Hemoglobin A1c Levels in Type 2 Diabetic Patients

    Ahmet Keskin; Murat (ü)nalacak; U(g)ur Bilge; Pinar Yildiz; Seda Güler; Engin Burak Sel(c)uk; Muzaffer Bilgin

    2015-01-01

    Background: Studies have reported the presence of sleep disorders in approximately 50-70% of diabetic patients, and these may contribute to poor glycemic control, diabetic neuropathy, and overnight hypoglycemia.The aim of this study was to determine the frequency of sleep disorders in diabetic patients, and to investigate possible relationships between scores of these sleep disorders and obstructive sleep apnea syndrome (OSAS) and diabetic parameters (fasting blood glucose, glycated hemoglobin A1c [HbA1c], and lipid levels).Methods: We used the Berlin questionnaire (BQ) for OSAS, the Epworth Sleepiness Scale (ESS), and the Pittsburgh Sleep Quality Index (PSQI) to determine the frequency of sleep disorders and their possible relationships with fasting blood glucose, HbA1c, and lipid levels.Results: The study included 585 type 2 diabetic patients admitted to family medicine clinics between October and December 2014.Sleep, sleep quality, and sleep scores were used as the dependent variables in the analysis.The ESS scores showed that 54.40% of patients experienced excessive daytime sleepiness, and according to the PSQI, 64.30% experienced poor-quality sleep.The BQ results indicated that 50.20% of patients were at high-risk of OSAS.HbA 1 c levels correlated significantly with the ESS and PSQI results (r =0.23, P < 0.001 and r =0.14, P =0.001, respectively), and were significantly higher in those with high-risk of OSAS as defined by the BQ (P < 0.001).These results showed that HbA 1 c levels were related to sleep disorders.Conclusions: Sleep disorders are common in diabetic patients and negatively affect the control of diabetes.Conversely, poor diabetes control is an important factor disturbing sleep quality.Addressing sleep disturbances in patients who have difficulty controlling their blood glucose has dual benefits: Preventing diabetic complications caused by sleep disturbance and improving diabetes control.

  12. Type I restriction endonucleases are true catalytic enzymes.

    Bianco, Piero R; Xu, Cuiling; Chi, Min

    2009-06-01

    Type I restriction endonucleases are intriguing, multifunctional complexes that restrict DNA randomly, at sites distant from the target sequence. Restriction at distant sites is facilitated by ATP hydrolysis-dependent, translocation of double-stranded DNA towards the stationary enzyme bound at the recognition sequence. Following restriction, the enzymes are thought to remain associated with the DNA at the target site, hydrolyzing copious amounts of ATP. As a result, for the past 35 years type I restriction endonucleases could only be loosely classified as enzymes since they functioned stoichiometrically relative to DNA. To further understand enzyme mechanism, a detailed analysis of DNA cleavage by the EcoR124I holoenzyme was done. We demonstrate for the first time that type I restriction endonucleases are not stoichiometric but are instead catalytic with respect to DNA. Further, the mechanism involves formation of a dimer of holoenzymes, with each monomer bound to a target sequence and, following cleavage, each dissociates in an intact form to bind and restrict subsequent DNA molecules. Therefore, type I restriction endonucleases, like their type II counterparts, are true enzymes. The conclusion that type I restriction enzymes are catalytic relative to DNA has important implications for the in vivo function of these previously enigmatic enzymes.

  13. Caenorhabditis elegans glutamylating enzymes function redundantly in male mating.

    Chawla, Daniel G; Shah, Ruchi V; Barth, Zachary K; Lee, Jessica D; Badecker, Katherine E; Naik, Anar; Brewster, Megan M; Salmon, Timothy P; Peel, Nina

    2016-09-15

    Microtubule glutamylation is an important modulator of microtubule function and has been implicated in the regulation of centriole stability, neuronal outgrowth and cilia motility. Glutamylation of the microtubules is catalyzed by a family of tubulin tyrosine ligase-like (TTLL) enzymes. Analysis of individual TTLL enzymes has led to an understanding of their specific functions, but how activities of the TTLL enzymes are coordinated to spatially and temporally regulate glutamylation remains relatively unexplored. We have undertaken an analysis of the glutamylating TTLL enzymes in C. elegans We find that although all five TTLL enzymes are expressed in the embryo and adult worm, loss of individual enzymes does not perturb microtubule function in embryonic cell divisions. Moreover, normal dye-filling, osmotic avoidance and male mating behavior indicate the presence of functional amphid cilia and male-specific neurons. A ttll-4(tm3310); ttll-11(tm4059); ttll-5(tm3360) triple mutant, however, shows reduced male mating efficiency due to a defect in the response step, suggesting that these three enzymes function redundantly, and that glutamylation is required for proper function of the male-specific neurons.

  14. Effects of Hemoglobin Variants on Hemoglobin A1c Values Measured Using a High-Performance Liquid Chromatography Method

    De-La-Iglesia, Silvia; Ropero, Paloma; Nogueira-Salgueiro, Patricia; Santana-Benitez, Jesus

    2014-01-01

    Hemoglobin A1c (HbA1c) is routinely used to monitor long-term glycemic control and for diagnosing diabetes mellitus. However, hemoglobin (Hb) gene variants/modifications can affect the accuracy of some methods. The potential effect of Hb variants on HbA1c measurements was investigated using a high-performance liquid chromatography (HPLC) method compared with an immunoturbimetric assay. Fasting plasma glucose (FPG) and HbA1c levels were measured in 42 371 blood samples. Samples producing abnormal chromatograms were further analyzed to characterize any Hb variants. Fructosamine levels were determined in place of HbA1c levels when unstable Hb variants were identified. Abnormal HPLC chromatograms were obtained for 160 of 42 371 samples. In 26 samples HbS was identified and HbA1c results correlated with FPG. In the remaining 134 samples HbD, Hb Louisville, Hb Las Palmas, Hb N-Baltimore, or Hb Porto Alegre were identified and HbA1c did not correlate with FPG. These samples were retested using an immunoturbidimetric assay and the majority of results were accurate; only 3 (with the unstable Hb Louisville trait) gave aberrant HbA1c results. Hb variants can affect determination of HbA1c levels with some methods. Laboratories should be aware of Hb variants occurring locally and choose an appropriate HbA1c testing method. PMID:25355712

  15. Microarray analyses of SREBP-1a and SREBP-1c target genes identify new regulatory pathways in muscle.

    Rome, Sophie; Lecomte, Virginie; Meugnier, Emmanuelle; Rieusset, Jennifer; Debard, Cyrille; Euthine, Vanessa; Vidal, Hubert; Lefai, Etienne

    2008-01-01

    International audience; In this study we have identified the target genes of sterol regulatory element binding protein (SREBP)-1a and SREBP-1c in primary cultures of human skeletal muscle cells, using adenoviral vectors expressing the mature nuclear form of human SREBP-1a or SREBP-1c combined with oligonucleotide microarrays. Overexpression of SREBP-1a led to significant changes in the expression of 1,315 genes (655 upregulated and 660 downregulated), whereas overexpression of SREBP-1c modifi...

  16. Enzyme Molecules in Solitary Confinement

    Raphaela B. Liebherr

    2014-09-01

    Full Text Available Large arrays of homogeneous microwells each defining a femtoliter volume are a versatile platform for monitoring the substrate turnover of many individual enzyme molecules in parallel. The high degree of parallelization enables the analysis of a statistically representative enzyme population. Enclosing individual enzyme molecules in microwells does not require any surface immobilization step and enables the kinetic investigation of enzymes free in solution. This review describes various microwell array formats and explores their applications for the detection and investigation of single enzyme molecules. The development of new fabrication techniques and sensitive detection methods drives the field of single molecule enzymology. Here, we introduce recent progress in single enzyme molecule analysis in microwell arrays and discuss the challenges and opportunities.

  17. Enzyme molecules in solitary confinement.

    Liebherr, Raphaela B; Gorris, Hans H

    2014-09-12

    Large arrays of homogeneous microwells each defining a femtoliter volume are a versatile platform for monitoring the substrate turnover of many individual enzyme molecules in parallel. The high degree of parallelization enables the analysis of a statistically representative enzyme population. Enclosing individual enzyme molecules in microwells does not require any surface immobilization step and enables the kinetic investigation of enzymes free in solution. This review describes various microwell array formats and explores their applications for the detection and investigation of single enzyme molecules. The development of new fabrication techniques and sensitive detection methods drives the field of single molecule enzymology. Here, we introduce recent progress in single enzyme molecule analysis in microwell arrays and discuss the challenges and opportunities.

  18. Structural studies of {delta}-endotoxin Cry 1 C from Bacillus thuringiensis

    Guimaraes, B.G.; Garratt, R.C.; Oliva, G. [Sao Paulo Univ., Sao Carlos, SP (Brazil). Inst. de Fisica; Lemos, M.V.F. [UNESP, Jaboticabal, SP (Brazil). Dept. de Biologia Aplicada Agropecuaria; Arantes, O.M.N. [Universidade Estadual de Londrina, PR (Brazil). Dept. de Biologia Geral

    1996-12-31

    Full text. The {delta}-endotoxins are a family of crystal protein by a soil bacterium, Bacillus thuringiensis. The study of these proteins has been of great interest due to their highly specific activity against insects of the orders Lepidoptera, Diptera and Coleoptera. Thus, the {delta}a-endotoxins have been used for more than two decades as biological insecticides to control agricultural pests and, more recently, insects vectors of some diseases. The knowledge of their three-dimensional structures is very important to understand their mechanism of action and their high specificity. To date, the structure of only three proteins of the {delta}-endotoxins family have been reported: Cry3A, a coleopteran-specific toxin (beetle toxin){sup 1}, Cry1Aa, a lepidopteran-specific toxin (butterfly toxin){sup 2} and CytB, a dipteran-specific toxin (mosquito toxin){sup 3} Our work is aimed at the determination of the crystallographic structure by X-ray diffraction of {delta}-endotoxin Cry1C, also toxic to insects of the Lepidoptera order but towards families other than those affected by Cry1Aa. A comparison between these structures may lead to important conclusions about the reasons for the specificity and would allow the planning of mutants with more efficient activity. The cry1C gene was cloned into an adequate vector and expressed in an acrystalliferous B. thuringiensis strain. After cell culture and sporulation the microcrystals of Cry1C were separated by ultra-centrifugation in sacharose. The protoxin inclusion bodies were activated by commercial trpsin and the protease-resistant core was purified by anion-exchange chromatography. Crystallization experiments are being conducted in order to obtain single crystals suitable for diffraction measurements. We intend to use the Protein Crystallograph Station of the LNLS to collect data as soon as it is available and we have suitable crystals. (author) 3 refs.

  19. Implementation of the high-order schemes QUICK and LECUSSO in the COMMIX-1C Program

    Sakai, K.; Sun, J.G.; Sha, W.T. [Argonne National Lab., IL (United States). Energy Technology Div.

    1995-08-01

    Multidimensional analysis computer programs based on the finite volume method, such as COMMIX-1C, have been commonly used to simulate thermal-hydraulic phenomena in engineering systems such as nuclear reactors. In COMMIX-1C, the first-order schemes with respect to both space and time are used. In many situations such as flow recirculations and stratifications with steep gradient of velocity and temperature fields, however, high-order difference schemes are necessary for an accurate prediction of the fields. For these reasons, two second-order finite difference numerical schemes, QUICK (Quadratic Upstream Interpolation for Convective Kinematics) and LECUSSO (Local Exact Consistent Upwind Scheme of Second Order), have been implemented in the COMMIX-1C computer code. The formulations were derived for general three-dimensional flows with nonuniform grid sizes. Numerical oscillation analyses for QUICK and LECUSSO were performed. To damp the unphysical oscillations which occur in calculations with high-order schemes at high mesh Reynolds numbers, a new FRAM (Filtering Remedy and Methodology) scheme was developed and implemented. To be consistent with the high-order schemes, the pressure equation and the boundary conditions for all the conservation equations were also modified to be of second order. The new capabilities in the code are listed. Test calculations were performed to validate the implementation of the high-order schemes. They include the test of the one-dimensional nonlinear Burgers equation, two-dimensional scalar transport in two impinging streams, von Karmann vortex shedding, shear driven cavity flow, Couette flow, and circular pipe flow. The calculated results were compared with available data; the agreement is good.

  20. II-Q restriction endonucleases--new class of type II enzymes.

    Degtyarev, S K; Rechkunova, N I; Kolyhalov, A A; Dedkov, V S; Zhilkin, P A

    1990-10-11

    Unique restriction endonucleases Bpu 10l and Bsil have been isolated from Bacillus pumilas and Bacillus sphaericus, respectively. The recognition sequences and cleavage points of these enzymes have been determinated as 5'-CC1TNAGC-3'/3'-GGANT1CG-5' for Bpu 10l and 5'-C1TCGTG-3'/3'-GAGCA1C-5' for Bsil. Restriction endonucleases Bpu 10l and Bsil represent a new class of enzymes which recognize non-palindromic nucleotide sequences and hydrolize DNA within the recognition sequence. Bpu 10l and Bsil recognition sequences may be regarded as quasipalindromic and the enzymes may be designated as type II-Q restriction endonucleases.

  1. shRNA screening identifies JMJD1C as being required for leukemia maintenance

    Sroczynska, Patrycja; Cruickshank, V Adam; Bukowski, John-Paul

    2014-01-01

    Epigenetic regulatory mechanisms are implicated in the pathogenesis of acute myeloid and lymphoid leukemia (AML and ALL). Recent progress suggests that proteins involved in epigenetic control are amenable to drug intervention, but little is known about the cancer-specific dependency on epigenetic...

  2. Diffusion properties of Cu(0 0 1)- c(2 × 2)-Pd surface alloys

    Eremeev, S. V.; Rusina, G. G.; Chulkov, E. V.

    2007-09-01

    Structural and diffusion properties of a Cu(0 0 1)- c(2 × 2)-Pd surface and sub-surface ordered alloys are studied by using interaction potentials obtained from the embedded-atom method. The calculated diffusion energies are in agreement with observed kinetics of the surface alloy formation and confirm stability of the underlayer alloy. Activation energy of planar diffusion of palladium at the initial stage of the alloy formation as well as the activation energy of the overlayer-underlayer diffusion of the Pd atoms are in good agreement with those obtained by the scanning tunneling microscopy and low energy electron diffraction measurements, respectively.

  3. System Design and In-orbit Verification of the HJ-1-C SAR Satellite

    Zhang Run-ning

    2014-06-01

    Full Text Available HJ-1-C is a SAR satellite owned by the Chinese Environment and Natural Disaster Monitoring constellation, and works together with the optical satellites HJ-1-A/B for monitoring environment and natural disasters. In this paper, the system design and characteristics of the first Chinese civil SAR satellite are described. In addition, the interface relation between SAR payload and platform is studied. Meanwhile, the data transmission capability, attitude, power, and temperature control that support SAR imaging are reviewed. Finally, the corresponding in-orbit verification results are presented.

  4. Coherent Performance Analysis of the HJ-1-C Synthetic Aperture Radar

    Li Hai-ying; Zhang Shan-shan; Li Shi-qiang; Zhang Hua-chun

    2014-01-01

    Synthetic Aperture Radar (SAR) is a coherent imaging radar. Hence, coherence is critical in SAR imaging. In a coherent system, several sources can degrade performance. Based on the HJ-1-C SAR system implementation and sensor characteristics, this study evaluates the effect of frequency stability and pulse-to-pulse timing jitter on the SAR coherent performance. A stable crystal oscillator with short-term stability of 10×1.0−10 / 5 ms is used to generate the reference frequency by using a direc...

  5. Heat Stable Enzymes from Thermophiles

    1998-02-01

    ultrafiltration and microfiltration that might be suitable. These utilize hollow fiber membranes manufactured in such a manner that they are free of...words) Alkaline phosphatase is widely used in the military and civilian sectors . Commercially available enzyme from calf intestine is the weak link in...widely used enzymes with numerous uses in both the military and civilian sectors . The commercially available enzyme from calf intestine breaks down

  6. Rev-erb beta regulates the Srebp-1c promoter and mRNA expression in skeletal muscle cells

    Ramakrishnan, Sathiya N.; Lau, Patrick; Crowther, Lisa M. [The University of Queensland, Institute for Molecular Bioscience, St. Lucia, Qld 4072 (Australia); Cleasby, Mark E. [Diabetes and Obesity Research Program, Garvan Institute of Medical Research, St. Vincent' s Hospital, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010 (Australia); Millard, Susan; Leong, Gary M. [The University of Queensland, Institute for Molecular Bioscience, St. Lucia, Qld 4072 (Australia); Cooney, Gregory J. [Diabetes and Obesity Research Program, Garvan Institute of Medical Research, St. Vincent' s Hospital, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010 (Australia); Muscat, George E.O., E-mail: g.muscat@imb.uq.edu.au [The University of Queensland, Institute for Molecular Bioscience, St. Lucia, Qld 4072 (Australia)

    2009-10-30

    The nuclear hormone receptor, Rev-erb beta operates as a transcriptional silencer. We previously demonstrated that exogenous expression of Rev-erb{beta}{Delta}E in skeletal muscle cells increased Srebp-1c mRNA expression. We validated these in vitro observations by injection of an expression vector driving Rev-erb{beta}{Delta}E expression into mouse tibialis muscle that resulted in increased Srebp-1c mRNA expression. Paradoxically, Rev-erb{beta} siRNA expression in skeletal muscle cells repressed Srebp-1c expression, and indicated that Rev-erb{beta} expression was necessary for Srebp-1c expression. ChIP analysis demonstrated that Rev-erb{beta} was recruited to the Srebp-1c promoter. Moreover, Rev-erb{beta} trans-activated the Srebp-1c promoter, in contrast, Rev-erb{beta} efficiently repressed the Rev-erb{alpha} promoter, a previously characterized target gene. Finally, treatment with the Rev-erb agonist (hemin) (i) increased the trans-activation of the Srebp-1c promoter by Rev-erb{beta}; and (ii) increased Rev-erb{beta} and Srebp-1c mRNA expression. These data suggest that Rev-erb{beta} has the potential to activate gene expression, and is a positive regulator of Srebp-1c, a regulator of lipogenesis.

  7. Enzyme therapeutics for systemic detoxification.

    Liu, Yang; Li, Jie; Lu, Yunfeng

    2015-08-01

    Life relies on numerous biochemical processes working synergistically and correctly. Certain substances disrupt these processes, inducing living organism into an abnormal state termed intoxication. Managing intoxication usually requires interventions, which is referred as detoxification. Decades of development on detoxification reveals the potential of enzymes as ideal therapeutics and antidotes, because their high substrate specificity and catalytic efficiency are essential for clearing intoxicating substances without adverse effects. However, intrinsic shortcomings of enzymes including low stability and high immunogenicity are major hurdles, which could be overcome by delivering enzymes with specially designed nanocarriers. Extensive investigations on protein delivery indicate three types of enzyme-nanocarrier architectures that show more promise than others for systemic detoxification, including liposome-wrapped enzymes, polymer-enzyme conjugates, and polymer-encapsulated enzymes. This review highlights recent advances in these nano-architectures and discusses their applications in systemic detoxifications. Therapeutic potential of various enzymes as well as associated challenges in achieving effective delivery of therapeutic enzymes will also be discussed.

  8. Multi-enzyme Process Modeling

    Andrade Santacoloma, Paloma de Gracia

    The subject of this thesis is to develop a methodological framework that can systematically guide mathematical model building for better understanding of multi-enzyme processes. In this way, opportunities for process improvements can be identified by analyzing simulations of either existing...... are affected (in a positive or negative way) by the presence of the other enzymes and compounds in the media. In this thesis the concept of multi-enzyme in-pot term is adopted for processes that are carried out by the combination of enzymes in a single reactor and implemented at pilot or industrial scale...

  9. Knockdown of CDKN1C (p57(kip2 and PHLDA2 results in developmental changes in bovine pre-implantation embryos.

    Ashley M Driver

    Full Text Available Imprinted genes have been implicated in early embryonic, placental, and neonatal development and alterations in expression levels of these genes can lead to growth abnormalities and embryonic lethality. However, little is known about the functions of bovine imprinted genes during the pre-implantation period. Therefore, the objective of this study was to assess the influence of altered expression of imprinted genes on developmental progress of embryos using small interfering RNA (siRNA. Expression levels of 18 imprinted genes (MAGEL2, UBE3A, IGF2R, NAP1L5, TSSC4, PEG3, NDN, CDKN1C, PHLDA2, MKRN3, USP29, NNAT, PEG10, RTL1, IGF2, H19, MIM1, and XIST were compared between embryos reaching the blastocyst stage and growth-arrested embryos (degenerates using quantitative real-time PCR (qRT-PCR. Ten genes were found to be differentially expressed between blastocysts and degenerates. The CDKN1C gene showed the highest upregulation in blastocysts whereas PHLDA2 was highly expressed in degenerates. To assess whether the observed differential gene expression was causative or resultant of embryo degeneration, these genes were selected for functional analysis using siRNA. Injection of siRNA specific to PHLDA2 into one-cell zygotes resulted in a substantial increase in blastocyst development, whereas injection of CDKN1C-specific siRNA resulted in a 45% reduction (P = 0.0006 in blastocyst development. RNA-Seq analysis of CDKN1C-siRNA-injected vs. non-injected embryos revealed 51 differentially expressed genes with functions in apoptosis, lipid metabolism, differentiation, and cell cycle regulation. Gene ontology analysis revealed nine pathways related to cell signaling, metabolism, and nucleic acid processing. Overall, our results show that proper expression levels of the imprinted genes CDKN1C and PHLDA2 are critical for embryo development, which suggests that these genes can be used as markers for normal blastocyst formation.

