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Sample records for recombinante heberbiovac hb

  1. HB - MAC: Improving the Random - HB # Authentication Protocol

    NASA Astrophysics Data System (ADS)

    Rizomiliotis, Panagiotis

    The Random - HB # protocol is a significant improvement of the HB + protocol introduced by Juels and Weis for the authentication of low-cost RFID tags. Random - HB # improves HB + in terms of both security and practicality. It is provably resistant against man-in-the-middle attacks, where the adversary can modify messages send from the reader to the tag and performs significantly better than HB + , since it reduces the transmission costs and provides more practical error rates. The only problem with Random - HB # is that the storage costs for the secret keys are insurmountable to low cost tags. The designers of the protocol have proposed also an enhanced variant which has less storage requirements, but it is not supported by a security proof. They call this variant just HB #. In this paper we propose a variant of the Random - HB #. The new proposal maintains the performance of the Random - HB #, but it requires significantly less storage for the key. To achieve that we add a lightweight message authentication code to protect the integrity of all the exchanged messages.

  2. A Novel Probabilistic Passive Attack on the Protocols HB and HB+

    NASA Astrophysics Data System (ADS)

    Carrijo, José; Tonicelli, Rafael; Imai, Hideki; Nascimento, Anderson C. A.

    We present a very simple probabilistic, passive attack against the protocols HB and HB+. Our attack presents some interesting features: it requires less captured transcripts of protocol executions when compared to previous results; It makes possible to trade the amount of required transcripts for computational complexity; the value of noise used in the protocols HB and HB+ need not be known.

  3. Hemoglobin (Hb) Val de Marne (Hb Footscray) in Brazil: the first case report.

    PubMed

    Okumura, J V; Shimauti, E L T; Silva, D G H; Torres, L S; Belini-Junior, E; Oliveira, R G; Patussi, E V; Herrero, J C M; Bonini-Domingos, C R

    2016-01-01

    Hemoglobin (Hb) variants involving alpha-chains are less common in the global population than Hb variants resulting from beta-chain alterations. Generally, alpha-chain Hb variants are caused by point mutations affecting alpha-1 and/or alpha-2 genes of the alpha-globin cluster (HBA1 and HBA2). In Brazil, the most prevalent alpha-chain Hb variant is Hb Hasharon. In this study, we present the first case of an Hb Val de Marne variant in the Americas, specifically in Brazil. PMID:27421014

  4. Adherence of Streptococcus salivarius HB and HB-7 to oral surfaces and saliva-coated hydroxyapatite.

    PubMed Central

    Weerkamp, A H; McBride, B C

    1980-01-01

    We compared the binding of Streptococcus salivarius HB and the mutant HB-7 to oral surfaces in vivo. Mutant HB-7 does not aggregate with saliva nor does it bind to buccal epithelium, but it does retain its ability to coaggregate with Veillonella and Fusobacterium. At 1 h after inoculation into the oral cavity of six volunteers, significantly more S. salivarius HB than HB-7 cells were found adhering to the buccal mucosa (P < 0.05) and to a cleaned tooth surface (P < 0.01); there was no significant difference in the numbers adhering to the tongue. The ratio of HB to HB-7 on the tongue increased in samples taken 1, 3, and 9 days after inoculation. The average time required to clear the mutant HB-7 from the oral cavity was 7 days, whereas that for the parent HB was greater than 20 days, and in some cases strain HB was still present 3 months after its inoculation. A representative S. salivarius serotype II strain, designated T3, behaved similarly to mutant HB-7 with respect to its adherence to the buccal mucosa. Strain HB adhered better to hydroxyapatite treated with human saliva than mutant HB-7; both strains adhered in similar numbers to untreated hydroxyapatite. Hydroxyapatite treated with rat saliva bound less HB than hydroxyapatite treated with human saliva, corresponding to the lower aggregating activity of rat saliva. Extraction of saliva with aggregating strains of S. salivarius reduced the ability of saliva to mediate attachment of strain HB to hydroxyapatite. PMID:7439971

  5. HbD Punjab/HbQ India Compound Heterozygosity: An Unusual Association

    PubMed Central

    Colaco, Stacy; Surve, Reema; Sawant, Pratibha; Nadkarni, Anita; Ghosh, Kanjaksha; Colah, Roshan

    2014-01-01

    Background Haemoglobinopathies are the commonest hereditary disorders in India and pose a major health problem. Both beta thalassaemia and structural haemoglobin variants are relatively common in northwestern India. Here we report a 29-year-old Sindhi female who was referred to us for a haemoglobinopathy work up and genetic counseling since her spouse was a classical beta thalassaemia carrier. Method A complete blood count was done on an automated cell counter. Haemoglobin analysis was carried out using HPLC Variant Haemoglobin Testing System. The cellulose acetate electrophoresis was carried out [pH 8.9]. Confirmation of mutations was done by automated DNA sequencing. Results HPLC analysis showed four major peaks, HbA0, a peak in the HbD window, an unknown peak [retention time 4.74 minutes] and a peak in the HbC window. The HbA2 level was 2.2%, and the HbF level was 0.7%. Cellulose acetate electrophoresis at alkaline pH, a slow moving band was seen at the HbS/D position along with a prominent band at the HbA2 position. DNA sequencing of the β and α genes showed presence of the two hemoglobin variants: Hb D [β 121GAA → CAA] and Hb Q [α 64 AAG → GAG]. The δ globin gene was normal. The additional peak in the HbC window was due to the formation of a heterodimer hybrid. Conclusion Both HbD Punjab and HbQ India are relatively common in India, but their co-inheritance has not been described in the country. This case is the third report of compound heterozygosity for HbQ India/HbD Punjab haemoglobinopathy globally and the second one from India. PMID:25408858

  6. The xerocytosis of Hb SC disease.

    PubMed

    Ballas, S K; Larner, J; Smith, E D; Surrey, S; Schwartz, E; Rappaport, E F

    1987-01-01

    Patients with Hb SC disease were found to have microcytic and hyperchromic red cell indices despite mild reticulocytosis. Iron deficiency anemia was ruled out by the finding of normal serum ferritin levels. In order to determine whether the microcytosis was due to coexistent alpha-thalassemia, restriction endonuclease mapping was performed on genomic DNA extracted from peripheral blood leukocytes. Patients with Hb SC disease had microcytic indices despite the presence of a full complement of four alpha-genes (alpha alpha/alpha alpha), suggesting that the microcytosis may be due to cellular dehydration (or xerocytosis), since the mean corpuscular hemoglobin concentration in Hb SC disease patients was significantly higher than in controls. This possibility was investigated further by the determination of RBC cation content. RBC Na levels were similar in SC and normal red cells. Hb SC RBCs, however, had significantly reduced K levels. These findings show that RBC cation content, and thus cell water, is decreased in Hb SC disease. The decreased RBC K level in the presence of normal cellular Na concentration suggests selective K loss that is not due to inhibition of the Na K pump. Ouabain-insensitive K+ efflux was increased to four times normal in SC cells. Cell dehydration was confirmed by the demonstration of increased high-density RBCs on discontinuous Stractan density gradients and by osmotic gradient ektacytometry. Cellular dehydration and its sequelae were worse in CC erythrocytes and milder in AC cells than in Hb SC red cells. Taken together, these data indicate that in Hb SC disease the RBCs are severely dehydrated and typically microcytic and hyperchromic. Hb SC RBCs seem to be dehydrated due to selective K loss. These findings suggest a functional interrelationship between Hb SC, the red cell membrane, and cation regulation. PMID:2947642

  7. Analysis of HB Type Vernier Motor

    NASA Astrophysics Data System (ADS)

    Suda, Hiroshi; Matsushima, Yoshitaro; Xu, Li; Anazawa, Yoshihisa

    Direct drive motors are used as actuators in numerous applications in which they must rotate at low speeds with high torque and low torque ripple. Recently, various types of vernier motor have been developed. The HB type vernier motor is one of them. The structure of rotor is the same as HB type stepping motor. Our model of HB type vernier motor has a winding as field system in the rotor, but stator has three-phase windings. Relationship between S, R and P is S ± P/2=R/2, where S, R and P are the numbers of stator and rotor slots and the number of poles. The rotor of the vernier motor moves at a sub-multiple of the angular velocity of the stator mmf. The multiplying factor is P/R. As a result of analysis, the voltage equation on the γ-δ axis of HB type vernier motor is equal to general synchronous machine. The tests were performed on the trial motor. The calculated pull-out torque agreed well with the measured values. Our model of HB type vernier motor is equivalent with the PM type vernier motor which has permanent magnets in the rotor. The result of this analysis is useful for the design of both types of vernier motor.

  8. Cation Homeostasis in Red Cells From Patients With Sickle Cell Disease Heterologous for HbS and HbC (HbSC Genotype)

    PubMed Central

    Hannemann, A.; Rees, D.C.; Tewari, S.; Gibson, J.S.

    2015-01-01

    Sickle cell disease (SCD) in patients of HbSC genotype is considered similar, albeit milder, to that in homozygous HbSS individuals — but with little justification. In SCD, elevated red cell cation permeability is critical as increased solute loss causes dehydration and encourages sickling. Recently, we showed that the KCl cotransporter (KCC) activity in red cells from HbSC patients correlated significantly with disease severity, but that in HbSS patients did not. Two transporters involved in red cell dehydration, the conductive channels Psickle and the Gardos channel, behaved similarly in red cells from the two genotypes, but were significantly less active in HbSC patients. By contrast, KCC activity was quantitatively greater in HbSC red cells. Results suggest that KCC is likely to have greater involvement in red cell dehydration in HbSC patients, which could explain its association with disease severity in this genotype. This work supports the hypothesis that SCD in HbSC patients is a distinct disease entity to that in HbSS patients. Results suggest the possibility of designing specific treatments of particular benefit to HbSC patients and a rationale for the development of prognostic markers, to inform early treatment of children likely to develop more severe complications of the disease. PMID:26870793

  9. Poly(4-hydroxybutyrate) (P4HB) production in recombinant Escherichia coli: P4HB synthesis is uncoupled with cell growth

    PubMed Central

    2013-01-01

    Background Poly(4-hydroxybutyrate) (P4HB), belonging to the family of bacterial polyhydroxyalkanoates (PHAs), is a strong, flexible and absorbable material which has a large variety of medical applications like tissue engineering and drug delivery. For efficient production of P4HB recombinant Escherichia coli has been employed. It was previously found that the P4HB synthesis is co-related with the cell growth. In this study, we aimed to investigate the physiology of P4HB synthesis, and to reduce the total production cost by using cheap and widely available xylose as the growth substrate and sodium 4-hydroxybutyrate (Na-4HB) as the precursor for P4HB synthesis. Results Six different E. coli strains which are able to utilize xylose as carbon source were compared for their ability to accumulate P4HB. E. coli JM109 was found to be the best strain regarding the specific growth rate and the P4HB content. The effect of growth conditions such as temperature and physiological stage of Na-4HB addition on P4HB synthesis was also studied in E. coli JM109 recombinant in batch culture. Under the tested conditions, a cellular P4HB content in the range of 58 to 70% (w w-1) and P4HB concentrations in the range of 2.76 to 4.33 g L-1 were obtained with a conversion yield (YP4HB/Na-4HB) of 92% w w-1 in single stage batch cultures. Interestingly, three phases were identified during P4HB production: the “growth phase”, in which the cells grew exponentially, the “accumulation phase”, in which the exponential cell growth stopped while P4HB was accumulated exponentially, and the “stagnation phase”, in which the P4HB accumulation stopped and the total biomass remained constant. Conclusions P4HB synthesis was found to be separated from the cell growth, i.e. P4HB synthesis mainly took place after the end of the exponential cell growth. High conversion rate and P4HB contents from xylose and precursor were achieved here by simple batch culture, which was only possible previously

  10. Hydroxyurea decreases hospitalizations in pediatric patients with Hb SC and Hb SB+ thalassemia

    PubMed Central

    Lebensburger, Jeffrey D; Patel, Rakeshkumar J; Palabindela, Prasannalaxmi; Bemrich-Stolz, Christina J; Howard, Thomas H; Hilliard, Lee M

    2015-01-01

    Purpose Patients with hemoglobin SC (Hb SC) and hemoglobin SB+ (Hb SB+) thalassemia suffer from frequent hospitalizations yet strong evidence of a clinical benefit of hydroxyurea (HU) in this population is lacking. Patients with recurrent hospitalizations for pain crisis are offered HU at our institution based on small cohort data and anecdotal benefit. This study identifies outcomes from a large cohort of patients with Hb SC and SB+ thalassemia who were treated with HU for 2 years. Materials and methods A retrospective review was conducted of 32 patients with Hb SC and SB+ thalassemia who were treated with HU. We reviewed the number, and reasons for hospitalization in the 2 years prior to, and 2 years post-HU treatment as well as laboratory changes from baseline, over 1 year. Results Patients with Hb SC and SB+ thalassemia started on HU for frequent pain, had a significant reduction in hospitalizations over 2 years as compared to the 2 years prior to HU initiation (mean total hospitalizations/year: pre-HU: 1.6 vs post-HU 0.4 hospitalizations, P<0.001; mean pain hospitalizations/year: pre-HU 1.5 vs post-HU 0.3 hospitalizations, P<0.001). Patients demonstrated hematologic changes including an increase in percent fetal hemoglobin (%HbF) pre–post HU (4.5% to 7.7%, P=0.002), mean corpuscular volume (74 to 86 fL, P<0,0001), and decrease in absolute neutrophil count (5.0 to 3.2×109/L, P=0.007). Patients with higher doses of HU demonstrated the greatest reduction in hospitalizations but this was unrelated to absolute neutrophil count. Conclusion This cohort of patients with Hb SC and SB+ thalassemia provides additional support for using HU in patients with recurrent hospitalizations for pain. A large randomized multicenter trial of HU to reduce pain admissions should be conducted to confirm these data and provide much needed evidence based recommendations for this population. PMID:26719735

  11. Detection of Hb Constant Spring by a capillary electrophoresis method.

    PubMed

    Liao, Can; Zhou, Jian-Ying; Xie, Xing-Mei; Li, Jian; Li, Ru; Li, Dong-Zhi

    2010-01-01

    Hb Constant Spring [Hb CS; alpha142, Term-->Gln (TAA>CAA in alpha2)] is the most prevalent nondeletional alpha-thalassemia (alpha-thal) anomaly in southern China. In conjunction with alpha(0)-thal, it can cause severe Hb H (beta(4)) disease. The present study was done to evaluate the efficiency of two diagnostic methods in detecting Hb CS. Automated high performance liquid chromatography (HPLC) and Sebia Capillarys 2, a capillary electrophoresis method, were applied to blood samples from 21 individuals with Hb CS trait. Of the 21 cases, all (100%) were detected by capillary electrophoresis, whereas only 16 (76.2%) were detected by HPLC. We concluded that the Sebia Capillarys 2 is the preferred method for Hb CS screening. PMID:20353355

  12. Measurements of HB photonic crystal fibers with low temperature sensitivity

    NASA Astrophysics Data System (ADS)

    Makara, Mariusz; Wojcik, Jan; Mergo, Pawel; Klimek, Jacek; Skorupski, Krzysztof; Kopeć, Jarosław

    2008-06-01

    We report on experimental studies of phase and group modal birefringence vs. temperature in two highly birefringent (HB) photonic crystal fibers, in which birefringence is caused by filling factor asymmetry. The sensitivity measurements were carried out at two wavelengths 633 and 834 nm. Our results show that temperature sensitivity in the HB photonic crystal fibers is two orders smaller then in traditional HB fibers. Simultaneously, our results exhibit weak dependence of group modal birefringence on temperature.

  13. First Case of a Compound Heterozygosity for Two Nondeletional α-Thalassemia mutations, Hb Constant Spring and Hb Quong Sze.

    PubMed

    Zhou, Jian-Ying; Yan, Jin-Mei; Li, Jian; Li, Dong-Zhi

    2016-06-01

    Nondeletional α-thalassemia (α-thal) is the result of point mutations in critical regions of the α-globin genes, affecting mRNA processing, mRNA translation, or α-globin stability. Hb Constant Spring (Hb CS, HBA2: c.427T > C) is the most common nondeletional α-thal that results from a nucleotide substitution at the termination codon of the α2-globin gene. Hb Quong Sze (Hb QS, HBA2: c.377T > C) is another nondeletional α-thal in South China with the missense mutation at codon 125 of the α2-globin gene making this hemoglobin (Hb) variant highly unstable. Although homozygosity for Hb CS (α(CS)α/α(CS)α) or Hb QS (α(QS)α/α(QS)α) has been reported, clinical pictures vary from severe hemolysis that developed early in life to only mild anemia, no clinical phenotypic data of compound heterozygosity for Hb CS/Hb QS (α(CS)α/α(QS)α) has been described. In this report we describe an adult case with such a compound heterozygosity who presented with a mild α-thal. PMID:26956449

  14. Dietary determinants for Hb-acrylamide and Hb-glycidamide adducts in Danish non-smoking women.

    PubMed

    Outzen, Malene; Egeberg, Rikke; Dragsted, Lars; Christensen, Jane; Olesen, Pelle T; Frandsen, Henrik; Overvad, Kim; Tjønneland, Anne; Olsen, Anja

    2011-05-01

    Acrylamide (AA) is a probable human carcinogen that is formed in heat-treated carbohydrate-rich foods. The validity of FFQ to assess AA exposure has been questioned. The aim of the present cross-sectional study was to investigate dietary determinants of Hb-AA and Hb-glycidamide (GA) adducts. The study included 537 non-smoking women aged 50-65 years who participated in the Diet, Cancer and Health cohort (1993-97). At study baseline, blood samples and information on dietary and lifestyle variables obtained from self-administered questionnaires were collected. From blood samples, Hb-AA and Hb-GA in erythrocytes were analysed by liquid chromatography/MS/MS. Dietary determinants were evaluated by multiple linear regression analyses adjusted for age and smoking behaviour among ex-smokers. The median for Hb-AA was 35 pmol/g globin (5th percentile 17, 95th percentile 89) and for Hb-GA 21 pmol/g globin (5th percentile 8, 95th percentile 49). Of the dietary factors studied, intakes of coffee and chips were statistically significantly associated with a 4 % per 200 g/d (95 % CI 2, 7; P < 0·0001) and an 18 % per 5 g/d (95 % CI 6, 31; P = 0·002) higher Hb-AA, respectively. This model explained 17 % of the variation in Hb-AA. Intakes of coffee and biscuits/crackers were statistically significantly associated with a 3 % per 200 g/d (95 % CI 1, 6; P = 0·005) and 12 % per 10 g/d (95 % CI 3, 23; P = 0·01) higher Hb-GA, respectively. This model explained 12 % of the variation in Hb-GA. In conclusion, only a few dietary determinants of Hb-AA and Hb-GA were identified. Thus, the present study implies that dietary intake measured by an FFQ explains only to a limited extent the variation in Hb-AA and Hb-GA concentrations. PMID:21272397

  15. The significance of disulfide bonding in biological activity of HB-EGF, a mutagenesis approach

    SciTech Connect

    Hoskins, J.T.; Zhou, Z.; Harding, P.A.

    2008-10-31

    A site-directed mutagenesis approach was taken to disrupt each of 3 disulfide bonds within human HB-EGF by substituting serine for both cysteine residues that contribute to disulfide bonding. Each HB-EGF disulfide analogue (HB-EGF-Cys/Ser{sub 108/121}, HB-EGF-Cys/Ser{sub 116/132}, and HB-EGF-Cys/Ser{sub 134/143}) was cloned under the regulation of the mouse metallothionein (MT) promoter and stably expressed in mouse fibroblasts. HB-EGF immunoreactive proteins with M{sub r} of 6.5, 21 and 24 kDa were observed from lysates of HB-EGF and each HB-EGF disulfide analogue. HB-EGF immunohistochemical analyses of each HB-EGF stable cell line demonstrated ubiquitous protein expression except HB-EGF-Cys/Ser{sub 108/121} and HB-EGF-Cys/Ser{sub 116/132} stable cell lines which exhibited accumulated expression immediately outside the nucleus. rHB-EGF, HB-EGF, and HB-EGF{sub 134/143} proteins competed with {sup 125}I-EGF in an A431 competitive binding assay, whereas HB-EGF-Cys/Ser{sub 108/121} and HB-EGF-Cys/Ser{sub 116/132} failed to compete. Each HB-EGF disulfide analogue lacked the ability to stimulate tyrosine phosphorylation of the 170 kDa EGFR. These results suggest that HB-EGF-Cys/Ser{sub 134/143} antagonizes EGFRs.

  16. Radioisotope Characterization of HB Line Low Activity Waste

    SciTech Connect

    Snyder, S.J.

    1999-08-05

    The purpose of this document is to provide a physical, chemical, hazardous and radiological characterization of Low-Level Waste (LLW) generated in HB-Line as required by the 1S Manual, Savannah River Site Waste Acceptance Criteria Manual.

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

    PubMed Central

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

    2016-01-01

    Glycated haemoglobin (HbA1c) 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 HbA1c 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 HbA1c. 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 HbA1c 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 HbA1c.
Capillary electrophoresis is a good method for detecting HbJ but does not seem suitable for evaluation of HbA1C value in patients in presence of HbJ variant. PMID:27346969

  18. HB-Line Plutonium Oxide Data Collection Strategy

    SciTech Connect

    Watkins, R.; Varble, J.; Jordan, J.