  10. The hepatic Raldh1 expression is elevated in Zucker fatty rats and its over-expression introduced the retinal-induced Srebp-1c expression in INS-1 cells.

    Yang Li

    Full Text Available The roles of vitamin A (VA in the development of metabolic diseases remain unanswered. We have reported that retinoids synergized with insulin to induce the expression of sterol-regulatory element-binding protein 1c gene (Srebp-1c expression in primary rat hepatocytes. Additionally, the hepatic Srebp-1c expression is elevated in Zucker fatty (ZF rats, and reduced in those fed a VA deficient diet. VA is metabolized to retinoic acid (RA for regulating gene expression. We hypothesized that the expression of RA production enzymes contributes to the regulation of the hepatic Srebp-1c expression. Therefore, we analyzed their expression levels in Zucker lean (ZL and ZF rats. The mRNA levels of retinaldehyde dehydrogenase family 1 gene (Raldh1 were found to be higher in the isolated and cultured primary hepatocytes from ZF rats than that from ZL rats. The RALDH1 protein level was elevated in the liver of ZF rats. Retinol and retinal dose- and time-dependently induced the expression of RA responsive Cyp26a1 gene in hepatocytes and hepatoma cells. INS-1 cells were identified as an ideal tool to study the effects of RA production on the regulation of gene expression because only RA, but not retinal, induced Srebp-1c mRNA expression in them. Recombinant adenovirus containing rat Raldh1 cDNA was made and used to infect INS-1 cells. The over-expression of RALDH1 introduced the retinal-mediated induction of Srebp-1c expression in INS-1 cells. We conclude that the expression levels of the enzymes for RA production may contribute to the regulation of RA responsive genes, and determine the responses of the cells to retinoid treatments. The elevated hepatic expression of Raldh1 in ZF rats may cause the excessive RA production from retinol, and in turn, result in higher Srebp-1c expression. This excessive RA production may be one of the factors contributing to the elevated lipogenesis in the liver of ZF rats.

  11. Digestive Enzyme Replacement Therapy: Pancreatic Enzymes and Lactase.

    Felicilda-Reynaldo, Rhea Faye D; Kenneally, Maria

    2016-01-01

    Maldigestion occurs when digestive enzymes are lacking to help break complex food components into absorbable nutrients within the gastrointestinal tract. Education is needed to help patients manage the intricacies of digestive enzyme replacement therapies and ensure their effectiveness in reducing symptoms of maldigestion.

  12. [The rise of enzyme engineering in China].

    Li, Gaoxiang

    2015-06-01

    Enzyme engineering is an important part of the modern biotechnology. Industrial biocatalysis is considered the third wave of biotechnology following pharmaceutical and agricultural waves. In 25 years, China has made a mighty advances in enzyme engineering research. This review focuses on enzyme genomics, enzyme proteomics, biosynthesis, microbial conversion and biosensors in the Chinese enzyme engineering symposiums and advances in enzyme preparation industry in China.

  13. In vivo – in vitro toxicogenomic comparison of TCDD-elicited gene expression in Hepa1c1c7 mouse hepatoma cells and C57BL/6 hepatic tissue

    Boverhof Darrell R

    2006-04-01

    Full Text Available Abstract Background In vitro systems have inherent limitations in their ability to model whole organism gene responses, which must be identified and appropriately considered when developing predictive biomarkers of in vivo toxicity. Systematic comparison of in vitro and in vivo temporal gene expression profiles were conducted to assess the ability of Hepa1c1c7 mouse hepatoma cells to model hepatic responses in C57BL/6 mice following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD. Results Gene expression analysis and functional gene annotation indicate that Hepa1c1c7 cells appropriately modeled the induction of xenobiotic metabolism genes in vivo. However, responses associated with cell cycle progression and proliferation were unique to Hepa1c1c7 cells, consistent with the cell cycle arrest effects of TCDD on rapidly dividing cells. In contrast, lipid metabolism and immune responses, representative of whole organism effects in vivo, were not replicated in Hepa1c1c7 cells. Conclusion These results identified inherent differences in TCDD-mediated gene expression responses between these models and highlighted the limitations of in vitro systems in modeling whole organism responses, and additionally identified potential predictive biomarkers of toxicity.

  14. Human cytosolic sulfotransferase SULT1C4 mediates the sulfation of doxorubicin and epirubicin.

    Luo, Lijun; Zhou, Chunyang; Hui, Ying; Kurogi, Katsuhisa; Sakakibara, Yoichi; Suiko, Masahito; Liu, Ming-Cheh

    2016-04-01

    Doxorubicin, an anthracycline, has been reported to be excreted in sulfate conjugated form. The current study aimed to identify the human cytosolic sulfotransferase(s) (SULT(s)) that is(are) capable of sulfating doxorubicin and its analog epirubicin, and to verify whether sulfation of doxorubicin and epirubicin may occur under metabolic conditions. A systematic analysis of thirteen known human SULTs, previously cloned, expressed, and purified, revealed SULT1C4 as the only human SULT capable of sulfating doxorubicin and epirubicin. Cultured HepG2 human hepatoma cells and Caco-2 human colon carcinoma cells were labeled with [(35)S]sulfate in the presence of different concentrations of doxorubicin or epirubicin. Analysis of spent labeling media showed the generation and release of [(35)S]sulfated doxorubicin and epirubicin by HepG2 cells and Caco-2 cells. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed the expression of SULT1C4 in both HepG2 cells and Caco-2 cells. These results provided a molecular basis underlying the previous finding that sulfate-conjugated doxorubicin was excreted in the urine of patients treated with doxorubicin.

  15. Expression of HNP1cDNA in CHO-dhfr- cells

    LIU Juan; SUN Yong-tao; DU De-wei; WANG Lin-xu; ZHAI Song; WANG Shao-yang; WANG Ding-cheng

    2004-01-01

    To prepare secretary recombinant human neutrophil peptide1 (HNP1)and test its antimicrobialactivity. Methods: The eukaryotic expression vector pcDNA3. 1/V5-His-TOPO-HNP1 was cotransfected with plasmidpDCH1P11 carrying dhfr gene into dhfr- negative CHO (CHO-dhfr-) cells and recombinant protein was verified by ELISA;G418 selective medium was used to screen the stably expressing cell clones followed by serial passages in 5 × 10-8 mol/L and5 × 10-7 mol/L methotrexate (MTX) for gene amplification. Finally 4 cell clones with high expression level were obtainedand confirmed by ELISA, RT-PCR and IFA. The bacteriastatic activity of concentrated supernatants was tested in vitro asthat was almost 200-fold increase than that in G418 selective medium. 303 bp segments were amplified from 4 tably tranfec-tant cloneswhich matched the length of HNP1 cDNA by RT-PCR. Strong fluorescence was visible in cell plasma in the sta-blly transfectant cells by IFA. K-B disc agar diffusion test showed obvious bacteriastatic diffusion on MH plate of E. Coli.Conclusion: HNP1cDNA can be strongly expressed in CHO-dhfr- cells, which supernatants exhibited high inhibitive effectagainst bacteria.

  16. Computational enzyme design: transitioning from catalytic proteins to enzymes.

    Mak, Wai Shun; Siegel, Justin B

    2014-08-01

    The widespread interest in enzymes stem from their ability to catalyze chemical reactions under mild and ecologically friendly conditions with unparalleled catalytic proficiencies. While thousands of naturally occurring enzymes have been identified and characterized, there are still numerous important applications for which there are no biological catalysts capable of performing the desired chemical transformation. In order to engineer enzymes for which there is no natural starting point, efforts using a combination of quantum chemistry and force-field based protein molecular modeling have led to the design of novel proteins capable of catalyzing chemical reactions not catalyzed by naturally occurring enzymes. Here we discuss the current status and potential avenues to pursue as the field of computational enzyme design moves forward.

  17. Stability of Enzymes in Granular Enzyme Products for Laundry Detergents

    Biran, Suzan; Bach, Poul; Simonsen, Ole

    Enzymes have long been of interest to the detergent industry due to their ability to improve the cleaning efficiency of synthetic detergents, contribute to shortening washing times, and reduce energy and water consumption, provision of environmentally friendlier wash water effluents and fabric care...... particles. However, enzymes may loose a significant part of their activity over a time period of several weeks. Possible causes of inactivation of enzymes in a granule may be related to the release of hydrogen peroxide from the bleaching chemicals in a moisture-containing atmosphere, humidity, autolysis...... and humidity by bubbling nitrogen gas through their corresponding solutions. An enzyme column, acting as a plug-flow reactor, was exposed to known concentrations of H2O2 (g) and humidity in a thermally stabilized chamber. Samples were analyzed for adsorptive behavior and residual enzyme activity. Since...

  18. Update on diabetes diagnosis: a historical review of the dilemma of the diagnostic utility of glycohemoglobin A1c and a proposal for a combined glucose-A1c diagnostic method.

    Aldasouqi, Saleh A; Gossain, Ved V

    2012-01-01

    The role of glycohemoglobin A1c (A1c) for the diagnosis of diabetes has been debated for over three decades. Recently, the American Diabetes Association (ADA) has recommended adding A1c as an additional criterion for diabetes diagnosis. In view of the continued debate about the diagnostic utility of A1c, and in view of the unabated burden of undiagnosed diabetes, the search for alternative diagnostic methods is discussed. A historical literature review is provided, in view of the new ADA diagnostic guidelines, and a proposal is provided for combining A1c and a glucose measurement as a diagnostic alternative/adjunct to the use of a single criterion. This proposal is based on the non-overlapping of the advantages and disadvantages of these individual tests. The cost-effectiveness of this method remains to be tested.

  19. Renal fructose-metabolizing enzymes: significance in hereditary fructose intolerance.

    Kranhold, J F; Loh, D; Morris, R C

    1969-07-25

    In patients with hereditary fructose intolerance, which is characterized by deficient aldolase activity toward fructose-1-phosphate, fructose induces a renal tubular dysfunction that implicates only the proximal convoluted tubule. Because normal metabolism of fructose by way of fructose-1-phosphate requires fructokinase, aldolase "B," and triokinase, the exclusively cortical location of these enzymes indicates that the medulla is not involved in the metabolic abnormality presumably causal of the renal dysfunction.

  20. Enzymic hydrolysis of chlorella cells

    Khraptsova, G.I.; Tsaplina, I.A.; Burdenko, L.G.; Khoreva, S.L.; Loginova, L.G.

    1981-01-01

    Treatment of C. ellipsoidea, C. pyrenoidosa, and C. vulgaris with cellulolytic enzymes (from Aspergillus terreus) and pectofoetidin p10x (from A. foetidus) resulted in the degradation and lysis of the algae cells. The cells were more sensitive to cellulase than to pectinase. The combination of both enzymes produced a synergistic effect on cell lysis.

  1. Phage lytic enzymes: a history

    David; Trudil

    2015-01-01

    There are many recent studies regarding the efficacy of bacteriophage-related lytic enzymes: the enzymes of ‘bacteria-eaters’ or viruses that infect bacteria. By degrading the cell wall of the targeted bacteria, these lytic enzymes have been shown to efficiently lyse Gram-positive bacteria without affecting normal flora and non-related bacteria. Recent studies have suggested approaches for lysing Gram-negative bacteria as well(Briersa Y, et al., 2014). These enzymes include: phage-lysozyme, endolysin, lysozyme, lysin, phage lysin, phage lytic enzymes, phageassociated enzymes, enzybiotics, muralysin, muramidase, virolysin and designations such as Ply, PAE and others. Bacteriophages are viruses that kill bacteria, do not contribute to antimicrobial resistance, are easy to develop, inexpensive to manufacture and safe for humans, animals and the environment. The current focus on lytic enzymes has been on their use as anti-infectives in humans and more recently in agricultural research models. The initial translational application of lytic enzymes, however, was not associated with treating or preventing a specifi c disease but rather as an extraction method to be incorporated in a rapid bacterial detection assay(Bernstein D, 1997).The current review traces the translational history of phage lytic enzymes–from their initial discovery in 1986 for the rapid detection of group A streptococcus in clinical specimens to evolving applications in the detection and prevention of disease in humans and in agriculture.

  2. Eplerenone ameliorates the phenotypes of metabolic syndrome with NASH in liver-specific SREBP-1c Tg mice fed high-fat and high-fructose diet.

    Wada, Tsutomu; Miyashita, Yusuke; Sasaki, Motohiro; Aruga, Yusuke; Nakamura, Yuto; Ishii, Yoko; Sasahara, Masakiyo; Kanasaki, Keizo; Kitada, Munehiro; Koya, Daisuke; Shimano, Hitoshi; Tsuneki, Hiroshi; Sasaoka, Toshiyasu

    2013-12-01

    Because the renin-angiotensin-aldosterone system has been implicated in the development of insulin resistance and promotion of fibrosis in some tissues, such as the vasculature, we examined the effect of eplerenone, a selective mineralocorticoid receptor (MR) antagonist, on nonalcoholic steatohepatitis (NASH) and metabolic phenotypes in a mouse model reflecting metabolic syndrome in humans. We adopted liver-specific transgenic (Tg) mice overexpressing the active form of sterol response element binding protein-1c (SREBP-1c) fed a high-fat and fructose diet (HFFD) as the animal model in the present study. When wild-type (WT) C57BL/6 and liver-specific SREBP-1c Tg mice grew while being fed HFFD for 12 wk, body weight and epididymal fat weight increased in both groups with an elevation in blood pressure and dyslipidemia. Glucose intolerance and insulin resistance were also observed. Adipose tissue hypertrophy and macrophage infiltration with crown-like structure formation were also noted in mice fed HFFD. Interestingly, the changes noted in both genotypes fed HFFD were significantly ameliorated with eplerenone. HFFD-fed Tg mice exhibited the histological features of NASH in the liver, including macrovesicular steatosis and fibrosis, whereas HFFD-fed WT mice had hepatic steatosis without apparent fibrotic changes. Eplerenone effectively ameliorated these histological abnormalities. Moreover, the direct suppressive effects of eplerenone on lipopolysaccharide-induced TNFα production in the presence and absence of aldosterone were observed in primary-cultured Kupffer cells and bone marrow-derived macrophages. These results indicated that eplerenone prevented the development of NASH and metabolic abnormalities in mice by inhibiting inflammatory responses in both Kupffer cells and macrophages.

  3. Sterol Regulatory Element-Binding Protein-1c Regulates Inflammasome Activation in Gingival Fibroblasts Infected with High-Glucose-Treated Porphyromonas gingivalis

    Kuo, Hsing-Chun; Chang, Li-Ching; Chen, Te-Chuan; Lee, Ko-Chao; Lee, Kam-Fai; Chen, Cheng-Nan; Yu, Hong-Ren

    2016-01-01

    Background: Porphyromonas gingivalis is a major bacterial species implicated in the progression of periodontal disease, which is recognized as a common complication of diabetes. The interleukin (IL)-1β, processed by the NLR family pyrin domain containing 3 (NLRP3) inflammasome, has been identified as a target for pathogenic infection of the inflammatory response. However, the effect of P. gingivalis in a high-glucose situation in the modulation of inflammasome activation in human gingival fibroblasts (HGFs) is not well-understood. Methods: P. gingivalis strain CCUG25226 was used to study the mechanisms underlying the regulation of HGF NLRP3 expression by the infection of high-glucose-treated P. gingivalis (HGPg). Results: HGF infection with HGPg increases the expression of IL-1β and NLRP3. We further demonstrated that the upregulation of sterol regulatory element-binding protein (SREBP)-1c by activation of the Akt and p70S6K pathways is critical for HGPg-induced NLRP3 expression. We showed that the inhibition of Janus kinase 2 (JAK2) blocks the Akt- and p70S6K-mediated SREBP-1c, NLRP3, and IL-1β expression. The effect of HGPg on HGF signaling and NLRP3 expression is mediated by β1 integrin. In addition, gingival tissues from diabetic patients with periodontal disease exhibited higher NLRP3 and SREBP-1c expression. Conclusions: Our findings identify the molecular pathways underlying HGPg-dependent NLRP3 inflammasome expression in HGFs, providing insight into the effect of P. gingivalis invasion in HGFs. PMID:28083517

  4. Subcellular location and molecular mobility of human cytosolic sulfotransferase 1C1 in living human embryonic kidney 293 cells.

    Sheng, Jonathan J; Acquaah-Mensah, George K

    2011-08-01

    Cytosolic sulfotransferases were first isolated from the hepatic cytosol, and they have been localized in the cytoplasm of formaldehyde-fixed human cell samples. The current work was carried out to determine the subcellular localization and molecular mobility of cytosolic sulfotransferases in living human embryonic kidney (HEK) 293 cells. In this work, the subcellular location of human cytosolic sulfotransferase 1C1 (SULT1C1) was studied in cultured HEK293 cells using confocal laser-scanning microscopy. A green fluorescent protein (GFP)-tagged SULT1C1 protein was localized in the cytoplasm of living HEK293 cells. This is consistent with results from previous studies on several other cytosolic sulfotransferase isoforms. Fluorescence recovery after photobleaching microscopy was performed to assess the molecular mobility of the expressed GFP-SULT1C1 molecules. The results suggested that the expressed recombinant GFP-SULT1C1 molecules in living HEK293 cells may include both mobile and immobile populations. To obtain additional insights into the subcellular location of SULT1C1, two machine learning algorithms, Sequential Minimal Optimization and Multilayer Perceptron, were used to compute the probability distribution for the localization of SULT1C1 in nine selected cellular compartments. The resulting probability distribution suggested that the most likely subcellular location of SULT1C1 is the cytosol.

  5. Expression of the melatonin receptor Mel(1c) in neural tissues of the reef fish Siganus guttatus.

    Park, Yong-Ju; Park, Ji-Gweon; Jeong, Hyung-Bok; Takeuchi, Yuki; Kim, Se-Jae; Lee, Young-Don; Takemura, Akihiro

    2007-05-01

    The golden rabbitfish, Siganus guttatus, is a reef fish exhibiting a restricted lunar-related rhythm in behavior and reproduction. Here, to understand the circadian rhythm of this lunar-synchronized spawner, a melatonin receptor subtype-Mel(1c)-was cloned. The full-length Mel(1c) melatonin receptor cDNA comprised 1747 bp with a single open reading frame (1062 bp) that encodes a 353-amino acid protein, which included 7 presumed transmembrane domains. Real-time PCR revealed high Mel(1c) mRNA expression in the retina and brain but not in the peripheral tissues. When the fish were reared under light/dark (LD 12:12) conditions, Mel(1c) mRNA in the retina and brain was expressed with daily variations and increased during nighttime. Similar variations were noted under constant conditions, suggesting that Mel(1c) mRNA expression is regulated by the circadian clock system. Daily variations of Mel(1c) mRNA expression with a peak at zeitgeber time (ZT) 12 were observed in the cultured pineal gland under LD 12:12. Exposure of the cultured pineal gland to light at ZT17 resulted in a decrease in Mel(1c) mRNA expression. When light was obstructed at ZT5, the opposite effect was obtained. These results suggest that light exerts certain effects on Mel(1c) mRNA expression directly or indirectly through melatonin actions.

  6. Studies directed toward the total synthesis of discodermolide: asymmetric synthesis of the C1-C14 fragment.

    Arefolov, Alexander; Panek, James S

    2002-07-11

    [structure: see text] A convergent and stereoselective assembly of the C1-C14 subunit of marine natural product (+)-discodermolide has been completed. The approach employs chiral allylsilane bond construction methodology to establish four of the eight stereogenic centers. Key fragment coupling is achieved via an efficient stereoselective acetate aldol reaction between C1-C6 and C7-C14 subunits.

  7. 7 CFR 1c.120 - Evaluation and disposition of applications and proposals for research to be conducted or...

    2010-01-01

    ... proposals for research to be conducted or supported by a Federal Department or Agency. 1c.120 Section 1c.120... disposition of applications and proposals for research to be conducted or supported by a Federal Department or Agency. (a) The department or agency head will evaluate all applications and proposals involving...

  8. Role of HbA1c in post-partum screening of women with gestational diabetes mellitus

    Rickard Claesson

    2015-03-01

    Conclusion: Proposed thresholds of HbA1c had low diagnostic sensitivity. Combined with a fasting glucose test, the performance was no better than with using a fasting glucose test alone. Combining a fasting glucose test with a lower HbA1c cut-point may be an alternative approach for selection of women for an OGTT.

  9. Survey and analysis of correlation of HbA1c with other parameters in 4386 employees

    胡守岳

    2012-01-01

    Objective To understand the HbA1c level and analyze its relationship with human physiological indexes. Methods The HbA1c level was measured in enterprise employees aged 45 years or more,using Japanese Tosoh HLC-723 G7 automatic glycohemoglobin analyzer,and the FPG,TC,TG,hsC-RP

  10. PERFORMANCE OF A1C VERSUS OGTT FOR THE DIAGNOSIS OF PREDIABETES IN A COMMUNITY-BASED SCREENING

    Camacho, Jenny E.; Shah, Vallabh O.; Schrader, Ronald; Wong, Craig S.; Burge, Mark R.

    2017-01-01

    Objective Reliable identification of individuals at risk for developing diabetes is critical to instituting preventative strategies. Studies suggest that the accuracy of using A1c as a sole diagnostic criterion for diabetes may be variable across different ethnic groups. We postulate that there will be lack of concordance between A1c and the Oral Glucose Tolerance Test (OGTT) for diagnosing prediabetes across Hispanic and Non-Hispanic White (NHW) populations. Research Design and Methods 218 asymptomatic adults at risk for Type 2 Diabetes (T2D) were assessed with A1c and OGTT for the diagnosis of prediabetes. Glucose homeostasis status was assigned as no diabetes (A1c 6.4%). Inclusion criteria were age > 18 years and at least one of the following: a family history of diabetes, a history of gestational diabetes, Hispanic ethnicity, non-Caucasian race, or obesity. Subjects received a fasting 75-gram OGTT and A1c on the same day. Bowker’s Test of Symmetry was employed to determine agreement between the tests. Results Data from 99 Hispanic patients and 79 NHW patients were analyzed. There was no concordance between A1c and OGTT for Hispanic (p=0.002) or NHW individuals (p=0.003) with prediabetes. Conclusions A1c is discordant with OGTT among Hispanic and NHW subjects for the diagnosis of prediabetes. Sole use of A1c to designate glycemic status will result in a greater prevalence of prediabetes among Hispanic and NHW New Mexicans. PMID:27482613

  11. 7 CFR 1c.103 - Assuring compliance with this policy-research conducted or supported by any Federal Department or...

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Assuring compliance with this policy-research... Secretary of Agriculture PROTECTION OF HUMAN SUBJECTS § 1c.103 Assuring compliance with this policy—research... research covered by the assurance and by § 1c.103 of this Policy has been reviewed and approved by the...

  12. Common Variants at 10 Genomic Loci Influence Hemoglobin A(1C) Levels via Glycemic and Nonglycemic Pathways

    Soranzo, Nicole; Sanna, Serena; Wheeler, Eleanor; Gieger, Christian; Radke, Doerte; Dupuis, Josee; Bouatia-Naji, Nabila; Langenberg, Claudia; Prokopenko, Inga; Stolerman, Elliot; Sandhu, Manjinder S.; Heeney, Matthew M.; Devaney, Joseph M.; Reilly, Muredach P.; Ricketts, Sally L.; Stewart, Alexandre F. R.; Voight, Benjamin F.; Willenborg, Christina; Wright, Benjamin; Altshuler, David; Arking, Dan; Balkau, Beverley; Barnes, Daniel; Boerwinkle, Eric; Boehm, Bernhard; Bonnefond, Amelie; Bonnycastle, Lori L.; Boomsma, Dorret I.; Boinstein, Stefan R.; Boettcher, Yvonne; Bumpstead, Suzannah; Burnett-Miller, Mary Susan; Campbell, Harry; Cao, Antonio; Chambers, John; Clark, Robert; Collins, Francis S.; Coresh, Josef; de Geus, Eco J. C.; Dei, Mariano; Deloukas, Panos; Doering, Angela; Egan, Josephine M.; Elosua, Roberto; Ferrucci, Luigi; Forouhi, Nita; Fox, Caroline S.; Franklin, Christopher; Franzosi, Maria Grazia; Gallina, Sophie; Goe, Anuj; Graessler, Juergen; Grallert, Harald; Greinacher, Andreas; Hadley, David; Hall, Alistair; Hamsten, Anders; Hayward, Caroline; Heath, Simon; Herder, Christian; Homuth, Georg; Hottenga, Jouke-Jan; Hunter-Merrill, Rachel; Illig, Thomas; Jackson, Anne U.; Jula, Antti; Kleber, Marcus; Knouff, Christopher W.; Kong, Augustine; Kooner, Jaspal; Koettgen, Anna; Kovacs, Peter; Krohn, Knut; Kuehne, Brigitte; Kuusisto, Johanna; Laakso, Markku; Lathrop, Mark; Lecoeur, Cecile; Li, Man; Li, Mingyao; Loos, Ruth J. F.; Luan, Jian'an; Lyssenko, Valeriya; Maegi, Reedik; Magnusson, Patrik K. E.; Maelarstig, Anders; Mangino, Massimo; Martinez-Larrad, Maria Teresa; Maerz, Winfried; McArdle, Wendy L.; McPherson, Ruth; Meisinger, Christa; Meitinger, Thomas; Melander, Olle; Mohlke, Karen L.; Mooser, Vincent E.; Morken, Mario A.; Narisu, Narisu; Nathan, David M.; Nauck, Matthias; O'Donne, Chris; Oexle, Konrad; Olla, Nazario; Pankow, James S.; Payne, Felicity; Peden, John F.; Pedersen, Nancy L.; Peltonen, Leena; Perola, Markus; Polasek, Ozren; Porcu, Eleonora; Rader, Daniel J.; Rathmann, Wolfgang; Ripatti, Samuli; Rocheleau, Ghislain; Roden, Michael; Rudan, Igor; Salomaa, Veikko; Saxena, Richa; Schlessinger, David; Schunkert, Heribert; Schwarz, Peter; Seedorf, Udo; Selvin, Elizabeth; Serrano-Rios, Manuel; Shrader, Peter; Silveira, Angela; Siscovick, David; Song, Kjioung; Spector, Timothy D.; Stefansson, Kari; Steinthorsdottir, Valgerdur; Strachan, David P.; Strawbridge, Rona; Stumvoll, Michael; Surakka, Ida; Swift, Amy J.; Tanaka, Toshiko; Teumer, Alexander; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Toenjes, Anke; Usalai, Gianluca; Vitart, Veronique; Voelzke, Henry; Wallaschofski, Henri; Waterworth, Dawn M.; Watkins, Hugh; Wichmann, H-Erich; Wild, Sarah H.; Willemsen, Gonneke; Williams, Gordon H.; Wilson, James F.; Winkelmann, Juliane; Wright, Alan F.; Zabena, Carina; Zhao, Jing Hua; Epstein, Stephen E.; Erdmann, Jeanette; Hakonarson, Hakon H.; Kathiresan, Sekar; Khaw, Kay-Tee; Roberts, Robert; Samani, Nilesh J.; Fleming, Mark D.; Sladek, Robert; Abecasis, Goncalo; Boehnke, Michael; Froguel, Philippe; Groop, Leif; McCarthy, Mark I.; Kao, W. H. Linda; Florez, Jose C.; Uda, Manuela; Wareham, Nicholas J.; Barroso, Ines; Meigs, James B.; van der Hout, Annemarie

    2010-01-01

    OBJECTIVE-Glycated hemoglobin (HbA(1c)), used to monitor and diagnose diabetes, is influenced by average glycemia over a 2- to 3-month period. Genetic factors affecting expression, turnover, and abnormal glycation of hemoglobin could also be associated with increased levels of HbA(1c). We aimed to i

  13. Meta-analysis of data from the Psychiatric Genomics Consortium and additional samples supports association of CACNA1C with risk for schizophrenia.

    Takahashi, Sakae; Glatt, Stephen J; Uchiyama, Makoto; Faraone, Stephen V; Tsuang, Ming T

    2015-10-01

    Recently, numerous genome-wide association studies (GWASs) have identified numerous risk loci for schizophrenia, but follow-up studies are still essential to confirm those results. Therefore, we followed up on top GWAS hits by genotyping implicated loci in additional schizophrenia family samples from our own collection. Five-hundred thirty-six Asian families (comprising 1633 members including 698 schizophrenics) were genotyped in this study. We analyzed 12 single nucleotide polymorphisms (SNPs) in strongly implicated candidate genes revealed by GWASs and their follow-up studies. We then used meta-analysis to combine our results with those of the Schizophrenia Working Group of the Psychiatric Genomics Consortium (PGC). In our newly genotyped samples, there were no significant associations of any of the 12 candidate SNPs with schizophrenia; however, all genome-wide significant results from the schizophrenia PGC analysis were maintained after combination with our new data by meta-analysis. One SNP (rs4765905 in CACNA1C) showed a stronger effect and decreased p-value (5.14e-17) after meta-analysis relative to the original PGC results, with no significant between-study heterogeneity. The findings of this study support the significant results in the PGC, especially for CACNA1C. The sample size in our study was considerably smaller than that in the PGC-SCZ study; thus, the weights carried by our samples in the meta-analysis were small. Therefore, our data could not vastly reduce PGC association signals. However, we considered that the well replicated results from the PGC hold up in our new samples, and may suggest that the top hits from the PGC are generalizable, even to other ancestral groups.

  14. Microstructure and mechanical properties of 0. 1C steel with Nb

    Gau, J.S.

    1981-04-01

    This study was undertaken in order to strengthen the ferrite matrix by enhancing precipitation through the presence of strong carbide-forming elements Nb and Mo. This is, in light of the conceptual implication of the mixture rule, an attempt to affect the stress in the ferrite at the ultimate strength of martensite. A further objective is to study the effect of processing variables on the mechanical properties and resultant microstructure. (MOW)

  15. Statistical Mechanics of Allosteric Enzymes.

    Einav, Tal; Mazutis, Linas; Phillips, Rob

    2016-07-07

    The concept of allostery in which macromolecules switch between two different conformations is a central theme in biological processes ranging from gene regulation to cell signaling to enzymology. Allosteric enzymes pervade metabolic processes, yet a simple and unified treatment of the effects of allostery in enzymes has been lacking. In this work, we take a step toward this goal by modeling allosteric enzymes and their interaction with two key molecular players-allosteric regulators and competitive inhibitors. We then apply this model to characterize existing data on enzyme activity, comment on how enzyme parameters (such as substrate binding affinity) can be experimentally tuned, and make novel predictions on how to control phenomena such as substrate inhibition.

  16. Moonlighting enzymes in parasitic protozoa.

    Collingridge, Peter W; Brown, Robert W B; Ginger, Michael L

    2010-08-01

    Enzymes moonlight in a non-enzymatic capacity in a diverse variety of cellular processes. The discovery of these non-enzymatic functions is generally unexpected, and moonlighting enzymes are known in both prokaryotes and eukaryotes. Importantly, this unexpected multi-functionality indicates that caution might be needed on some occasions in interpreting phenotypes that result from the deletion or gene-silencing of some enzymes, including some of the best known enzymes from classic intermediary metabolism. Here, we provide an overview of enzyme moonlighting in parasitic protists. Unequivocal and putative examples of moonlighting are discussed, together with the possibility that the unusual biological characteristics of some parasites either limit opportunities for moonlighting to arise or perhaps contribute to the evolution of novel proteins with clear metabolic ancestry.

  17. Hemoglobin A1c Level Is Not Related to the Severity of Atherosclerosis in Patients with Acute Coronary Syndrome

    Xinhong Wang

    2015-01-01

    Full Text Available Background. The relationship between hemoglobin A1c (HbA1c levels and the extent of coronary artery stenosis in patients with acute coronary syndrome (ACS remains uncertain. The present study aimed to assess the correlation of HbA1c level with angiographic coronary atherosclerosis. Methods. 292 consecutive ACS patients were enrolled and stratified into three groups according to HbA1c levels (group 1: 40 by logistic regression analysis. Diabetes mellitus (DM and LVEF levels were two independent risk factors for high Gensini score. Conclusions. HbA1c level is not a significant and independent marker for the severity of angiography in ACS patients, even in high-risk patients.

  18. Hemoglobin A1c as a tool for the diagnosis of type 2 diabetes in 208 premenopausal women with polycystic ovary syndrome

    Magnussen, Line Velling; Mumm, Hanne; Andersen, Marianne;

    2011-01-01

    To study hemoglobin A1c (HbA1c) as a tool for diagnosing diabetes and to study HbA1c as a cardiovascular risk marker in patients with polycystic ovary syndrome (PCOS).......To study hemoglobin A1c (HbA1c) as a tool for diagnosing diabetes and to study HbA1c as a cardiovascular risk marker in patients with polycystic ovary syndrome (PCOS)....

  19. Significance of HbA1c and its measurement in the diagnosis of diabetes mellitus: US experience

    Juarez DT

    2014-10-01

    Full Text Available Deborah Taira Juarez, Kendra M Demaris, Roy Goo, Christina Louise Mnatzaganian, Helen Wong SmithDaniel K Inouye College of Pharmacy, University of Hawaii at Hilo, Honolulu, HI, USAAbstract: The 2014 American Diabetes Association guidelines denote four means of diagnosing diabetes. The first of these is a glycosylated hemoglobin (HbA1c >6.5%. This literature review summarizes studies (n=47 in the USA examining the significance, strengths, and limitations of using HbA1c as a diagnostic tool for diabetes, relative to other available means. Due to the relatively recent adoption of HbA1c as a diabetes mellitus diagnostic tool, a hybrid systematic, truncated review of the literature was implemented. Based on these studies, we conclude that HbA1c screening for diabetes has been found to be convenient and effective in diagnosing diabetes. HbA1c screening is particularly helpful in community-based and acute care settings where tests requiring fasting are not practical. Using HbA1c to diagnose diabetes also has some limitations. For instance, HbA1c testing may underestimate the prevalence of diabetes, particularly among whites. Because this bias differs by racial group, prevalence and resulting estimates of health disparities based on HbA1c screening differ from those based on other methods of diagnosis. In addition, existing evidence suggests that HbA1c screening may not be valid in certain subgroups, such as children, women with gestational diabetes, patients with human immunodeficiency virus, and those with prediabetes. Further guidelines are needed to clarify the appropriate use of HbA1c screening in these populations.Keywords: diabetes mellitus, diagnosis, glycosylated hemoglobin, USA

  20. Design Optimization of Expansion Driven Components for the HJ-1-C Satellite

    Huang Zhi-rong

    2014-06-01

    Full Text Available Expansion-driven HJ-1-C satellite components are prone to fatigue and fracture; thus, a reliability study on the optimal design is performed. According to the Failure Mode and Effects Analysis (FMEA of the components, the main failure modes are stress relaxation and impact breakage of the torsion and scroll springs. On the basis of the failure modes, a prototype spring is tested, and the relative reliabilities are calculated. Then, reliability measures are proposed, and the design optimization of the springs is carried out. The improvements introduced by the prototype spring are indicative of the effectiveness and reliability of the design optimization process, which can help design and analyze similar antenna reflectors in the future.

  1. ADH1B and ADH1C Genotype, Alcohol Consumption and Biomarkers of Liver Function

    Lawlor, Debbie A; Benn, Marianne; Zuccolo, Luisa;

    2014-01-01

    1C genes as instrumental variables (IV) to estimate the causal effect of long-term alcohol consumption on alanine aminotransferase (ALT), γ-glutamyl-transferase (γ-GT), alkaline phosphatase (ALP), bilirubin and prothrombin action. Analyses were undertaken on 58,313 Danes (mean age 56). RESULTS......BACKGROUND: The effect of alcohol consumption on liver function is difficult to determine because of reporting bias and potential residual confounding. Our aim was to determine this effect using genetic variants to proxy for the unbiased effect of alcohol. METHODS: We used variants in ADH1B and ADH......: In both confounder adjusted multivariable and genetic-IV analyses greater alcohol consumption, amongst those who drank any alcohol, was associated with higher ALT [mean difference per doubling of alcohol consumption: 3.4% (95% CI: 3.1, 3.7) from multivariable analyses and 3.7% (-4.5, 11.9) from genetic...

  2. Evaluation of Demo 1C composite flywheel rotor burst test and containment design

    Kass, M.D.; McKeever, J.W.; Akerman, M.A.; Goranson, P.L.; Litherland, P.S.; O`Kain, D.U.

    1998-07-01

    Laboratory-Directed funds were provided in FY 1995 for research to develop flywheel containment specifications and to consider concepts that could satisfy these specifications and produce a prototype small, lightweight, inexpensive, mobile flywheel containment. Research activities have included an analytical and pictorial review of the Demo 1C flywheel failure test, which provided significant insight about radial and axial failure modes; calculations of the thickness of ultra-conservative pressure vessel containment; entertainment of advanced containment concepts using lightweight materials and armor literature; consideration of fabrication assembly procedures; and participation in a Flywheel Energy Storage Workshop during which additional flywheel failure experiences were discussed. Based on these activities, calculations, and results, a list of conclusions concerning flywheel containment and its relation to the flywheel are presented followed by recommendations for further research.

  3. Traumatic posterior atlantoaxial dislocation without related fractures of C1-C2

    Maruti Kambali

    2013-01-01

    Full Text Available Posterior dislocation without any associated fracture of odontoid is exceedingly rare and only 11 cases have been reported so far. A 32 year old male presented with pain, stiffness in neck, difficulty in breathing, associated lacerations on face and deformity of mandible and inability to open mouth. His plain radiographs, CT scan, MRI demonstrated a posterior dislocation of the atlas with respect of axis and a flake of bone from odontoid process on CT scan. He was successfully managed by closed reduction, C1C2 lateral mars pedicular screw stabilization and inter facetal fusion with synthetic bone graft substitute. At 10 months followup he had lost only 30° cervical rotation. The case is reported in view of rarity and to discuss the treatment rationale.

  4. Application Capacity Evaluation of HJ-1-C towards Ice Disaster during On-orbit Test Period

    Zhang Wei

    2014-06-01

    Full Text Available On November 19, 2012, HJ-1-C was launched successfully, which is the first civil Synthetic Aperture Radar (SAR satellite in China and is also the only S-band SAR on-orbit satellite in the world. During the on-orbit period, National Disaster Reduction Center of China (NDRCC preliminarily evaluated the application capacity towards the ice disaster, and also evaluated the relative precision by using multispectral images of ZY-3 satellite. The result shows that, the S-band SAR satellite has super response towards ice. Entirely freeze-up area, non entirely freeze-up area and drift ice area can be effectively identified, and the S-band SAR satellite has better disaster reduction application capacity. The S-band SAR satellite data will fill up the band’s blank of SAR satellite in China and even the world, and its disaster reduction potentiality remains to be excavated further more.

  5. C1-C2 spondylodiscitis in an adult with SAPHO syndrome: an unusual presentation.

    Harifi, Ghita; Belkhou, Ahlam; El Bouchti, Imane; Ouali Idrissi, Meryem; Chérif Idrissi, Najat; Ousehal, Ahmed; El Hassani, Selma

    2012-02-01

    The main advantage of recognition and diagnosis of SAPHO syndrome is the avoidance of unnecessary prolonged antibiotic treatment and repeated invasive procedures. The combination of synovitis, acne, pustulosis, hyperostosis and aseptic osteitis is known as SAPHO syndrome. The most common site of the disease is the upper anterior chest wall, characterized by predominantly osteosclerotic lesions, hyperostosis, and arthritis of the adjacent joints. Osteosclerosis of the vertebral bodies, hyperostosis, and erosions of the vertebral plates are rarely encountered. We present a case of SAPHO syndrome with C1-C2 spondylodiscitis. Diagnosis of SAPHO syndrome was established using Khan et al. criteria (Schilling, SAPHO syndrome, Encyclopedie Orphanet, 2004). CT showed osteosclerotic lesions of dens axis. MRI sequences reveal inflammatory bone marrow oedema. Radiologists should be aware of this unusual syndrome to avoid misdiagnosis (tumour/infection), unnecessary surgery, and antibiotic therapy.

  6. Stability of Enzymes in Granular Enzyme Products for Laundry Detergents

    Biran, Suzan; Jensen, Anker Degn; Kiil, Søren; Bach, Poul; Simonsen, Ole

    2010-01-01

    Enzymes have long been of interest to the detergent industry due to their ability to improve the cleaning efficiency of synthetic detergents, contribute to shortening washing times, and reduce energy and water consumption, provision of environmentally friendlier wash water effluents and fabric care. However, incorporating enzymes in detergent formulations gives rise to numerous practical problems due to their incompatibility with and stability against various detergent components. In powdered...