    2015-05-26

    HB-Line and H-Canyon will handle and process plutonium material to produce plutonium oxide for feed to the Mixed Oxide Fuel Fabrication Facility (MFFF). However, the plutonium oxide product will not be transferred to the MFFF directly from HB-Line until it is packaged into a qualified DOE-STD-3013-2012 container. In the interim, HB-Line will load plutonium oxide into an inner, filtered can. The inner can will be placed in a filtered bag, which will be loaded into a filtered outer can. The outer can will be loaded into a certified 9975 with getter assembly in compliance with onsite transportation requirement, for subsequent storage and transfer to the K-Area Complex (KAC). After DOE-STD-3013-2012 container packaging capabilities are established, the product will be returned to HB-Line to be packaged into a qualified DOE-STD-3013-2012 container. To support the transfer of plutonium oxide to KAC and then eventually to MFFF, various material and packaging data will have to be collected and retained. In addition, data from initial HB-Line processing operations will be needed to support future DOE-STD-3013-2012 qualification as amended by the HB-Line DOE Standard equivalency. As production increases, the volume of data to collect will increase. The HB-Line data collected will be in the form of paper copies and electronic media. Paper copy data will, at a minimum, consist of facility procedures, nonconformance reports (NCRs), and DCS print outs. Electronic data will be in the form of Adobe portable document formats (PDFs). Collecting all the required data for each plutonium oxide can will be no small effort for HB-Line, and will become more challenging once the maximum annual oxide production throughput is achieved due to the sheer volume of data to be collected. The majority of the data collected will be in the form of facility procedures, DCS print outs, and laboratory results. To facilitate complete collection of this data, a traveler form will be developed which

  19. Factors influencing the release of Mitragyna speciosa crude extracts from biodegradable P(3HB-co-4HB).

    PubMed

    Chee, Jee-Wei; Amirul, A A; Majid, M I A; Mansor, S M

    2008-09-01

    Copolyesters of 3-hydroxybutyrate (3HB) and 4-hydroxybutyrate (4HB) were produced by Cupriavidus sp. (USMAA2-4) (DSM 19379) from carbon sources of 1,4-butanediol and gamma-butyrolactone. The composition of copolyesters produced varied from 0 to 45 mol% 4HB, depending on the combination of carbon sources supplied. The P(3HB-co-4HB) films containing Mitragyna speciosa crude extract were prepared with the ratio varying from 10 to 40% (w/w). The in vitro crude extract release of the films was studied in 0.1M phosphate buffer (pH 7.4) at 37 degrees C. Although the release rate was slow, it was maintained at a constant rate. This suggests that the crude extract release was due to the polymer degradation because the amount of crude extract released was consistent. The amount of degradation was based on the films' dry weight loss, decrease in molecular weight and surface morphology changes. The degradation rate increased with the 4HB content. This showed that the polymer degradation is dependant on the molecular weight, crystallinity, thermal properties and water permeability. The different drug loading ratio which led to surface morphology changes also gave an effect on polymer degradation. PMID:18584978

  20. Why the DNA self-depurination mechanism operates in HB-β but not in β-globin paralogs HB-δ, HB-ɛ1, HB-γ1 and HB-γ2.

    PubMed

    Amosova, Olga; Alvarez-Dominguez, Juan R; Fresco, Jacques R

    2015-08-01

    The human β-globin, δ-globin and ɛ-globin genes contain almost identical coding strand sequences centered about codon 6 having potential to form a stem-loop with a 5'GAGG loop. Provided with a sufficiently stable stem, such a structure can self-catalyze depurination of the loop 5'G residue, leading to a potential mutation hotspot. Previously, we showed that such a hotspot exists about codon 6 of β-globin, with by far the highest incidence of mutations across the gene, including those responsible for 6 anemias (notably Sickle Cell Anemia) and β-thalassemias. In contrast, we show here that despite identical loop sequences, there is no mutational hotspot in the δ- or ɛ1-globin potential self-depurination sites, which differ by only one or two base pairs in the stem region from that of the β-globin gene. These differences result in either one or two additional mismatches in the potential 7-base pair-forming stem region, thereby weakening its stability, so that either DNA cruciform extrusion from the duplex is rendered ineffective or the lifetime of the stem-loop becomes too short to permit self-catalysis to occur. Having that same loop sequence, paralogs HB-γ1 and HB-γ2 totally lack stem-forming potential. Hence the absence in δ- and ɛ1-globin genes of a mutational hotspot in what must now be viewed as non-functional homologs of the self-depurination site in β-globin. Such stem-destabilizing variants appeared early among vertebrates and remained conserved among mammals and primates. Thus, this study has revealed conserved sequence determinants of self-catalytic DNA depurination associated with variability of mutation incidence among human β-globin paralogs. PMID:26042536

  1. Plasmid-associated aggregation in Thermus thermophilus HB8

    SciTech Connect

    Mather, M.W.; Fee, J.A. )

    1990-01-01

    Thermus thermophilus HB8, a moderate thermophile, exhibits visible aggregation when growing on a rich broth. Strain HB8 also contains two cryptic plasmids. The authors isolated cured strains from HB8 and observed that loss of the 47-MDa plasmid was correlated with loss of aggregation. An enrichment procedure was developed for aggregating cells and used to demonstrate that aggregation was restored upon transformation of a cured strain with plasmid DNA. The aggregation phenotype of transformed cells was variably stable; most did not retain either the plasmid or the phenotype for prolonged periods of growth. Hybridization experiments using a partial sequence from the 47-MDa plasmid suggested the presence of a repeated DNA sequence on this plasmid and on the chromosome. This is the first report of a phenotype associated with a plasmid from a Thermus strain.

  2. Cryo-stability of HB-Cesic optics

    NASA Astrophysics Data System (ADS)

    Krödel, Matthias

    2011-09-01

    The technical requirements for large future space optics are becoming more and more challenging. This is particularly the case with respect to thermal stability under cryogenic conditions. During the past two years, ECM together with its industrial partners carried out extensive cryo-stability tests of its HB-Cesic® optical material under a range of conditions. In this paper we report the test configurations and results of two of these tests and qualification campaigns. The first of the tests was carried out with a 600-mm HB-Cesic® mirror that was polished directly without any overcoating. The second of the tests was carried out with an 800-mm HB-Cesic® mirror whose optical surface was coated with a silicon layer prior to polishing. The 600-mm mirror was tested to a cryogenic temperature of 93 K. The 800-mm mirror was tested to a cryogenic temperature of 18 K.

  3. Preparation of hemoglobin (Hb) imprinted polymer by Hb catalyzed eATRP and its application in biosensor.

    PubMed

    Sun, Yue; Du, Hongying; Lan, Yuting; Wang, Wenjing; Liang, Yuejian; Feng, Chunliang; Yang, Mei

    2016-03-15

    Molecularly imprinted polymer (MIP) was prepared on the surface of Au electrode by electrochemically mediated atom transfer radical polymerization (eATRP) with hemoglobin (Hb) both as catalyst and template molecule. Firstly, the condition for eATRP such as the potential, time and Hb concentration were selected and determined to be -0.51 V, 120 min and 20mg/mL, respectively. Further, the electrode modified with MIP (MIP/Au) was carefully examined by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and scanning electron microscope (SEM). Finally, the MIP/Au electrode was used as a biosensor and successfully applied for the determination of Hb by differential pulse voltammetry (DPV) measurement. The results of experiments showed that the proposed biosensor displayed a broader linear range and a lower detection limit for Hb determination when it was compared to those Hb sensors based on MIP. The linear range was from 1.0 × 10(-10) to 1.0 × 10(1)mg/L with a detection limit of 7.8 × 10(-11)mg/L (S/N=3.3). In a word, the work of this paper established a useful way for the preparation and application of biosensor based on protein imprinted polymers. PMID:26520252

  4. Integrated UV fluxes and the HB morphology of Globular Clusters

    NASA Astrophysics Data System (ADS)

    Landsman, W. B.; Catelan, M.; O'Connell, R. W.; Pereira, D.; Stecher, T. P.

    2001-12-01

    The UV ( ~ 1500 Å) flux of a globular cluster will be dominated by its blue horizontal branch (HB) population, provided that such a population is present. Thus, the integrated UV - V color of a globular cluster can provide an indication of its HB morphology, without the need to resolve the cluster into a color-magnitude diagram. To date, UV photometry of extragalactic clusters are available for only a few globulars in M31 (e.g. Bohlin et al. 1993, ApJ, 417, 127), but additional UV photometry of extragalactic globulars is soon expected from GALEX (Yi et al. 2001, AAS, 198, 5501), and from STIS FUV-MAMA observations of M87 (HST program 8643). Here we calibrate the relation between UV flux and HB morphology for Galactic globular clusters. The OAO-2 and ANS data tabulated by deBoer (1985, A&A, 142, 321) are supplemented with photometry of 14 globular clusters observed with the Ultraviolet Imaging Telescope (UIT), and a few cluster cores observed with the STIS FUV-MAMA. The UIT data is especially useful since its 40' diameter FOV was sufficient to completely encompass most of the observed clusters, while allowing isolation of hot field and UV-bright stars. We compare the observed Galactic UV color - HB morphology relation with synthetic HB models as a function of age and metallicity. We also estimate the effect of radiative levitation of heavy metals in hot HB stars (e.g. Moehler et al. 2000, , A&A, 360, 120) on the integrated UV flux. This work is funded by STScI grant GO-8358.01.

  5. Mitochondrial Changes in β0-Thalassemia/Hb E Disease.

    PubMed

    Khungwanmaythawee, Kornpat; Sornjai, Wannapa; Paemanee, Atchara; Jaratsittisin, Janejira; Fucharoen, Suthat; Svasti, Saovaros; Lithanatudom, Pathrapol; Roytrakul, Sittiruk; Smith, Duncan R

    2016-01-01

    The compound β°-thalassemia/Hb E hemoglobinopathy is characterized by an unusually large range of presentation from essentially asymptomatic to a severe transfusion dependent state. While a number of factors are known that moderate presentation, these factors do not account for the full spectrum of presentation. Mitochondria are subcellular organelles that are pivotal in a number of cellular processes including oxidative phosphorylation and apoptosis. A mitochondrial protein enriched proteome was determined and validated from erythroblasts from normal controls and β°-thalassemia/Hb E patients of different severities. Mitochondria were evaluated through the use of mitotracker staining, analysis of relative mitochondrial genome number and evaluation of mitochondrial gene expression in addition to assay of overall cellular redox status through the use of alamarBlue assays. Fifty differentially regulated mitochondrial proteins were identified. Mitotracker staining revealed significant differences in staining between normal control erythroblasts and those from β°-thalassemia/Hb E patients. Differences in relative mitochondria number and gene expression were seen primarily in day 10 cells. Significant differences were seen in redox status as evaluated by alamarBlue staining in newly isolated CD34+ cells. Mitochondria mediate oxidative phosphorylation and apoptosis, both of which are known to be dysregulated in differentiating erythrocytes from β°-thalassemia/Hb E patients. The evidence presented here suggest that there are inherent differences in these cells as early as the erythroid progenitor cell stage, and that maximum deficit is seen coincident with high levels of globin gene expression. PMID:27092778

  6. Mitochondrial Changes in β0-Thalassemia/Hb E Disease

    PubMed Central

    Khungwanmaythawee, Kornpat; Sornjai, Wannapa; Paemanee, Atchara; Jaratsittisin, Janejira; Fucharoen, Suthat; Svasti, Saovaros; Lithanatudom, Pathrapol; Roytrakul, Sittiruk

    2016-01-01

    The compound β°-thalassemia/Hb E hemoglobinopathy is characterized by an unusually large range of presentation from essentially asymptomatic to a severe transfusion dependent state. While a number of factors are known that moderate presentation, these factors do not account for the full spectrum of presentation. Mitochondria are subcellular organelles that are pivotal in a number of cellular processes including oxidative phosphorylation and apoptosis. A mitochondrial protein enriched proteome was determined and validated from erythroblasts from normal controls and β°-thalassemia/Hb E patients of different severities. Mitochondria were evaluated through the use of mitotracker staining, analysis of relative mitochondrial genome number and evaluation of mitochondrial gene expression in addition to assay of overall cellular redox status through the use of alamarBlue assays. Fifty differentially regulated mitochondrial proteins were identified. Mitotracker staining revealed significant differences in staining between normal control erythroblasts and those from β°-thalassemia/Hb E patients. Differences in relative mitochondria number and gene expression were seen primarily in day 10 cells. Significant differences were seen in redox status as evaluated by alamarBlue staining in newly isolated CD34+ cells. Mitochondria mediate oxidative phosphorylation and apoptosis, both of which are known to be dysregulated in differentiating erythrocytes from β°-thalassemia/Hb E patients. The evidence presented here suggest that there are inherent differences in these cells as early as the erythroid progenitor cell stage, and that maximum deficit is seen coincident with high levels of globin gene expression. PMID:27092778

  7. HB-Cesic composite for space optics and structures

    NASA Astrophysics Data System (ADS)

    Kroedel, Matthias R.; Ozaki, Tsuyoshi

    2007-09-01

    One of the key technologies for next generation space telescopes requiring large-scale reflectors are light-weight materials having high specific strength, high specific stiffness, low coefficient of thermal expansion and high coefficient of thermal conductivity. Several candidates, such as fused silica, beryllium, silicon carbide and carbon fiber reinforced composites, have been evaluated. An example of the latter material is a Hybrid Carbon-Fiber Reinforced SiC composite or HB-Cesic - a trademark of ECM - which has been developed by ECM and MELCO to meet the stringent space telescope requirements. Mechanical performance, such as stiffness, bending strength and fracture toughness, were significantly improved using HB-Cesic compared to our classic Cesic material. Thermal expansion and thermal conductivity of HB-Cesic at cryogenic temperatures are now partly established and excellent performance for large future space mirrors and structures are expected. In this paper we will report on the current status of development of HB-Cesic and describe the first successful applications made with this new improved material.

  8. ASCA observations of HB 21 and Kes 27

    NASA Astrophysics Data System (ADS)

    Rho, Jeonghee

    1999-04-01

    While shell-like, Crab-like, and composite supernova remnants (SNRs) represent well-defined classes, another group of SNRs with center-filled X-ray and shell-like radio morphology, forms an unique category of ``mixed morphology" (MM) SNR because of distinct physical and environmental properties (Rho & Petre 1998, ApJL, 503, 167). We present ASCA observations of two candidate MM supernova remnants HB 21 and Kes 27. Two pointings (north and east) were observed to cover most bright part of HB21 and one pointing to cover Kes 27. The exposure time of HB21 for good data is 35-40 ks for each pointing, and that of Kes 27 is 20 ks. The ASCA images for both remnants confirm that the X-ray morphology is centrally concentrated within the well-defined radio shell. The emission is smoothly distributed in the interior, and additionally two X-ray bright peaks appear in Kes 27. The ASCA spectra for both remnants reveal that the emission is primarily thermal, HB21 with strong Si and S lines, and weak Fe L, Mg and Ar lines, and Kes 27 with strong lines of Mg, Si, S, and Fe K. The HB 21 spectra fitting yields an acceptable fit with a thermal (Raymond-Smith or Mekal) model with a line of sight absorption of N_H ~ 1.5*E(21) cm(-2) , and a temperature kT ~ 0.68 keV, and no emission above 6 keV was detected from HB21. The temperature distribution of HB 21 is uniform, similar to those of the archetypes of MM SNR (MSH 11-61A and W44). In contrast, the Kes 27 spectra show a hard energy tail (between 5 to 10 keV). Although the Galactic plane region toward Kes 27 has complicated Galactic Ridge emission (GRE), the hard energy maps prove that the hard emission is indeed from the remnant itself. The hard emission peak is located between the two X-ray bright peaks, implying that there is spectral variation across Kes 27. The spectral distribution is different between the two remnants despite of similarity of center-filled X-ray morphology. I will discuss the ISM environments of the remnants using

  9. Characterization of a Novel Anti-Human HB-EGF Monoclonal Antibody Applicable for Paraffin-Embedded Tissues and Diagnosis of HB-EGF-Related Cancers

    PubMed Central

    Iwamoto, Ryo; Takagi, Mika; Akatsuka, Jun-ichi; Ono, Ken-ichiro; Kishi, Yoshiro

    2016-01-01

    Heparin-binding EGF-like growth factor (HB-EGF) is a member of the EGF family of growth factors that bind to and activate the EGF receptor (EGFR/ErbB1) and ErbB4. HB-EGF plays pivotal roles in pathophysiological processes, including cancer. Thus, monoclonal antibodies (mAbs) for HB-EGF detection could be an important tool in the therapeutic diagnosis of HB-EGF-related cancers and other diseases. However, few mAbs, especially those applicable for immunohistochemistry (IHC), have been established to date. In this study, we generated a clone of hybridoma-derived mAb 2-108 by immunizing mice with recombinant human HB-EGF protein expressed by human cells. The mAb 2-108 specifically bound to human HB-EGF but not to mouse HB-EGF and was successful in immunoblotting, even under reducing conditions, immunoprecipitation, and immunofluorescence for unfixed as well as paraformaldehyde-fixed cells. Notably, this mAb was effective in IHC of paraffin-embedded tumor specimens. Epitope mapping analysis showed that mAb 2-108 recognized the N-terminal prodomain in HB-EGF. These results indicate that this new anti-HB-EGF mAb 2-108 would be useful in the diagnosis of HB-EGF-related cancers and would be a strong tool in both basic and clinical research on HB-EGF. PMID:26974561

  10. Hb Wilde and Hb Patagonia: two novel elongated beta-globin variants causing dominant beta-thalassemia.

    PubMed

    Scheps, Karen G; Hasenahuer, Marcia A; Parisi, Gustavo; Fornasari, María S; Pennesi, Sandra P; Erramouspe, Beatriz; Basack, Felisa N; Veber, Ernesto S; Aversa, Luis; Elena, Graciela; Varela, Viviana

    2015-06-01

    We describe here the molecular and hematological characteristics of novel frameshift mutations in exon 2 of the HBB gene (in heterozygous state) found in two Argentinean pediatric patients with dominant β-thalassemia-like features. In Hb Wilde, HBB:c.270_273delTGAG(p.Glu90Cysfs*67), we detected the deletion of the third base of the codon 89 (T) and the codon 90 (GAG), whereas in Hb Patagonia, HBB:c.296_297dupGT(p.Asp99Trpfs*59), the frameshift mutation was due to a duplication of a 'GT' dinucleotide after the second base of codon 98 (GTG). The Hb Patagonia and Hb Wilde mutations would result in elongated β-globin chains with modified C-terminal sequences and a total of 155 and 157 amino acids residues, respectively. Based on bioinformatics and structural analysis, as well as protein modeling, we predict that the elongated β-globins would affect the formation of the αβ dimers and their stability, which would further support the mechanism for the observed clinical features in both patients. PMID:25284604

  11. Hb H disease with various β hemoglobinopathies: molecular, hematological and diagnostic aspects.

    PubMed

    Fucharoen, Supan; Fucharoen, Goonnapa

    2012-01-01

    We report the molecular, hematological and diagnostic features of three Thai patients with Hb H (β4) disease in combination with different β hemoglobinopathies. The first case was a boy with a hitherto undescribed condition of Hb H-Hb Tak (HBB:c.441_442insAC) syndrome. The second case was an adult male with the Hb H-Hb Hope (HBB:c.410G>A) disease. The last case was a male patient with a combination of Hb H-Hb Constant Spring (Hb CS) (HBA2:c.427T>C) and a high Hbs A(2)/F β(0)-thalassemia (β-thal) trait (the 3.4 kb deletion). In all cases, no Hb H was detected and Hb H inclusion was absent, accurate diagnosis could be obtained after DNA analysis. All of them had mild hypochromic microcytic anemia with hemoglobin (Hb) values ranging from 8.8-10.4 g/dL, PCV 0.31-0.36 L/L and MCV 57.6-66.9 fL and none had ever received a blood transfusion. The levels of Hb Tak (7.8%) and Hb Hope (21.6%), respectively, observed in the first two cases were relatively lower than values found in heterozygotes for these two variants. In the last case, the level of Hb A(2) (4.8%) was within the diagnostic range for a β-thal trait. The Hb F level was not elevated but a small amount of Hb Bart's was observed. Hematological findings and diagnostics using combined Hb and polymerase chain reaction (PCR) analyses are presented and compared with those of the other Thai patients with Hb H-β(0)-thal, Hb H-Hb CS-Hb J-Bangkok (HBB:c.170G>A) and Hb H-Hb CS-Hb Pyrgos (HBB:c.251G>A) previously observed in our series. PMID:22145566

  12. Expression Profiles, Characterization and Function of HbTCTP in Rubber Tree (Hevea brasiliensis)

    PubMed Central

    Deng, Zhi; Chen, Jiangshu; Leclercq, Julie; Zhou, Zhuangzhi; Liu, Changren; Liu, Hui; Yang, Hong; Montoro, Pascal; Xia, Zhihui; Li, Dejun

    2016-01-01

    As a highly conserved protein, the translationally controlled tumor protein (TCTP) carries out vital roles in various life processes. In rubber tree, two TCTP genes, HbTCTP and HbTCTP1, were cloned, but only HbTCTP1 was studied in details. In this study, cis-acting regulatory elements, expression patterns, subcellular localization, interacting proteins, and antioxidant activity of HbTCTP were systematically analyzed. Besides the common cis-acting regulatory elements, HbTCTP promoter also harbored various known cis-elements that respond to hormone/stresses. Being consistent with the aforementioned results, HbTCTP was regulated by drought, low temperature, high salt, ethylene (ET), wounding, H2O2, and methyl jasmonate (MeJA) treatments. HbTCTP was expressed throughout different tissues and developmental stages of leaves. In addition, HbTCTP was associated with tapping panel dryness (TPD). HbTCTP was localized in the membrane, cytoplasm and the nucleus, and interacted with four proteins rubber elongation factor (REF), 17.5 kDa heat shock family protein, annexin, and REF-like stress related protein 1. Being similar to HbTCTP1, HbTCTP also indicated antioxidant activity in metal-catalyzed oxidation (MCO) system. Our results are useful for further understanding the molecular characterization and expression profiles of HbTCTP, but also lay a solid foundation for elucidating the function of HbTCTP in rubber tree. PMID:27375647

  13. Rare hemoglobin variants: Hb G-Szuhu (HBB: c.243C>G), Hb G-Coushatta (HBB: c.68A>C) and Hb Mizuho (HBB: c.206T>C) in Sri Lankan families.

    PubMed

    Perera, P Shiromi; Silva, Ishari; Hapugoda, Menaka; Wickramarathne, Merita N; Wijesiriwardena, Indira; Efremov, Dimitar G; Fisher, Christopher A; Weatherall, David J; Premawardhena, Anuja

    2015-01-01

    In this short communication, we describe the clinical presentation of unusual hemoglobin (Hb), variants in three Sri Lankan cases under study for β-thalassemia intermedia (β-TI). We believe this is the first report on their occurrence in Sri Lanka as well as from the Indian subcontinent. During a molecular study performed on β-TI patients, we identified three unusual Hb variants as Hb G-Szuhu (HBB: c.243C>G), Hb G-Coushatta (HBB: c.68A>C) and Hb Mizuho (HBB: c.206T>C) in three unrelated families. Hb G-Szuhu and Hb G-Coushatta were found in combination with the common β-thalassemia (β-thal) mutation, IVS-I-5 (G>C). Both probands had mild anemia with greatly reduced red cell indices and had non palpable livers and spleens, however, by ultrasound, both were observed to be enlarged. The final Hb variant, Hb Mizuho, was identified as a heterozygous mutation found in both proband and his mother. Both family members had severe anemia and were regularly transfused and had increased red cell parameters. PMID:25572187

  14. Glutathione Redox System in β-Thalassemia/Hb E Patients

    PubMed Central

    Tangjaidee, Thongchai; Hatairaktham, Suneerat; Charoensakdi, Ratiya; Panichkul, Narumol; Siritanaratkul, Noppadol; Fucharoen, Suthat

    2013-01-01

    β-thalassemia/Hb E is known to cause oxidative stress induced by iron overload. The glutathione system is the major endogenous antioxidant that protects animal cells from oxidative damage. This study aimed to determine the effect of disease state and splenectomy on redox status expressed by whole blood glutathione (GSH)/glutathione disulfide (GSSG) and also to evaluate glutathione-related responses to oxidation in β-thalassemia/Hb E patients. Twenty-seven normal subjects and 25 β-thalassemia/Hb E patients were recruited and blood was collected. The GSH/GSSG ratio, activities of glutathione-related enzymes, hematological parameters, and serum ferritin levels were determined in individuals. Patients had high iron-induced oxidative stress, shown as significantly increased serum ferritin, a decreased GSH/GSSG ratio, and increased activities of glutathione-related enzymes. Splenectomy increased serum ferritin levels and decreased GSH levels concomitant with unchanged glutathione-related enzyme activities. The redox ratio had a positive correlation with hemoglobin levels and negative correlation with levels of serum ferritin. The glutathione system may be the body's first-line defense used against oxidative stress and to maintain redox homeostasis in thalassemic patients based on the significant correlations between the GSH/GSSH ratio and degree of anemia or body iron stores. PMID:24223032

  15. Hb E/beta-thalassaemia: a common & clinically diverse disorder

    PubMed Central

    Olivieri, Nancy F.; Pakbaz, Zahra; Vichinsky, Elliott

    2011-01-01

    Haemoglobin E-beta thalassaemia (Hb E/β-thalassaemia) is the genotype responsible for approximately one-half of all severe beta-thalassaemia worldwide. The disorder is characterized by marked clinical variability, ranging from a mild and asymptomatic anaemia to a life-threatening disorder requiring transfusions from infancy. The phenotypic variability of Hb E/β-thalassaemia and the paucity of long-term clinical data, present challenges in providing definitive recommendations for the optimal management of patients. Genetic factors influencing the severity of this disorder include the type of beta-thalassaemia mutation, the co-inheritance of alpha-thalassaemia, and polymorphisms associated with increased production of foetal haemoglobin. Other factors, including a variable increase in serum erythropoietin in response to anaemia, previous or ongoing infection with malaria, previous splenectomy and other environmental influences, may be involved. The remarkable variation, and the instability, of the clinical phenotype of Hb E beta-thalassaemia suggests that careful tailoring of treatment is required for each patient, and that therapeutic approaches should be re-assessed over-time. PMID:22089616

  16. Inhibition of Hb Binding to GP1bα Abrogates Hb-Mediated Thrombus Formation on Immobilized VWF and Collagen under Physiological Shear Stress

    PubMed Central

    Peng, Yuandong; Guchhait, Prasenjit

    2016-01-01

    Background Reports including our own describe that intravascular hemolysis increases the risk of thrombosis in hemolytic disorders. Our recent study shows that plasma Hb concentrations correlate directly with platelet activation in patients with paroxysmal nocturnal hemoglobinuria (PNH). The binding of Hb to glycoprotein1bα (GP1bα) increases platelet activation. A peptide AA1-50, designed from N-terminal amino acid sequence of GP1bα significantly inhibits the Hb binding to GP1bα as well as Hb-induced platelet activation. This study further examined if the Hb-mediated platelet activation plays any significant role in thrombus formation on subendothelium matrix under physiological flow shear stresses and the inhibition of Hb-platelet interaction can abrogate the above effects of Hb. Methods and Results Study performed thrombus formation assay in vitro by perfusing whole blood over immobilized VWF or collagen type I in presence of Hb under shear stresses simulating arterial or venous flow. The Hb concentrations ranging from 5 to 10 μM, commonly observed level in plasma of the hemolytic patients including PNH, dose-dependently increased thrombus formation on immobilized VWF under higher shear stress of 25 dyne/cm2, but not at 5 dyne/cm2. The above Hb concentrations also increased thrombus formation on immobilized collagen under both shear stresses of 5 and 25 dyne/cm2. The peptide AA1-50 abrogated invariably the above effects of Hb on thrombus formation. Conclusions and Significance This study therefore indicates that the Hb-induced platelet activation plays a crucial role in thrombus formation on immobilized VWF or collagen under physiological flow shear stresses. Thus suggesting a probable role of this mechanism in facilitating thrombosis under hemolytic conditions. PMID:27105433

  17. Simultaneous dual syringe electrospinning system using benign solvent to fabricate nanofibrous P(3HB-co-4HB)/collagen peptides construct as potential leave-on wound dressing.