  7. To establish trimester-specific reference ranges for glycated haemoglobin (HbA1c) in pregnancy

    O'Connor, CM

    2011-09-01

    Background and aims: Diabetes in Pregnancy imposes additional risks to both mother and infant. These poor outcomes are considered to be primarily related to glycaemic control which is monitored longitudinally through pregnancy by means of HbA1c. The correlation between HbA1c levels with clinical outcomes emphasises the need to measure HbA1c accurately, precisely and for data interpretation comparison to appropriately defined reference intervals. From July 1st 2010, the HbA1c assay in Irish laboratories became fully metrologically traceable to the IFCC standard, permitting HbA1c to be reported in IFCC units (mmol\\/mol) and derived DCCT\\/NGSP units (%) using the IFCC-DCCT\\/NGSP master equation (DCCT = Diabetes Control and Complications Trial, NGSP = National Glycohemoglobin standardisation program). The aim of this project is to establish trimester-specific reference ranges in pregnancy for IFCC standardised HbA1c in non-diabetic Caucasian women. This will allow us to define the goal for HbA1c during pregnancy complicated by diabetes.\\r\

  8. Monoclonal antibody targeting of fibroblast growth factor receptor 1c ameliorates obesity and glucose intolerance via central mechanisms.

    Christopher J Lelliott

    Full Text Available We have generated a novel monoclonal antibody targeting human FGFR1c (R1c mAb that caused profound body weight and body fat loss in diet-induced obese mice due to decreased food intake (with energy expenditure unaltered, in turn improving glucose control. R1c mAb also caused weight loss in leptin-deficient ob/ob mice, leptin receptor-mutant db/db mice, and in mice lacking either the melanocortin 4 receptor or the melanin-concentrating hormone receptor 1. In addition, R1c mAb did not change hypothalamic mRNA expression levels of Agrp, Cart, Pomc, Npy, Crh, Mch, or Orexin, suggesting that R1c mAb could cause food intake inhibition and body weight loss via other mechanisms in the brain. Interestingly, peripherally administered R1c mAb accumulated in the median eminence, adjacent arcuate nucleus and in the circumventricular organs where it activated the early response gene c-Fos. As a plausible mechanism and coinciding with the initiation of food intake suppression, R1c mAb induced hypothalamic expression levels of the cytokines Monocyte chemoattractant protein 1 and 3 and ERK1/2 and p70 S6 kinase 1 activation.

  9. IMPACT OF NLRP3 INFLAMMASOME ON THE DEVELOPMENT OF HYPERTENSION AND RENAL AND CARDIAC HYPERTROPHY IN 2K1C AND DOCA/SALT MICE

    Q. Wang

    2012-06-01

    Full Text Available NLRP3 inflammasome is formed by NLRP3, the adaptor ASC, and caspase-1, functions as a sensor of danger signals and triggers processing and release of interleukin-1beta (IL-1β. Recent animal studies demonstrate that NLRP3 inflammasome promotes renal inflammation. However, little is known on the role of NLRP3 in hypertension. We have investigated the effect of NLRP3 inflammasome on blood pressure, plasma renin activity and concentration (PRA and PRC, renal and cardiac hypertrophy in NALP3 and ASC deficient mice on which the two-kidney, one clip (2K1C and the deoxycorticosterone-acetate (DOCA/salt models were applied. MBP, PRA, PRC, and HW/BW were significantly increased at week 12 in WT-2K1C mice compared to the sham. Neither NLAP3-KO nor ASC-KO 2K1C treated mice developed hypertension and had lower circulating levels of PRA and PRC and serum amyloid A (SAA and IL6 compared to the control. RNA levels of SAA, NLRP3, IL1β and IL1α were increased in the ischemic kidney in C57BL/6J mice. Administration of anti-IL1β antibody to the WT mice attenuated the increases of blood pressure and renin in 2K1C mice. With chronic administration of DOCA/salt, MBPs in both NLRP3-KO and WT mice were comparable and not significantly increased compared to tap water group. PRA and PRC in both NALP3-KO and WT mice were significantly suppressed by DOCA/salt. HW/BW and KW/BW in both DOCA/salt treated NALP3-KO and WT mice were significantly increased. DOCA/salt induced hypokalemia was comparable between Nlrp3 KO and WT groups. However, the heart and kidney index in DOCA/salt NLRP3-KO mice was significantly lower than that in DOCA/salt WT mice. Our data show that NLRP3 mediated IL1β is linked to development of renovascular hypertension and suggest that a novel target for the treatment of hypertension. The results also implicate that NLRP3 contributes to the development of cardiac and renal hypertrophy independently of blood pressure in the DOCA/salt model.

  10. Diabetes mellitus: The long way of standardization of HbA1c to the level of highest metrological order

    Kaiser, Patricia

    2011-01-01

    Full Text Available Glycated haemoglobin (HbA1c measurements are used in clinical studies and for the management of diabetic patients. Various efforts were made to standardize the HbA1c measurements with consensus standards and standards based on a reference measurement procedure with external calibration. According to ISO 17511 a standard should meet highest accuracy possible, have a defined uncertainty of measurement and the calibration should be traceable to SI units. For HbA1c this has been realized using a LC-ID-MS procedure based on the existing reference measurement procedure.

  11. Standardization of the hemoglobin A1c reporting: transferring global consensus to the local community – Special report

    Vucic Lovrencic, Marijana; Metelko, Zeljko

    2011-01-01

    This Special report is being simultaneuosly published in 2010/2011 in Biochemia Medica, Diabe-tologia Croatica and croatian-translated version in Liječnički vjesnik. Copying with attribution allowed for only non-commercial use of work. Long-term controversies regarding hemoglobin A1c (HbA1c) standardization seem to have finally reached the global consensus point. Hemoglobin A1c, an integrated measure of glycaemic con-trol, has been widely used as a „gold-standard” in management of diabetes me...

  12. Changes in levels of haemoglobin A1c during the first 6 years after diagnosis of clinical type 2 diabetes

    Olivarius, Niels de Fine; Siersma, V.; Hansen, Lars Jørgen;

    2009-01-01

    OBJECTIVE: To assess the variability in levels of glycosylated haemoglobin (HbA(1c)) during the first six years after diagnosis of clinical type 2 diabetes in relation to possible predictors. MATERIAL AND METHODS: Data were from a population-based sample from general practice of 581 newly diagnosed...... the first 6 years after the diagnosis of clinical type 2 diabetes, changes in levels of HbA(1c) show considerable inter-individual variability with age as the only long-term predictor. The results indicate that it is important to monitor changes in HbA(1c) more closely and intensify treatment of those often...

  13. Photosynthetic fuel for heterologous enzymes

    Mellor, Silas Busck; Vavitsas, Konstantinos; Nielsen, Agnieszka Janina Zygadlo

    2017-01-01

    , competition from native pathways and inefficient electron transfer rates present major obstacles, which limit the productivity of heterologous reactions coupled to photosynthesis. We discuss specific approaches to address these bottlenecks and ensure high productivity of such enzymes in a photosynthetic...... of reducing power. Recent work on the metabolic engineering of photosynthetic organisms has shown that the electron carriers such as ferredoxin and flavodoxin can be used to couple heterologous enzymes to photosynthetic reducing power. Because these proteins have a plethora of interaction partners and rely...... on electrostatically steered complex formation, they form productive electron transfer complexes with non-native enzymes. A handful of examples demonstrate channeling of photosynthetic electrons to drive the activity of heterologous enzymes, and these focus mainly on hydrogenases and cytochrome P450s. However...

  14. GRE Enzymes for Vector Analysis

    U.S. Environmental Protection Agency — Microbial enzyme data that were collected during the 2004-2006 EMAP-GRE program. These data were then used by Moorhead et al (2016) in their ecoenzyme vector...

  15. Controlled enzyme catalyzed heteropolysaccharide degradation

    Rasmussen, Louise Enggaard

    The work presented in this PhD thesis has provided a better understanding of the enzyme kinetics and quantitative phenomena of the hydrolysis of xylan substrates by selected pure enzyme preparations. Furthermore, the options for producing specific substituted xylooligosaccharides from selected...... substrates by specific xylanase treatment have been examined. The kinetics of the enzymatic degradation of water-extractable wheat arabinoxylan (WE-AX) during designed treatments with selected monocomponent enzymes was investigated by monitoring the release of xylose and arabinose. The results of different...... between -xylosidase and the α-L-arabinofuranosidases on the xylose release were low as compared to the effect of xylanase addition with β-xylosidase, which increased the xylose release by ~25 times in 30 minutes. At equimolar addition levels of the four enzymes, the xylanase activity was thus rate...

  16. Enzymes: principles and biotechnological applications.

    Robinson, Peter K

    2015-01-01

    Enzymes are biological catalysts (also known as biocatalysts) that speed up biochemical reactions in living organisms, and which can be extracted from cells and then used to catalyse a wide range of commercially important processes. This chapter covers the basic principles of enzymology, such as classification, structure, kinetics and inhibition, and also provides an overview of industrial applications. In addition, techniques for the purification of enzymes are discussed.

  17. Mitochondrial genome sequences reveal evolutionary relationships of the Phytophthora 1c clade species.

    Lassiter, Erica S; Russ, Carsten; Nusbaum, Chad; Zeng, Qiandong; Saville, Amanda C; Olarte, Rodrigo A; Carbone, Ignazio; Hu, Chia-Hui; Seguin-Orlando, Andaine; Samaniego, Jose A; Thorne, Jeffrey L; Ristaino, Jean B

    2015-11-01

    Phytophthora infestans is one of the most destructive plant pathogens of potato and tomato globally. The pathogen is closely related to four other Phytophthora species in the 1c clade including P. phaseoli, P. ipomoeae, P. mirabilis and P. andina that are important pathogens of other wild and domesticated hosts. P. andina is an interspecific hybrid between P. infestans and an unknown Phytophthora species. We have sequenced mitochondrial genomes of the sister species of P. infestans and examined the evolutionary relationships within the clade. Phylogenetic analysis indicates that the P. phaseoli mitochondrial lineage is basal within the clade. P. mirabilis and P. ipomoeae are sister lineages and share a common ancestor with the Ic mitochondrial lineage of P. andina. These lineages in turn are sister to the P. infestans and P. andina Ia mitochondrial lineages. The P. andina Ic lineage diverged much earlier than the P. andina Ia mitochondrial lineage and P. infestans. The presence of two mitochondrial lineages in P. andina supports the hybrid nature of this species. The ancestral state of the P. andina Ic lineage in the tree and its occurrence only in the Andean regions of Ecuador, Colombia and Peru suggests that the origin of this species hybrid in nature may occur there.

  18. Tissue factor pathway inhibitor-2 may interact with nuclear protein RASSF1C

    Xudong Chen; Zhenwu Li; Jin Zhang; Zuohua Mao; Duan Ma; Huijun Wang

    2012-01-01

    Tissue factor pathway inhibitor-2 (TFPI-2) is a 32 kDa matrix-associated Kunitz-type serine proteinase inhibitor consisting of a short amino-terminal region,three tandem Kunitz-type domains,and a positively charged carboxyterminal tail.Human TFPI-2 (hTFPI-2) inhibits a broad spectrum of serine proteinases (including trypsin,plasmin,plasma kallikrein,XIa,and chymotrypsin) almost exclusively via its first Kunitz-type domain,and potentially plays an important role in the regulation of extracellular matrix digestion and remodeling [1].Reduced TFPI-2 synthesis has been related to numerous pathophysiological processes such as inflammation,angiogenesis,atherosclerosis [2,3],retinal degeneration,and tumor growth/metastasis [4-6].It has been suggested that TFPI-2 is a tumor suppressor gene in some cancers [7,8].However,the specific physiological functions of hTFPI-2 in humans are unclear,particularly its interactions with other proteins.To better understand the physiological function of hTFPI-2,we used yeast two-hybrid system screening and bioinformatics analysis to identify its interacting proteins and confirm its interactions with nuclear protein RASSF1C using confocal microscopy and co-immunoprecipitation.

  19. Standalone GPS L1 C/A Receiver for Lunar Missions.

    Capuano, Vincenzo; Blunt, Paul; Botteron, Cyril; Tian, Jia; Leclère, Jérôme; Wang, Yanguang; Basile, Francesco; Farine, Pierre-André

    2016-03-09

    Global Navigation Satellite Systems (GNSSs) were originally introduced to provide positioning and timing services for terrestrial Earth users. However, space users increasingly rely on GNSS for spacecraft navigation and other science applications at several different altitudes from the Earth surface, in Low Earth Orbit (LEO), Medium Earth Orbit (MEO), Geostationary Earth Orbit (GEO), and feasibility studies have proved that GNSS signals can even be tracked at Moon altitude. Despite this, space remains a challenging operational environment, particularly on the way from the Earth to the Moon, characterized by weaker signals with wider gain variability, larger dynamic ranges resulting in higher Doppler and Doppler rates and critically low satellite signal availability. Following our previous studies, this paper describes the proof of concept "WeakHEO" receiver; a GPS L1 C/A receiver we developed in our laboratory specifically for lunar missions. The paper also assesses the performance of the receiver in two representative portions of an Earth Moon Transfer Orbit (MTO). The receiver was connected to our GNSS Spirent simulator in order to collect real-time hardware-in-the-loop observations, and then processed by the navigation module. This demonstrates the feasibility, using current technology, of effectively exploiting GNSS signals for navigation in a MTO.

  20. NOAA Climate Data Record (CDR) of AMSU-A Level 1c Brightness Temperature, Version 1.0

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset contains Level 1c inter-calibrated brightness temperatures from the Advanced Microwave Sounding Unit-A (AMSU-A) sensors onboard six polar orbiting...

  1. Predicting of Trend of Hemoglobin A1c in Type 2 Diabetes: A Longitudinal Linear Mixed Model

    Elahe Kazemi

    2014-01-01

    Conclusions: The present study shows that regular visits of diabetic patients as well as controlling blood pressure, lipid profile, and weight loss can improve the trend of HbA1c levels during the time.

  2. Point-of-care testing of HbA1c in diabetes care and preventable hospital admissions

    Kristensen, Troels; Rose Olsen, Kim

    , socioeconomic covariates, municipality classifications and case mix measure in terms of the charlson index and costs of care in primary care and secondary care. Results: There was a significant link between POCT of HbA1c among diabetes patients in general practice and an ACSC-measure of preventable out......Background: Point-of-care testing (POCT) of HbA1c may result in improved diabetic control, better patient outcomes and enhanced clinical efficiency with fewer patient visits and subsequent reductions in hospitalizations and costs. In 2008, the Danish regulators agreed to create a new tariff...... for the remuneration of POCT of HbA1c in primary care. Aim: The aim of this study is to assess whether there is an association between the use of POCT of HbA1c and preventable hospital admissions among diabetes patients in general practice. Method: We apply logistic regression analyses to examine whether...

  3. Geo-correction Algorithm Based on Equivalent RD Model for ScanSAR of HJ-1-C Satellite

    Liu Jia-yin

    2014-06-01

    Full Text Available HJ-1-C satellite is the first Synthetic Aperture Radar (SAR satellite for civilian use in China, and it has a strip and scan mode. According to the characteristics of the ScanSAR of the HJ-1-C satellite, a geo-correction algorithm based on an equivalent RD model has been outlined in this paper on the basis of an ECS image processing algorithm and a traditional Range-Doppler location method. An azimuth mosaic was presented by a time series relationship, then the different burst was stitched by range, and the equivalent parameters were fitted to locations on the RD model. Finally, the ScanSAR image was geo-corrected. The HJ-1-C satellite data results showed that the location accuracy of ScanSAR for the HJ-1-C satellite was less than 100 m, and the geo-correction algorithm was realized in 10 s in fewer than 24 parallel cores.

  4. Engineering Cellulase Enzymes for Bioenergy

    Atreya, Meera Elizabeth

    Sustainable energy sources, such as biofuels, offer increasingly important alternatives to fossil fuels that contribute less to global climate change. The energy contained within cellulosic biofuels derives from sunlight energy stored in the form of carbon-carbon bonds comprising sugars such as glucose. Second-generation biofuels are produced from lignocellulosic biomass feedstocks, including agricultural waste products and non-food crops like Miscanthus, that contain lignin and the polysaccharides hemicellulose and cellulose. Cellulose is the most abundant biological material on Earth; it is a polymer of glucose and a structural component of plant cell walls. Accessing the sugar is challenging, as the crystalline structure of cellulose resists degradation; biochemical and thermochemical means can be used to depolymerize cellulose. Cellulase enzymes catalyze the biochemical depolymerization of cellulose into glucose. Glucose can be used as a carbon source for growth of a biofuel-producing microorganism. When it converts glucose to a hydrocarbon fuel, this microbe completes the biofuels process of transforming sunlight energy into accessible, chemical energy capable of replacing non-renewable transportation fuels. Due to strong intermolecular interactions between polymer chains, cellulose is significantly more challenging to depolymerize than starch, a more accessible polymer of glucose utilized in first-generation biofuels processes (often derived from corn). While most mammals cannot digest cellulose (dietary fiber), certain fungi and bacteria produce cellulase enzymes capable of hydrolyzing it. These organisms secrete a wide variety of glycoside hydrolase and other classes of enzymes that work in concert. Because cellulase enzymes are slow-acting and expensive to produce, my aim has been to improve the properties of these enzymes as a means to make a cellulosic biofuels process possible that is more efficient and, consequently, more economical than current

  5. Role of HbA1c in the Screening of Diabetes Mellitus in a Korean Rural Community

    Jae Hyun Kim

    2012-02-01

    Full Text Available BackgroundRecently, the measurement of glycated hemoglobin (HbA1c was recommended as an alternative to fasting plasma glucose or oral glucose tolerance tests for diagnosing diabetes mellitus (DM. In this study, we analyzed HbA1c levels for diabetes mellitus screening in a Korean rural population.MethodsWe analyzed data from 10,111 subjects from a Korean Rural Genomic Cohort study and generated a receiver operating characteristic curve to determine an appropriate HbA1c cutoff value for diabetes.ResultsThe mean age of the subjects was 56.3±8.1 years. Fasting plasma glucose and 2-hour plasma glucose after 75 g oral glucose tolerance tests were 97.5±25.6 and 138.3±67.1 mg/dL, respectively. The mean HbA1c level of the subjects was 5.7±0.9%. There were 8,809 non-DM patients (87.1% and 1,302 DM patients (12.9%. A positive relationship between HbA1c and plasma glucose levels and between HbA1c and 2-hour plasma glucose levels after oral glucose tolerance tests was found in a scatter plot of the data. Using Youden's index, the proper cutoff level of HbA1c for diabetes mellitus screening was 5.95% (sensitivity, 77%; specificity, 89.4%.ConclusionOur results suggest that the optimal HbA1c level for DM screening is 5.95%.

  6. Updated survey of the steroid-converting enzymes in human adipose tissues.

    Tchernof, André; Mansour, Mohamed Fouad; Pelletier, Mélissa; Boulet, Marie-Michèle; Nadeau, Mélanie; Luu-The, Van

    2015-03-01

    Over the past decade, adipose tissues have been increasingly known for their endocrine properties, that is, their ability to secrete a number of adipocytokines that may exert local and/or systemic effects. In addition, adipose tissues have long been recognized as significant sites for steroid hormone transformation and action. We hereby provide an updated survey of the many steroid-converting enzymes that may be detected in human adipose tissues, their activities and potential roles. In addition to the now well-established role of aromatase and 11β-hydroxysteroid dehydrogenase (HSD) type 1, many enzymes have been reported in adipocyte cell lines, isolated mature cells and/or preadipocytes. These include 11β-HSD type 2, 17β-HSDs, 3β-HSD, 5α-reductases, sulfatases and glucuronosyltransferases. Some of these enzymes are postulated to bear relevance for adipose tissue physiology and perhaps for the pathophysiology of obesity. This elaborate set of steroid-converting enzymes in the cell types of adipose tissue deserves further scientific attention. Our work on 20α-HSD (AKR1C1), 3α-HSD type 3 (AKR1C2) and 17β-HSD type 5 (AKR1C3) allowed us to clarify the relevance of these enzymes for some aspects of adipose tissue function. For example, down-regulation of AKR1C2 expression in preadipocytes seems to potentiate the inhibitory action of dihydrotestosterone on adipogenesis in this model. Many additional studies are warranted to assess the impact of intra-adipose steroid hormone conversions on adipose tissue functions and chronic conditions such as obesity, diabetes and cancer.