    PubMed

    Vigneswari, S; Murugaiyah, V; Kaur, G; Abdul Khalil, H P S; Amirul, A A

    2016-09-01

    The main focus of this study is the incorporation of collagen peptides to fabricate P(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] nano-fiber construct to further enhance surface wettability and support cell growth while harbouring desired properties for biodegradable wound dressing. Simultaneous electrospinning of nanofiber P(3HB-co-4HB)/collagen peptides construct was carried out using dual syringe system. The wettability of the constructs increased with the increase in 4HB molar fraction from 20mol% 4HB [53.2°], P(3HB-co-35mol%4HB)[48.9°], P(3HB-co-50mol%4HB)[44.5°] and P(3HB-co-82mol%4HB) [37.7°]. In vitro study carried out using mouse fibroblast cells (L929) grown on nanofiber P(3HB-co-4HB)/collagen peptides construct showed an increase in cell proliferation. In vivo study using animal model (Sprague Dawley rats) showed that nanofibrous P(3HB-co-4HB)/collagen peptides construct had a significant effect on wound contractions with the highest percentage of wound closure of 79%. Hence, P(3HB-co-4HB)/collagen peptides construct suitable for wound dressing have been developed using nano-fabrication technique. PMID:27207048

  18. Molecular Cloning of HbPR-1 Gene from Rubber Tree, Expression of HbPR-1 Gene in Nicotiana benthamiana and Its Inhibition of Phytophthora palmivora

    PubMed Central

    Khunjan, Uraiwan; Ekchaweng, Kitiya; Panrat, Tanate; Tian, Miaoying; Churngchow, Nunta

    2016-01-01

    This is the first report to present a full-length cDNA (designated HbPR-1) encoding a putative basic HbPR-1 protein from rubber tree (Hevea brasiliensis) treated with salicylic acid. It was characterized and also expressed in Nicotiana benthamiana using Agrobacterium-mediated transient gene expression system in order to investigate the role of HbPR-1 gene in rubber tree against its oomycete pathogen Phytopthora palmivora and to produce recombinant HbPR-1 protein for microbial inhibition test. The HbPR-1 cDNA was 647 bp long and contained an open reading frame of 492 nucleotides encoding 163 amino acid residues with a predicted molecular mass of 17,681 Da and an isoelectric point (pI) of 8.56, demonstrating that HbPR-1 protein belongs to the basic PR-1 type. The predicted 3D structure of HbPR-1 was composed of four α-helices, three β-sheets, seven strands, and one junction loop. Expression and purification of recombinant HbPR-1 protein were successful using Agrobacterium-mediated transient expression and one-step of affinity chromatography. Heterologous expression of HbPR-1 in N. benthamiana reduced necrosis areas which were inoculated with P. palmivora zoospores, indicating that the expressed HbPR-1 protein played an important role in plant resistance to pathogens. The purified recombinant HbPR-1 protein was found to inhibit 64% of P. palmivora zoospore germination on a water agar plate compared with control, suggesting that it was an antimicrobial protein against P. palmivora. PMID:27337148

  19. Molecular Cloning of HbPR-1 Gene from Rubber Tree, Expression of HbPR-1 Gene in Nicotiana benthamiana and Its Inhibition of Phytophthora palmivora.

    PubMed

    Khunjan, Uraiwan; Ekchaweng, Kitiya; Panrat, Tanate; Tian, Miaoying; Churngchow, Nunta

    2016-01-01

    This is the first report to present a full-length cDNA (designated HbPR-1) encoding a putative basic HbPR-1 protein from rubber tree (Hevea brasiliensis) treated with salicylic acid. It was characterized and also expressed in Nicotiana benthamiana using Agrobacterium-mediated transient gene expression system in order to investigate the role of HbPR-1 gene in rubber tree against its oomycete pathogen Phytopthora palmivora and to produce recombinant HbPR-1 protein for microbial inhibition test. The HbPR-1 cDNA was 647 bp long and contained an open reading frame of 492 nucleotides encoding 163 amino acid residues with a predicted molecular mass of 17,681 Da and an isoelectric point (pI) of 8.56, demonstrating that HbPR-1 protein belongs to the basic PR-1 type. The predicted 3D structure of HbPR-1 was composed of four α-helices, three β-sheets, seven strands, and one junction loop. Expression and purification of recombinant HbPR-1 protein were successful using Agrobacterium-mediated transient expression and one-step of affinity chromatography. Heterologous expression of HbPR-1 in N. benthamiana reduced necrosis areas which were inoculated with P. palmivora zoospores, indicating that the expressed HbPR-1 protein played an important role in plant resistance to pathogens. The purified recombinant HbPR-1 protein was found to inhibit 64% of P. palmivora zoospore germination on a water agar plate compared with control, suggesting that it was an antimicrobial protein against P. palmivora. PMID:27337148

  20. Draft genome sequence of Bacillus amyloliquefaciens HB-26

    PubMed Central

    Liu, Xiao-Yan; Min, Yong; Wang, Kai-Mei; Wan, Zhong-Yi; Zhang, Zhi-Gang; Cao, Chun-Xia; Zhou, Rong-Hua; Jiang, Ai-Bing; Liu, Cui-Jun; Zhang, Guang-Yang; Cheng, Xian-Liang; Zhang, Wei; Yang, Zi-Wen

    2014-01-01

    Bacillus amyloliquefaciens HB-26, a Gram-positive bacterium was isolated from soil in China. SDS-PAGE analysis showed this strain secreted six major protein bands of 65, 60, 55, 34, 25 and 20 kDa. A bioassay of this strain reveals that it shows specific activity against P. brassicae and nematode. Here we describe the features of this organism, together with the draft genome sequence and annotation. The 3,989,358 bp long genome (39 contigs) contains 4,001 protein-coding genes and 80 RNA genes. PMID:25197462

  1. Variability in the interaction of beta-thalassemia with the alpha-chain variants Hb G-Philadelphia and Hb Rampa.

    PubMed

    Huisman, T H; Gravely, M E; Henson, J; Felice, A; Wilson, J B; Abraham, E C; Vella, F; Little, M W

    1978-08-01

    Two unrelated families are reported in which beta-thalassemia trait occurred with a heterozygosity of Hb G-Philadelphia (alpha2 68(E17)Asn leads to Lys beta2) in one family and with Hb Rampa (alpha2 95(G2)Pro leads to Ser beta2) in the other. The percentage of Hb G-Philadelphia was not influenced by the simultaneous presence of a beta-thalassemai determinant, but that of Hb Rampa was descreased from 20% in the simple heterozygote to about 6% in persons with the Hb Rampa-beta-thalassemia combination. Data from in vitro recombination experiments with isolated alpha X, alpha A, and beta A chains, with heme attached, indicated a preferential formation of Hb A over Hb Rampa but not over Hb G-Philadelphia in conditions of relative beta-chain deficiency. This suggests that the rate of assembly of monomers to form dimers or tetramers can be an important mechanism of controlling the quantity of certain hemoglobin variants with critical substitutions in heterozygotes. PMID:681817

  2. Genetic analysis of lipolytic activities in Thermus thermophilus HB27.

    PubMed

    Leis, Benedikt; Angelov, Angel; Li, Haijuan; Liebl, Wolfgang

    2014-12-10

    The extremely thermophilic bacterium Thermus thermophilus HB27 displays lipolytic activity for the hydrolysis of triglycerides. In this study we performed a mutational in vivo analysis of esterases and lipases that confer growth on tributyrin. We interrupted 10 ORFs suspected to encode lipolytic enzymes. Two chromosomal loci were identified that resulted in reduced hydrolysis capabilities against tributyrin and various para-nitrophenyl acyl esters. By implementation of a convenient new one-step method which abstains from the use of selectable markers, a mutant strain with multiple scar-less deletions was constructed by sequentially deleting ORFs TT_C1787, TT_C0340, TT_C0341 and TT_C0904. The quadruple deletion mutant of T. thermophilus exhibited significantly lower lipolytic activity (approximately 25% residual activity compared to wild type strain) over a broad range of fatty acyl esters and had lost the ability to grow on agar plates containing tributyrin as the sole carbon source. Furthermore, we were able to determine the impact of each gene disruption on the lipolytic activity profile in this model organism and show that the esterase activity in T. thermophilus HB27 is due to a concerted action of several hydrolases having different substrate preferences and activities. The esterase-less T. thermophilus multi-deletion mutant from this study can be used as a screening and expression host for esterase genes from thermophiles or metagenomes. PMID:25102235

  3. Application of CRISPRi for prokaryotic metabolic engineering involving multiple genes, a case study: Controllable P(3HB-co-4HB) biosynthesis.

    PubMed

    Lv, Li; Ren, Yi-Lin; Chen, Jin-Chun; Wu, Qiong; Chen, Guo-Qiang

    2015-05-01

    Clustered regularly interspaced short palindromic repeats interference (CRISPRi) is used to edit eukaryotic genomes. Here, we show that CRISPRi can also be used for fine-tuning prokaryotic gene expression while simultaneously regulating multiple essential gene expression with less labor and time consumption. As a case study, CRISPRi was used to control polyhydroxyalkanoate (PHA) biosynthesis pathway flux and to adjust PHA composition. A pathway was constructed in Escherichia coli for the production of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] from glucose. The native gene sad encoding E. coli succinate semi-aldehyde dehydrogenase was expressed under the control of CRISPRi using five specially designed single guide RNAs (sgRNAs) for regulating carbon flux to 4-hydroxybutyrate (4HB) biosynthesis. The system allowed formation of P(3HB-co-4HB) consisting of 1-9mol% 4HB. Additionally, succinate, generated by succinyl-coA synthetase and succinate dehydrogenase (respectively encoded by genes sucC, sucD and sdhA, sdhB) was channeled preferentially to the 4HB precursor by using selected sgRNAs such as sucC2, sucD2, sdhB2 and sdhA1 via CRISPRi. The resulting 4HB content in P(3HB-co-4HB) was found to range from 1.4 to 18.4mol% depending on the expression levels of down-regulated genes. The results show that CRISPRi is a feasible method to simultaneously manipulate multiple genes in E. coli. PMID:25838211

  4. NITRATE CONVERSION OF HB-LINE REILLEXTM HPQ RESIN

    SciTech Connect

    Steimke, J.; Williams, M.; Steeper, T.; Leishear, R.

    2012-05-29

    Reillex{trademark} HPQ ion exchange resin is used by HB Line to remove plutonium from aqueous streams. Reillex{trademark} HPQ resin currently available from Vertellus Specialties LLC is a chloride ionic form, which can cause stress corrosion cracking in stainless steels. Therefore, HB Line Engineering requested that Savannah River National Laboratory (SRNL) convert resin from chloride form to nitrate form in the Engineering Development Laboratory (EDL). To perform this task, SRNL treated two batches of resin in 2012. The first batch of resin from Reilly Industries Batch 80302MA was initially treated at SRNL in 2001 to remove chloride. This batch of resin, nominally 30 liters, has been stored wet in carboys since that time until being retreated in 2012. The second batch of resin from Batch 23408 consisted of 50 kg of new resin purchased from Vertellus Specialties in 2012. Both batches were treated in a column designed to convert resin using downflow of 1.0 M sodium nitrate solution through the resin bed followed by rinsing with deionized water. Both batches were analyzed for chloride concentration, before and after treatment, using Neutron Activation Analysis (NAA). The resin specification [Werling, 2003] states the total chlorine and chloride concentration shall be less than 250 ppm. The resin condition for measuring this concentration is not specified; however, in service the resin would always be fully wet. Measurements in SRNL showed that changing from oven dry resin to fully wet resin, with liquid in the particle interstices but no supernatant, increases the total weight by a factor of at least three. Therefore, concentration of chlorine or chloride expressed as parts per million (ppm) decreases by a factor of three. Therefore, SRNL recommends measuring chlorine concentration on an oven dry basis, then dividing by three to estimate chloride concentration in the fully wet condition. Chloride concentration in the first batch (No.80302MA) was nearly the same

  5. HB LED color mixture traffic light solution based on EZ-color

    NASA Astrophysics Data System (ADS)

    Hong, Qunhuan; Wang, Weijian; Xiao, Zhihong

    2010-02-01

    This paper introduces a traffic light design solution using HB LED color mixture,namely an implementation method using a set of traffic lights composed of red, green and blue HB LED to replace ordinary red, yellow and green lights. This scheme realizes HB LED color mixture lighting design on the basis of Cypress EZ-Color controller and codeless embedded design software PSoC Express.

  6. Association of Hb Thailand [α56(E5)Lys→Thr] and Hb Phnom Penh [α117(GH5)-Ile-α118(H1)] with α(0)-thalassemia: molecular and hematological features and differential diagnosis.

    PubMed

    Singha, Kritsada; Srivorakun, Hataichanok; Fucharoen, Goonnapa; Changtrakul, Yossombat; Komwilaisak, Patcharee; Jetsrisuparb, Arunee; Puangplruk, Rawiwan; Fucharoen, Supan

    2013-01-01

    We report the molecular and hematological characteristics of two rare hemoglobin (Hb) variants found in associations with a common α(0)-thalassemia (α(0)-thal) in Thai patients. The first case (P1) was a generally healthy 27-year-old man discovered during our ongoing thalassemia screening program. Hemoglobin and DNA analyses identified a previously undescribed condition of compound heterozygosity for Hb Thailand [α56(E5)Lys→Thr] and α(0)-thal (SEA deletion). The second case (P2) was a 4-year-old boy with hypochromic microcytic anemia. Hemoglobin and DNA analyses also identified a compound heterozygosity for Hb Phnom Penh [α117(GH5)-Ile-α118(H1)] in association with α(0)-thal (SEA deletion). Although Hb H (β(4)) inclusion bodies were observed in both cases, Hb analysis using both high performance liquid chromatography (HPLC) and capillary electrophoresis (CE) did not show Hb H. While the two Hb variants could be recognized on Hb HPLC analysis, their corresponding Hb A(2) derivatives: the Hb A(2)-Thailand and Hb A(2)-Phnom Penh, were clearly observed on CE. Apparently, combination of these two Hb variants with α(0)-thal are not expressed as Hb H disease. The two Hb variants could be confirmed by polymerase chain restriction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific PCR assays. PMID:23215800

  7. Structure of fully liganded Hb ζ2β2 s trapped in a tense conformation

    PubMed Central

    Safo, Martin K.; Ko, Tzu-Ping; Abdulmalik, Osheiza; He, Zhenning; Wang, Andrew H.-J.; Schreiter, Eric R.; Russell, J. Eric

    2013-01-01

    A variant Hb ζ2β2 s that is formed from sickle hemoglobin (Hb S; α2β2 s) by exchanging adult α-globin with embryonic ζ-globin subunits shows promise as a therapeutic agent for sickle-cell disease (SCD). Hb ζ2β2 s inhibits the polymerization of deoxy­genated Hb S in vitro and reverses characteristic features of SCD in vivo in mouse models of the disorder. When compared with either Hb S or with normal human adult Hb A (α2β2), Hb ζ2β2 s exhibits atypical properties that include a high oxygen affinity, reduced cooperativity, a weak Bohr effect and blunted 2,3-­diphosphoglycerate allostery. Here, the 1.95 Å resolution crystal structure of human Hb ζ2β2 s that was expressed in complex transgenic knockout mice and purified from their erythrocytes is presented. When fully liganded with carbon monoxide, Hb ζ2β2 s displays a central water cavity, a ζ1–βs2 (or ζ2–βs1) interface, intersubunit salt-bridge/hydrogen-bond interactions, C-terminal βHis146 salt-bridge interactions, and a β-cleft, that are highly unusual for a relaxed hemoglobin structure and are more typical of a tense conformation. These quaternary tense-like features contrast with the tertiary relaxed-like conformations of the ζ1βs1 dimer and the CD and FG corners, as well as the overall structures of the heme cavities. This crystallographic study provides insights into the altered oxygen-transport properties of Hb ζ2β2 s and, moreover, decouples tertiary- and quaternary-structural events that are critical to Hb ligand binding and allosteric function. PMID:24100324

  8. The heparin-binding domain of HB-EGF mediates localization to sites of cell-cell contact and prevents HB-EGF proteolytic release

    SciTech Connect

    Prince, Robin N.; Schreiter, Eric R.; Zou, Peng; Wiley, H. S.; Ting, Alice Y.; Lee, Richard T.; Lauffenburger, Douglas A.

    2010-07-01

    Heparin-binding EGF-like growth factor (HB-EGF) is a ligand for EGF receptor (EGFR) and possesses the ability to signal in juxtacrine, autocrine and/or paracrine mode, with these alternatives being governed by the degree of proteolytic release of the ligand. Although the spatial range of diffusion of released HB-EGF is restricted by binding heparan-sulfate proteoglycans (HSPGs) in the extracellular matrix and/or cellular glycocalyx, ascertaining mechanisms governing non-released HB-EGF localization is also important for understanding its effects. We have employed a new method for independently tracking the localization of the extracellular EGFlike domain of HB-EGF and the cytoplasmic C-terminus. A striking observation was the absence of the HB-EGF transmembrane proform from the leading edge of COS-7 cells in a wound-closure assay; instead, this protein localized in regions of cell-cell contact. A battery of detailed experiments found that this localization derives from a trans interaction between extracellular HSPGs and the HBEGF heparin-binding domain, and that disruption of this interaction leads to increased release of soluble ligand and a switch in cell phenotype from juxtacrine-induced growth inhibition to autocrine-induced proliferation. Our results indicate that extracellular HSPGs serve to sequester the transmembrane pro-form of HB-EGF at the point of cell-cell contact, and that this plays a role in governing the balance between juxtacrine versus autocrine and paracrine signaling.

  9. Simulation Analysis for HB-Line Dissolver Mixing

    SciTech Connect

    Lee, S

    2006-03-22

    In support of the HB-Line Engineering agitator mixing project, flow pattern calculations have been made for a 90{sup o} apart and helical pitch agitator submerged in a flat tank containing dissolver baskets. The work is intended to determine maximum agitator speed to keep the dissolver baskets from contacting the agitator for the nominal tank liquid level. The analysis model was based on one dissolver basket located on the bottom surface of the flat tank for a conservative estimate. The modeling results will help determine acceptable agitator speeds and tank liquid levels to ensure that the dissolver basket is kept from contacting the agitator blade during HB-Line dissolver tank operations. The numerical modeling and calculations have been performed using a computational fluid dynamics approach. Three-dimensional steady-state momentum and continuity equations were used as the basic equations to estimate fluid motion driven by an agitator with four 90{sup o} pitched blades or three flat blades. Hydraulic conditions were fully turbulent (Reynolds number about 1 x 10{sup 5}). A standard two-equation turbulence model ({kappa},{var_epsilon}), was used to capture turbulent eddy motion. The commercial finite volume code, Fluent [5], was used to create a prototypic geometry file with a non-orthogonal mesh. Hybrid meshing was used to fill the computational region between the round-edged tank bottom and agitator regions. The nominal calculations and a series of sensitivity runs were made to investigate the impact of flow patterns on the lifting behavior of the dissolver basket. At high rotational speeds and low tank levels, local turbulent flow reaches the critical condition for the dissolver basket to be picked up from the tank floor and to touch the agitator blades during the tank mixing operations. This is not desirable in terms of mixing performance. The modeling results demonstrate that the flow patterns driven by the agitators considered here are not strong enough to

  10. 75 FR 36152 - Savings Association Holding Company Report H-(b)11

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-24

    ... Office of Thrift Supervision Savings Association Holding Company Report H-(b)11 AGENCY: Office of Thrift... Association Holding Company Report H- (b)11 OMB Number: 1550-0060. Form Number: OTS Form H-(b)11. Regulation... applicable statutes, regulations, and conditions of approval to acquire an insured savings association....

  11. HB 1347 and Its Relationship to Foodservice Outsourcing in Illinois Public Schools

    ERIC Educational Resources Information Center

    Brashear, Gary L.

    2012-01-01

    This study examined foodservice outsourcing in the State of Illinois. School administrators currently outsourcing foodservice were surveyed about their perceptions of HB1347 and its components. This study looked at HB1347 in Illinois, and its effects on outsourcing in school districts. Data for this study was collected from a survey sent to 100%…

  12. GENETIC FACTORS INFLUENCING HEMOGLOBIN F LEVEL IN β-THALASSEMIA/HB E DISEASE.

    PubMed

    Ruangrai, Waraporn; Jindadamrongwech, Sumalee

    2016-01-01

    Genetic factors influencing Hb F content in adult red blood cells include β-thalassemia genotypes, co-inheritance of α-thalassemia traits and single nucleotide polymorphisms (SNPs). Genotyping of α- and β-thalassemia and five SNPs in β-globin gene cluster previously identified in genome-wide association studies as being markers of elevated Hb F in β-thalassemia were performed in 81 subjects diagnosed with β-thalassemia/Hb E. Hb F levels are higher (0.9-7.1 g/dl) in subjects (n = 57) with the severe compared to mild β-thalassemia (0.8-2.5 g/ dl) (n = 4) genotypes, and are similarly low (0.7-3.5 g/dl) in those (n = 15) with α-thalassemia co-inheritance. Hb F levels in non-thalassemia controls (n = 150) range from 0 to 0.15 g/dl. The presence of homozygous minor alleles of the 5 SNPs are significant indicators of β-thalassemia/Hb E individuals with high Hb F (> 4 g/dl), independent of their thalassemia genotypes. Given that re-activation of γ-globin genes leads to amelioration of β-thalassemia severity, understanding how genetic factors up-regulate Hb F production may lead to possible therapeutic interventions, genetically or pharmacologically, of this debilitating disease in the not too distant future. PMID:27086429

  13. 75 FR 10863 - Savings Association Holding Company Report H-(b)11

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-09

    ... Office of Thrift Supervision Savings Association Holding Company Report H-(b)11 AGENCY: Office of Thrift... collection. Title of Proposal: Savings Association Holding Company Report H- (b)11. OMB Number: 1550-0060. Form Numbers: OTS Form H-(b)11. Regulation requirement: 12 CFR part 584.1. Description: Section...