  7. Expression of SREBP-1c Requires SREBP-2-mediated Generation of a Sterol Ligand for LXR in Livers of Mice

    Rong, Shunxing; Cortés, Víctor A; Rashid, Shirya; Anderson, Norma N; McDonald, Jeffrey G; Liang, Guosheng; Moon, Young-Ah; Hammer, Robert E; Horton, Jay D

    2017-01-01

    The synthesis of cholesterol and fatty acids (FA) in the liver is independently regulated by SREBP-2 and SREBP-1c, respectively. Here, we genetically deleted Srebf-2 from hepatocytes and confirmed that SREBP-2 regulates all genes involved in cholesterol biosynthesis, the LDL receptor, and PCSK9; a secreted protein that degrades LDL receptors in the liver. Surprisingly, we found that elimination of Srebf-2 in hepatocytes of mice also markedly reduced SREBP-1c and the expression of all genes involved in FA and triglyceride synthesis that are normally regulated by SREBP-1c. The nuclear receptor LXR is necessary for Srebf-1c transcription. The deletion of Srebf-2 and subsequent lower sterol synthesis in hepatocytes eliminated the production of an endogenous sterol ligand required for LXR activity and SREBP-1c expression. These studies demonstrate that cholesterol and FA synthesis in hepatocytes are coupled and that flux through the cholesterol biosynthetic pathway is required for the maximal SREBP-1c expression and high rates of FA synthesis. DOI: http://dx.doi.org/10.7554/eLife.25015.001 PMID:28244871

  8. Quantitative measurement of HbA1c by an immunoturbidimetric assay compared to a standard HPLC method.

    Hamwi, A; Schweiger, C R; Veitl, M; Schmid, R

    1995-07-01

    Determination of hemoglobin A1c (HbA1c) is one of the most important monitoring procedures for long-term control of diabetes mellitus. Several analytical methods have been developed for the measurement of glycohemoglobin (GHb). Those most frequently used are ion-exchange chromatography for HbA1c and affinity chromatography for total GHb. In this study, a new turbidimetric immunoassay for HbA1c (Boehringer Mannheim, Germany) was evaluated that was performed on a Hitachi 911 clinical chemistry analyzer (Boehringer Mannheim). Good linearity in the range of 5% to 15% HbA1c, within-run and between-run coefficients of variation ranging from 2.4% to 5.9% were obtained. Results of 179 diabetic and nondiabetic patients showed good correlation to those of a routine HPLC method (r = 0.96). In addition, HbA2, HbS, and HbF in samples from nondiabetic patients were not detected by the immunoturbimetric assay and the "labile" HbA1c fraction (Schiff base) did not interfere with the new test.

  9. Modeling autosomal recessive cutis laxa type 1C in mice reveals distinct functions for Ltbp-4 isoforms

    Insa Bultmann-Mellin

    2015-04-01

    Full Text Available Recent studies have revealed an important role for LTBP-4 in elastogenesis. Its mutational inactivation in humans causes autosomal recessive cutis laxa type 1C (ARCL1C, which is a severe disorder caused by defects of the elastic fiber network. Although the human gene involved in ARCL1C has been discovered based on similar elastic fiber abnormalities exhibited by mice lacking the short Ltbp-4 isoform (Ltbp4S−/−, the murine phenotype does not replicate ARCL1C. We therefore inactivated both Ltbp-4 isoforms in the mouse germline to model ARCL1C. Comparative analysis of Ltbp4S−/− and Ltbp4-null (Ltbp4−/− mice identified Ltbp-4L as an important factor for elastogenesis and postnatal survival, and showed that it has distinct tissue expression patterns and specific molecular functions. We identified fibulin-4 as a previously unknown interaction partner of both Ltbp-4 isoforms and demonstrated that at least Ltbp-4L expression is essential for incorporation of fibulin-4 into the extracellular matrix (ECM. Overall, our results contribute to the current understanding of elastogenesis and provide an animal model of ARCL1C.

  10. Effect of the systemic inflammatory response, as provoked by elective orthopaedic surgery, on HbA1c.

    Chadburn, Andrew J; Garman, Elizabeth; Abbas, Raad; Modupe, Anu; Ford, Clare; Thomas, Osmond L; Chugh, Sanjiv; Deshpande, Shreeram; Gama, Rousseau

    2017-01-01

    Background In acutely ill patients with new onset hyperglycaemia, plasma glucose cannot reliably distinguish between stress hyperglycaemia and undiagnosed diabetes mellitus. We, therefore, investigated the diagnostic reliability of glycated haemoglobin (HbA1c) in acute illness by prospectively evaluating the effect of the systemic inflammatory response, as provoked by elective orthopaedic surgery, on HbA1c. Methods HbA1c and serum C-reactive protein concentrations were compared before and two days after elective knee or hip surgery in 30 patients without diabetes. C-reactive protein was used to assess the systemic inflammatory response. Results The mean (standard deviation) serum C-reactive protein increased following surgery (4.8 [7.5] vs. 179.7 [61.9] mg/L; P<0.0001). HbA1c was similar before and after surgery (39.2 [5.4] vs. 38.1 [5.1] mmol/moL, respectively; P = 0.4363). Conclusions HbA1c is unaffected within two days of a systemic inflammatory response as provoked by elective orthopaedic surgery. This suggests that HbA1c may be able to differentiate newly presenting type 2 diabetes mellitus from stress hyperglycaemia in acutely ill patients with new onset hyperglycaemia.

  11. Angiotensin converting enzyme gene polymorphism in type II diabetics with nephropathy

    Naresh, V. V. S.; Reddy, A. L. K.; Sivaramakrishna, G.; Sharma, P. V. G. K.; Vardhan, R. V.; Kumar, V. Siva

    2009-01-01

    Nephropathy is an important and a frequent complication of long-term type II diabetic nephropathy. Strong evidence exists that genetic predisposition plays a major role in the development of diabetic nephropathy. Recent studies have implicated association between angiotensin converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and nephropathy. The deletion gene polymorphism of ACE gene has been shown to be associated with increased activity of this enzyme. This study examines th...

  12. Polysaccharides Purified from Wild Cordyceps Activate FGF2/FGFR1c Signaling

    ZENG Yangyang; HAN Zhangrun; YU Guangli; HAO Jiejie; ZHANG Lijuan

    2015-01-01

    Land animals as well as all organisms in ocean synthesize sulfated polysaccharides. Fungi split from animals about 1.5 billion years ago. As fungi make the evolutionary journey from ocean to land, the biggest changes in their living environment may be a sharp decrease in salt concentration. It is established that sulfated polysaccharides interact with hundreds of signaling molecules and facilitate many signaling transduction pathways, including fibroblast growth factor (FGF) and FGF receptor signaling pathway. The disappearance of sulfated polysaccharides in fungi and plants on land might indicate that polysaccharides without sulfation might be sufficient in facilitating protein ligand/receptor interactions in low salinity land. Recently, it was reported that plants on land start to synthesize sulfated polysaccharides in high salt environment, suggesting that fungi might be able to do the same when ex-posed in such environment. Interestingly, Cordyceps, a fungus habituating inside caterpillar body, is the most valued traditional Chi-nese Medicine. One of the important pharmaceutical active ingredients in Cordyceps is polysaccharides. Therefore, we hypothesize that the salty environment inside caterpillar body might allow the fungi to synthesize sulfated polysaccharides. To test the hypothesis, we isolated polysaccharides from both lava and sporophore of wild Cordyceps and also fromCordyceps militaris cultured without or with added salts. We then measured the polysaccharide activity using a FGF2/FGFR1c signaling-dependent BaF3 cell proliferation assay and found that polysaccharides isolated from wild Cordyceps activated FGF2/FGFR signaling, indicating that the polysaccha-rides synthesized by wild Cordyceps are indeed different from those by the cultured mycelium.

  13. Polysaccharides purified from wild Cordyceps activate FGF2/FGFR1c signaling

    Zeng, Yangyang; Han, Zhangrun; Yu, Guangli; Hao, Jiejie; Zhang, Lijuan

    2015-02-01

    Land animals as well as all organisms in ocean synthesize sulfated polysaccharides. Fungi split from animals about 1.5 billion years ago. As fungi make the evolutionary journey from ocean to land, the biggest changes in their living environment may be a sharp decrease in salt concentration. It is established that sulfated polysaccharides interact with hundreds of signaling molecules and facilitate many signaling transduction pathways, including fibroblast growth factor (FGF) and FGF receptor signaling pathway. The disappearance of sulfated polysaccharides in fungi and plants on land might indicate that polysaccharides without sulfation might be sufficient in facilitating protein ligand/receptor interactions in low salinity land. Recently, it was reported that plants on land start to synthesize sulfated polysaccharides in high salt environment, suggesting that fungi might be able to do the same when exposed in such environment. Interestingly, Cordyceps, a fungus habituating inside caterpillar body, is the most valued traditional Chinese Medicine. One of the important pharmaceutical active ingredients in Cordyceps is polysaccharides. Therefore, we hypothesize that the salty environment inside caterpillar body might allow the fungi to synthesize sulfated polysaccharides. To test the hypothesis, we isolated polysaccharides from both lava and sporophore of wild Cordyceps and also from Cordyceps militaris cultured without or with added salts. We then measured the polysaccharide activity using a FGF2/FGFR1c signaling-dependent BaF3 cell proliferation assay and found that polysaccharides isolated from wild Cordyceps activated FGF2/FGFR signaling, indicating that the polysaccharides synthesized by wild Cordyceps are indeed different from those by the cultured mycelium.

  14. MDR1 C3435T polymorphism in Mexican patients with breast cancer.

    Macías-Gómez, N M; Gutiérrez-Angulo, M; Leal-Ugarte, E; Ramírez-Reyes, L; Peregrina-Sandoval, J; Meza-Espinoza, J P; Ramos Solano, F; de la Luz Ayala-Madrigal, M; Santoyo Telles, F

    2014-07-04

    We investigated whether the MDR1 C3435T polymorphism is associated with fibrocystic changes (FCC), infiltrating ductal breast cancer (IDBC), and/or clinical-pathological features of IDBC in Mexican patients. Samples from women who received surgical treatment in 2007 at the Centro Médico de Occidente (México) were included in the analysis. Genotyping was performed by polymerase chain reaction-restricted fragment length polymorphisms in 64 paraffin-embedded breast samples with IDBC, 64 samples with FCC, and 183 peripheral blood samples of healthy females designated as the healthy group (HG). The frequency of the T allele was 41, 45, and 52% for the FCC, IDBC, and HG samples, respectively. Significant differences were only found between the FCC and HG samples [odds ratio (OR) = 0.64, 95% confidence interval (CI) = 0.43-0.96; P = 0.032]. The prevalence of the T/T genotype was 8, 13, and 24% for FCC, IDBC, and HG samples, respectively. Again, statistical differences were only found between FCC and HG samples for the T/T genotype (OR = 0.28, 95%CI = 0.106-0.77; P = 0.009). Although the T allele and the T/T genotype were less frequent in the IDBC group than in the HG, the differences were not significant. Furthermore, no associations were found between the C3435T polymorphism and clinical-pathological features of the IDBC group. Both the FCC and IDBC groups had a high frequency of the C allele relative to the HG in this sample of women from Western Mexico.

  15. Heavy enzymes--experimental and computational insights in enzyme dynamics.

    Swiderek, Katarzyna; Ruiz-Pernía, J Javier; Moliner, Vicent; Tuñón, Iñaki

    2014-08-01

    The role of protein motions in the chemical step of enzyme-catalyzed reactions is the subject of an open debate in the scientific literature. The systematic use of isotopically substituted enzymes has been revealed as a useful tool to quantify the role of these motions. According to the Born-Oppenheimer approximation, changing the mass of the protein does not change the forces acting on the system but alters the frequencies of the protein motions, which in turn can affect the rate constant. Experimental and theoretical studies carried out in this field are presented in this article and discussed in the framework of Transition State Theory.

  16. Cdkn1c Boosts the Development of Brown Adipose Tissue in a Murine Model of Silver Russell Syndrome.

    Van De Pette, Matthew; Tunster, Simon J; McNamara, Grainne I; Shelkovnikova, Tatyana; Millership, Steven; Benson, Lindsay; Peirson, Stuart; Christian, Mark; Vidal-Puig, Antonio; John, Rosalind M

    2016-03-01

    The accurate diagnosis and clinical management of the growth restriction disorder Silver Russell Syndrome (SRS) has confounded researchers and clinicians for many years due to the myriad of genetic and epigenetic alterations reported in these patients and the lack of suitable animal models to test the contribution of specific gene alterations. Some genetic alterations suggest a role for increased dosage of the imprinted CYCLIN DEPENDENT KINASE INHIBITOR 1C (CDKN1C) gene, often mutated in IMAGe Syndrome and Beckwith-Wiedemann Syndrome (BWS). Cdkn1c encodes a potent negative regulator of fetal growth that also regulates placental development, consistent with a proposed role for CDKN1C in these complex childhood growth disorders. Here, we report that a mouse modelling the rare microduplications present in some SRS patients exhibited phenotypes including low birth weight with relative head sparing, neonatal hypoglycemia, absence of catch-up growth and significantly reduced adiposity as adults, all defining features of SRS. Further investigation revealed the presence of substantially more brown adipose tissue in very young mice, of both the classical or canonical type exemplified by interscapular-type brown fat depot in mice (iBAT) and a second type of non-classic BAT that develops postnatally within white adipose tissue (WAT), genetically attributable to a double dose of Cdkn1c in vivo and ex-vivo. Conversely, loss-of-function of Cdkn1c resulted in the complete developmental failure of the brown adipocyte lineage with a loss of markers of both brown adipose fate and function. We further show that Cdkn1c is required for post-transcriptional accumulation of the brown fat determinant PR domain containing 16 (PRDM16) and that CDKN1C and PRDM16 co-localise to the nucleus of rare label-retaining cell within iBAT. This study reveals a key requirement for Cdkn1c in the early development of the brown adipose lineages. Importantly, active BAT consumes high amounts of energy to

  17. The Emerging Role of Reactive Oxygen Species Signaling during Lateral Root Development1[C][W

    Manzano, Concepción; Pallero-Baena, Mercedes; Casimiro, Ilda; De Rybel, Bert; Orman-Ligeza, Beata; Van Isterdael, Gert; Beeckman, Tom; Draye, Xavier; Casero, Pedro; del Pozo, Juan C.

    2014-01-01

    Overall root architecture is the combined result of primary and lateral root growth and is influenced by both intrinsic genetic programs and external signals. One of the main questions for root biologists is how plants control the number of lateral root primordia and their emergence through the main root. We recently identified S-phase kinase-associated protein2 (SKP2B) as a new early marker for lateral root development. Here, we took advantage of its specific expression pattern in Arabidopsis (Arabidopsis thaliana) in a cell-sorting and transcriptomic approach to generate a lateral root-specific cell sorting SKP2B data set that represents the endogenous genetic developmental program. We first validated this data set by showing that many of the identified genes have a function during root growth or lateral root development. Importantly, genes encoding peroxidases were highly represented in our data set. Thus, we next focused on this class of enzymes and showed, using genetic and chemical inhibitor studies, that peroxidase activity and reactive oxygen species signaling are specifically required during lateral root emergence but, intriguingly, not for primordium specification itself. PMID:24879433

  18. Optimal Glycemic and Hemoglobin A1c Thresholds for Diagnosing Diabetes Based on Prevalence of Retinopathy in an Iranian Population

    Samadi Aidenloo, Naser; Mehdizadeh, Alireza; Valizadeh, Neda; Abbaszadeh, Mohammad; Qarequran, Siavash; Khalkhali, Hamidreza

    2016-01-01

    Background The use of glycemic thresholds for diabetes diagnosis is controversial. However, no information is available regarding glycemic and glycated hemoglobin (HbA1c) thresholds for detecting diabetic retinopathy (DR) in the Iranian population. Objectives The main purpose of the current investigation was to examine the association of fasting plasma glucose (FPG) and HbA1c levels with diabetic retinopathy (DR), and to determine the relevant cut-off levels in an Iranian population. Patients and Methods This cross-sectional, population-based study was performed during 2012-2013 in Urmia, the capital of West Azerbaijan province, Iran. The subjects were 3,010 Iranians aged 40-81 years. The FPG levels were determined using the glucose oxidase method whereas, the HbA1c values were measured using a standardized assay by high performance liquid chromatography. DR was evaluated by an examination of the fundus photograph of each eye. The photographs were graded according to the international clinical diabetic retinopathy disease severity scale by photograph graders who were masked to the clinical information. Results Of the subjects, 59 had DR. The prevalence of DR increased steeply between the ninth and the tenth deciles for both variables. The ROC curve analysis showed overall glycemic thresholds for DR of 6.5 mmol/L (117 mg/dL) for FPG and 6.2% (44 mmol/mol) for HbA1c. The sensitivities and specificities were 78.0% and 87.1% for FPG and 89.8% and 89.5% for HbA1c, respectively. The areas under the ROC curves indicated that HbA1c was a stronger discriminator of retinopathy: the area under curve was 0.880 for FPG and 0.946 for HbA1c P diabetes in the Iranian population are lower than the current diagnostic criteria. PMID:27781118

  19. Expression of CYP1C1 and CYP1A in Fundulus heteroclitus during PAH-induced carcinogenesis

    Wang Lu [Pharmacology and Environmental Toxicology, University of Mississippi, University, MS (United States); Camus, Alvin C. [Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA (United States); Dong, Wu; Thornton, Cammi [Pharmacology and Environmental Toxicology, University of Mississippi, University, MS (United States); Willett, Kristine L., E-mail: kwillett@olemiss.edu [Pharmacology and Environmental Toxicology, University of Mississippi, University, MS (United States)

    2010-09-15

    CYP1C1 is a relatively newly identified member of the cytochrome P450 family 1 in teleost fish. However, CYP1C1's expression and physiological roles relative to the more recognized CYP1A in polycyclic aromatic hydrocarbons (PAHs) induced toxicities are unclear. Fundulus heteroclitus fry were exposed at 6-8 days post-hatch (dph) and again at 13-15 dph for 6 h to dimethyl sulfoxide (DMSO) control, 5 mg/L benzo[a]pyrene (BaP), or 5 mg/L dimethylbenzanthracene (DMBA). Fry were euthanized at 0, 6, 18, 24 and 30 h after the second exposure. In these groups, both CYP1A and CYP1C1 protein expression were induced within 6 h after the second exposure. Immunohistochemistry (IHC) results from fry revealed strongest CYP1C1 expression in renal tubular and intestinal epithelial cells. Additional fish were examined for liver lesions 8 months after initial exposure. Gross lesions were observed in 20% of the BaP and 35% of the DMBA-treated fish livers. Histopathologic findings included foci of cellular alteration and neoplasms, including hepatocellular adenoma, hepatocellular carcinoma and cholangioma. Strong CYP1A immunostaining was detected diffusely in altered cell foci and on the invading margin of hepatocelluar carcinomas. Lower CYP1A expression was seen in central regions of the neoplasms. In contrast, CYP1C1 was only detectable and highly expressed in proliferated bile duct epithelial cells. Our CYP1C1 results suggest the potential for tissue specific CYP1C1-mediated PAH metabolism but not a more chronic role in progression to liver hepatocellular carcinoma.

  20. Expression of CYP1C1 and CYP1A in Fundulus heteroclitus during PAH-induced carcinogenesis

    Wang, Lu; Camus, Alvin C.; Dong, Wu; Thornton, Cammi; Willett, Kristine L.