  14. GENERAL VIEW OF TYPE HB54s (BUILDINGS T1088 TO T1093) & ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GENERAL VIEW OF TYPE HB-54s (BUILDINGS T-1088 TO T-1093) & CONVERTED TYPE HB-54S (BUILDINGS T-1094 TO T-1096), LOOKING SOUTHWEST; BUILDING T-1088 AT LEFT, BUILDING T-1096 AT RIGHT - Fort McCoy, Building No. T-1096, South side of South Ninth Avenue, Block 10, Sparta, Monroe County, WI

  15. [Effect of sheep haptoglobin on the hemoglobin molecule in the Hp-Hb complex].

    PubMed

    Beĭsembaeva, R U; Dzhusupova, R Zh

    1986-01-01

    Sheep haptoglobin (HpC) binding hemoglobin increases the stability of the latter to acid denaturation and oxidation by atmospheric O2. HpC is also capable of binding methemoglobin (MetHb) denaturated at pH 3.5 to form a stable complex. This process is accompanied by partial reconstitution of the structural integrity and peroxidase activity of MetHb. Consequently, the formation of a HpC-MetHb complex leads to changes in the tertiary structure of the MetHb molecule. The increase in the peroxidase activity of MetHb at pH less than or equal to 4.0 after its binding to HpC is due to the stabilizing and stimulating activity of HpC. PMID:3006800

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

    PubMed

    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 (<4%) by HPLC method but were in the normal or higher range by TINIA method. TINIA method did not agree with HPLC method on Bland Altman plot in the 38 cases with below normal HbA(1)c levels, [Mean bias -5.2(-9.3 to 1.0), 95% CI] but agreed very well [mean bias -0.21 (-0.84 to 0.42), y=1.1037+0.776X; r(2)=0.30, p<0.01] in controls. In control group mean MCV was 83.80±7.48 and in study group was 73.65±10.44. Alkaline electrophoresis confirmed the variant hemoglobin to be HbE. The fasting blood sugar levels of all the 72 cases correlated strongly with TINIA method (r(2) =0.75, p<0.0001) but not with HPLC (r = 0.24, p=0.13). In our regions where populations have a high prevalence of 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

  17. Fasting blood glucose and HbA1c in children with ADHD.

    PubMed

    Lindblad, Frank; Eickhoff, Malin; Forslund, Anders H; Isaksson, Johan; Gustafsson, Jan

    2015-04-30

    Reports of hypocortisolism and overweight in pediatric ADHD motivate an investigation of blood glucose regulation in this group. Fasting blood glucose and HbA1c were investigated in 10 children (10-15 years) with ADHD and 22 comparisons. Fasting blood glucose was similar in both groups. HbA1c values were higher in the ADHD-group. BMI-SDS was also higher in the ADHD-group but did not predict HbA1c. The results suggest an association between ADHD and an altered blood glucose homeostasis. PMID:25747679

  18. Complete Genome Sequence of a Phenanthrene Degrader, Burkholderia sp. HB-1 (NBRC 110738)

    PubMed Central

    Moriya, Azusa; Kato, Hiromi; Ogawa, Natsumi; Nagata, Yuji; Tsuda, Masataka

    2015-01-01

    The phenanthrene-degrading Burkholderia sp. HB-1 was isolated from a phenanthrene-enrichment culture seeded with a pristine farm soil sample. We report the complete genome sequence of HB-1, which has been deposited to the stock culture (NBRC 110738) at Biological Resource Center, National Institute of Technology and Evaluation (NITE), Tokyo, Japan. The genome of strain HB-1 comprises two circular chromosomes of 4.1 Mb and 3.1 Mb. The finishing was facilitated by the computational tools GenoFinisher, AceFileViewer, and ShortReadManager. PMID:26543118

  19. Comparison Among HB-inspired Algorithms for Continuous-Spin Systems and Gauge Fields

    NASA Astrophysics Data System (ADS)

    Cucchieri, A.; Frigori, R. B.; Mendes, T.; Mihara, A.

    2006-09-01

    We propose a new local algorithm for the thermalization of n-vector spin models, which can also be used in the numerical simulation of SU(N) lattice gauge theories. The algorithm combines heat-bath (HB) and micro-canonical updates in a single step -- as opposed to the hybrid overrelaxation method, which alternates between the two kinds of update steps -- while preserving ergodicity. We test our proposed algorithm in the case of the one-dimensional 4-vector spin model and compare its performance with the standard HB algorithm and with other HB-inspired algorithms.

  20. Spectra of the HB 21 supernova remnant: Evidence of spectrum flattening at the low frequencies

    NASA Astrophysics Data System (ADS)

    Borka, D.; Borka Jovanovic, V.; Uroševic, D.

    2012-04-01

    We use observations of the continuum radio emission at 1420, 820, 408, 34.5 and 22 MHz to estimate the mean brightness temperatures of the HB 21 supernova remnant (SNR) at five frequencies. We also present mean spectral index of HB1. The spectra of HB 21 are estimated from mean temperatures versus frequency plots for 1420, 820, 408, 34.5 and 22 MHz. We also present T-T plots of three frequency pairs: between 1420-34.5, 1420-22, 34.5-22 MHz. We notice flatter spectral indices at frequencies below 408 MHz. Probably this is due to the absorption by thermal plasma at low frequencies.

  1. α-Thalassemia Associated with Hb Instability: A Tale of Two Features. The Case of Hb Rogliano or α1 Cod 108(G15)Thr→Asn and Hb Policoro or α2 Cod 124(H7)Ser→Pro.

    PubMed Central

    Musollino, Gennaro; Cardiero, Giovanna; Flagiello, Angela; La Porta, Gaetana; Lagona, Laura; Prezioso, Romeo; Qualtieri, Gabriele; Gaudiano, Carlo; Medulla, Emilia; Merlino, Antonello; Pucci, Piero; Lacerra, Giuseppina

    2015-01-01

    We identified two new variants in the third exon of the α-globin gene in families from southern Italy: the Hb Rogliano, α1 cod108 ACC>AAC or α1[α108(G15)Thr→Asn] and the Hb Policoro, α2 cod124 TCC>CCC or α2[α124(H7)Ser→Pro]. The carriers showed mild α-thalassemia phenotype and abnormal hemoglobin stability features. These mutations occurred in the G and H helices of the α-globin both involved in the specific recognition of AHSP and β1 chain. Molecular characterization of mRNA, globin chain analyses and molecular modelling studies were carried out to highlight the mechanisms causing the α-thalassemia phenotype. The results demonstrated that the α-thalassemia defect associated with the two Hb variants originated by different defects. Hb Rogliano showed an intrinsic instability of the tetramer due to anomalous intra- and inter-chain interactions suggesting that the variant chain is normally synthesized and complexed with AHSP but rapidly degraded because it is unable to form the α1β1 dimers. On the contrary in the case of Hb Policoro two different molecular mechanisms were shown: the reduction of the variant mRNA level by an unclear mechanism and the protein instability due to impairment of AHSP interaction. These data highlighted that multiple approaches, including mRNA quantification, are needed to properly identify the mechanisms leading to the α-thalassemia defect. Elucidation of the specific mechanism leads to the definition of a given phenotype providing important guidance for the diagnosis of unstable variants. PMID:25730315

  2. DETAIL VIEW OF A FOREIGN OBSTACLE DEBRIS NET, HB3, FACING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DETAIL VIEW OF A FOREIGN OBSTACLE DEBRIS NET, HB-3, FACING WEST - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  3. GENERAL VIEW OF VEHICLE ACCESS PLATFORM CNORTH, HB3, FACING NORTHEAST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GENERAL VIEW OF VEHICLE ACCESS PLATFORM C-NORTH, HB-3, FACING NORTHEAST - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  4. GENERAL VIEW OF VEHICLE ACCESS PLATFORM ENORTH, HB3, FACING NORTH ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GENERAL VIEW OF VEHICLE ACCESS PLATFORM E-NORTH, HB-3, FACING NORTH - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  5. GENERAL VIEW OF VEHICLE ACCESS PLATFORM ENORTH, HB3, FACING NORTHWEST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GENERAL VIEW OF VEHICLE ACCESS PLATFORM E-NORTH, HB-3, FACING NORTHWEST - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  6. GENERAL VIEW OF VEHICLE ACCESS PLATFORM DNORTH, HB3, FACING NORTHWEST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GENERAL VIEW OF VEHICLE ACCESS PLATFORM D-NORTH, HB-3, FACING NORTHWEST - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  7. GENERAL VIEW OF VEHICLE ACCESS PLATFORM CNORTH, HB3, FACING NORTHWEST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GENERAL VIEW OF VEHICLE ACCESS PLATFORM C-NORTH, HB-3, FACING NORTHWEST - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  8. GENERAL VIEW OF NORTH VEHICLE ACCESS PLATFORMS, HB3, FACING NORTHEAST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GENERAL VIEW OF NORTH VEHICLE ACCESS PLATFORMS, HB-3, FACING NORTHEAST TOWARDS CEILING - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  9. GENERAL VIEW OF VEHICLE ACCESS PLATFORM BNORTH, HB3, FACING NORTHEAST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GENERAL VIEW OF VEHICLE ACCESS PLATFORM B-NORTH, HB-3, FACING NORTHEAST - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  10. GENERAL VIEW OF VEHICLE ACCESS PLATFORM DNORTH, HB3, FACING NORTH ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GENERAL VIEW OF VEHICLE ACCESS PLATFORM D-NORTH, HB-3, FACING NORTH - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  11. GENERAL VIEW OF VEHICLE ACCESS PLATFORM BNORTH, HB3, FACING NORTH ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GENERAL VIEW OF VEHICLE ACCESS PLATFORM B-NORTH, HB-3, FACING NORTH - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  12. GENERAL VIEW OF NORTH VEHICLE ACCESS PLATFORMS, HB3, FACING NORTH ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GENERAL VIEW OF NORTH VEHICLE ACCESS PLATFORMS, HB-3, FACING NORTH TOWARDS FLOOR - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  13. Clinical, Hematological and Molecular Analysis of Homozygous Hb E (HBB: c.79G > A) in the Indian Population.

    PubMed

    Jayasree, Divya; Shaji, Ramachandran V; George, Biju; Mathews, Vikram; Srivastava, Alok; Edison, Eunice S

    2016-01-01

    Homozygous Hb E [β26(B8)Glu→Lys; HBB: c.79G > A] is a clinically mild disease with no significant symptoms. Very few studies are available on clinical variability in Hb E disorders. We report the profile of a series of homozygous Hb E patients in the Indian population. We analyzed various genetic factors that contribute to the heterogeneity in the phenotype of homozygous Hb E patients. Analysis of these parameters further enhances our understanding of the Hb E syndrome. PMID:26554862

  14. Guanidine hydrochloride and urea effects upon thermal stability of Glossoscolex paulistus hemoglobin (HbGp).

    PubMed

    Carvalho, Francisco A O; Alves, Fernanda R; Carvalho, José W P; Tabak, Marcel

    2015-03-01

    Glossoscolex paulistus hemoglobin (HbGp) has a molecular mass of 3600kDa. It belongs to the hexagonal bilayer hemoglobin class, which consists of highly cooperative respiratory macromolecules found in mollusks and annelids. The present work focusses on oxy-HbGp thermal stability, in the presence of urea and guanidine hydrochloride (GuHCl), monitored by several techniques. Initially, dynamic light scattering data show that the presence of GuHCl induces the protein oligomeric dissociation, followed by a significant 11-fold increase in the hydrodynamic diameter (DH) values, due to the formation of protein aggregates in solution. In contrast, urea promotes the HbGp oligomeric dissociation, followed by unfolding process at high temperatures, without aggregation. Circular dichroism data show that unfolding critical temperature (Tc) of oxy-HbGp decreases from 57°C, at 0.0 mol/L of the denaturant, to 45°C, in the presence of 3.5 mol/L of urea, suggesting the reduction of HbGp oligomeric stability. Moreover, differential scanning calorimetry results show that at lower GuHCl concentrations, some thermal stabilization of the hemoglobin is observed, whereas at higher concentrations, the reduction of stability takes place. Besides, HbGp is more stable in the presence of urea when compared with the guanidine effect, as deduced from the differences in the concentration range of denaturants. PMID:25433131

  15. Targeting autocrine HB-EGF signaling with specific ADAM12 inhibition using recombinant ADAM12 prodomain

    NASA Astrophysics Data System (ADS)

    Miller, Miles A.; Moss, Marcia L.; Powell, Gary; Petrovich, Robert; Edwards, Lori; Meyer, Aaron S.; Griffith, Linda G.; Lauffenburger, Douglas A.

    2015-10-01

    Dysregulation of ErbB-family signaling underlies numerous pathologies and has been therapeutically targeted through inhibiting ErbB-receptors themselves or their cognate ligands. For the latter, “decoy” antibodies have been developed to sequester ligands including heparin-binding epidermal growth factor (HB-EGF); however, demonstrating sufficient efficacy has been difficult. Here, we hypothesized that this strategy depends on properties such as ligand-receptor binding affinity, which varies widely across the known ErbB-family ligands. Guided by computational modeling, we found that high-affinity ligands such as HB-EGF are more difficult to target with decoy antibodies compared to low-affinity ligands such as amphiregulin (AREG). To address this issue, we developed an alternative method for inhibiting HB-EGF activity by targeting its cleavage from the cell surface. In a model of the invasive disease endometriosis, we identified A Disintegrin and Metalloproteinase 12 (ADAM12) as a protease implicated in HB-EGF shedding. We designed a specific inhibitor of ADAM12 based on its recombinant prodomain (PA12), which selectively inhibits ADAM12 but not ADAM10 or ADAM17. In endometriotic cells, PA12 significantly reduced HB-EGF shedding and resultant cellular migration. Overall, specific inhibition of ligand shedding represents a possible alternative to decoy antibodies, especially for ligands such as HB-EGF that exhibit high binding affinity and localized signaling.

  16. Significance of HbA1c Test in Diagnosis and Prognosis of Diabetic Patients

    PubMed Central

    Sherwani, Shariq I.; Khan, Haseeb A.; Ekhzaimy, Aishah; Masood, Afshan; Sakharkar, Meena K.

    2016-01-01

    Diabetes is a global endemic with rapidly increasing prevalence in both developing and developed countries. The American Diabetes Association has recommended glycated hemoglobin (HbA1c) as a possible substitute to fasting blood glucose for diagnosis of diabetes. HbA1c is an important indicator of long-term glycemic control with the ability to reflect the cumulative glycemic history of the preceding two to three months. HbA1c not only provides a reliable measure of chronic hyperglycemia but also correlates well with the risk of long-term diabetes complications. Elevated HbA1c has also been regarded as an independent risk factor for coronary heart disease and stroke in subjects with or without diabetes. The valuable information provided by a single HbA1c test has rendered it as a reliable biomarker for the diagnosis and prognosis of diabetes. This review highlights the role of HbA1c in diagnosis and prognosis of diabetes patients. PMID:27398023

  17. Significance of HbA1c Test in Diagnosis and Prognosis of Diabetic Patients.

    PubMed

    Sherwani, Shariq I; Khan, Haseeb A; Ekhzaimy, Aishah; Masood, Afshan; Sakharkar, Meena K

    2016-01-01

    Diabetes is a global endemic with rapidly increasing prevalence in both developing and developed countries. The American Diabetes Association has recommended glycated hemoglobin (HbA1c) as a possible substitute to fasting blood glucose for diagnosis of diabetes. HbA1c is an important indicator of long-term glycemic control with the ability to reflect the cumulative glycemic history of the preceding two to three months. HbA1c not only provides a reliable measure of chronic hyperglycemia but also correlates well with the risk of long-term diabetes complications. Elevated HbA1c has also been regarded as an independent risk factor for coronary heart disease and stroke in subjects with or without diabetes. The valuable information provided by a single HbA1c test has rendered it as a reliable biomarker for the diagnosis and prognosis of diabetes. This review highlights the role of HbA1c in diagnosis and prognosis of diabetes patients. PMID:27398023

  18. Relationship of HbA1c variability, absolute changes in HbA1c, and all-cause mortality in type 2 diabetes: a Danish population-based prospective observational study

    PubMed Central

    Skriver, Mette V; Sandbæk, Annelli; Kristensen, Jette K; Støvring, Henrik

    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 with type 2 diabetes during 2001–2006 were identified from public data files, with at least three HbA1c measurements: one index measure, one closing measure 22–26 months later, and one measurement in-between. Medium index HbA1c was 7.3%, median age was 63.9 years, and 48% were women. HbA1c variability was defined as the mean absolute residual around the line connecting index value with closing value. Cox proportional hazard models with restricted cubic splines were used, with all-cause mortality as the outcome. Results Variability between 0 and 0.5 HbA1c percentage point was not associated with mortality, but for index HbA1c ≤8% (64 mmol/mol), a variability above 0.5 was associated with increased mortality (HR of 1 HbA1c percentage point variability was 1.3 (95% CI 1.1 to 1.5) for index HbA1c 6.6–7.4%). For index HbA1c≤8%, mortality increased when HbA1c declined, but was stable when HbA1c rose. For index HbA1c>8%, change in HbA1c was associated with mortality, with the lowest mortality for greatest decline (HR=0.9 (95% CI 0.80 to 0.98) for a 2-percentage point decrease). Conclusions For individuals with an index HbA1c below 8%, both high HbA1c variability and a decline in HbA1c were associated with increased mortality. For individuals with index HbA1c above 8%, change in HbA1c was associated with mortality, whereas variability was not. PMID:25664182

  19. Description of Three New α Variants and Four New β Variants: Hb Montluel [α110(G17)Ala → Val; HBA1: c.332C > T], Hb Cap d'Agde [α131(H14)Ser → Cys; HBA2: c.395C > G] and Hb Corsica [α100(G7)Leu → Pro; HBA1: 302T > C]; Hb Nîmes [β104(G6)Arg → Gly; HBB: c.313A > G], Hb Saint Marcellin [β112(G14)Cys → Gly; HBB: c.337T > G], Hb Saint Chamond [β80(EF4)Asn → 0; HBB: c.241_243delAAC] and Hb Dompierre [β29(B11)Gly → Arg; HBB: c.88G > C].

    PubMed

    Renoux, Céline; Feray, Cécile; Joly, Philippe; Lacan, Philippe; Francina, Alain

    2015-01-01

    We present here seven new hemoglobin (Hb) variants identified during routine Hb analysis. All of them are caused by a missense mutation except Hb Saint Chamond, which results from an in-frame deletion of the asparagine residue at β80. All these variants are clinically silent in the heterozygous state but two of them (Hb Cap d'Agde and Hb Dompierre) may be unstable, whereas Hb Nîmes could present a very slightly elevated oxygen affinity. These data are to be confirmed by appropriate biochemical tests. PMID:26100115

  20. The impact of the HbA1c level of type 2 diabetics on the structure of haemoglobin.

    PubMed

    Ye, Shaoying; Ruan, Ping; Yong, Junguang; Shen, Hongtao; Liao, Zhihong; Dong, Xiaolei

    2016-01-01

    This study explores the impact of HbA1c levels on the structure of haemoglobin (Hb) in patients with type 2 diabetes. Seventy-four diabetic patients were classified into the following two groups based on their level of HbA1c: group A, patients with good glycaemic control (HbA1c < 7.0%, n = 36); group B, patients with persistent hyperglycaemia (HbA1c ≥ 9.0%, n = 38). Thirty-four healthy people served as controls (group H). Hb structure was examined by Fourier transform infrared spectroscopy (FTIR), and diabetic erythrocytes were modelled to estimate the impact of glucose on these cells and Hb. Increasing glucose concentrations altered both erythrocyte parameters and the Hb secondary structure. Group B differed significantly from group H (p < 0.05): in the former, the ordered Hb secondary structure had a strong tendency to transform into a disordered secondary structure, decreasing structural stability. We presumed here that high HbA1c levels might be a factor contributing to Hb structural modifications in diabetic patients. FTIR spectral analysis can provide a novel way to investigate the pathogenesis of type 2 diabetes mellitus. PMID:27624402

  1. Evolution, Three-Dimensional Model and Localization of Truncated Hemoglobin PttTrHb of Hybrid Aspen

    PubMed Central

    Dumont, Estelle; Jokipii-Lukkari, Soile; Parkash, Vimal; Vuosku, Jaana; Sundström, Robin; Nymalm, Yvonne; Sutela, Suvi; Taskinen, Katariina; Kallio, Pauli T.; Salminen, Tiina A.; Häggman, Hely

    2014-01-01

    Thus far, research on plant hemoglobins (Hbs) has mainly concentrated on symbiotic and non-symbiotic Hbs, and information on truncated Hbs (TrHbs) is scarce. The aim of this study was to examine the origin, structure and localization of the truncated Hb (PttTrHb) of hybrid aspen (Populus tremula L. × tremuloides Michx.), the model system of tree biology. Additionally, we studied the PttTrHb expression in relation to non-symbiotic class1 Hb gene (PttHb1) using RNAi-silenced hybrid aspen lines. Both the phylogenetic analysis and the three-dimensional (3D) model of PttTrHb supported the view that plant TrHbs evolved vertically from a bacterial TrHb. The 3D model suggested that PttTrHb adopts a 2-on-2 sandwich of α-helices and has a Bacillus subtilis -like ligand-binding pocket in which E11Gln and B10Tyr form hydrogen bonds to a ligand. However, due to differences in tunnel cavity and gate residue (E7Ala), it might not show similar ligand-binding kinetics as in Bs-HbO (E7Thr). The immunolocalization showed that PttTrHb protein was present in roots, stems as well as leaves of in vitro -grown hybrid aspens. In mature organs, PttTrHb was predominantly found in the vascular bundles and specifically at the site of lateral root formation, overlapping consistently with areas of nitric oxide (NO) production in plants. Furthermore, the NO donor sodium nitroprusside treatment increased the amount of PttTrHb in stems. The observed PttTrHb localization suggests that PttTrHb plays a role in the NO metabolism. PMID:24520401

  2. The Clinical Significance of HbA1c in Operable Chronic Thromboembolic Pulmonary Hypertension

    PubMed Central

    Richter, Manuel Jonas; Milger, Katrin; Haase, Sarah; Sommer, Natascha; Tello, Khodr; Seeger, Werner; Mayer, Eckhard; Wiedenroth, Christoph Benjamin; Grimminger, Friedrich; George, Wolfgang; Ghofrani, Hossein Ardeschir; Guth, Stefan; Gall, Henning

    2016-01-01

    Background Glycosylated hemoglobin A1c (HbA1c) has been proposed as an independent predictor of long-term prognosis in pulmonary arterial hypertension. However, the clinical relevance of HbA1c in patients with operable chronic thromboembolic pulmonary hypertension (CTEPH) remains unknown. The aim of the present study was to investigate the clinical significance of HbA1c as a biomarker in CTEPH. Methods Prospectively, 102 patients underwent pulmonary endarterectomy (PEA) in our national referral center between March 2013 and March 2014, of which after exclusion 45 patients were analyzed. HbA1c- levels, hemodynamic and exercise parameters were analyzed prior and one-year post-PEA. Results 45 patients (BMI: 27.3 ± 6.0 kg/m2; age: 62.7 ± 12.3 years) with a mean pulmonary arterial pressure (mPAP) of 43.6 ± 9.4 mmHg, a pulmonary vascular resistance (PVR) of 712.1 ± 520.4 dyn*s/cm5, a cardiac index (CI) of 2.4 ± 0.5 l/min/m2 and a mean HbA1c-level of 39.8 ± 5.6 mmol/mol were included. One-year post-PEA pulmonary hemodynamic and functional status significantly improved in our cohort. Baseline HbA1c-levels were significantly associated with CI, right atrial pressure, peak oxygen uptake and the change of 6-minute walking distance using linear regression analysis. However, using logistic regression analysis baseline HbA1c-levels were not significantly associated with residual post-PEA PH. Conclusions This is the first prospective study to describe an association of HbA1c-levels with pulmonary hemodynamics and exercise capacity in operable CTEPH patients. Our preliminary results indicate that in these patients impaired glucose metabolism as assessed by HbA1c is of clinical significance. However, HbA1c failed as a predictor of the hemodynamic outcome one-year post-PEA. PMID:27031508

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

    PubMed Central

    Renz, Paula Breitenbach; Cavagnolli, Gabriela; Weinert, Letícia Schwerz; Silveiro, Sandra Pinho; Camargo, Joíza Lins

    2015-01-01

    Aims 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. Methods 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. Results 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. Conclusions Our results show that combined HbA1c and OGTT measurements may be useful in diagnosing GDM. PMID:26292213

  4. A Family with γ-Thalassemia and High Hb A2 Levels.

    PubMed

    Parmeggiani, Giulia; Gualandi, Francesca; Selvatici, Rita; Rimessi, Paola; Bigoni, Stefania; Taddei Masieri, Marina; Dolcini, Bernadetta; Venturoli, Anna; Cappabianca, Maria P; Ferlini, Alessandra; Ravani, Anna

    2016-06-01

    We describe a family carrying a γ-globin gene deletion associated with an increase of Hb A2 level beyond the normal range. The family included the proband, his sister and their father, all with increased Hb A2 and normal Hb F levels. The proband and his sister showed borderline values of mean corpuscular volume (MCV) and reduced values of mean corpuscular hemoglobin (Hb) (MCH). The proband was referred to our Medical Genetics Service for preconception counseling together with his partner, a typical β-thalassemia (β-thal) carrier. The results were negative for the most frequent α-thalassemia (α-thal) mutations, and had no significant sequence variations of the coding sequences and promoter of the β- and δ-globin genes. Quantitative analysis by multiplex ligation-dependent probe amplification (MPLA) of the β-globin gene cluster detected a heterozygous deletion, ranging between 2.1 and 4.7 kb, in the proband, his sister and the father. The deletion involved the (G)γ gene and (G)γ-(A)γ intergenic region, whereas the 3' region of the (A)γ gene was preserved. A subsequent gap-polymerase chain reaction (gap-PCR) showed that a hybrid (GA)γ fusion gene was present. The deletion segregated with the elevation of Hb A2. The MLPA analysis of the β-globin gene cluster in 150 control alleles excluded a common polymorphism. Despite stronger evidence being needed, the described family suggests a possible role of this γ-globin gene deletion in contributing to Hb A2 elevation, possibly by altering the transcription regulation of the cluster. We propose γ-globin gene dosage analysis to be performed in patients with unexplained elevated Hb A2 levels. PMID:27117568

  5. Identification and Expression Analysis of a Novel HbCIPK2-Interacting Ferredoxin from Halophyte H. brevisubulatum

    PubMed Central

    Zhang, Chao; Ge, Rongchao; Zhang, Junwen; Chen, Yajuan; Wang, Hongzhi; Wei, Jianhua; Li, Ruifen

    2015-01-01

    Ferredoxin is a small iron-sulfer protein involved in various one-eletron transfer pathways. Little is known about how ferredoxin is regulated to distribute electron under abiotic stress. Our previous study has showed that HbCIPK2 conferred salinity and drought tolerance. Thus, we hypothesized that HbCIPK2 could mediate the activities of interacting partners as a signal transducer. In this report, we identified a novel HbCIPK2-interacting ferredoxin (HbFd1) from halophyte Hordeum brevisubulatum by yeast two-hybrid screens, confirmed this interaction by BiFC in vivo and CoIP in vitro, and presented the expression pattern of HbFd1. HbFd1 was down-regulated under salinity and cold stress but up-regulated under PEG stress, its expression showed tissue-specific, mainly in shoot chloroplast, belonging to leaf-type subgroup. Moreover, HbCIPK2 could recruit HbFd1 to the nucleus for their interaction. The C-terminal segment in HbFd1 protein was involved in the interaction with HbCIPK2. These results provided insight into the connection between CBL-CIPK signaling network and Fd-dependent metabolic pathways. PMID:26636581

  6. Excess HB-EGF, which promotes VEGF signaling, leads to hydrocephalus

    PubMed Central

    Shim, Joon W.; Sandlund, Johanna; Hameed, Mustafa Q.; Blazer-Yost, Bonnie; Zhou, Feng C.; Klagsbrun, Michael; Madsen, Joseph R.

    2016-01-01

    Heparin binding epidermal growth factor-like growth factor (HB-EGF) is an angiogenic factor mediating radial migration of the developing forebrain, while vascular endothelial growth factor (VEGF) is known to influence rostral migratory stream in rodents. Cell migratory defects have been identified in animal models of hydrocephalus; however, the relationship between HB-EGF and hydrocephalus is unclear. We show that mice overexpressing human HB-EGF with β-galactosidase reporter exhibit an elevated VEGF, localization of β-galactosidase outside the subventricular zone (SVZ), subarachnoid hemorrhage, and ventriculomegaly. In Wistar polycystic kidney rats with hydrocephalus, alteration of migratory trajectory is detected. Furthermore, VEGF infusions into the rats result in ventriculomegaly with an increase of SVZ neuroblast in rostral migratory stream, whereas VEGF ligand inhibition prevents it. Our results support the idea that excess HB-EGF leads to a significant elevation of VEGF and ventricular dilatation. These data suggest a potential pathophysiological mechanism that elevated HB-EGF can elicit VEGF induction and hydrocephalus. PMID:27243144

  7. Excess HB-EGF, which promotes VEGF signaling, leads to hydrocephalus.

    PubMed

    Shim, Joon W; Sandlund, Johanna; Hameed, Mustafa Q; Blazer-Yost, Bonnie; Zhou, Feng C; Klagsbrun, Michael; Madsen, Joseph R

    2016-01-01

    Heparin binding epidermal growth factor-like growth factor (HB-EGF) is an angiogenic factor mediating radial migration of the developing forebrain, while vascular endothelial growth factor (VEGF) is known to influence rostral migratory stream in rodents. Cell migratory defects have been identified in animal models of hydrocephalus; however, the relationship between HB-EGF and hydrocephalus is unclear. We show that mice overexpressing human HB-EGF with β-galactosidase reporter exhibit an elevated VEGF, localization of β-galactosidase outside the subventricular zone (SVZ), subarachnoid hemorrhage, and ventriculomegaly. In Wistar polycystic kidney rats with hydrocephalus, alteration of migratory trajectory is detected. Furthermore, VEGF infusions into the rats result in ventriculomegaly with an increase of SVZ neuroblast in rostral migratory stream, whereas VEGF ligand inhibition prevents it. Our results support the idea that excess HB-EGF leads to a significant elevation of VEGF and ventricular dilatation. These data suggest a potential pathophysiological mechanism that elevated HB-EGF can elicit VEGF induction and hydrocephalus. PMID:27243144

  8. Low HbA1c and Increased Mortality Risk-is Frailty a Confounding Factor?

    PubMed Central

    Abdelhafiz, Ahmed H; Sinclair, Alan J

    2015-01-01

    Diabetes mellitus is increasingly becoming an older person disease due to the increased survival and aging of the population. Previous studies which showed benefits of tight glycemic control and a linear relationship between HbA1c and mortality have largely included younger patients newly diagnosed with diabetes and with less comorbidities. Recent studies, which included older population with diabetes, have shown a U-shaped relationship of increased mortality associated with low HbA1c. The mechanism of such relationship is unclear. There was no direct causal link between low HbA1c and mortality. It appears that malnutrition, inflammation and functional decline are characteristics shared by the populations that showed increased mortality and low HbA1c. In these studies functional status, disability or frailty was not routinely measured. Therefore, although adjustment for comorbidities was made there may be a residual confounding by unmeasured factors such as frailty. Thus, frailty or decline in functional reserve may be the main confounding factor explaining the relationship between increased mortality risk and low HbA1c. PMID:26236548

  9. Recent achievements with a cryogenic ultra-lightweighted HB-Cesic mirror

    NASA Astrophysics Data System (ADS)

    Krödel, Matthias R.; Hofbauer, Peter; Devilliers, Christophe; Sodnik, Zoran; Robert, Patrick

    2010-07-01

    During the past two years, ECM, Germany, together with Mitsubishi Electric Corporation (MELCO), Japan, developed a new carbon-fiber-reinforced SiC material, called HB-Cesic®, which possesses superior mechanical and thermal cryogenic properties compared to traditional Cesic®. This combination makes HB-Cesic® an excellent choice for large cryogenic mirrors, which will be required for future scientific space missions, such as SPICA and DARWIN. ESA contracted Thales Alenia Space (TAS), France, to design a super-lightweighted HB-Cesic® mirror with a diameter of 600 mm, isostatic fixations, and a special astigmatism compensation device (ACD) for mirror shape control. The mirror was manufactured by ECM, polished and coated by Société Européenne de Systèmes Optiques (SESO), France, and tested to cryogenic temperatures by TAS. The measured wave-front error at ambient and cryogenic temperatures demonstrated the excellent homogeneity of HB-Cesic® and TAS' expertise in mirror mounting. Furthermore, when thermally actuated, the ACD exhibited perfect control of the mirror shape. This success confirmed HB-Cesic®'s superior material properties and its applicability to future cryogenic space mirrors. In this paper we describe the design and fabrication process of this cryogenic mirror and give test results at ambient and cryogenic temperatures.

  10. Cytogenetic characterization of HB2 epithelial cells from the human breast.

    PubMed

    Caradonna, Fabio; Luparello, Claudio

    2014-01-01

    HB2 is a cell line originated by subcloning of MTSV1-7 mammary luminal epithelial cells isolated from human milk and immortalization via introduction of the gene encoding simian virus 40 (SV40) large T antigen. Despite its wide utilization as non-neoplastic counterpart in assays aimed to elucidating various biochemical and genetical aspects of normal and tumoral breast cells, to our knowledge no literature data have so far appeared concerning the chromosomal characterization of the HB2 cells. Here, we report the cytogenetic characterization of the karyotype of HB2 cells, which puts in evidence the occurrence of changes in chromosomal number and structure and the presence of unidentified chromosomal markers in variable amount. Our results do not detract from the utility of HB2 cells in illustrating fundamental aspects of breast cell biology, but rather interject a note of caution into generalizing results obtained with this cell line to other non-immortalized epithelial cell populations from the human breast. Therefore, this work represents a useful resource for all who want to perform appropriate and focused future studies on this cell line and proposes precise indications for a knowledgeable use of HB2 cells. PMID:23982912

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

    PubMed

    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. PMID:26138753

  12. Characterization of DNA transport in the thermophilic bacterium Thermus thermophilus HB27.

    PubMed

    Schwarzenlander, Cornelia; Averhoff, Beate

    2006-09-01

    Horizontal gene transfer has been a major force for genome plasticity over evolutionary history, and is largely responsible for fitness-enhancing traits, including antibiotic resistance and virulence factors. In particular, for adaptation of prokaryotes to extreme environments, lateral gene transfer seems to have played a crucial role. Recently, by performing a genome-wide mutagenesis approach with Thermus thermophilus HB27, we identified the first genes in a thermophilic bacterium for the uptake of free DNA, a process called natural transformation. Here, we present the first data on the biochemistry and bioenergetics of the DNA transport process in this thermophile. We report that linear and circular plasmid DNA are equally well taken up with a high maximal velocity of 1.5 microg DNA.(mg protein)(-1).min(-1), demonstrating an extremely efficient binding and uptake rate of 40 kb.s(-1).cell(-1). Uncouplers and ATPase inhibitors immediately inhibited DNA uptake, providing clear evidence that DNA translocation in HB27 is an energy-dependent process. DNA uptake studies with genomic DNA of Bacteria, Archaea and Eukarya revealed that Thermus thermophilus HB27 takes up DNA from members of all three domains of life. We propose that the extraordinary broad substrate specificity of the highly efficient Thermus thermophilus HB27 DNA uptake system may contribute significantly to thermoadaptation of Thermus thermophilus HB27 and to interdomain DNA transfer in hot environments. PMID:16939619

  13. Investigation of local heterogeneity of hbO2 and hb in working dog heart in situ under isovolemic hemodilution and critical coronary stenosis

    NASA Astrophysics Data System (ADS)

    Krug, Alfons; Kessler, Manfred D.; Khuri, Raja; Lust, Robert; Chitwood, Randolph

    1996-12-01

    A tissue spectrophotometer (EMPHO II) working with 70 micrometer micro lightguide sensors enables recording of spectra in the visible wavelength range (500 - 630 nm). During an initial period arterial hypoxia and hyperoxia were induced on working dog heart by mechanical ventilation with oxygen fractions (fiO2) of 0.1 and 0.5. Under these conditions the effects of low and high fiO2 on oxygenation distribution of intracapillary hemoglobin were investigated. In the second part of the experiment the relation between systemic hematocrit, local hemoglobin concentration, local hemoglobin oxygenation and the oxygen regulation mechanism were studied in detail. In the final part of the experiment the effect of critical coronary stenosis on hb and hbO2 was measured. Critical stenosis was achieved by partial clamping of the left anterior coronary artery (LAD).

  14. A spectral-spatial-dynamic hierarchical Bayesian (SSD-HB) model for estimating soybean yield

    NASA Astrophysics Data System (ADS)

    Kazama, Yoriko; Kujirai, Toshihiro

    2014-10-01

    A method called a "spectral-spatial-dynamic hierarchical-Bayesian (SSD-HB) model," which can deal with many parameters (such as spectral and weather information all together) by reducing the occurrence of multicollinearity, is proposed. Experiments conducted on soybean yields in Brazil fields with a RapidEye satellite image indicate that the proposed SSD-HB model can predict soybean yield with a higher degree of accuracy than other estimation methods commonly used in remote-sensing applications. In the case of the SSD-HB model, the mean absolute error between estimated yield of the target area and actual yield is 0.28 t/ha, compared to 0.34 t/ha when conventional PLS regression was applied, showing the potential effectiveness of the proposed model.

  15. [HbC/beta-thalassemia association. Eleven cases observed in Tunisia].

    PubMed

    Fattoum, S; Guemira, F; Abdennebi, M; Ben Abdeladhim, A

    1993-01-01

    Eleven cases of simultaneous HbC hemoglobinopathy and beta-thalassemia were detected during a study of 11,200 subjects at high risk for inherited hemoglobin anomalies. In seven cases, main clinical manifestations were anemia and enlargement of the spleen, whereas the four other patients were apparently free of symptoms and were diagnosed during routine tests in family members of affected patients. Microcytosis and hypochromia were found in every case. Most of the patients were from the North-Western part of Tunisia. Blood transfusions were required in only one patient, who was an infant with HbC/beta + thalassemia. PMID:8442646

  16. Anaesthesia in a patient with subarachanoidal haemorrhage and high oxygen affinity haemoglobinopathy (HB york): case report

    PubMed Central

    2012-01-01

    Background Approximately 90 haemoglobinopathies have been identified that result in abnormally high oxygen affinity. One of these is haemoglobinopathy York (HbY), first described in 1976. HbY causes an extreme leftward shift of the oxygen dissociation curve with the P50 value changing to 12.5 - 15.5 mmHg (normal value 26.7 mmHg), indicating that approximately half of the haemoglobin is not available as oxygen carrier. Patients with haemoglobinopathies with increased oxygen affinity could suffer from the risk developing ischaemic complications due to a lack of functional oxygen carriers. This is, to best of our knowledge, the first case report on a patient with HbY published in connection with anesthesia. Case Presentation A 42-year-old female with a severe headache and Glasgow coma scale (GCS) of 15 was admitted to the neurosurgical intensive care unit with a ruptured, right sided ICA aneurysm with consecutive subarachnoid haemorrhage [Fisher III, World Federation of Neurosurgical Societies (WFNS) I)]. The medical history of the patient included an erythrocytosis (Hb 17.5 g/dl) on the base of a high-oxygen-affinity haemoglobinopathy, called Hb York (HbY). With no time available to take special preoperative precautions, rapid blood loss occurred during the first attempt to clip the aneurysm. General transfusion procedures, according to the guidelines based on haemoglobin and haematocrit values, could not be applied due to the uncertainty in the oxygen carrier reduction. To maintain tissue oxygen supply, clinical indicators of ischaemia were instead utilized to gauge the appropriate required blood products, crystalloids and colloids replacements. Despite this, the patient survived the neurosurgical intervention without any neurological deficit. Conclusions Family members of patients with HbY (and other haemoglobinopathies with increased oxygen affinity) should undergo clinical assessment, particularly if they are polycythaemic. If the diagnosis of HbY is confirmed

  17. Incidental Identification of Possible Delta-Beta Thalassemia Trait in a Family: A Rare Cause of Elevated Hb F.

    PubMed Central

    Choccalingam, Chidambharam; Samuel, Premila

    2016-01-01

    Delta-Beta thalassaemia is an unusual variant of thalassaemia with elevated level of foetal haemoglobin (HbF). The clinical presentation of delta-beta thalassaemia is mild in both heterozygote and homozygote cases. We hereby describe a rare cause of elevated Hb F in a father and his two daughters. A 52-year-old diabetic male patient, on evaluation of chromatogram of cation exchange HPLC for HbA1c, we incidentally identified elevated Hb F of approximately 20%. Haematological investigation of the patient revealed decreased haemoglobin, normal RBC, leucocyte and platelet count, decreased MCV and MCH. Red cell morphology showed predominantly normocytic normochromic cells with mild anisopoikilocytosis, few microcytes and hypochromic cells seen. His liver function test was normal. Haemoglobin variant analysis revealed decreased Hb A (79.4%), normal Hb A2 (2%) and increased Hb F (19.75%). A possible diagnosis of heterozygous δ β-thalassaemia was considered. Since most laboratories perform HbA1c by cation exchange HPLC method, a careful evaluation of the chromatogram yields useful information. In our case, the elevated Hb F in a father and further careful evaluation of clinical and haematological parameters in the family members made us to possibly think of rare disorders like heterozygous Delta-Beta thalassaemia in the family and provide valuable genetic counseling. PMID:27134860

  18. Incidental Identification of Possible Delta-Beta Thalassemia Trait in a Family: A Rare Cause of Elevated Hb F.

    PubMed

    Kumar, B Vinodh; Choccalingam, Chidambharam; Samuel, Premila

    2016-03-01

    Delta-Beta thalassaemia is an unusual variant of thalassaemia with elevated level of foetal haemoglobin (HbF). The clinical presentation of delta-beta thalassaemia is mild in both heterozygote and homozygote cases. We hereby describe a rare cause of elevated Hb F in a father and his two daughters. A 52-year-old diabetic male patient, on evaluation of chromatogram of cation exchange HPLC for HbA1c, we incidentally identified elevated Hb F of approximately 20%. Haematological investigation of the patient revealed decreased haemoglobin, normal RBC, leucocyte and platelet count, decreased MCV and MCH. Red cell morphology showed predominantly normocytic normochromic cells with mild anisopoikilocytosis, few microcytes and hypochromic cells seen. His liver function test was normal. Haemoglobin variant analysis revealed decreased Hb A (79.4%), normal Hb A2 (2%) and increased Hb F (19.75%). A possible diagnosis of heterozygous δ β-thalassaemia was considered. Since most laboratories perform HbA1c by cation exchange HPLC method, a careful evaluation of the chromatogram yields useful information. In our case, the elevated Hb F in a father and further careful evaluation of clinical and haematological parameters in the family members made us to possibly think of rare disorders like heterozygous Delta-Beta thalassaemia in the family and provide valuable genetic counseling. PMID:27134860

  19. TGF{beta} induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells

    SciTech Connect

    Ebi, Masahide; Kataoka, Hiromi; Shimura, Takaya; Kubota, Eiji; Hirata, Yoshikazu; Mizushima, Takashi; Mizoshita, Tsutomu; Tanaka, Mamoru; Mabuchi, Motoshi; Tsukamoto, Hironobu; Tanida, Satoshi; Kamiya, Takeshi; Higashiyama, Shigeki; Joh, Takashi

    2010-11-19

    Research highlights: {yields} TGF{beta} induces EGFR transactivation through proHB-EGF shedding by activated ADAM members in gastric cancer cells. {yields} TGF{beta} induces nuclear translocation of HB-EGF-CTF cleaved by ADAM members. {yields} TGF{beta} enhances cell growth by EGFR transactivation and HB-EGF-CTF nuclear translocation and ADAM inhibitors block these effects. {yields} Silencing of ADAM17 also blocks EGFR transactivation, HB-EGF-CTF nuclear translocation and cancer cell growth by TGF{beta}. {yields} ADAM17 may play a crucial role in this TGF{beta}-HB-EGF signal transduction. -- Abstract: Background and aims: Transforming growth factor-beta (TGF{beta}) is known to potently inhibit cell growth. Loss of responsiveness to TGF{beta} inhibition on cell growth is a hallmark of many types of cancer, yet its mechanism is not fully understood. Membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) ectodomain is cleaved by a disintegrin and metalloproteinase (ADAM) members and is implicated in epidermal growth factor receptor (EGFR) transactivation. Recently, nuclear translocation of the C-terminal fragment (CTF) of pro-HB-EGF was found to induce cell growth. We investigated the association between TGF{beta} and HB-EGF signal transduction via ADAM activation. Materials and methods: The CCK-8 assay in two gastric cancer cell lines was used to determine the effect for cell growth by TGF{beta}. The effect of two ADAM inhibitors was also evaluated. Induction of EGFR phosphorylation by TGF{beta} was analyzed and the effect of the ADAM inhibitors was also examined. Nuclear translocation of HB-EGF-CTF by shedding through ADAM activated by TGF{beta} was also analyzed. EGFR transactivation, HB-EGF-CTF nuclear translocation, and cell growth were examined under the condition of ADAM17 knockdown. Result: TGF{beta}-induced EGFR phosphorylation of which ADAM inhibitors were able to inhibit. TGF{beta} induced shedding of proHB-EGF allowing HB-EGF-CTF to

  20. Hb lepore/β0-thalassaemia with α+-thalassaemia interactions, a potential diagnostic pitfall.

    PubMed

    Alauddin, Hafiza; Mohamad Nasir, Suziana; Ahadon, Madzlifah; Raja Sabudin, Raja Zahratul Azma; Ithnin, Azlin; Hussin, Noor Hamidah; Alias, Hamidah; Loh, C-Khai; Abdul Latiff, Zarina; Abdul Murad, Nor Azian; Othman, Ainoon

    2015-12-01

    Haemoglobin (Hb) Lepore is a variant Hb consisting of two α-globin and two δβ-globin chains. In a heterozygote, it is associated with clinical findings of thalassaemia minor, but interactions with other haemoglobinopathies can lead to various clinical phenotypes and pose diagnostic challenges. We reported a pair of siblings from a Malay family, who presented with pallor and hepatosplenomegaly at the ages of 21 months and 14 months old. The red cell indices and peripheral blood smears of both patients showed features of thalassaemia intermedia. Other laboratory investigations of the patients showed conflicting results. However, laboratory investigation results of the parents had led to a presumptive diagnosis of compound heterozygote Hb Lepore/β-thalassaemia and co-inheritance α+-thalassaemia (-α3.7). Hb Lepore has rarely been detected in Southeast Asian countries, particularly in Malaysia. These two cases highlight the importance of family studies for accurate diagnosis, hence appropriate clinical management and genetic counseling. PMID:26712677