    2010-01-01

    CYP1C1 is a relatively newly identified member of the cytochrome P450 family 1 in teleost fish. However, CYP1C1’s expression and physiological roles relative to the more recognized CYP1A in polycyclic aromatic hydrocarbons (PAHs) induced toxicities are unclear. Fundulus heteroclitus fry were exposed at 6–8 days post-hatch (dph) and again at 13–15 dph for 6 hr to dimethyl sulfoxide (DMSO) control, 5 mg/L benzo[a]pyrene (BaP), or 5 mg/L dimethylbenzanthracene (DMBA). Fry were euthanized at 0, 6, 18, 24 and 30 hr after the second exposure. In these groups, both CYP1A and CYP1C1 protein expression were induced within 6 hr after the second exposure. Immunohistochemistry (IHC) results from fry revealed strongest CYP1C1 expression in renal tubular and intestinal epithelial cells. Additional fish were examined for liver lesions eight months after initial exposure. Gross lesions were observed in 20% of the BaP and 35% of the DMBA-treated fish livers. Histopathologic findings included foci of cellular alteration and neoplasms, including hepatocellular adenoma, hepatocellular carcinoma and cholangioma. Strong CYP1A immunostaining was detected diffusely in altered cell foci and on the invading margin of hepatocelluar carcinomas. Lower CYP1A expression was seen in central regions of the neoplasms. In contrast, CYP1C1 was only detectable and highly expressed in proliferated bile duct epithelial cells. Our CYP1C1 results suggest the potential for tissue specific CYP1C1-mediated PAH metabolism but not a more chronic role in progression to liver hepatocellular carcinoma. PMID:20621368

  1. SREBP-1c, regulated by the insulin and AMPK signaling pathways, plays a role in nonalcoholic fatty liver disease.

    Kohjima, Motoyuki; Higuchi, Nobito; Kato, Masaki; Kotoh, Kazuhiro; Yoshimoto, Tsuyoshi; Fujino, Tatsuya; Yada, Masayoshi; Yada, Ryoko; Harada, Naohiko; Enjoji, Munechika; Takayanagi, Ryoichi; Nakamuta, Makoto

    2008-04-01

    Nonalcoholic fatty liver disease (NAFLD) is a common liver disease whose prevalence has increased markedly. We reported previously that fatty acid synthesis was enhanced in NAFLD with the accumulation of fatty acids. To clarify the disorder, we evaluated the expression of genes regulating fatty acid synthesis by real-time PCR using samples from NAFLD (n=22) and normal liver (control; n=10). A major regulator of fatty acids synthesis is sterol regulatory element-binding protein-1c (SREBP-1c). Its expression was significantly higher in NAFLD, nearly 5-fold greater than the controls. SREBP-1c is positively regulated by insulin signaling pathways, including insulin receptor substrate (IRS)-1 and -2. In NAFLD, IRS-1 expression was enhanced and correlated positively with SREBP-1c expression. In contrast, IRS-2 expression decreased by 50% and was not correlated with SREBP-1c. Forkhead box protein A2 (Foxa2) is a positive regulator of fatty acid oxidation and is itself negatively regulated by IRSs. Foxa2 expression increased in NAFLD and showed a negative correlation with IRS-2, but not with IRS-1, expression. It is known that SREBP-1c is negatively regulated by AMP-activated protein kinase (AMPK) but expression levels of AMPK in NAFLD were almost equal to those of the controls. These data indicate that, in NAFLD, insulin signaling via IRS-1 causes the up-regulation of SREBP1-c, leading to the increased synthesis of fatty acids by the hepatocytes; negative feedback regulation via AMPK does not occur and the activation of Foxa2, following a decrease of IRS-2, up-regulates fatty acid oxidation.

  2. Enzymes in CO2 Capture

    Fosbøl, Philip Loldrup; Gladis, Arne; Thomsen, Kaj

    of carbon capture is the application of enzymes for acceleration of typically slow ternary amines or inorganic carbonates. There is a hidden potential to revive currently infeasible amines which have an interesting low energy consumption for regeneration but too slow kinetics for viable CO2 capture. The aim......The enzyme Carbonic Anhydrase (CA) can accelerate the absorption rate of CO2 into aqueous solutions by several-fold. It exist in almost all living organisms and catalyses different important processes like CO2 transport, respiration and the acid-base balances. A new technology in the field...... of this work is to discuss the measurements of kinetic properties for CA promoted CO2 capture solvent systems. The development of a rate-based model for enzymes will be discussed showing the principles of implementation and the results on using a well-known ternary amine for CO2 capture. Conclusions...

  3. Mitotic Phosphorylation of TREX1 C Terminus Disrupts TREX1 Regulation of the Oligosaccharyltransferase Complex.

    Kucej, Martin; Fermaintt, Charles S; Yang, Kun; Irizarry-Caro, Ricardo A; Yan, Nan

    2017-03-14

    TREX1 mutations are associated with several autoimmune and inflammatory diseases. The N-terminal DNase domain of TREX1 is important for preventing self-DNA from activating the interferon response. The C terminus of TREX1 is required for ER localization and regulation of oligosacchariyltransferase (OST) activity. Here, we show that during mitosis TREX1 is predominately phosphorylated at the C-terminal Serine-261 by Cyclin B/CDK1. TREX1 is dephosphorylated quickly at mitotic exit, likely by PP1/PP2-type serine/threonine phosphatase. Mitotic phosphorylation does not affect TREX1 DNase activity. Phosphomimetic mutations of mitotic phosphorylation sites in TREX1 disrupted the interaction with the OST subunit RPN1. RNA-seq analysis of Trex1(-/-) mouse embryonic fibroblasts expressing TREX1 wild-type or phosphor-mutants revealed a glycol-gene signature that is elevated when TREX1 mitotic phosphorylation sites are disrupted. Thus, the cell-cycle-dependent post-translation modification of TREX1 regulates its interaction with OST, which may have important implications for immune disease associated with the DNase-independent function of TREX1.

  4. [Glycosylated hemoglobin A1c as a diagnostic test for diabetes mellitus in adolescents with overweight and obesity].

    Rivera-Hernández, Aleida; Zurita-Cruz, Jessie Nallely; Garrido-Magaña, Eulalia; Fiorentini-Fayad, Gigliola Margaretta; Nishimura-Meguro, Elisa

    2015-01-01

    Introducción: en 2009 se introdujo un criterio diagnóstico para la diabetes mellitus 2 (DM2) en población adulta, basado en los niveles de hemoglobina glucosilada (HbA1c) mayor o igual a 6.5 %; el punto de corte en población pediátrica podría ser menor. Se buscó determinar la utilidad de este criterio en adolescentes mexicanos con sobrepeso u obesidad. Métodos: se hizo somatometría completa, revisión del estadio de Tanner y presión arterial, glucemia, curva de tolerancia a la glucosa (CTOG) y HbA1c. Se calculó especificidad, sensibilidad, valores predictivos positivos y negativos y curva ROC para el diagnóstico de DM con HbA1c. Resultados: se estudiaron 109 pacientes entre 10 y 16 años referidos por obesidad o sobrepeso más comorbilidades, 58 % mujeres, edad 13 ± 1.74 años, IMC percentil 95.3 y HbA1c 5.73 ± 0.9 %. Se estableció el diagnóstico de DM en 9 casos (8.3 %), prediabetes en 8 (7.3 %) y tolerancia normal a la glucosa en 92 (84.4 %), el promedio de HbA1c fue de 5.6 ± 0.04, 5.7 ± 0.4 y 5.6 ± 0.73 %, respectivamente. La HbA1c mayor o igual a 6.5 % tuvo una sensibilidad de 12.5 %, especificidad de 89.8 %, VPP 10.65 y VPN 14.28. El mejor punto de corte para diagnosticar DM por curva ROC de HbA1c fue de 5.45 %, con sensibilidad de 62.5 % y especificidad de 57.1 %, VPP 2.53 y VPN 33.3. Conclusiones: el nivel de HbA1c mayor o igual a 6.5% tuvo baja sensibilidad y especificidad para diagnosticar DM. Un punto de corte menor es insuficiente para utilizar la HbA1c como criterio diagnóstico.

  5. Pathogenesis of POLR1C-dependent Type 3 Treacher Collins Syndrome revealed by a zebrafish model.

    Lau, Marco Chi Chung; Kwong, Ernest Man Lok; Lai, Keng Po; Li, Jing-Woei; Ho, Jeff Cheuk Hin; Chan, Ting-Fung; Wong, Chris Kong Chu; Jiang, Yun-Jin; Tse, William Ka Fai

    2016-06-01

    Treacher Collins Syndrome (TCS) is a rare congenital birth disorder (1 in 50,000 live births) characterized by severe craniofacial defects, including the downward slanting palpebral fissures, hypoplasia of the facial bones, and cleft palate (CP). Over 90% of patients with TCS have a mutation in the TCOF1 gene. However, some patients exhibit mutations in two new causative genes, POLR1C and POLR1D, which encode subunits of RNA polymerases I and III, that affect ribosome biogenesis. In this study, we examine the role of POLR1C in TCS using zebrafish as a model system. Our data confirmed that polr1c is highly expressed in the facial region, and dysfunction of this gene by knockdown or knock-out resulted in mis-expression of neural crest cells during early development that leads to TCS phenotype. Next generation sequencing and bioinformatics analysis of the polr1c mutants further demonstrated the up-regulated p53 pathway and predicted skeletal disorders. Lastly, we partially rescued the TCS facial phenotype in the background of p53 mutants, which supported the hypothesis that POLR1C-dependent type 3 TCS is associated with the p53 pathway.

  6. Degenerate Operators and the $1/c$ Expansion: Lorentzian Resummations, High Order Computations, and Super-Virasoro Blocks

    Chen, Hongbin; Kaplan, Jared; Li, Daliang; Wang, Junpu

    2016-01-01

    One can obtain exact information about Virasoro conformal blocks by analytically continuing the correlators of degenerate operators. We argued in recent work that this technique can be used to explicitly resolve information loss problems in AdS$_3$/CFT$_2$. In this paper we use the technique to perform calculations in the small $1/c \\propto G_N$ expansion: (1) we prove the all-orders resummation of logarithmic factors $\\propto \\frac{1}{c} \\log z$ in the Lorentzian regime, demonstrating that $1/c$ corrections directly shift Lyapunov exponents associated with chaos, as claimed in prior work, (2) we perform another all-orders resummation in the limit of large $c$ with fixed $cz$, interpolating between the early onset of chaos and late time behavior, (3) we explicitly compute the Virasoro vacuum block to order $1/c^2$ and $1/c^3$, corresponding to $2$ and $3$ loop calculations in AdS$_3$, and (4) we derive the heavy-light vacuum blocks in theories with $\\mathcal{N}=1,2$ superconformal symmetry.

  7. Biologic variability in plasma glucose, hemoglobin A1c, and advanced glycation end products associated with diabetes complications.

    Leslie, R David G; Cohen, Robert M

    2009-07-01

    Plasma glucose plays a key role in the complications of diabetes mellitus. Hemoglobin A1c (HbA1c) and circulating concentrations of advanced glycation end products (AGEs) are central to diabetes clinical care and pathophysiology. However, there is evidence for variation between individuals in the relationship of plasma glucose to both these measures and to specific complications. The glycation gap (GG) and hemoglobin glycation index represent tools for quantitating the variability in the relationship between plasma glucose and HbA1c useful for identification of underlying mechanisms. Recent evidence demonstrates the heritability of HbA1c, the GG, and AGEs, yet not of glycated serum proteins. There has been tremendous effort devoted to identifying the heritable basis of types 1 and 2 diabetes; however, studies on the heritable contributors to these mediators of glucose effect on complications are only beginning. New evidence for normal biologic variation in the distribution of glucose into the red blood cell (RBC) intracellular compartment and RBC lifespan in people with and without diabetes represent candidates for heritable mechanisms and contributors to the rise in HbA1c with age. Taken as a whole, genetic and mechanistic evidence suggests new potential targets for complications prevention and improvement in complications risk estimation. These observations could help tilt the risk-benefit balance in glycemic control toward a more beneficial outcome.

  8. Toothbrushing, Blood Glucose and HbA1c: Findings from a Random Survey in Chinese Population.

    Su, Lingyu; Liu, Wenzhao; Xie, Bingwu; Dou, Lei; Sun, Jun; Wan, Wenjuan; Fu, Xiaoming; Li, Guangyue; Huang, Jiao; Xu, Ling

    2016-07-07

    Both diabetes and periodontal disease are prevalent in China. Poor oral hygiene practice is the major cause of periodontal disease. An association between oral hygiene practice and blood glucose level was reported in individuals with diabetes, but not in the general population. We examined the association in a population-based random survey recruiting 2,105 adults without previously diagnosed diabetes in Chongqing city, China. Plasma glucose and hemoglobin A1c (HbA1c) were measured, and a 2-hour oral glucose tolerance test was conducted for each respondent. Self-reported toothbrushing frequency was used as a proxy for oral hygiene practice. In a linear model controlling for potential confounders (demographic characteristics, socio-economic status, lifestyle risk factors, BMI, dental visit frequency, etc.), urban residents who barely brushed their teeth had an increase of 0.50 (95% CI: 0.10-0.90) mmol/L in fasting plasma glucose, and an increase of 0.26% (0.04-0.47%) in HbA1c, relative to those brushing ≥twice daily; for rural residents, the effects were 0.26 (0.05-0.48) mmol/L in fasting plasma glucose and 0.20% (0.09-0.31%) in HbA1c. Individuals with better oral practice tended to have lower level of blood glucose and HbA1c. Establishing good oral health behavioral habits may be conducive to diabetes prevention and control in the general population.

  9. Effect of low glycemic load diet on glycated hemoglobin (HbA1c) in poorly-controlled diabetes patients.

    Ziaee, Amir; Afaghi, Ahmad; Sarreshtehdari, Majied

    2011-12-29

    Different carbohydrate diets have been administrated to diabetic patients to evaluate the glycemic response, while Poor-controlled diabetes is increasing world wide. To investigate the role of an alternative carbohydrate diet on glycemic control, we explored the effect of a low glycemic load (Low GL)-high fat diet on glycemic response and also glycated hemoglobin (HbA1c) of poor-controlled diabetes patients. Hundred poorly-controlled diabetes patients, HbA1c > 8, age 52.8 ± 4.5 y, were administrated a low GL diet , GL = 67 (Energy 1800 kcal; total fat 36%; fat derived from olive oil and nuts 15%; carbohydrate 42%; protein 22%) for 10 weeks. Patients did their routine life style program during intervention. Fasting blood glucose and HbA1c before and after intervention with significant reduction were: 169 ± 17, 141 ± 12; 8.85% (73 mmol/mol) ± 0.22%, and 7.81% (62 mmol/mol) ± 0.27%; respectively (P HbA1c by 1.1% (11 mmol/mol) ± 0.3% (P=0.001). There was positive moderate correlation between HbA1c concentration before intervention and FBS reduction after intervention (P diet can be effective in glycemic control.

  10. Taking the Mystery Out of Enzymes.

    DeYoung, H. Garrett

    1984-01-01

    Discusses structure and function of enzymes, design of new enzymes and enzyme substitutes, and enzyme uses in industry, medicine, and wastewater treatment. The latter is a low-cost method which can remove as much as 99 percent of toxic substances found in many industrial wastewater streams. (JN)

  11. A Model of Extracellular Enzymes in Free-Living Microbes: Which Strategy Pays Off?

    Thygesen, Uffe H.; Riemann, Lasse; Stedmon, Colin A.

    2015-01-01

    An initial modeling approach was applied to analyze how a single, nonmotile, free-living, heterotrophic bacterial cell may optimize the deployment of its extracellular enzymes. Free-living cells live in a dilute and complex substrate field, and to gain enough substrate, their extracellular enzymes must be utilized efficiently. The model revealed that surface-attached and free enzymes generate unique enzyme and substrate fields, and each deployment strategy has distinctive advantages. For a solitary cell, surface-attached enzymes are suggested to be the most cost-efficient strategy. This strategy entails potential substrates being reduced to very low concentrations. Free enzymes, on the other hand, generate a radically different substrate field, which suggests significant benefits for the strategy if free cells engage in social foraging or experience high substrate concentrations. Swimming has a slight positive effect for the attached-enzyme strategy, while the effect is negative for the free-enzyme strategy. The results of this study suggest that specific dissolved organic compounds in the ocean likely persist below a threshold concentration impervious to biological utilization. This could help explain the persistence and apparent refractory state of oceanic dissolved organic matter (DOM). Microbial extracellular enzyme strategies, therefore, have important implications for larger-scale processes, such as shaping the role of DOM in ocean carbon sequestration. PMID:26253668

  12. Sensor potency of the moonlighting enzyme-decorated cytoskeleton: the cytoskeleton as a metabolic sensor

    Norris Vic

    2013-02-01

    Full Text Available Abstract Background There is extensive evidence for the interaction of metabolic enzymes with the eukaryotic cytoskeleton. The significance of these interactions is far from clear. Presentation of the hypothesis In the cytoskeletal integrative sensor hypothesis presented here, the cytoskeleton senses and integrates the general metabolic activity of the cell. This activity depends on the binding to the cytoskeleton of enzymes and, depending on the nature of the enzyme, this binding may occur if the enzyme is either active or inactive but not both. This enzyme-binding is further proposed to stabilize microtubules and microfilaments and to alter rates of GTP and ATP hydrolysis and their levels. Testing the hypothesis Evidence consistent with the cytoskeletal integrative sensor hypothesis is presented in the case of glycolysis. Several testable predictions are made. There should be a relationship between post-translational modifications of tubulin and of actin and their interaction with metabolic enzymes. Different conditions of cytoskeletal dynamics and enzyme-cytoskeleton binding should reveal significant differences in local and perhaps global levels and ratios of ATP and GTP. The different functions of moonlighting enzymes should depend on cytoskeletal binding. Implications of the hypothesis The physical and chemical effects arising from metabolic sensing by the cytoskeleton would have major consequences on cell shape, dynamics and cell cycle progression. The hypothesis provides a framework that helps the significance of the enzyme-decorated cytoskeleton be determined.

  13. A model of extracellular enzymes in free-living microbes: which strategy pays off?

    Traving, Sachia J; Thygesen, Uffe H; Riemann, Lasse; Stedmon, Colin A

    2015-11-01

    An initial modeling approach was applied to analyze how a single, nonmotile, free-living, heterotrophic bacterial cell may optimize the deployment of its extracellular enzymes. Free-living cells live in a dilute and complex substrate field, and to gain enough substrate, their extracellular enzymes must be utilized efficiently. The model revealed that surface-attached and free enzymes generate unique enzyme and substrate fields, and each deployment strategy has distinctive advantages. For a solitary cell, surface-attached enzymes are suggested to be the most cost-efficient strategy. This strategy entails potential substrates being reduced to very low concentrations. Free enzymes, on the other hand, generate a radically different substrate field, which suggests significant benefits for the strategy if free cells engage in social foraging or experience high substrate concentrations. Swimming has a slight positive effect for the attached-enzyme strategy, while the effect is negative for the free-enzyme strategy. The results of this study suggest that specific dissolved organic compounds in the ocean likely persist below a threshold concentration impervious to biological utilization. This could help explain the persistence and apparent refractory state of oceanic dissolved organic matter (DOM). Microbial extracellular enzyme strategies, therefore, have important implications for larger-scale processes, such as shaping the role of DOM in ocean carbon sequestration.

  14. Insolubilized enzymes for food synthesis

    Marshall, D. L.

    1972-01-01

    Cellulose matrix with numerous enzyme-coated silica particles of colloidal size permanently bound at various sites within matrix was produced that has high activity and possesses requisite physical characteristics for filtration or column operations. Product also allows coupling step in synthesis of edible food to proceed under mild conditions.

  15. Kathepsine C : Een allosterisch enzyme

    Gorter, Jeannette

    1969-01-01

    In chapter I an introduction into allosteric systems is given. In chapter II is a detailed method is described for the applica of Gly-Phe--p. nitroanilide (GPNA) as a substrate for the activity assay of the lysosomal enzyme cathepsin C. It is an allosteric which is activated by Cl-, Br-, 1-, CNS-, N

  16. Rapid-Equilibrium Enzyme Kinetics

    Alberty, Robert A.

    2008-01-01

    Rapid-equilibrium rate equations for enzyme-catalyzed reactions are especially useful because if experimental data can be fit by these simpler rate equations, the Michaelis constants can be interpreted as equilibrium constants. However, for some reactions it is necessary to use the more complicated steady-state rate equations. Thermodynamics is…

  17. Enzyme nanoassemblies for biomass conversion

    Biomass represents a vast resource for the production of the world’s fuel and chemical feedstock needs. The use of enzymes to effect these bioconversions offers an alternative that is potentially more specific and environmentally-friendly than harsher chemical methodologies. Some species of anaero...

  18. Silica-Immobilized Enzyme Reactors

    2007-08-01

    immobilized artificial membrane chromatography and lysophospholipid micellar electrokinetic chromatography . J. Chromatogr. A 1998, 810, 95-103. 50...Journal of Liquid Chromatography and Related Technologies. Air Force Research Laboratory Materials and Manufacturing Directorate Airbase...immobilized enzyme reactors (IMERs) can also be integrated directly to further analytical methods such as liquid chromatography or mass spectrometry.[6] In

  19. Enzyme recovery using reversed micelles.

    Dekker, M.

    1990-01-01

    The objective of this study was to develop a liquid-liquid extraction process for the recovery of extracellular enzymes. The potentials of reaching this goal by using reversed micelles in an organic solvent have been investigated.Reversed micelles are aggregates of surfactant molecules containing an

  20. The enzymes associated with denitrification

    Hochstein, L. I.; Tomlinson, G. A.

    1988-01-01

    The enzymes involved in the reduction of nitrogenous oxides are thought to be intermediates in denitrification processes. This review examines the roles of nitrate reductase, nitrite reductases, nitric oxide reductase, mechanisms of N-N bond formation, and nitrous oxide reductases.