  1. Viruses of Entamoeba histolytica. 3. Properties of the polyhedral virus of the HB-301 strain.

    PubMed

    Hruska, J F; Mattern, C F; Diamond, L S; Keister, D B

    1973-01-01

    Some biological characteristics and bioassay of a polyhedral virus isolated from normal-appearing strain HB-301 of Entamoeba histolytica are described. The virus produced lysis of susceptible strains of E. histolytica, yet it caused no cytopathological effect in the host strain, HB-301. The virus and host amoeba existed in an equilibrium; approximately 10(4) mean infective dose units of virus were produced per million HB-301 amoebae. Superinfection and antiviral antiserum treatment failed to disturb this equilibrium permanently. The mechanism of viral persistence in strain HB-301 amoebae remains to be determined. Purification of the virus was attempted. Ninety-nine percent of the viral infectivity was associated with a low-speed pellet which consisted of complexes of virus and cellular membranes. Various treatments of this low-speed pellet failed to release virus. Biologically active, membrane-free virus of low titer was prepared by differential centrifugation of supernatant solutions and employed in electron microscopy and other studies. PMID:4346278

  2. Gene expression profile in liver of hB1F transgenic mice

    PubMed Central

    Wang, Shui-Liang; Yang, Hua; Xie, You-Hua; Wang, Yuan; Li, Jian-Zhong; Wang, Long; Wang, Zhu-Gang; Fu, Ji-Liang

    2004-01-01

    AIM: To analyze the tissue morphologic phenotype and liver gene expression profile of hB1F transgenic mice. METHODS: Transgene expression was analyzed with RT-PCR and Western blotting. For one of the transgenic mouse lines, tissue expression pattern of the transgene was also examined with immunochemical methods. Pathological analysis was used to examine the tissue morphologic phenotype of established transgenic mice. The liver gene expression profile of transgenic mice was analyzed with microchip, and some of the differentially expressed genes were verified with RT-PCR. RESULTS: The expressions of hB1F were shown in livers from 6 of 7 transgenic mouse lines. The overexpression of hB1F transgene did not cause pathological changes. Expressions of three genes were up-regulated, while down-regulation was observed for 25 genes. CONCLUSION: The overexpression of hB1F transgene may cause changes of gene expression profiles in the liver of transgenic mice. PMID:15378783

  3. A successful twin pregnancy in a patient with HbE-β-thalassemia in western India

    PubMed Central

    Merchant, R; Italia, K; Ahmed, J; Ghosh, K; Colah, RB

    2015-01-01

    Improvements in medical facilities have helped a large number of clinically severe hemoglobin E (HbE)-β-thalassemia patients reach adulthood. Consequently, there is a new challenge, that of managing women with HbE-β-thalassemia during pregnancy. In particular, they have a high risk of abortion, preterm delivery, intrauterine growth restriction, and thromboembolism. A 27-year-old HbE-β-thalassemia patient on regular transfusion, who was splenectomized and heptatitis C (HCV)-positive, conceived for the first time without any infertility treatment. However, there was incomplete abortion with heavy bleeding at 3 months of gestation, which required bilateral uterine artery angiography. The angiogram showed the left uterine artery to be moderately hypertrophied. This was embolized with 300-500 micron polyvinyl alcohol (PVA) to stop the bleeding. Soon after, she conceived again with a twin pregnancy, and at 33.3 weeks of gestation, there was a normal delivery of twin girls without any postpartum hemorrhage or perineal tear. Both babies were given prematurity care. The mother and children were both normal up till the last follow-up 18 months after delivery, and both the girls are HbE heterozygous. Thorough monitoring of endocrine functions along with proper management of transfusions and iron overload can help in reducing the complications related to pregnancy in these patients. PMID:26119442

  4. Maximum uncertainty estimation for the HB-Line ventilation instrumentation readings

    SciTech Connect

    Melton, D.R.

    1992-12-04

    The HB-Line building vacuum instrumentation and glovebox vacuum instrumentation at the Savannah River Plant are described. The configuration and operation of the Foxboro 834 series transmitters and Moore 350 series controllers is detailed. In particular, the uncertainties in the differential pressure readings are explained.

  5. Replacement of PBNA in HB and HC polymers used in SRM propellant and liner

    NASA Technical Reports Server (NTRS)

    Levinthal, M. L.; Law, R. D.; Suisse, D. C.

    1981-01-01

    The antioxidant phenyl-beta-naphthylamine (PBNA) was used in both HB and HC polymers. The sole (domestic) supplier of PBNA has withdrawn this product from the market, primarily because of suspected health hazards. Commercially available substitute(s) were selected and qualified for use in the two polymers.

  6. Genotype-phenotype correlation in Iranian patients with Hb H disease.

    PubMed

    Ebrahimkhani, Saedieh; Azarkeivan, Azita; Bayat, Nooshin; Houry-Parvin, Mahdieh; Jalil-Nejad, Sayeh; Zand, Shima; Golkar, Zahra; Hadavi, Valeh; Imanian, Hashem; Oberkanins, Christian; Najmabadi, Hossein

    2011-01-01

    Thalassemia is the most common genetic disorder in Iran. Some α-globin genotypes leading to Hb H disease may cause severe anemia and dependence on regular blood transfusions. In this study, 40 patients were analyzed for the molecular basis and the genotype-phenotype correlation of Hb H disease in Iran. α-Globin molecular analysis was performed by polymerase chain reaction (PCR) followed by agarose gel electrophoresis, reverse hybridization test strips or DNA sequencing. The most frequently observed α-globin genotypes were -α(3.7)/- -(MED) in 10 patients (25%), - -(20.5)/α(-5nt)α in six patients (15%) and - -(20.5)/-α(3.7) in four patients (10%). A subset of the identified Hb H genotypes, including - -(MED)/α(CS)α, - -(MED)/α(PolyA2)α and α(CS)α/α(CS)α, was associated with a need for regular or irregular blood transfusions. Our findings provide a basis for predicting phenotype severity by identifying the Hb H genotype and making more selective decisions for prenatal diagnosis. PMID:21250880

  7. A mechanism of ineffective erythropoiesis in β-thalassemia/Hb E disease

    PubMed Central

    Lithanatudom, Pathrapol; Leecharoenkiat, Amporn; Wannatung, Tirawat; Svasti, Saovaros; Fucharoen, Suthat; Smith, Duncan R.

    2010-01-01

    Background Cells respond to stress stimuli through a number of response pathways, of which one of the most important and well characterized is the unfolded protein response. Despite a large body of work which suggests that stress in erythroblasts may play a pivotal role in the pathogenesis of β-thalassemia/Hb E disease, this pathway remains uninvestigated. Design and Methods Day 10 erythroblasts from normal controls and β-thalassemia/Hb E patients were subjected to internal (treatment with tunicamycin) and external (serum and growth factor withdrawal) stress stimuli and the activation of the unfolded protein response pathway was investigated. Results Normal erythroblasts responded to both internal and external stress by activating the unfolded protein response (UPR) pathway while in contrast, erythroblasts from β-thalassemia/Hb E patients only showed activation of the unfolded protein response pathway in response to internal stress. This was reflected by a markedly increased induction of apoptosis in serum and growth factor deprived β-thalassemia/Hb E erythroblasts as compared to control cells. Modulation of the levels of intracellular Ca2+ in thalassemic erythroblasts restored UPR activation during serum deprivation and significantly reduced the level of serum deprivation induced apoptosis to control levels. Conclusions These results suggest the failure of thalassemic erythroblasts to cope with cellular stress caused by an impaired UPR function as a result of high Ca2+ levels may exacerbate thalassemic cell death during erythropoiesis. PMID:20015891

  8. VIEW OF HB1 (VAB HIGH BAY) WITH MOBILE LAUNCHER PLATFORM ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF HB-1 (VAB HIGH BAY) WITH MOBILE LAUNCHER PLATFORM (VEHICLE ACCESS PLATFORMS ARE VISIBLE IN THE CENTER), FACING WEST - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  9. Prevalence of sickle cell trait and HbC-trait in Blacks from low socioeconomic conditions.

    PubMed Central

    Hicks, E J; Miller, G D; Horton, R

    1978-01-01

    In the present investigation we did not observe age or sex differentials in the prevalence of sickle cell or HbC-traits in Black males or females of low socioeconomic status. When our data were compared to those of others, we found no evidence for a socioeconomic differential in the prevalence of these traits. PMID:717622

  10. A successful twin pregnancy in a patient with HbE-β-thalassemia in western India.

    PubMed

    Merchant, R; Italia, K; Ahmed, J; Ghosh, K; Colah, R B

    2015-01-01

    Improvements in medical facilities have helped a large number of clinically severe hemoglobin E (HbE)-β-thalassemia patients reach adulthood. Consequently, there is a new challenge, that of managing women with HbE-β-thalassemia during pregnancy. In particular, they have a high risk of abortion, preterm delivery, intrauterine growth restriction, and thromboembolism. A 27-year-old HbE-β-thalassemia patient on regular transfusion, who was splenectomized and heptatitis C (HCV)-positive, conceived for the first time without any infertility treatment. However, there was incomplete abortion with heavy bleeding at 3 months of gestation, which required bilateral uterine artery angiography. The angiogram showed the left uterine artery to be moderately hypertrophied. This was embolized with 300-500 micron polyvinyl alcohol (PVA) to stop the bleeding. Soon after, she conceived again with a twin pregnancy, and at 33.3 weeks of gestation, there was a normal delivery of twin girls without any postpartum hemorrhage or perineal tear. Both babies were given prematurity care. The mother and children were both normal up till the last follow-up 18 months after delivery, and both the girls are HbE heterozygous. Thorough monitoring of endocrine functions along with proper management of transfusions and iron overload can help in reducing the complications related to pregnancy in these patients. PMID:26119442

  11. Effect of HB complexation on the optical rotatory power of oxiranes

    NASA Astrophysics Data System (ADS)

    Zborowski, Krzysztof; Proniewicz, Leonard M.; Alkorta, Ibon; Elguero, José

    2005-06-01

    The effect produced by the formation of hydrogen bonded complexes on the optical rotatory power of two oxiranes has been studied theoretically using DFT and MP2 methods. The results obtained have been rationalized based on a model oxirane where the chirality is induced by the HB formed. In addition, the effect of solvent continuum models has been calculated for the complexes.

  12. Mild Microcytic Anemia in an Infant with a Compound Heterozygosity for Hb C (HBB: c.19G > A) and Hb Osu Christiansborg (HBB: c.157G > A).

    PubMed

    Boucher, Maria O; Chui, David H K; Woda, Bruce A; Newburger, Peter E

    2016-06-01

    We report an infant with a compound heterozygosity for Hb C (HBB: c.19G > A) and Hb Osu Christiansborg (HBB: c.157G > A) and a phenotype of mild microcytic anemia with target cell morphology but without overt hemolysis. PMID:27117572

  13. A novel β-globin gene mutation HBB.c.22 G>C produces a hemoglobin variant (Hb Vellore) mimicking HbS in HPLC.

    PubMed

    Edison, E S; Sathya, M; Rajkumar, S V; Nair, S C; Srivastava, A; Shaji, R V

    2012-10-01

    Hemoglobinopathies are highly prevalent in Indian population. DNA analysis to detect causative mutations is required for identifying rare hemoglobin variants or when hematological results are discordant with the clinical phenotype. In this report, we describe a novel hemoglobin variant caused by a mutation in beta-globin gene, Codon 7 GAG→CAG (Glu→Gln) that elutes in the position of sickle haemoglobin (HbS) in cation exchange high performance liquid chromatography. This report highlights possible diagnostic pitfalls in interpreting data solely based on haemoglobin analysis and usefulness of mutation screening in definitive diagnosis of hemoglobinopathies. PMID:22471768

  14. Mild pyrolysis of P3HB/Switchgrass blends for the production of bio-oil enriched with crotonic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The mild pyrolysis of switchgrass/poly-3-hydroxybutyrate (P3HB) blends that mimic P3HB-producing switchgrass lines was studied in a pilot scale fluidized bed reactor with the goal of simultaneously producing crotonic acid and switchgrass-based bio-oil. Factors such as pyrolysis temperature, residenc...

  15. Multi centric origin of Hb D-Punjab [beta121(GH4)Glu-->Gln, GAA>CAA].

    PubMed

    Yavarian, Majid; Karimi, Mehran; Paran, Farideh; Neven, Catherine; Harteveld, Cornelis L; Giordano, Piero C

    2009-01-01

    Hb D-Punjab [beta121(GH4)Glu-->Gln, GAA>CAA], common in the northern Indian province, is often unexpectedly found in other populations. To study the multi centric origin of this variant which is causing sickle cell disease in association with Hb S [beta6(A3)Glu-->Val, GAG>GTG], we have examined the haplotype of the Hb D allele in different populations. We studied 43 alleles from south Iran (Hormozgan and Fars provinces) and 14 from Holland and Belgium using high performance liquid chromatography (HPLC), capillary electrophoresis, direct sequencing and/or restriction enzyme analysis. In Iranians, four haplotypes were observed at different frequencies: haplotype I [+ - - - -,+ +] at 67.5%, subhaplotype I' [+ - - - -,- +] at 17.5%, haplotype V [- + - - +,+ +] at 10.0% and haplotype III [- + - + +,+ +] at 5.0%. All European cases were on haplotype I. The occurrence of high Hb D frequencies on a single haplotype in specific regions can be expected if we consider founder effect and genetic drift mechanisms. However, considering that haplotype I is the most common haplotype worldwide, that Hb D-Punjab is reported in different populations on different haplotypes, and that codon beta121 is a site on which six different mutations are reported, we may expect to observe Hb D-Punjab in different populations, possibly because of a relatively higher occurrence of de novo mutations, generating unexpected risk from mixtures of allochtonous Hb S and indigenous Hb D-Punjab or vice versa. PMID:19958184

  16. Structural basis for the antipolymer activity of Hb ζ2βs2 trapped in a tense conformation

    NASA Astrophysics Data System (ADS)

    Safo, Martin K.; Ko, Tzu-Ping; Schreiter, Eric R.; Eric Russell, J.

    2015-11-01

    The phenotypical severity of sickle cell disease (SCD) can be mitigated by modifying mutant hemoglobin S (Hb s, Hb α2β 2s) to contain embryonic ζ globin in place of adult α-globin subunits (Hb ζ2β2s). Crystallographical analyses of liganded Hb ζζ2β2s, though, demonstrate a tense (T-state) quaternary structure that paradoxically predicts its participation in--rather than its exclusion from--pathological deoxyHb S polymers. We resolved this structure-function conundrum by examining the effects of α → ζ exchange on the characteristics of specific amino acids that mediate sickle polymer assembly. Superposition analyses of the βs subunits of T-state deoxyHb α2β2s and T-state CO-liganded Hb ζ2β2s reveal significant displacements of both mutant βsVal6 and conserved β-chain contact residues, predicting weakening of corresponding polymer-stabilizing interactions. Similar comparisons of the α- and ζ-globin subunits implicate four amino acids that are either repositioned or undergo non-conservative substitution, abrogating critical polymer contacts. CO-Hb ζ2βs2 additionally exhibits a unique trimer-of-heterotetramers crystal packing that is sustained by novel intermolecular interactions involving the pathological βsVal6, contrasting sharply with the classical double-stranded packing of deoxyHb S. Finally, the unusually large buried solvent-accessible surface area for CO-Hb ζ2β2s suggests that it does not co-assemble with deoxyHb S in vivo. In sum, the antipolymer activities of Hb ζ203b2;2s appear to arise from both repositioning and replacement of specific α- and βs-chain residues, favoring an alternate T-state solution structure that is excluded from pathological deoxyHb S polymers. These data account for the antipolymer activity of Hb ζ2β2s, and recommend the utility of SCD therapeutics that capitalize on α-globin exchange strategies.

  17. A novel α(0) -thalassemia deletion in a Greek patient with HbH disease and β-thalassemia trait.

    PubMed

    Phylipsen, Marion; Traeger-Synodinos, Jan; van der Kraan, Martijn; van Delft, Peter; Bakker, Greet; Geerts, Mariska; Kanavakis, Emmanuel; Stamoulakatou, Alexandra; Karagiorga, Markissia; Giordano, Piero C; Harteveld, Cornelis L

    2011-12-30

    Objectives:  To determine the molecular basis in a Greek child suspected of having HbH disease and β-thalassemia trait. Methods:  Standard hematology, Hb electrophoresis and HPLC. MLPA, direct sequencing and breakpoint characterization by NimbleGen fine-tiling array analysis. Results:  The index patient showed a moderate microcytic hypochromic anemia with normal ZPP and elevated HbA(2) , indicative for β-thalassemia trait. However the moderate microcytic hypochromic anemia, along with the observation of HbH inclusions in occasional red blood cells suggested a co-existing α-thalassemia. Molecular analysis indicated that the propositus inherited the β(+) -thalassemia mutation IVS2-745 (c>g) and a novel α(0) -thalassemia deletion from the mother, and the common non-deletion α-thalassemia allele α(2) (-5nt)α from the father. The α(0) -thalassemia deletion is approximately 131.6 kb in length. It removes the major regulatory elements along with the functional α-globin genes, but leaves the theta-gene intact. Conclusions:  The compound interaction of a β-thalassemia defect along with a single functional α-globin gene is quite rare. Although patients with HbH/β-thal and simple HbH disease, have comparable levels of Hb, the absence of free β-globin chains and thus detectable non-functional HbH means that in HbH/β-thal the levels of functional Hb are higher, resulting in a better compensated functional anemia. Rare large deletions as the one described here remain undetected by gap-PCR in routine molecular screening. The introduction of MLPA as a diagnostic screening tool may improve laboratory diagnostics for these defects. The use of NimbleGen fine tiling arrays may give additional information about the precise location of breakpoints. © 2011 John Wiley & Sons A/S. PMID:22211883

  18. High Frequency of Hb E-Saskatoon (HBB: c.67G > A) in Brazilians: A New Genetic Origin?

    PubMed

    Wagner, Sandrine C; Lindenau, Juliana D; Castro, Simone M de; Santin, Ana Paula; Zaleski, Carina F; Azevedo, Laura A; Ribeiro Dos Santos, Ândrea K C; Dos Santos, Sidney E B; Hutz, Mara H

    2016-08-01

    Hb E-Saskatoon [β22(B4)Glu→Lys, HBB: c.67G > A] is a rare, nonpathological β-globin variant that was first described in a Canadian woman of Scottish and Dutch ancestry and has since then been detected in several populations. The aim of the present study was to identify the origin of Hb E-Saskatoon in Brazil using β-globin haplotypes and genetic ancestry in carriers of this hemoglobin (Hb) variant. Blood samples were investigated by isoelectric focusing (IEF) and high performance liquid chromatography (HPLC) using commercial kits. Hb E-Saskatoon was confirmed by amplification of the HBB gene, followed by sequence analysis. Haplotypes of the β-globin gene were determined by polymerase chain reaction (PCR), followed by digestion with specific restriction enzymes. Individual ancestry was estimated with 48 biallelic insertion/deletions using three 16-plex PCR amplifications. The IEF pattern was similar to Hbs C (HBB: c.19G > A) and Hb E (HBB: c.79G > A) [isoelectric point (pI): 7.59-7.65], and HPLC results showed an elution in the Hb S (HBB: c.20A > T) window [retention time (RT): 4.26-4.38]. DNA sequencing of the amplified β-globin gene showed a mutation at codon 22 (GAA>AAA) corresponding to Hb E-Saskatoon. A total of 11 cases of this variant were identified. In nine unrelated individuals, Hb E-Saskatoon was in linkage disequilibrium with haplotype 2 [+ - - - -]. All subjects showed a high degree of European contribution (mean = 0.85). Hb E-Saskatoon occurred on the β-globin gene of haplotype 2 in all Brazilian carriers. These findings suggest a different genetic origin for this Hb variant from that previously described. PMID:27250692

  19. Identification, Functional Study, and Promoter Analysis of HbMFT1, a Homolog of MFT from Rubber Tree (Hevea brasiliensis).

    PubMed

    Bi, Zhenghong; Li, Xiang; Huang, Huasun; Hua, Yuwei

    2016-01-01

    A homolog of MOTHER OF FT AND TFL1 (MFT) was isolated from Hevea brasiliensis and its biological function was investigated. Protein multiple sequence alignment and phylogenetic analysis revealed that HbMFT1 conserved critical amino acid residues to distinguish MFT, FLOWERING LOCUS T (FT) and TERMINAL FLOWER1 (TFL1)-like proteins and showed a closer genetic relationship to the MFT-like group. The accumulation of HbMFT1 was generally detected in various tissues except pericarps, with the highest expression in embryos and relatively higher expression in roots and stems of seedlings, flowering inflorescences, and male and female flowers. HbMFT1 putative promoter analysis showed that tissue-specific, environmental change responsive and hormone-signaling responsive elements were generally present. HbMFT1 was strongly induced under a short-day condition at 28 °C, with the highest expression after the onset of a day. Overexpression of HbMFT1 inhibited seed germination, seedling growth, and flowering in transgenic Arabidopsis. The qRT-PCR further confirmed that APETALA1 (AP1) and FRUITFULL (FUL) were drastically down-regulated in 35S::HbMFT1 plants. A histochemical β-glucuronidase (GUS) assay showed that HbMFT1::GUS activity was mainly detected in stamens and mature seeds coinciding with its original expression and notably induced in rosette leaves and seedlings of transgenic Arabidopsis by exogenous abscisic acid (ABA) due to the presence of ABA cis-elements in HbMFT1 promoter. These results suggested that HbMFT1 was mainly involved in maintenance of seed maturation and stamen development, but negatively controlled germination, growth and development of seedlings and flowering. In addition, the HbMFT1 promoter can be utilized in controlling transgene expression in stamens and seeds of rubber tree or other plant species. PMID:26950112

  20. Significance of HbA1c and its measurement in the diagnosis of diabetes mellitus: US experience.

    PubMed

    Juarez, Deborah Taira; Demaris, Kendra M; Goo, Roy; Mnatzaganian, Christina Louise; Wong Smith, Helen

    2014-01-01

    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. PMID:25349480

  1. Identification, Functional Study, and Promoter Analysis of HbMFT1, a Homolog of MFT from Rubber Tree (Hevea brasiliensis)

    PubMed Central

    Bi, Zhenghong; Li, Xiang; Huang, Huasun; Hua, Yuwei

    2016-01-01

    A homolog of MOTHER OF FT AND TFL1 (MFT) was isolated from Hevea brasiliensis and its biological function was investigated. Protein multiple sequence alignment and phylogenetic analysis revealed that HbMFT1 conserved critical amino acid residues to distinguish MFT, FLOWERING LOCUS T (FT) and TERMINAL FLOWER1 (TFL1)-like proteins and showed a closer genetic relationship to the MFT-like group. The accumulation of HbMFT1 was generally detected in various tissues except pericarps, with the highest expression in embryos and relatively higher expression in roots and stems of seedlings, flowering inflorescences, and male and female flowers. HbMFT1 putative promoter analysis showed that tissue-specific, environmental change responsive and hormone-signaling responsive elements were generally present. HbMFT1 was strongly induced under a short-day condition at 28 °C, with the highest expression after the onset of a day. Overexpression of HbMFT1 inhibited seed germination, seedling growth, and flowering in transgenic Arabidopsis. The qRT-PCR further confirmed that APETALA1 (AP1) and FRUITFULL (FUL) were drastically down-regulated in 35S::HbMFT1 plants. A histochemical β-glucuronidase (GUS) assay showed that HbMFT1::GUS activity was mainly detected in stamens and mature seeds coinciding with its original expression and notably induced in rosette leaves and seedlings of transgenic Arabidopsis by exogenous abscisic acid (ABA) due to the presence of ABA cis-elements in HbMFT1 promoter. These results suggested that HbMFT1 was mainly involved in maintenance of seed maturation and stamen development, but negatively controlled germination, growth and development of seedlings and flowering. In addition, the HbMFT1 promoter can be utilized in controlling transgene expression in stamens and seeds of rubber tree or other plant species. PMID:26950112

  2. DNA studies are necessary for accurate patient diagnosis in compound heterozygosity for Hb Adana (HBA2:c.179>A) with deletional or nondeletional α-thalassaemia.

    PubMed

    Tan, Jin Ai Mary Anne; Kho, Siew Leng; Ngim, Chin Fang; Chua, Kek Heng; Goh, Ai Sim; Yeoh, Seoh Leng; George, Elizabeth

    2016-01-01

    Haemoglobin (Hb) Adana (HBA2:c.179>A) interacts with deletional and nondeletional α-thalassaemia mutations to produce HbH disorders with varying clinical manifestations from asymptomatic to severe anaemia with significant hepatosplenomegaly. Hb Adana carriers are generally asymptomatic and haemoglobin subtyping is unable to detect this highly unstable α-haemoglobin variant. This study identified 13 patients with compound heterozygosity for Hb Adana with either the 3.7 kb gene deletion (-α(3.7)), Hb Constant Spring (HbCS) (HBA2:c.427T>C) or Hb Paksé (HBA2:429A>T). Multiplex Amplification Refractory Mutation System was used for the detection of five deletional and six nondeletional α-thalassaemia mutations. Duplex-PCR was used to confirm Hb Paksé and HbCS. Results showed 84.6% of the Hb Adana patients were Malays. Using DNA studies, compound heterozygosity for Hb Adana and HbCS (α(codon 59)α/α(CS)α) was confirmed in 11 patients. A novel point in this investigation was that DNA studies confirmed Hb Paksé for the first time in a Malaysian patient (α(codon 59)α/α(Paksé)α) after nine years of being misdiagnosis with Hb Adana and HbCS (α(codon 59)α/α(CS)α). Thus, the reliance on haematology studies and Hb subtyping to detect Hb variants is inadequate in countries where thalassaemia is prevalent and caused by a wide spectrum of mutations. PMID:27271331

  3. DNA studies are necessary for accurate patient diagnosis in compound heterozygosity for Hb Adana (HBA2:c.179>A) with deletional or nondeletional α-thalassaemia

    PubMed Central

    Tan, Jin Ai Mary Anne; Kho, Siew Leng; Ngim, Chin Fang; Chua, Kek Heng; Goh, Ai Sim; Yeoh, Seoh Leng; George, Elizabeth

    2016-01-01

    Haemoglobin (Hb) Adana (HBA2:c.179>A) interacts with deletional and nondeletional α-thalassaemia mutations to produce HbH disorders with varying clinical manifestations from asymptomatic to severe anaemia with significant hepatosplenomegaly. Hb Adana carriers are generally asymptomatic and haemoglobin subtyping is unable to detect this highly unstable α-haemoglobin variant. This study identified 13 patients with compound heterozygosity for Hb Adana with either the 3.7 kb gene deletion (-α3.7), Hb Constant Spring (HbCS) (HBA2:c.427T>C) or Hb Paksé (HBA2:429A>T). Multiplex Amplification Refractory Mutation System was used for the detection of five deletional and six nondeletional α-thalassaemia mutations. Duplex-PCR was used to confirm Hb Paksé and HbCS. Results showed 84.6% of the Hb Adana patients were Malays. Using DNA studies, compound heterozygosity for Hb Adana and HbCS (αcodon 59α/αCSα) was confirmed in 11 patients. A novel point in this investigation was that DNA studies confirmed Hb Paksé for the first time in a Malaysian patient (αcodon 59α/αPakséα) after nine years of being misdiagnosis with Hb Adana and HbCS (αcodon 59α/αCSα). Thus, the reliance on haematology studies and Hb subtyping to detect Hb variants is inadequate in countries where thalassaemia is prevalent and caused by a wide spectrum of mutations. PMID:27271331

  4. Reducing audible noise for distribution transformer with HB1 amorphous core

    NASA Astrophysics Data System (ADS)

    Chang, Yeong-Hwa; Hsu, Chang-Hung; Lin, Hung-Wei; Tseng, Ching-Pei

    2011-04-01

    In this paper, the way to reduce the audible noise of a distribution transformer is presented by incorporating a newly developed transformer core and a rigid-structure tank. The vibrations related tothe core structure and tank frame are considered, so that a distribution transformer with accelerometers mounted on the internal core and external tank, respectively, is addressed. In practice, the core with a new joint structure and the tank with a strong rigid-frame (H-type) are applied to a single-phase amorphous HB1-cored transformer with capacity 167 kVA for performance verification. Finally, a personal computer-based data acquisition platform is setup for signal measurement and processing. Experimental results demonstrate that the HB1 amorphous-cored transformer with the proposed core joint and rigid-structure tank can be performed well in the aspect of audible noise reduction.

  5. HbSC Disease and Spontaneous Epidural Hematoma with Kernohan's Notch Phenomena

    PubMed Central

    Yogarajah, Meera; Agu, Chidozie Charles; Sivasambu, Bhradeev; Mittler, Mark A.

    2015-01-01

    Spontaneous (nontraumatic) acute epidural hematoma is a rare and poorly understood complication of sickle cell disease. A 19-year-old African American male with hemoglobin SC disease (HbSC) presented with generalized body aches and was managed for acute painful crisis. During his hospital stay he developed rapid deterioration of his mental status and computed topography revealed a spontaneous massive epidural hematoma with mass effect and midline shift with Kernohan's notch phenomena for which urgent craniotomy and evacuation was done. We report the first case of HbSC disease associated with catastrophic epidural hematoma progressing to transtentorial herniation and Kernohan's notch phenomena within few hours with rapid clinical deterioration. The etiopathogenesis and the rare presentation are discussed in detail in this case report. PMID:26576305

  6. Hb Toranomon [beta 112(G14)Cys-->Trp]: a new unstable electrophoretically silent hemoglobin.

    PubMed

    Harano, T; Harano, K; Kawasaki, R; Kawakami, K

    1996-11-01

    We describe a silent and unstable hemoglobin variant, Hb Toranomon, which was discovered by high performance liquid chromatography in an apparently healthy Japanese male during a Hb A1c assay. Isoelectrofocusing of his hemolysate and chromatographic separation of globin on a CM-cellulose column revealed no abnormality. The isopropanol precipitation test gave a positive result. Amino acid analysis of all peptides isolated from the tryptic digests of the aminoethylated and non-aminoethylated beta chain (beta A + beta X) by reversed phase high performance liquid chromatography indicated a substitution of Cys-->Trp at position 112 of the beta chain, which was confirmed by protein sequencing. cDNA sequencing showed the nucleotide sequence of the beta 112 codon to be TGG instead of TGT, confirming the amino acid substitution described above. The globin biosynthesis ratio (beta/alpha) was 1.00. PMID:8936462

  7. HB Les Andelys [alpha83(F4)LEU-->PRO]: a new moderately unstable variant.

    PubMed

    Wajcman, H; Promé, D; Préhu, C; Déon, C; Riou, J; Bouanga, J C; Papassotiriou, I; Lahary, A; Galactéros, F

    1998-03-01

    Hb Les Andelys [alpha83(F4)Leu-->Pro] is a mildly unstable variant that was found during glycated hemoglobin measurement in a French family. In this hemoglobin molecule the affected site, in the alpha chain, and the amino acid substitution are identical to those of Hb Santa Ana, an unstable beta chain variant. The structural abnormality was demonstrated by protein chemistry methods, involving, in addition to the classical techniques, a selective precipitation of the abnormal hemoglobin by isopropanol and a mass spectrometry analysis of the alphaT-9 peptide following carboxypeptidase digestion. DNA sequencing demonstrated that the mutation was CTG-->CCG at codon 83 of the alpha2 gene. PMID:9576330

  8. Brain Activity Evaluation Using Oxy-Hb by Difference in the Strength of Sound Stimulus

    NASA Astrophysics Data System (ADS)

    Osawa, Takeru; Asano, Hirotoshi; Ide, Hideto

    We carried out a psychological study involving physiological measurements. We used the VAS to research the feeling. The physiological factor measured was the oxy-Hb. It was found that an auditory stimulus of 70[dB] is more uncomfortable than auditory stimulus of 50[dB]. Furthermore, the decrease in oxy-Hb was greater for the auditory stimulus of 70[dB] as compared to the auditory stimulus of 50[dB]. This tendency was found in the center of the forehead (ch22-ch25). There was a difference between the brain activity for the auditory stimulus of 70[dB] and that for the auditory stimulus of 50[dB]. It was also found that the sound level affects the comfort level of humans. It is necessary to obtain additional details on the effects from physiological index to psychological index in a future study.

  9. Production of mirrors made of HB-Cesic® for an airborne reconnaissance telescope system

    NASA Astrophysics Data System (ADS)

    Krödel, Matthias R.; Hofbauer, Peter; Luichtel, Georg; Katzer, J.; Tausendfreund, M.; Derst, Gerhard

    2009-08-01

    In support of a new airborne telescope system the Multi-Spectral Telescope for a new Reconnaissance Program ECM was contracted by Carl Zeiss Optronics to produce 20 mirrors made of HB-Cesic®, each mirror with a diameter of 315 mm. The contract requirements were that the mirrors remain stable under extreme mechanical and thermal loads and that the production schedule is 12 months. The main challenges of the project were achieving consistent optical performance of the mirrors and meeting the tight schedule of delivering the mirrors, in lots of four, every two months for a total delivery time of twelve months. In this paper we present the lessons learned in producing the HB-Cesic® mirrors, including all the steps up to the final integration of the mirrors into the telescope system and establishing reliable repeatability of the production cycles.

  10. VizieR Online Data Catalog: Hot HB stars in ω Cen (Moehler+, 2011)

    NASA Astrophysics Data System (ADS)

    Moehler, S.; Dreizler, S.; Lanz, T.; Bono, G.; Sweigart, A. V.; Calamida, A.; Nonino, M.

    2011-05-01

    Moderately high resolution spectra of hot HB stars in the globular cluster omega Cen were analysed for radial velocity variations, atmospheric parameters, and abundances using LTE and non-LTE model atmospheres. The spectroscopic data were obtained in 2005 (4 observations) and in 2006 (5 observations) in Service Mode using the MEDUSA mode of the multi-object fiber spectrograph FLAMES + GIRAFFE on the UT2 Telescope of the VLT. We used the low spectroscopic resolution mode with the spectral range 3964Å-4567Å (LR2, R=6400) and observed spectra for a total of 109 blue hook and canonical blue HB/EHB star candidates (see Table 1) and for 17 sky background positions. Each observation had an exposure time of 2550s to keep the total execution time of the observing block shorter than one hour. (3 data files).

  11. Ultra-lightweighted HB-Cesic one-meter mirror demonstrator

    NASA Astrophysics Data System (ADS)

    Krödel, Matthias R.; Hofbauer, Peter

    2010-07-01

    Future space missions, such as SPICA and DARWIN, require large, light-weighted, and stiff mirrors with excellent stability. During the past years, ECM fabricated a number of light-weighted mirrors. However, future large missions require further advances with light-weighting, pushing this technology to the limit possible with recently developed composite materials, new fabrication processes, and innovative designs. In 2009, ECM took steps in this direction by fabricating successfully an ultra-lightweighted HB-Cesic® mirror demonstrator 1 m in size. We demonstrated that HB-Cesic®, due to its extreme light-weighting capability and manufacturing versatility, combined with high stiffness, high mechanical strength, and low CTE at cryogenic temperatures, is able to fully meet the requirements of future large cryogenic space mirrors. In this paper we describe the fabrication process of this demonstrator and its physical characteristics.

  12. In-situ observation of HB GaAs crystal growth

    NASA Astrophysics Data System (ADS)

    Kuo, J. Y.; Guo, Y. D.; Hsu, Juei-Tsang

    1992-10-01

    In-situ monitoring of horizontal Bridgman (HB) growth of GaAs crystals through the furnace window can reveal whether the growth condition is good or not. Good growth conditions are characterized by straight melt/crystal interface and (111) facet growth striations on the grown crystal surface. Abnormal growth conditions including twinning, lineaging and polycrystallizing in the growing crystals usually show curved or irregular-shaped melt/crystal interface and various slanted lines distributed over the crystal surfaces. The monitoring process can spot these defective conditions in the early stage of their formations, and growth parameters thus can be adjusted in real time for correction. It provides a convenient way to help understand the relations between growth parameters and defects formation. The yield and quality of the M2T-HB grown crystals are both increased by this method.

  13. High Resolution Radio Observations of the SNR G160.9+2.6 (HB9)

    NASA Astrophysics Data System (ADS)

    Leahy, D. A.; Roger, R. S.

    New observations of the continuum emission from HB 9 at 408 MHz and 1420 MHz are reported which reveal significant filamentary structure not previously detected. The radio filamentary structure closely follows the optical structure. The radio, optical and particularly, the X-ray surface brightness are all diminished in the northern and northwestern portions of the remnant, in directions approximately coincident with an extensive molecular cloud detected in CO.

  14. Fermi LAT and WMAP observations of the supernova remnant HB 21

    SciTech Connect

    Pivato, G.; Hewitt, J. W.; Tibaldo, L.; Acero, F.; Brandt, T. J.; Ballet, J.; Janssen, G. H.; Jóhannesson, G.; Smith, D. A. E-mail: john.w.hewitt@nasa.gov

    2013-12-20

    We present the analysis of Fermi Large Area Telescope γ-ray observations of HB 21 (G89.0+4.7). We detect significant γ-ray emission associated with the remnant: the flux >100 MeV is 9.4 ± 0.8 (stat) ± 1.6 (syst) × 10{sup –11} erg cm{sup –2} s{sup –1}. HB 21 is well modeled by a uniform disk centered at l = 88.°75 ± 0.°04, b = +4.°65 ± 0.°06 with a radius of 1.°19 ± 0.°06. The γ-ray spectrum shows clear evidence of curvature, suggesting a cutoff or break in the underlying particle population at an energy of a few GeV. We complement γ-ray observations with the analysis of the WMAP 7 yr data from 23 to 93 GHz, achieving the first detection of HB 21 at these frequencies. In combination with archival radio data, the radio spectrum shows a spectral break, which helps to constrain the relativistic electron spectrum, and, in turn, parameters of simple non-thermal radiation models. In one-zone models multiwavelength data favor the origin of γ rays from nucleon-nucleon collisions. A single population of electrons cannot produce both γ rays through bremsstrahlung and radio emission through synchrotron radiation. A predominantly inverse-Compton origin of the γ-ray emission is disfavored because it requires lower interstellar densities than are inferred for HB 21. In the hadronic-dominated scenarios, accelerated nuclei contribute a total energy of ∼3 × 10{sup 49} erg, while, in a two-zone bremsstrahlung-dominated scenario, the total energy in accelerated particles is ∼1 × 10{sup 49} erg.

  15. Dysregulation of ferroportin gene expression in β(0)-thalassemia/Hb E disease.

    PubMed

    Sornjai, Wannapa; Jaratsittisin, Janejira; Khungwanmaythawee, Kornpat; Svasti, Saovaros; Fucharoen, Suthat; Lithanatudom, Pathrapol; Smith, Duncan R

    2016-02-01

    During erythropoiesis, iron levels need to be carefully regulated to ensure there is sufficient iron available for hemoglobin synthesis, but that there is no excess to cause damage to the developing erythroblast. Iron influx to the developing erythroblast is controlled by the expression of the transferrin receptor, while iron efflux is regulated by ferroportin (FPN), the sole iron-exporting protein. FPN is encoded through multiple messenger RNAs (mRNAs) some of which contain an iron-responsive element (variant I mRNAs) and some of which do not (variant II mRNAs). This study sought to investigate the expression of the FPN mRNAs in developing erythroblasts from normal controls and β(0)-thalassemia/Hb E patients. While levels of FPN protein were relatively constant, marked reductions of the variant I message were seen in erythroblasts from β(0)-thalassemia/Hb E patients as compared to normal control cells, particularly in late erythropoiesis. Variant II mRNAs were generally increased during erythroid differentiation. No difference was seen in levels of either transferrin or ferritin heavy chain expression. While no difference was observed in labile iron pools under normal culture conditions, erythroblasts from β(0)-thalassemia/Hb E patients showed a significantly reduced expression of total FPN message under high iron conditions as compared to normal control erythroblasts. These results are consisted with dysregulation of iron efflux from the maturing erythroblast in β(0)-thalassemia/Hb E patients, and this dysregulation possibly contributes to ineffective erythropoiesis seen in these patients. PMID:26666535

  16. Fermi LAT and WMAP Observations of the Supernova Remnant HB 21

    NASA Astrophysics Data System (ADS)

    Pivato, G.; Hewitt, J. W.; Tibaldo, L.; Acero, F.; Ballet, J.; Brandt, T. J.; de Palma, F.; Giordano, F.; Janssen, G. H.; Jóhannesson, G.; Smith, D. A.

    2013-12-01

    We present the analysis of Fermi Large Area Telescope γ-ray observations of HB 21 (G89.0+4.7). We detect significant γ-ray emission associated with the remnant: the flux >100 MeV is 9.4 ± 0.8 (stat) ± 1.6 (syst) × 10-11 erg cm-2 s-1. HB 21 is well modeled by a uniform disk centered at l = 88.°75 ± 0.°04, b = +4.°65 ± 0.°06 with a radius of 1.°19 ± 0.°06. The γ-ray spectrum shows clear evidence of curvature, suggesting a cutoff or break in the underlying particle population at an energy of a few GeV. We complement γ-ray observations with the analysis of the WMAP 7 yr data from 23 to 93 GHz, achieving the first detection of HB 21 at these frequencies. In combination with archival radio data, the radio spectrum shows a spectral break, which helps to constrain the relativistic electron spectrum, and, in turn, parameters of simple non-thermal radiation models. In one-zone models multiwavelength data favor the origin of γ rays from nucleon-nucleon collisions. A single population of electrons cannot produce both γ rays through bremsstrahlung and radio emission through synchrotron radiation. A predominantly inverse-Compton origin of the γ-ray emission is disfavored because it requires lower interstellar densities than are inferred for HB 21. In the hadronic-dominated scenarios, accelerated nuclei contribute a total energy of ~3 × 1049 erg, while, in a two-zone bremsstrahlung-dominated scenario, the total energy in accelerated particles is ~1 × 1049 erg.

  17. Gas Generation Testing of Neptunium Oxide Generated Using the HB-Line Phase IIFlowsheet

    SciTech Connect

    Duffey, J

    2003-08-29

    The hydrogen (H{sub 2}) gas generation rate for neptunium dioxide (NpO{sub 2}) samples produced on a laboratory scale using the HB-Line Phase II flowsheet has been measured following exposure to 75% relative humidity (RH). As expected, the observed H{sub 2} generation rates for these samples increase with increasing moisture content. A maximum H{sub 2} generation rate of 1.8 x 10{sup -6} moles per day per kilogram (mol {center_dot} day{sup -1} kg{sup -1}) was observed for NpO{sub 2} samples with approximately one and one-half times (1 1/2 X) the expected specific surface area (SSA) for the HB-Line Phase II product. The SSA of NpO{sub 2} samples calcined at 650 C is similar to plutonium dioxide (PuO{sub 2}) calcined at 950 C according to the Department of Energy (DOE) standard for packaging and storage of PuO{sub 2}. This low SSA of the HB-Line Phase II product limits moisture uptake to less than 0.2 weight percent (wt %) even with extended exposure to 75% RH.

  18. Evaluation of the HB&L System for the Microbiological Screening of Storage Medium for Organ-Cultured Corneas.

    PubMed

    Camposampiero, D; Grandesso, S; Zanetti, E; Mazzucato, S; Solinas, M; Parekh, M; Frigo, A C; Gion, M; Ponzin, D

    2013-01-01

    Aims. To compare HB&L and BACTEC systems for detecting the microorganisms contaminating the corneal storage liquid preserved at 31°C. Methods. Human donor corneas were stored at 4°C followed by preservation at 31°C. Samples of the storage medium were inoculated in BACTEC Peds Plus/F (aerobic microorganisms), BACTEC Plus Anaerobic/F (anaerobic microorganisms), and HB&L bottles. The tests were performed (a) after six days of storage, (b) end of storage, and (c) after 24 hours of preservation in deturgescent liquid sequentially. 10,655 storage and deturgescent media samples were subjected to microbiological control using BACTEC (6-day incubation) and HB&L (24-hour incubation) systems simultaneously. BACTEC positive/negative refers to both/either aerobic and anaerobic positives/negatives, whereas HB&L can only detect the aerobic microbes, and therefore the positives/negatives depend on the presence/absence of aerobic microorganisms. Results. 147 (1.38%) samples were identified positive with at least one of the two methods. 127 samples (134 identified microorganisms) were positive with both HB&L and BACTEC. 14 HB&L+/BACTEC- and 6 BACTEC+/HB&L- were identified. Sensitivity (95.5%), specificity (99.8%), and positive (90.1%) and negative predictive values (99.9%) were high with HB&L considering a 3.5% annual contamination rate. Conclusion. HB&L is a rapid system for detecting microorganisms in corneal storage medium in addition to the existing methods. PMID:24069532

  19. Evaluation of the HB&L System for the Microbiological Screening of Storage Medium for Organ-Cultured Corneas

    PubMed Central

    Camposampiero, D.; Grandesso, S.; Zanetti, E.; Mazzucato, S.; Solinas, M.; Parekh, M.; Frigo, A. C.; Gion, M.; Ponzin, D.

    2013-01-01

    Aims. To compare HB&L and BACTEC systems for detecting the microorganisms contaminating the corneal storage liquid preserved at 31°C. Methods. Human donor corneas were stored at 4°C followed by preservation at 31°C. Samples of the storage medium were inoculated in BACTEC Peds Plus/F (aerobic microorganisms), BACTEC Plus Anaerobic/F (anaerobic microorganisms), and HB&L bottles. The tests were performed (a) after six days of storage, (b) end of storage, and (c) after 24 hours of preservation in deturgescent liquid sequentially. 10,655 storage and deturgescent media samples were subjected to microbiological control using BACTEC (6-day incubation) and HB&L (24-hour incubation) systems simultaneously. BACTEC positive/negative refers to both/either aerobic and anaerobic positives/negatives, whereas HB&L can only detect the aerobic microbes, and therefore the positives/negatives depend on the presence/absence of aerobic microorganisms. Results. 147 (1.38%) samples were identified positive with at least one of the two methods. 127 samples (134 identified microorganisms) were positive with both HB&L and BACTEC. 14 HB&L+/BACTEC− and 6 BACTEC+/HB&L− were identified. Sensitivity (95.5%), specificity (99.8%), and positive (90.1%) and negative predictive values (99.9%) were high with HB&L considering a 3.5% annual contamination rate. Conclusion. HB&L is a rapid system for detecting microorganisms in corneal storage medium in addition to the existing methods. PMID:24069532

  20. Capsicum annuum homeobox 1 (CaHB1) is a nuclear factor that has roles in plant development, salt tolerance, and pathogen defense

    SciTech Connect

    Oh, Sang-Keun; Yoon, Joonseon; Choi, Gyung Ja; Jang, Hyun A; Kwon, Suk-Yoon; Choi, Doil

    2013-12-06

    Highlights: •The CaHB1 is a nuclear factor, belonging to HD-Zip proteins. •SA and ET, as signal molecules, modulate CaHB1-mediated responses. •Overexpression of CaHB1 in tomato resulted in a thicker cell wall. •CaHB1-transgenic tomato confers resistance to Phytophthora infestans. •CaHB1 enhanced tolerance to saline stress in tomato. -- Abstract: Homeodomain-leucine zipper (HD-Zip) family proteins are unique to plants, but little is known about their role in defense responses. CaHB1 is a nuclear factor in peppers, belonging to subfamily II of HD-Zip proteins. Here, we determined the role of CaHB1 in the defense response. CaHB1 expression was induced when pepper plants were challenged with Phytophthora capsici, a plant pathogen to which peppers are susceptible, or environmental stresses such as drought and salt stimuli. CaHB1 was also highly expressed in pepper leaves following application of SA, whereas ethephon and MeJA had a moderate effect. To further investigate the function of CaHB1 in plants, we performed gain-of-function study by overexpression of CaHB1 in tomato. CaHB1-transgenic tomatoes showed significant growth enhancement including increased leaf thickness and enlarged cell size (1.8-fold larger than control plants). Microscopic analysis revealed that leaves from CaHB1-transgenic plants had thicker cell walls and cuticle layers than those from controls. Moreover, CaHB1-transgenic plants displayed enhanced resistance against Phytophthora infestans and increased tolerance to salt stress. Additionally, RT-PCR analysis of CaHB1-transgenic tomatoes revealed constitutive up-regulation of multiple genes involved in plant defense and osmotic stress. Therefore, our findings suggest roles for CaHB1 in development, salt stress, and pathogen defense.