  1. A novel EB-1/AIDA-1 isoform, AIDA-1c, interacts with the Cajal body protein coilin

    Hebert Michael D

    2005-04-01

    Full Text Available Abstract Background Cajal bodies (CBs are nuclear suborganelles that play a role in the biogenesis of small nuclear ribonucleoproteins (snRNPs, which are crucial for pre-mRNA splicing. Upon nuclear reentry, Sm-class snRNPs localize first to the CB, where the snRNA moiety of the snRNP is modified. It is not clear how snRNPs target to the CB and are released from this structure after their modification. Coilin, the CB marker protein, may participate in snRNP biogenesis given that it can interact with snRNPs and SMN. SMN is crucial for snRNP assembly and is the protein mutated in the neurodegenerative disease Spinal Muscular Atrophy. Coilin knockout mice display significant viability problems and altered CB formation. Thus characterization of the CB and its associated proteins will give insight into snRNP biogenesis and clarify the dynamic organization of the nucleus. Results In this report, we identify a novel protein isoform of EB-1/AIDA-1, termed AIDA-1c, that interacts with the CB marker protein, coilin. Northern and nested PCR experiments reveal that the AIDA-1c isoform is expressed in brain and several cancer cell lines. Competition binding experiments demonstrate that AIDA-1c competes with SmB' for coilin binding sites, but does not bind SMN. When ectopically expressed, AIDA-1c is predominantly nuclear with no obvious accumulations in CBs. Interestingly, another EB-1/AIDA-1 nuclear isoform, AIDA-1a, does not bind coilin in vivo as efficiently as AIDA-1c. Knockdown of EB-1/AIDA-1 isoforms by siRNA altered Cajal body organization and reduced cell viability. Conclusion These data suggest that specific EB-1/AIDA-1 isoforms, such as AIDA-1c, may participate in the regulation of nucleoplasmic coilin protein interactions in neuronal and transformed cells.

  2. Hemoglobin A1c induced down-regulation of CD36 of Plasmodium Falciparum parasitized red cell

    Hassan Hijazi, Atif Alagib, Hisham Waggiallah

    2014-03-01

    Full Text Available Objective: High values of glycosylated hemoglobin have been found to correlate with decreased deformability of erythrocyte. CD36 (Cluster of Differentiation 36 is an integral membrane protein found on the surface of many cell types of class B scavenger receptor family. Plasmodium falciparum and diabetes mellitus is associated many complications. Aim of this study to investigate the down-regulation of HbA1c to CD36 on P. falciparum parasitized red blood cells Diabetes mellitus patients. Methods: This is cross section study conducted among diabetic patients attending in Jabir Abo Eleiz diabetic center in Khartoum state. Venous blood samples were collected in heparin containers for Plasmodium falciparum culture, and random blood sugar. For HbA1c in 0.04 mg EDTA anticoagulant, 2-5 ml of blood was collected. Sample size was 45 samples and was collected from known diabetic patients with HbA1c more than 8%. All data were analyzed by using Statistical Package for Social Science (SPSS. Results: show the mean difference between CD36 negative control and CD36 positive control was found to be statistically significant increasing of CD36 presence at P. value =0.001 (P ≤0.001. The mean difference between CD36 positive control and diabetic patients with HbA1C more 8% was found to be statistically significant reduction of CD36 expression at p=0.001. Conclusion: Hyperglycemia (HbA1c leads to decrease of CD36 expression and interfere with innate and active immunity. In this study HbA1c participates in increasing of P. falciparum malaria complications.

  3. HbA1c Predicts Time to Diagnosis of Type 1 Diabetes in Children at Risk.

    Helminen, Olli; Aspholm, Susanna; Pokka, Tytti; Hautakangas, Milla-Riikka; Haatanen, Nora; Lempainen, Johanna; Ilonen, Jorma; Simell, Olli; Knip, Mikael; Veijola, Riitta

    2015-05-01

    Prediction of type 1 diabetes is based on the detection of multiple islet autoantibodies in subjects who are at increased genetic risk. Prediction of the timing of diagnosis is challenging, however. We assessed the utility of HbA1c levels in predicting the clinical disease in genetically predisposed children with multiple autoantibodies. Cord blood samples from 168,055 newborn infants were screened for class II HLA genotypes in Finland, and 14,876 children with increased genetic risk for type 1 diabetes were invited to participate in regular follow-ups, including screening for diabetes-associated autoantibodies. When two or more autoantibodies were detected, HbA1c levels were analyzed at each visit. During follow-up, multiple (two or more) autoantibodies developed in 466 children; type 1 diabetes was diagnosed in 201 of these children (43%, progressors), while 265 children remained disease free (nonprogressors) by December 2011. A 10% increase in HbA1c levels in samples obtained 3-12 months apart predicted the diagnosis of clinical disease (hazard ratio [HR] 5.7 [95% CI 4.1-7.9]) after a median time of 1.1 years (interquartile range [IQR] 0.6-3.1 years) from the observed rise of HbA1c. If the HbA1c level was ≥5.9% (41 mmol/mol) in two consecutive samples, the median time to diagnosis was 0.9 years (IQR 0.3-1.5, HR 11.9 [95% CI 8.8-16.0]). In conclusion, HbA1c is a useful biochemical marker when predicting the time to diagnosis of type 1 diabetes in children with multiple autoantibodies.

  4. The correlation between the Glycated hemoglobin (HbA1c) in non-diabetics and cardiovascular risk factors.

    Wu, Xinling; Zhao, Youmin; Chai, Jianwen; Hao, Dongqin

    2016-01-01

    This study aimed to discuss the relativity between the glycated hemoglobin (HbA1c) in non-diabetics and cardiovascular risk factors and definite the significance of predicting the cardiovascular risk factors through cross-sectional research method. There were 2007 cases volunteers (including 650 cases of male, 1357 cases of female) from city community with complete information involved in the research of diabetes. The value of HbA1c 6.5% was set as the diagnose boundary of the diabetes. Differences were considered to be statistically significant at Prisk factors. Then we analyzed the number of risk factors for individuals in different HbA1c groups. Meanwhile, patients were grouped into zero, one, two, three, four or more groups with reference to the number of risk factors they had in order to compare the values of risk factors in different groups through Logistic regression. The results showed that (1) For those people who had no less than three risk factors, the frequency of risk factors was on the rise with the increase of HbA1c levels. (2) The value of HbA1c in different groups of risk factors rose with the increasing number of risk factors. There was a significant difference (Prisk factors. HbA1c levels, which can be a prediction index for cardiovascular risk factors dependent from other cardiovascular risk factors for non-diabetics, and it were highly relevant with impaired glucose tolerance (IGT) and impaired fasting blood glucose (FBG).

  5. HbA1c Levels among Primary Healthcare Patients with Type 2 Diabetes Mellitus in Oman

    Jawad A Al-Lawati

    2012-11-01

    Full Text Available Objectives: To investigate whether younger patients with type 2 diabetes mellitus have higher glycated hemoglobin A1c (HbA1c levels compared to older patients, and to determine the factors associated with higher HbA1c levels.Methods: Data from 1,266 patients from all over Oman were used to obtain the mean HbA1c level, odds ratios (OR, and 95% confidence intervals (CI from multiple logistic regression models with age groups, sex, duration of diabetes, diabetes treatment, body mass index, estimated glomerular filtration rate (eGFR, tobacco use, and healthcare index as predictors of good (HbA1c <7% vs.poor (≥7% glycemic control.Results: Mean HbA1c levels were 8.9, 8.3, and 7.8 in the age groups 20-39, 40-59 and 60+ years, respectively. After controlling for all other covariates, the OR of good glycemic control increased with age, 40-59 years old (OR=1.7; 95% CI 1.1 to 2.6 and 60+ year (OR=2.5; 95% CI 1.6 to 4.0, female gender (OR=1.5; 95% CI 1.2 to 2.0 and in patients with eGFR ≥60 mL/min/1.73 m2 (OR=1.9; 95% CI 1.1 to 3.3. Longer duration of diabetes (≥5years and treatment with oral agents or insulin were inversely related to good glycemic control.Conclusion: Younger Omani adults exhibit worse glycemic levels compared to older adults posing a formidable challenge to diabetes care teams.

  6. (+)Lysergic acid diethylamide, but not its nonhallucinogenic congeners, is a potent serotonin 5HT1C receptor agonist

    Burris, K.D.; Breeding, M.; Sanders-Bush, E. (Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (United States))

    1991-09-01

    Activation of central serotonin 5HT2 receptors is believed to be the primary mechanism whereby lysergic acid diethylamide (LSD) and other hallucinogens induce psychoactive effects. This hypothesis is based on extensive radioligand binding and electrophysiological and behavioral studies in laboratory animals. However, the pharmacological profiles of 5HT2 and 5HT1C receptors are similar, making it difficult to distinguish between effects due to activation of one or the other receptor. For this reason, it was of interest to investigate the interaction of LSD with 5HT1C receptors. Agonist-stimulated phosphoinositide hydrolysis in rat choroid plexus was used as a direct measure of 5HT1C receptor activation. (+)LSD potently stimulated phosphoinositide hydrolysis in intact choroid plexus and in cultures of choroid plexus epithelial cells, with EC50 values of 9 and 26 nM, respectively. The effect of (+)LSD in both systems was blocked by 5HT receptor antagonists with an order of activity consistent with interaction at 5HT1C receptors. Neither (+)-2-bromo-LSD nor lisuride, two nonhallucinogenic congeners of LSD, were able to stimulate 5HT1C receptors in cultured cells or intact choroid plexus. In contrast, lisuride, like (+)LSD, is a partial agonist at 5HT2 receptors in cerebral cortex slices and in NIH 3T3 cells transfected with 5HT2 receptor cDNA. The present finding that (+)LSD, but not its nonhallucinogenic congeners, is a 5HT1C receptor agonist suggests a possible role for these receptors in mediating the psychoactive effects of LSD.

  7. Virulence-Associated Enzymes of Cryptococcus neoformans

    2015-01-01

    Enzymes play key roles in fungal pathogenesis. Manipulation of enzyme expression or activity can significantly alter the infection process, and enzyme expression profiles can be a hallmark of disease. Hence, enzymes are worthy targets for better understanding pathogenesis and identifying new options for combatting fungal infections. Advances in genomics, proteomics, transcriptomics, and mass spectrometry have enabled the identification and characterization of new fungal enzymes. This review f...

  8. Thermodynamics of Enzyme-Catalyzed Reactions Database

    SRD 74 Thermodynamics of Enzyme-Catalyzed Reactions Database (Web, free access)   The Thermodynamics of Enzyme-Catalyzed Reactions Database contains thermodynamic data on enzyme-catalyzed reactions that have been recently published in the Journal of Physical and Chemical Reference Data (JPCRD). For each reaction the following information is provided: the reference for the data, the reaction studied, the name of the enzyme used and its Enzyme Commission number, the method of measurement, the data and an evaluation thereof.

  9. Platelet enzyme abnormalities in leukemias

    S Sharma

    2011-01-01

    Full Text Available Aim of the Study: The aim of this study was to evaluate platelet enzyme activity in cases of leukemia. Materials and Methods: Platelet enzymes glucose-6-phosphate dehydrogenase (G6PD, pyruvate kinase (PK and hexokinase (HK were studied in 47 patients of acute and chronic leukemia patients, 16 patients with acute myeloid leukemia (AML(13 relapse, three in remission, 12 patients with acute lymphocytic leukemia (ALL (five in relapse, seven in remission, 19 patients with chronic myeloid leukemia (CML. Results: The platelet G6PD activity was significantly low in cases of AML, ALL and also in CML. G6PD activity was normalized during AML remission. G6PD activity, although persistently low during ALL remission, increased significantly to near-normal during remission (P < 0.05 as compared with relapse (P < 0.01. Platelet PK activity was high during AML relapse (P < 0.05, which was normalized during remission. Platelet HK however was found to be decreased during all remission (P < 0.05. There was a significant positive correlation between G6PD and PK in cases of AML (P < 0.001 but not in ALL and CML. G6PD activity did not correlate with HK activity in any of the leukemic groups. A significant positive correlation was however seen between PK and HK activity in cases of ALL remission (P < 0.01 and CML (P < 0.05. Conclusions: Both red cell and platelet enzymes were studied in 36 leukemic patients and there was no statistically significant correlation between red cell and platelet enzymes. Platelet enzyme defect in leukemias suggests the inherent abnormality in megakaryopoiesis and would explain the functional platelet defects in leukemias.

  10. Enzymes involved in triglyceride hydrolysis.

    Taskinen, M R; Kuusi, T

    1987-08-01

    The lipolytic enzymes LPL and HL play important roles in the metabolism of lipoproteins and participate in lipoprotein interconversions. LPL was originally recognized to be the key enzyme in the hydrolysis of chylomicrons and triglyceride, but it also turned out to be one determinant of HDL concentration in plasma. When LPL activity is high, chylomicrons and VLDL are rapidly removed from circulation and a concomitant rise of the HDL2 occurs. In contrast, low LPL activity impedes the removal of triglyceride-rich particles, resulting in the elevation of serum triglycerides and a decrease of HDL (HDL2). Concordant changes of this kind in LPL and HDL2 are induced by many physiological and pathological perturbations. Finally, the operation of LPL is also essential for the conversion of VLDL to LDL. This apparently clear-cut role of LPL in lipoprotein interconversions is contrasted with the enigmatic actions of HL. The enzyme was originally thought to participate in the catalyses of chylomicron and VLDL remnants generated in the LPL reaction. However, substantial in vitro and in vivo data indicate that HL is a key enzyme in the degradation of plasma HDL (HDL2) in a manner which opposes LPL. A scheme is presented for the complementary actions of the two enzymes in plasma HDL metabolism. In addition, recent studies have attributed a role to HL in the catabolism of triglyceride-rich lipoproteins, particularly those containing apo E. However, this function becomes clinically important only under conditions where the capacity of the LPL-mediated removal system is exceeded. Such a situation may arise when the input of triglyceride-rich particles (chylomicrons and/or VLDL) is excessive or LPL activity is decreased or absent.

  11. Serum Uric Acid Levels were Dynamically Coupled with Hemoglobin A1c in the Development of Type 2 Diabetes

    Wei, Fengjiang; Chang, Baocheng; Yang, Xilin; Wang, Yaogang; Chen, Liming; Li, Wei-Dong

    2016-06-01

    The aim of the study was to decipher the relationship between serum uric acid (SUA) and glycated hemoglobin A1c (HbA1c) or fasting plasma glucose (FPG) in both type 2 diabetes mellitus (T2DM) patients and normal subjects. A total of 2,250 unrelated T2DM patients and 4,420 Han Chinese subjects from a physical examination population were recruited for this study. In T2DM patients SUA levels were negatively correlated with HbA1c (rs = ‑0.109, P = 0.000) and 2 h plasma glucose levels (rs = ‑0.178, P = 0.000). In the physical examination population, SUA levels were inversely correlated with HbA1c (rs = ‑0.175, P = 0.000) and FPG (rs = ‑0.131, P = 0.009) in T2DM patients but positively correlated with HbA1c (rs = 0.040, P = 0.012) and FPG (rs = 0.084, P = 0.000) in normal-glucose subjects. Multivariate analyses showed that HbA1c was significantly negatively associated with HUA both in T2DM patients (OR = 0.872, 95% CI: 0.790~0.963) and in the physical examination T2DM patients (OR = 0.722, 95% CI: 0.539~0.968). Genetic association studies in T2DM patients showed that alleles of two glucose-uric acid transporter genes, ABCG2 and SLC2A9 were significantly associated with SUA levels (P < 0.05). SUA level is inversely correlated with HbA1c in T2DM patients but positively correlated with HbA1c in normal-glucose subjects. The reverse transporting of uric acid and glucose in renal tubules might be accounted for these associations.

  12. Geo-correction Algorithm Based on Equivalent RD Model for ScanSAR of HJ-1-C Satellite

    Liu Jia-yin; Wen Shuang-yan; Zhang Hong-yi; Hong Wen

    2014-01-01

    HJ-1-C satellite is the first Synthetic Aperture Radar (SAR) satellite for civilian use in China, and it has a strip and scan mode. According to the characteristics of the ScanSAR of the HJ-1-C satellite, a geo-correction algorithm based on an equivalent RD model has been outlined in this paper on the basis of an ECS image processing algorithm and a traditional Range-Doppler location method. An azimuth mosaic was presented by a time series relationship, then the different burst was stitched b...

  13. An Atomic Force Microscopy Investigation of the Tracks Made by C+1-C+4 Bombardment on CR-39 Detectors

    赵葵; 吴秀坤; 郭继宇; 隋丽; 梅俊平; 倪嵋楠; 包轶文

    2003-01-01

    Carbon micro-clusters are accelerated by an HI-13 tandem accelerator.The plastic nuclear track detectors CR-39are irradiated by C1-C4 beams from the HI-13 tandem accelerator and the tracks in CR-39 are studied using an atomic force microscope(AFM).The depths and diameters of C1-C4 tracks are measured for the first time in a nanometre scale.An enhancement of the energy loss is obtained for carbon clusters related to single carbon ions with the same velocity.The results show that the AFM observation is very useful in the quantitative analysis of clusters in the track detector CR-39.

  14. Neuropathological staging of spinocerebellar ataxia type 2 by semiquantitative 1C2-positive neuron typing. Nuclear translocation of cytoplasmic 1C2 underlies disease progression of spinocerebellar ataxia type 2.

    Koyano, Shigeru; Yagishita, Saburo; Kuroiwa, Yoshiyuki; Tanaka, Fumiaki; Uchihara, Toshiki

    2014-11-01

    Spinocerebellar ataxia type 2 (SCA2) is a hereditary neurodegenerative disorder caused by the expansion of the trinucleotide CAG repeats encoding elongated polyglutamine tract in ataxin-2, the SCA2 gene product. Polyglutamine diseases comprise nine genetic entities, including seven different forms of spinocerebellar ataxias, Huntington's disease, and spinal and bulbar muscular atrophy. These are pathologically characterized by neuronal loss and intranuclear aggregates or inclusions of mutant proteins including expanded polyglutamine in selected neuronal groups. Previously, we examined immunolocalization of ubiquitin, expanded polyglutamine (probed by 1C2 antibody), and ataxin-2 in genetically confirmed SCA2 patients. In the present study, we expanded this approach by distinguishing different patterns of subcellular 1C2 immunoreactivity ("granular cytoplasmic," "cytoplasmic and nuclear" and "nuclear with inclusions.") and by quantifying their regional frequencies in three autopsied SCA2 brains at different stage of the disease. Comparison with neuronal loss and gliosis revealed that overall 1C2 immunoreactivity was paralleled with their severity. Furthermore, appearance of granular cytoplasmic pattern corresponded to early stage, cytoplasmic and nuclear pattern to active stage, and nuclear with inclusions pattern to final stage. We conclude that this 1C2-immunoreactive typing may be useful for evaluating the overall severity and extent of affected regions and estimating the neuropathological stage of SCA2.

  15. A single-step enzyme immunoassay capillary sensor composed of functional multilayer coatings for the diagnosis of marker proteins.

    Funano, Shun-ichi; Sugahara, Masato; Henares, Terence G; Sueyoshi, Kenji; Endo, Tatsuro; Hisamoto, Hideaki

    2015-03-07

    A single-step, easy-to-use enzyme immunoassay capillary sensor, composed of functional multilayer coatings, was developed in this study. The coatings were composed of substrate-immobilized hydrophobic coating, hydrogel coating, and soluble coating containing an enzyme-labeled antibody. The response mechanism involved a spontaneous immunoreaction triggered by capillary action-mediated introduction of a sample antigen solution and subsequent separation of unreacted enzyme-labeled antibodies and antigen-enzyme-labeled antibody complexes by the molecular sieving effect of the hydrogel. An enzyme reaction at the substrate-immobilized hydrophobic coating/hydrogel coating interface resulted in a protein-selective fluorescence response. An antigen concentration-dependent response was obtained for diagnostic marker protein samples (hemoglobin A1c (HbA1c), 7.14-16.7 mg mL(-1); alpha-fetoprotein (AFP), 1.4-140 ng mL(-1); C-reactive protein (CRP), 0.5-10 μg mL(-1)) that cover a clinically important concentration range. The successful measurement of CRP in diluted serum samples demonstrated the application of this capillary sensor.

  16. 7 CFR 58.436 - Rennet, pepsin, other milk clotting enzymes and flavor enzymes.

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Rennet, pepsin, other milk clotting enzymes and flavor enzymes. 58.436 Section 58.436 Agriculture Regulations of the Department of Agriculture (Continued... clotting enzymes and flavor enzymes. Enzyme preparations used in the manufacture of cheese shall be...

  17. Partial characterization of proteolytic enzymes of Microsporum canis and Microsporum cookei.

    Simpanya, M F; Baxter, M

    1996-01-01

    Characterization by proteinase inhibitors of the enzymes produced by Microsporum spp. revealed that Microsporum canis and Microsporum cookei produce serine proteinase(s), but only M. canis expresses aspartic and cysteine proteinases and probably a metalloproteinase. Both M. canis and M. cookei expressed metalloelastinolytic proteinases. All the proteinase types have been implicated in the pathogenicity of a wide range of microorganisms.

  18. Molecular diversity of RelA enzyme in marine bacteria- A bioinformatics analysis

    Nath, A; Tresa, R.A; Alornekar, A; Varghese, N

    of proteins. The RelA enzyme is present in different marine bacteria. Since the VBNC state is generally implicated in pathogenesis and the outbreak of diseases, the molecular study of RelA is important. Hence, the present study analyzes the data of the RelA...

  19. Enzyme technology: Key to selective biorefining

    Meyer, Anne S.

    2014-01-01

    to the reaction is a unique trait of enzyme catalysis. Since enzyme selectivity means that a specific reaction is catalysed between particular species to produce definite products, enzymes are particularly fit for converting specific compounds in mixed biomass streams. Since enzymes are protein molecules...... their rational use in biorefinery processes requires an understanding of the basic features of enzymes and reaction traits with respect to specificity, kinetics, reaction optima, stability and structure-function relations – we are now at a stage where it is possible to use nature’s enzyme structures as starting...... point and then improve the functional traits by targeted mutation of the protein. The talk will display some of our recent hypotheses related to enzyme action, recently obtained results within knowledge-based enzyme improvements as well as cast light on research methods used in optimizing enzyme...

  20. Visualizing Changes in Cdkn1c Expression Links Early-Life Adversity to Imprint Mis-regulation in Adults

    Mathew Van de Pette

    2017-01-01

    Full Text Available Imprinted genes are regulated according to parental origin and can influence embryonic growth and metabolism and confer disease susceptibility. Here, we designed sensitive allele-specific reporters to non-invasively monitor imprinted Cdkn1c expression in mice and showed that expression was modulated by environmental factors encountered in utero. Acute exposure to chromatin-modifying drugs resulted in de-repression of paternally inherited (silent Cdkn1c alleles in embryos that was temporary and resolved after birth. In contrast, deprivation of maternal dietary protein in utero provoked permanent de-repression of imprinted Cdkn1c expression that was sustained into adulthood and occurred through a folate-dependent mechanism of DNA methylation loss. Given the function of imprinted genes in regulating behavior and metabolic processes in adults, these results establish imprinting deregulation as a credible mechanism linking early-life adversity to later-life outcomes. Furthermore, Cdkn1c-luciferase mice offer non-invasive tools to identify factors that disrupt epigenetic processes and strategies to limit their long-term impact.

  1. Visualizing Changes in Cdkn1c Expression Links Early-Life Adversity to Imprint Mis-regulation in Adults.

    Van de Pette, Mathew; Abbas, Allifia; Feytout, Amelie; McNamara, Gráinne; Bruno, Ludovica; To, Wilson K; Dimond, Andrew; Sardini, Alessandro; Webster, Zoe; McGinty, James; Paul, Eleanor J; Ungless, Mark A; French, Paul M W; Withers, Dominic J; Uren, Anthony; Ferguson-Smith, Anne C; Merkenschlager, Matthias; John, Rosalind M; Fisher, Amanda G

    2017-01-31

    Imprinted genes are regulated according to parental origin and can influence embryonic growth and metabolism and confer disease susceptibility. Here, we designed sensitive allele-specific reporters to non-invasively monitor imprinted Cdkn1c expression in mice and showed that expression was modulated by environmental factors encountered in utero. Acute exposure to chromatin-modifying drugs resulted in de-repression of paternally inherited (silent) Cdkn1c alleles in embryos that was temporary and resolved after birth. In contrast, deprivation of maternal dietary protein in utero provoked permanent de-repression of imprinted Cdkn1c expression that was sustained into adulthood and occurred through a folate-dependent mechanism of DNA methylation loss. Given the function of imprinted genes in regulating behavior and metabolic processes in adults, these results establish imprinting deregulation as a credible mechanism linking early-life adversity to later-life outcomes. Furthermore, Cdkn1c-luciferase mice offer non-invasive tools to identify factors that disrupt epigenetic processes and strategies to limit their long-term impact.

  2. L-1-C-11-tyrosine PET in patients with laryngeal carcinomas : Comparison of standardized uptake value and protein synthesis rate

    de Boer, [No Value; Pruim, J; van der Laan, BFAM; Que, TH; Willemsen, ATM; Albers, FWJ; Vaalburg, W

    2003-01-01

    PET with L-1-C-11-tyrosine (TYR) can measure and quantify increased protein synthesis in tumor tissue in vivo. For quantification of the protein synthesis rate (PSR), arterial cannulation with repeated blood sampling to obtain the plasma input function and a dynamic TYR PET study to calculate a time

  3. Short synthesis of the C1-C14 stretch of discodermolide from building blocks prepared by asymmetric catalysis.

    Cao, Huanyan; Parker, Kathlyn A

    2008-04-01

    A convergent and stereoselective synthesis of the C1-C14 stretch of (+)-discodermolide demonstrates the utility of the "asymmetric catalysis approach" to complex polypropionates. The preparation of this complex synthon requires 15 steps in the longest linear sequence and 19 steps total from inexpensive materials.

  4. Identification of Orch3, a locus controlling dominant resistance to autoimmune orchitis, as kinesin family member 1C.

    Roxana del Rio

    Full Text Available Experimental autoimmune orchitis (EAO, the principal model of non-infectious testicular inflammatory disease, can be induced in susceptible mouse strains by immunization with autologous testicular homogenate and appropriate adjuvants. As previously established, the genome of DBA/2J mice encodes genes that are capable of conferring dominant resistance to EAO, while the genome of BALB/cByJ mice does not and they are therefore susceptible to EAO. In a genome scan, we previously identified Orch3 as the major quantitative trait locus controlling dominant resistance to EAO and mapped it to chromosome 11. Here, by utilizing a forward genetic approach, we identified kinesin family member 1C (Kif1c as a positional candidate for Orch3 and, using a transgenic approach, demonstrated that Kif1c is Orch3. Mechanistically, we showed that the resistant Kif1c(D2 allele leads to a reduced antigen-specific T cell proliferative response as a consequence of decreased MHC class II expression by antigen presenting cells, and that the L(578 → P(578 and S(1027 → P(1027 polymorphisms distinguishing the BALB/cByJ and DBA/2J alleles, respectively, can play a role in transcriptional regulation. These findings may provide mechanistic insight into how polymorphism in other kinesins such as KIF21B and KIF5A influence susceptibility and resistance to human autoimmune diseases.

  5. Standardized uptake value and quantification of metabolism for breast cancer imaging with FDG and L-[1-C-11]tyrosine PET

    Kole, AC; Nieweg, OE; Pruim, J; Paans, AMJ; Plukker, JTM; Hoekstra, HJ; Vaalburg, W; Schraffordt Koops, H.

    1997-01-01

    The aims of the study were to compare the value of L-[1-C-11]tyrosine (TYR) and [F-18]fluoro-2-deoxy-D-glucose (FDG) as tumor tracers in patients with breast cancer, to investigate the correlation between quantitative values and standardized uptake values (SUVs) and to estimate the value of SUVs for

  6. Deeply embedded objects and shocked molecular hydrogen : The environment of the FU Orionis stars RNO 1B/1C

    Quanz, S. P.; Henning, Th.; Bouwman, J.; Linz, H.; Lahuis, F.

    2007-01-01

    We present Spitzer IRAC and IRS observations of the dark cloud L1287. The mid-infrared ( MIR) IRAC images show deeply embedded infrared sources in the vicinity of the FU Orionis objects RNO 1B and RNO 1C, suggesting their association with a small young stellar cluster. We resolve for the first time

  7. Medtner: Konzert für Klavier und Orchester Nr. 1 c-Moll op. 33 / Volkmar Fischer

    Fischer, Volkmar

    1992-01-01

    Uuest heliplaadist "Medtner: Konzert für Klavier und Orchester Nr. 1 c-Moll op. 33, Sonaten-Ballade für Klavier Fis-Dur op. 27. London Philharmonic Orchestra / Neeme Järvi". Chandos/Koch CD9039 (WD:54'28")

  8. Dose-response relationship between periodontal inflamed surface area and HbA1c in type 2 Diabetics

    Nesse, Willem; Linde, Annemiek; Abbas, Frank; Spijkervet, Frederik Karst Lucien; Dijkstra, Pieter Ubele; de Brabander, Eric Carl; Gerstenbluth, Izzy; Vissink, Arjan

    2009-01-01

    Nesse W, Linde A, Abbas F, Spijkervet FKL, Dijkstra PU, de Brabander EC, Gerstenbluth I, Vissink A. Dose-response relationship between periodontal inflamed surface area and HbA1c in type 2 diabetics. J Clin Periodontol 2009; 36: 295-300. doi: 10.1111/j.1600-051X.2009.01377.x. A dose-response relatio

  9. 26 CFR 1.404(a)-6 - Pension and annuity plans; limitations under section 404(a)(1)(C).

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Pension and annuity plans; limitations under... Plans, Etc. § 1.404(a)-6 Pension and annuity plans; limitations under section 404(a)(1)(C). (a... year of the employer which does not end with or within a taxable year of the pension trust or...

  10. Changes in Bone Alkaline Phosphatase and Procollagen Type-1 C-Peptide after Static and Dynamic Exercises

    Kubo, Keitaro; Yuki, Kazuhito; Ikebukuro, Toshihiro

    2012-01-01

    We investigated the effects of two types of nonweight-bearing exercise on changes in bone-specific alkaline phosphatase (BAP) and pro-collagen type 1 C-peptide (P1P). BAP is a specific marker of bone synthesis, whereas P1P reflects synthesis of type 1 collagen in other organs as well as bone. Eight participants performed static and dynamic…

  11. Prediabetic increase in hemoglobin A1c compared with impaired fasting glucose in patients receiving antipsychotic drugs

    Manu, Peter; Correll, Christoph U.; Wampers, Martien; van Winkel, Ruud; Yu, Weiping; Mitchell, Alex J.; De Hert, Marc

    2013-01-01

    Background: In 2010, the American Diabetes Association recommended that individuals with hemoglobin A1c 5.7-6.4% be classified as prediabetic even in the absence of impaired fasting glucose (IFG). Aim of study: To compare the clinical and metabolic characteristics of patients receiving antipsychotic

  12. Drosophila HP1c is regulated by an auto-regulatory feedback loop through its binding partner Woc.

    Jochen Abel

    Full Text Available HP1 is a major component of chromatin and regulates gene expression through its binding to methylated histone H3. Most eukaryotes express at least three isoforms of HP1 with similar domain architecture. However, despite the common specificity for methylated histone H3, the three HP1 isoforms bind to different regions of the genome. Most of the studies so far focused on the HP1a isoform and its role in transcriptional regulation. As HP1a requires additional factors to bind methylated chromatin in vitro, we wondered whether another isoform might also require additional targeting factors. Indeed, we found that HP1c interacts with the DNA binding factors Woc and Row and requires Woc to become targeted to chromatin in vivo. Moreover, we show that the interaction between HP1c and Woc constitutes a transcriptional feedback loop that operates to balance the concentration of HP1c within the cell. This regulation may prevent HP1c from binding to methylated heterochromatin.

  13. A novel processing system of sterol regulatory element-binding protein-1c regulated by polyunsaturated fatty acid.

    Nakakuki, Masanori; Kawano, Hiroyuki; Notsu, Tatsuto; Imada, Kazunori; Mizuguchi, Kiyoshi; Shimano, Hitoshi

    2014-05-01

    The proteolytic cascade is the key step in transactivation of sterol regulatory element-binding proteins (SREBPs), a transcriptional factor of lipid synthesis. Proteolysis of SREBP-2 is strictly regulated by sterols, but that of SREBP-1c was not strongly sterol-regulated, but inhibited by polyunsaturated fatty acids (PUFAs). In this study, the proteolytic processing of SREBP-1 and -2 was examined by transfection studies of cDNA-encoding mutants in which all the known cleavage sites were disrupted. In cultured cells, sterol-regulated SREBP-2 processing was completely eliminated by mutation of cleavage sites. In contrast, the corresponding SREBP-1c mutants as well as wild type exhibited large amounts of cleaved products in the nuclear extracts from culture cells and murine liver in vivo. The nuclear form of the mutant SREBP-1c was induced by delipidated condition and suppressed by eicosapentaenoic acid, an n-3 PUFA, but not by sterols. This novel processing mechanism was affected by neither SREBP cleavage-activating protein (SCAP) nor insulin-induced gene (Insig)-1, unlike SREBP-2, but abolished by a serine protease inhibitor. Through analysis of deletion mutant, a site-2 protease recognition sequence (DRSR) was identified to be involved in this novel processing. These findings suggest that SREBP-1c cleavage could be subjected to a novel PUFA-regulated cleavage system in addition to the sterol-regulatory SCAP/Insig system.

  14. JMJD1C demethylates MDC1 to regulate the RNF8 and BRCA1-mediated chromatin response to DNA breaks

    Watanabe, Sugiko; Watanabe, Kenji; Akimov, Vyacheslav;

    2013-01-01

    Chromatin ubiquitylation flanking DNA double-strand breaks (DSBs), mediated by RNF8 and RNF168 ubiquitin ligases, orchestrates a two-branch pathway, recruiting repair factors 53BP1 or the RAP80-BRCA1 complex. We report that human demethylase JMJD1C regulates the RAP80-BRCA1 branch of this DNA...

  15. Hipk2 and PP1c Cooperate to Maintain Dvl Protein Levels Required for Wnt Signal Transduction

    Nobuyuki Shimizu

    2014-09-01

    Full Text Available The phosphoprotein Dishevelled (Dvl is a common essential component of Wnt/β-catenin and Wnt/planar cell polarity (PCP signaling pathways. However, the regulation and significance of Dvl phosphorylation are not fully understood. Here, we show that homeodomain-interacting protein kinase 2 (Hipk2 facilitates protein phosphatase 1 catalytic subunit (PP1c-mediated dephosphorylation of Dvl via its C-terminal domain and that this dephosphorylation blocks ubiquitination and consequent degradation mediated by the E3 ubiquitin ligase Itch, which targets the phosphorylated form of Dvl proteins. Inhibition of Hipk2 or PP1c function reduces Dvl protein levels and suppresses Wnt/β-catenin and Wnt/PCP pathway-dependent events in mammalian cells and zebrafish embryos, suggesting that Hipk2 and PP1c are essential for maintaining Dvl protein levels that are sufficient to activate Wnt signaling. We also show that Wnt-3a, a Wnt/β-catenin ligand, induces dissociation of the Dvl-Hipk2-PP1c complex and Dvl degradation under high-cell-density conditions. This regulation may be a negative feedback mechanism that fine-tunes Wnt/β-catenin signaling.

  16. Distinct morphophenotypic features of chronic B-cell leukaemias identified with CD1c and CD23 antibodies.

    Orazi, A; Cattoretti, G; Polli, N; Delia, D; Rilke, F

    1991-07-01

    Morphological criteria usually applied to diagnose various subtypes of B-cell chronic lymphoid leukaemia are largely subjective. Immunophenotyping of 61 relevant cases using a selected panel of monoclonal antibodies (mAb), showed that CD1c and CD23 mAb were able to separate B-cell chronic lymphocytic leukaemia (B-CLL) from other chronic B-cell lymphoproliferative diseases. Lymphocytes of B-CLL were CD1c-, CD23+, whereas those of other types of chronic B-cell leukaemia were CD1c+/-, CD23-, and CD38/-. Non-B-CLL cases had a significantly higher amount of large peroxidase-negative (unstained) cells analyzed with an automated blood cell counter (Technicon H6000). This type of volumetric assessment allowed a separation between typical and "atypical" B-CLL, which otherwise were both CD1c-, and CD23+. These combinations of phenotypic markers corresponded to well-defined haematopathologic entities, conventionally diagnosed on peripheral blood (PB) and bone marrow smears, and on histologic sections of lymph nodes and spleen.

  17. Functional analysis of naturally occurring DCLRE1C mutations and correlation with the clinical phenotype of ARTEMIS deficiency

    K. Felgentreff (Kerstin); Y.N. Lee (Yu Nee); F. Frugoni (Francesco); L. Du (Likun); M. van der Burg (Mirjam); S. Giliani; I. Tezcan (Ilhan); I. Reisli (Ismail); E. Mejstříková (Ester); J.P. de Villartay; B.P. Sleckman (Barry P.); J. Manis (John); L.D. Notarangelo (Luigi Daniele)

    2015-01-01

    textabstractBackground The endonuclease ARTEMIS, which is encoded by the DCLRE1C gene, is a component of the nonhomologous end-joining pathway and participates in hairpin opening during the V(D)J recombination process and repair of a subset of DNA double-strand breaks. Patients with ARTEMIS deficien

  18. Regulation of the New Arabidopsis Imprinted Gene AtBMI1C Requires the Interplay of Different Epigenetic Mechanisms

    Fabian Bratzel; ChaoYang; Alexandra Ancelova; Gema López-Torrejón; Marcus Koch; Juan Carlos del Pozo; Myriam Calonje

    2012-01-01

    Recently,it has been shown that plants contain homologs to the animal Polycomb repressive complex 1 (PRC1)components BMI1 and RING1A/B.In Arabidopsis,there are three BMI1-like genes,two of which,AtBMI1A and B,are required during post-embryonic plant growth to repress embryonic traits and allow cell differentiation.However,little is known about the third BMI1-like gene,AtBMI1C.In this work,we show that AtBMI1C is only expressed during endosperm and stamen development.AtBMI1C is an imprinted gene expressed from the maternal allele in the endosperm but biallelically expressed in stamen.We found that the characteristic expression pattern of AtBMI1C is the result of a complex epigenetic regulation that involves CG DNA methylation,RNA-directed non-CG DNA methylation (RdDM),and PcG activity.Our results show the orchestrated interplay of different epigenetic mechanisms in regulating gene expression throughout development,shedding light on the current hypotheses for the origin and mechanism of imprinting in plant endosperm.

  19. Variation in point-of-care testing of HbA1c in diabetes care general practice

    Kristensen, Troels

    2016-01-01

    Background and Aims Point-of-care testing (POCT) for HbA1c may result in improved diabetic control, better patient outcomes and enhanced clinical efficiency with fewer patient visits and subsequent reductions in costs. In 2008, the Danish regulators agreed to create a new fee for the remuneration...... of POCT of HbA1c in primary care. The aim of this study is to describe and analyze the variation in use of POCT of HbA1c among diabetes patients in Danish general practice and municipalities. Method We use register data from the year 2011 to define a population of 172,906 diabetes patients. The POCT fee...... is used to measure the amount of POCT of HbA1c among diabetes patients. Next we apply descriptive statistics to analyze variation in the prevalence of POCT versus laboratory testing at patient, clinic and municipality level. We include patient characteristics such as gender, age, socioeconomic markers...

  20. Role of Altered Venous Blood Lactate and HbA1c in Women with Gestational Diabetes Mellitus

    Santhosh, N U; Krishnamurthy, N; Chethan, Chethana; Shilpashree, M K

    2016-01-01

    Introduction Being a mirror image of metabolic syndrome, Gestational Diabetes Mellitus (GDM) is associated with significant maternal and fetal morbidity. Increased blood lactate concentration and alterations of substrate utilization are partly involved in development of insulin resistance in GDM. Fetuses born to such mothers have shown low umbilical vein oxygen saturation and low oxygen content and increased lactate concentrations. These changes may certainly reflect enhanced fetal metabolism as a result of hyperglycaemia and hyperinsulinemia and therefore, these fetuses deserve intense surveillance at term and during delivery. Ideally, HbA1c should be maintained below 5% during their first trimesters and below 6% during third trimester. We planned to investigate GDM women for their HbA1c levels too. Aim To know if there is any alteration in blood lactate and/or HbA1c levels and to know if there is any correlation between these two parameters in GDM pregnancies, in comparison with the previous studies which measured lactate in cord blood and placental vessels of GDM women. Materials and Methods It was a hospital based prospective study on 40 women with gestational diabetes and 40 age-matched normal pregnant women. We analysed the biochemical and metabolic mileau in these women by estimating venous blood lactate and HbA1c levels. We paid special attention to follow them up regarding maternal complications if any and perinatal outcomes. The independent samples t-test and Pearson’s correlation test were applied. Results GDM mothers showed significantly higher lactate and HbA1c levels than normal pregnant women, both with p<0.001. Blood pressure and fetal birth weight were also significantly higher in GDM group than Normal Pregnant (NP) group, both with p-values of <0.001. Further, this increased lactate levels showed significant positive correlation with HbA1c, blood pressure and fetal birth weight. Conclusion Maternal blood lactate and HbA1c levels have a