  1. Hb Dapu (HBA2: c.52G > T): A Novel Nondeletional α-Thalassemia Mutation.

    PubMed

    Yang, Yu; Li, Dong-Zhi; He, Ping

    2016-08-01

    We report a novel mutation on the α2-globin gene, Hb Dapu [α17(A15)Val →Phe (α2); HBA2: c.52G > T] detected in a Chinese family. This mutation gives rise to a previously undescribed hemoglobin (Hb) variant that was undetectable by electrophoretic or chromatographic methods. The combination of this mutation with an in cis deletion of a double α-globin gene resulting in a mild form of Hb H (β4) disease, is consistent with a thalassemic phenotype associated with the novel mutation. PMID:27258683

  2. Analysis of glycosylated hemoglobin (HbA1c) level on maxillofacial fascial space infection in diabetic patients

    PubMed Central

    Jang, Jong-Won; Kim, Moon-Young

    2015-01-01

    Objectives This study was performed to evaluate the impact of glycosylated hemoglobin (HbA1c) level on characteristics and prognosis of maxillofacial fascial infection in diabetic patients. Materials and Methods We reviewed the medical records of 72 patients (35 patients with HbA1c lower than 7.0% and 37 patients with HbA1c higher than 7.0%) diagnosed with maxillofacial fascial space infection and hospitalized for treatment at the Department of Oral and Maxillofacial Surgery in Dankook University Hospital (Cheonan, Korea) from January 2005 to February 2014. We compared demographics, parameters of glucoregulation (HbA1c), laboratory parameters of inflammation (white blood cell [WBC], C-reactive protein [CRP] count), type and number of involved spaces, type and number of antibiotics, period of hospitalization, number of surgical operations, need for tracheostomy, complications, computed tomography (CT), and microorganisms between the two groups. Results Compared with the well-controlled diabetes mellitus (DM) group (HbA1c <7.0%), patients in the poorly-controlled (HbA1c ≥7.0%) DM group had the following characteristics: longer hospitalization periods, higher values of laboratory parameters of inflammation (WBC, CRP count) at the time of admission, higher number of antibiotics prescribed, more frequent complications, frequent deep neck space involvement, and distinctive main causative microorganisms. As the HbA1c level increases, hospitalization periods and incidence of complications increase gradually. Conclusion This retrospective study suggests that regulation of DM significantly impacts maxillofacial fascial infection. Poorly controlled DM with high HbA1c level negatively influences the prognosis of infection. PMID:26568927

  3. Source Terms for HFIR Beam Tube Shielding Analyses, and a Complete Shielding Analysis of the HB-3 Tube

    SciTech Connect

    Bucholz, J.A.

    2000-07-01

    The High Flux Isotope Reactor (HFIR) at the Oak Ridge National Laboratory is in the midst of a massive upgrade program to enhance experimental facilities. The reactor presently has four horizontal experimental beam tubes, all of which will be replaced or redesigned. The HB-2 beam tube will be enlarged to support more guide tubes, while the HB-4 beam tube will soon include a cold neutron source.

  4. 2D imaging of intracapillary Hb-concentration and oxygenation in the skin of the human forehead in different ages

    NASA Astrophysics Data System (ADS)

    Kessler, Manfred D.; Cristea, Paul D.; Knaelmann, Rainer; Wittwer, Philipp

    2002-06-01

    On the capillary level of intact organs of humans and mammals, fields of gradients of all measurable parameters are found exclusively. Therefore, a precise monitoring e.g. of hemoglobin concentration (Hb) and oxygenation (HbO2) in the microcosm of blood capillaries is only possible when the heterogeneity of tissue data is recorded at a representative number of measuring points. For the collecting of the required data both stochastic or imaging techniques can be applied.

  5. Persistent sodium current contributes to induced voltage oscillations in locomotor-related hb9 interneurons in the mouse spinal cord.

    PubMed

    Ziskind-Conhaim, Lea; Wu, Linying; Wiesner, Eric P

    2008-10-01

    Neurochemically induced membrane voltage oscillations and firing episodes in spinal excitatory interneurons expressing the HB9 protein (Hb9 INs) are synchronous with locomotor-like rhythmic motor outputs, suggesting that they contribute to the excitatory drive of motoneurons during locomotion. Similar to central pattern generator neurons in other systems, Hb9 INs are interconnected via electrical coupling, and their rhythmic activity does not depend on fast glutamatergic synaptic transmission. The primary objective of this study was to determine the contribution of fast excitatory and inhibitory synaptic transmission and subthreshold voltage-dependent currents to the induced membrane oscillations in Hb9 INs in the postnatal mouse spinal cord. The non-N-methyl-D-aspartate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) reduced the amplitude of voltage oscillations but did not alter their frequency. CNQX suppressed rhythmic motor activity. Blocking glycine and GABAA receptor-mediated inhibitory synapses as well as cholinergic transmission did not change the properties of CNQX-resistant membrane oscillations. However, disinhibition triggered new episodes of slow motor bursting that were not correlated with induced locomotor-like rhythms in Hb9 INs. Our observations indicated that fast excitatory and inhibitory synaptic inputs did not control the frequency of induced rhythmic activity in Hb9 INs. We next examined the contribution of persistent sodium current (INaP) to subthreshold membrane oscillations in the absence of primary glutamatergic, GABAergic and glycinergic synaptic drive to Hb9 INs. Low concentrations of riluzole that blocked the slow-inactivating component of sodium current gradually suppressed the amplitude and reduced the frequency of voltage oscillations. Our finding that INaP regulates locomotor-related rhythmic activity in Hb9 INs independently of primary synaptic transmission supports the concept that these neurons constitute an

  6. Two new hemoglobin variants: Hb Aix-Les-Bains [β5(A2)Pro→Leu; HBB:c.17 C>T] and Hb Dubai [α122(H5)His→Leu (α2); HBA2:c.368 A>T].

    PubMed

    Joly, Philippe; Garcia, Caroline; Lacan, Philippe; Couprie, Nicole; Francina, Alain

    2011-01-01

    We report two new hemoglobin (Hb) variants; one causing an impairment of the N-terminal glycation of the β-globin chain and the other a hematological phenotype of α-thalassemia (α-thal). The first variant is Hb Aix-les-Bains [β5(A2)Pro→Leu] and the second Hb Dubai [α122(H5)His→Leu (α2)]. These two new Hb variants were detected by chromatographic and electrophoretic methods and characterized by molecular studies. Hb Dubai gives an α-thalassemic phenotype and should be routinely detected for preventing severe Hb H disease in couples at-risk for α-thal. PMID:21417572

  7. Denaturant effects on HbGp hemoglobin as monitored by 8-anilino-1-naphtalene-sulfonic acid (ANS) probe.

    PubMed

    Barros, Ana E B; Carvalho, Francisco A O; Alves, Fernanda R; Carvalho, José W P; Tabak, Marcel

    2015-03-01

    Glossoscolex paulistus extracellular hemoglobin (HbGp) stability has been monitored in the presence of denaturant agents. 8-Anilino-1-naphtalene-sulfonic acid (ANS) was used, and spectroscopic and hydrodynamic studies were developed. Dodecyltrimethylammonium bromide (DTAB) induces an increase in ANS fluorescence emission intensity, with maximum emission wavelength blue-shifted from 517 to 493 nm. Two transitions are noticed, at 2.50 and 9.50 mmol/L of DTAB, assigned to ANS interaction with pre-micellar aggregates and micelles, respectively. In oxy-HbGp, ANS binds to protein sites less exposed to solvent, as compared to DTAB micelles. In DTAB-HbGp-ANS ternary system, at pH 7.0, protein aggregation, oligomeric dissociation and unfolding were observed, while, at pH 5.0, aggregation is absent. DTAB induced unfolding process displays two transitions, one due to oligomeric dissociation and the second one, probably, to the denaturation of dissociated subunits. Moreover, guanidine hydrochloride and urea concentrations above 1.5 and 4.0 mol/L, respectively, induce the full HbGp denaturation, with reduction of ANS-bound oxy-HbGp hydrophobic patches, as noticed by fluorescence quenching up to 1.0 and 5.0 mol/L of denaturants. Our results show clearly the differences in probe sensitivity to the surfactant, in the presence and absence of protein, and new insights into the denaturant effects on HbGp unfolding. PMID:25546245

  8. The Chinese medicine formula HB01 reduces choroidal neovascularization by regulating the expression of vascular endothelial growth factor

    PubMed Central

    2012-01-01

    Background Choroidal neovascularization (CNV) remains the leading cause of newly acquired blindness in the developed world. Currently anti-vascular endothelial growth factor (VEGF) therapies are broadly used to treat neovascular ocular disorders. Here we demonstrate the effect of a traditional Chinese medicine formula, HB01, on CNV. Methods A rat model of laser-induced CNV was used to investigate the effect of HB01 in vivo. The CNV lesions in the eye were evaluated using fundus fluorescein angiography and visualized/quantified using confocal microscopy. Expression of VEGF in the choroidal and retinal tissues was measured using quantitative real-time PCR and immunohistochemistry. Results We demonstrated that a traditional Chinese Medicine formula, named HB01, significantly reduced neovascularization in a rat CNV model. The effect of HB01 on CNV was comparable to the intravitreal injection of bevacizumab (Avastin). Our results also suggested that HB01 may reduce CNV partially through inhibiting the expression of VEGF. Conclusions These data support HB01 as an alternative therapy for ocular neovascular disorders. PMID:22676316

  9. Does cigarette smoking affect the diagnostic reliability of hemoglobin alpha 2 delta 2 (HbA2)?

    PubMed

    Tarazi, Issa S; Sirdah, Mahmoud M; El Jeadi, Hesham; Al Haddad, Rami M

    2008-01-01

    Quantitation of hemoglobin alpha 2 delta 2 (HbA2) is a basic and confirmatory test in diagnosing the carrier state of beta-thalassemia. The present study was designed to investigate the effect of cigarette smoking on the diagnostic reliability of HbA2. A total of 2,867 (654 smokers and 2,213 never smokers) male subjects were involved in the present study. The subjects were categorized into three groups according to their laboratory findings: beta-thalassemia minor, iron deficient, and normal groups. Complete blood count (CBC) parameters and HbA2 levels were compared between smokers and never smokers of each group according to the independent-samples t-test using the SPSS program, significance results were reported at P<0.05. The results showed a significant increase in red blood cell (RBC) mass (RBC count and hematocrit [Hct]) and Hb concentration in smokers of all groups; however, no significant differences were reported in the HbA2 level between smokers and never smokers in all groups. It was concluded that cigarette smoking does not affect the diagnostic reliability of the HbA2 test. PMID:18348310

  10. On the ΔV bump HB Parameter in Globular Clusters

    NASA Astrophysics Data System (ADS)

    Di Cecco, A.; Bono, G.; Stetson, P. B.; Pietrinferni, A.; Becucci, R.; Cassisi, S.; Degl'Innocenti, S.; Iannicola, G.; Prada Moroni, P. G.; Buonanno, R.; Calamida, A.; Caputo, F.; Castellani, M.; Corsi, C. E.; Ferraro, I.; Dall'Ora, M.; Monelli, M.; Nonino, M.; Piersimoni, A. M.; Pulone, L.; Romaniello, M.; Salaris, M.; Walker, A. R.; Zoccali, M.

    2010-03-01

    We present new empirical estimates of the ΔV bump HB parameter for 15 Galactic globular clusters (GGCs) using accurate and homogeneous ground-based optical data. Together with similar evaluations available in the literature, we ended up with a sample of 62 GGCs covering a very broad range in metal content (-2.16 dex <= [M/H] <= -0.58 dex). Adopting the homogeneous metallicity scale provided either by Kraft & Ivans or by Carretta et al., we found that the observed ΔV bump HB parameters are larger than predicted. In the metal-poor regime ([M/H] <~ -1.7, -1.6 dex) 40% of GCs show discrepancies of 2σ (≈0.40 mag) or more. Evolutionary models that account either for α- and CNO-enhancement or for helium enhancement do not alleviate the discrepancy between theory and observations. The outcome is the same if we use the new solar heavy-element mixture. The comparison between α- and CNO-enhanced evolutionary models and observations in the Carretta et al. metallicity scale also indicates that observed ΔV bump HB parameters, in the metal-rich regime ([M/H] >= 0), might be systematically smaller than predicted. Based in part on data obtained from the ESO/ST-ECF Science Archive Facility, from the Isaac Newton Group Archive which is maintained as part of the CASU Astronomical Data Centre at the Institute of Astronomy, Cambridge, and from the Canadian Astronomy Data Centre operated by the National Research Council of Canada with the support of the Canadian Space Agency.

  11. Beyond HbA1c: Environmental Risk Factors for Diabetic Retinopathy

    PubMed Central

    Nwanyanwu, Kristen Harris; Newman-Casey, Paula-Anne; Gardner, Thomas W; Lim, Jennifer I

    2015-01-01

    Diabetic retinopathy affects 4.2 million people in the United States and is the leading cause of blindness in working-aged people. As the prevalence of diabetes continues to rise, cost-effective interventions to decrease blindness from diabetic retinopathy will be paramount. While HbA1c and duration of disease are known risk factors, they account for only 11% of the risk of developing microvascular complications from the disease. The assessment of environmental risk factors for diabetic eye disease allows for the determination of modifiable population-level challenges that may be addressed to facilitate the end of blindness from diabetes. PMID:26973797

  12. Characterization of Neptunium Oxide Generated Using the HB-Line Phase II Flowsheet

    SciTech Connect

    Duffey, J

    2003-08-29

    Approximately 98 grams of neptunium(IV) oxide (NpO{sub 2}) were produced at the Savannah River Technology Center (SRTC) for use in gas generation tests to support the neptunium stabilization program at the Savannah River Site (SRS). The NpO{sub 2} was produced according to the anticipated HB-Line flowsheet consisting of anion exchange, oxalate precipitation, filtration, and calcination. Characterization of the NpO{sub 2} product to be used in gas generation tests included bulk and tap density measurements, X-ray diffraction, particle size distribution, specific surface area measurements, and moisture analysis.

  13. Many Ingredients, One Sublime Dish: The Recipe for the Passage of Illinois HB5412 Into Law.

    PubMed

    Baté-Ambrus, Venoncia M; Castillo, Amparo; Martinez, Erica; Campbell, Jamie; Boughton-Price, Leticia; Gutierrez Kapheim, Melissa; Arrom, José O; Hernandez, Wandy; Waddy, Jeffery; Castillo, Sheila; Schaps, Margie; Williams, Yolonda

    2015-01-01

    This article contextualizes the need for Illinois House Bill 5412 (HB5412), which calls for the establishment of a state board to create recommendations for the community health worker (CHW) field in Illinois, including a scope of practice, core competencies, training and certification standards, and sustainable funding and reimbursement mechanisms. Multisectorial partnerships and their outputs, coupled with frontline CHW interventions, created a synergistic climate conducive to the passing of this historic CHW legislation. This article provides a timeline and recipe for legislative success as described through processes and activities collaboratively undertaken, concentrating on a 5-year period (2009-2014). PMID:26049653

  14. VizieR Online Data Catalog: NGC6656 spectroscopy of 71 blue HB stars (Salgado+, 2013)

    NASA Astrophysics Data System (ADS)

    Salgado, C.; Moni Bidin, C.; Villanova, S.; Geisler, D.; Catelan, M.

    2013-08-01

    Spectroscopically-derived parameters of 71 blue HB stars. The temperature, gravity, and surface helium abundance were derived fitting the Balmer and helium lines with synthetic spectra. Reddening and mass were estimated from these parameters. Spectra were obtained with the Hydra optical spectrograph mounted on the Blanco 4.0m telescope. It was used the grating KPGL1, coupled with the BG39 filter and the 200μ slit plate. The spectra were obtained on August 27, 2010 and cover the wavelength range of 3700-4900Å with a spectral resolution of 2.7Å. (2 data files).

  15. ECSS-E-HB-32-26 Handbook for Spacecraft Loads Analysis

    NASA Astrophysics Data System (ADS)

    Calvi, Adriano

    2012-07-01

    The determination and assessment of the mechanical loads acting on the spacecraft is a crucial and difficult task in the design and verification processes of a space project. For this reason European Cooperation for Space Standardization (ECSS) has approved the development of a specific handbook, ECSS-E-HB-32-26, titled “Spacecraft Loads Analysis”. The paper provides an overview of the handbook in particular in terms of objectives and technical contents. The aim is to promote the use of the handbook within the space community.

  16. Simplified white-light interferometric strain sensor based on HB fiber with automatic temperature compensation

    NASA Astrophysics Data System (ADS)

    Ma, Jianjun; Bock, Wojtek J.; Urbanczyk, Waclaw

    2003-02-01

    A simplified white-light interferometric strain sensor based on HB fibers with automatic temperature compensation is presented. A variety of experiments conducted within this study confirm an adequate temperature compensation could be achieved. Several different sensor structures were investigated during these experiments. One of the most important results shows that the interference contrast could significantly influence the measurement accuracy achievable by the system. Consequently, a 1% or even better absolute accuracy for short sensing fibers is possible if the contrast is enhanced to 0.5. A quasi-distributed cascade containing several discrete sensors with 0.5 contrast is also suggested.

  17. VizieR Online Data Catalog: Parameters of HB stars in ω Cen (Moni Bidin+, 2012)

    NASA Astrophysics Data System (ADS)

    Moni Bidin, C.; Villanova, S.; Piotto, G.; Moehler, S.; Cassisi, S.; Momany, Y.

    2012-10-01

    Our observations targeted 115 HB stars in ω Cen, selected from the optical photometry of Bellini et al. (2009, Cat. J/A+A/493/959). The data were collected at the Paranal Observatory in service mode, with the FORS2 spectrograph mounted on the UT1 telescope, in 2006 from January to April. The temperatures, gravities, and surface helium abundances were derived fitting the Balmer and helium lines with synthetic model spectra. Reddening and mass were estimated from these parameters. (1 data file).

  18. The helium content of globular clusters: light element abundance correlations and HB morphology. I. NGC 6752

    NASA Astrophysics Data System (ADS)

    Villanova, S.; Piotto, G.; Gratton, R. G.

    2009-06-01

    Context: In the context of the multiple stellar population scenario in globular clusters (GC), helium (He) has been proposed as the key element to interpret the observed multiple main sequences (MS), subgiant branches (SGB) and red giant branches (RGB), as well as the complex horizontal branch (HB) morphology. However, up to now, He has never been directly measured in GC stars (8500 < T_eff < 11 500 K) to verify this hypothesis. Aims: We studied hot blue horizontal branch (BHB) stars in the GC NGC 6752 to measure their He content. Our goal is to verify the feasibility of He measurement from high resolution spectra in stars cooler than 11 500 K, where chemical abundances are not altered by sedimentation or levitation. Methods: We observed 7 BHB stars using the UVES@VLT2 spectroscopic facility. Spectra of S/N~200 were obtained and the very weak He line at 5875 Å measured. We compared this feature with synthetic spectra to obtain He abundances. In addition, iron peak (Fe, Cr), α (Si, Ti), light (O, Na), and s-element (Ba) abundances were measured. Results: We could measure He abundance only for stars warmer than T_eff = 8500 K. All our targets with measurable He are zero age HB (ZAHB) objects and turned out to have a homogeneous He content with a mean value of Y = 0.245±0.012, compatible with the most recent measurements of the primordial He content of the Universe (Y~0.25). The whole sample of stars has a metallicity of [Fe/H] = -1.56±0.03 and [ α/Fe] = +0.21±0.03, in agreement with other studies available in the literature. Our HB targets show the same Na-O anticorrelation identified among the TO-SGB-RGB stars. Conclusions: This is the first direct measurement of the He abundance for a significative sample of GC stars in a temperature regime where the He content is not altered by sedimentation or extreme mixing as suggested for the hottest, late helium flasher HB stars.

  19. Complementary p-MODFET and n-HB MESFET (Al,Ga)As transistors

    NASA Astrophysics Data System (ADS)

    Kiehl, R. A.; Gossard, A. C.

    1984-12-01

    A complementary transistor structure that utilizes a p-channel modulation-doped FET (p-MODFET) to produce improved p-channel characteristics if reported for the first time. The structure also includes a new type of n-channel MESFET in which the electrons are confined by an n-p heterojunction barrier (n-HB MESFET). The complementary transistor pair is fabricated on a novel MBE-grown n-GaAs/p-(Al,Ga)As/i-GaAs heterostructure. The experimental current-voltage characteristics are presented and demonstrate that this is a promising approach for the development of GaAs-based high-speed complementary logic circuits.

  20. The Impact of HbA1c Testing on Total Annual Healthcare Expenditures Among Newly Diagnosed Patients with Diabetes

    PubMed Central

    Bhounsule, Prajakta; Peterson, Andrew M.

    2015-01-01

    Background In 2010, diabetes was the seventh leading cause of death in the United States. Diabetes also imposes a huge financial burden on the US economy. In 2009, the American Diabetes Association International Expert Committee recommended the use of the glycated hemoglobin (HbA1c) test as a uniform diagnostic measure to identify patients with diabetes. Although HbA1c is a convenient diagnostic test, it is also more expensive than older tests and could, therefore, have an impact on patients’ healthcare expenditures. Objectives To determine if HbA1c testing has an impact on total annual healthcare expenditures among newly diagnosed patients with diabetes and to analyze the factors that are associated with the total healthcare expenditures among diabetic patients before and after HbA1c was implemented as a standard diagnostic factor. Methods This was an observational, retrospective, cross-sectional study. The Medical Expenditure Panel Survey-Household Component 2009 and 2011 databases were used to form the study cohort of patients with diabetes. The total mean healthcare expenditures among patients with diabetes formed the dependent variable. A proxy variable representing a diagnosis of diabetes with and without the use of HbA1c testing in 2009 and in 2011, respectively, formed the main independent variable along with demographic factors, comorbidities, and healthcare services utilization in both years. A generalized linear regression was conducted to determine the association of HbA1c testing with total diabetes-related healthcare expenditures. Results The mean total healthcare expenditure decreased in 2011 compared with 2009. The HbA1c test did not show an association with the total healthcare expenditures versus earlier diabetes-related diagnostic factors. The total expenditures were associated with private insurance, the incidence of a previous heart attack, prescription drug refills, inpatient hospital stays, home care, hospital discharges, and visits to

  1. PET studies with low and high affinity dopamine D2 receptor radioligands: Effects of 4-hydroxybutyrate (4HB)

    SciTech Connect

    Gatley, S.J.; Fowler, J.S.; Dewey, S.

    1994-05-01

    D2 radioligands of varying affinities have been developed as PET and SPECT radiotracers, but no consensus has been reached on the abilities of these tracers to quantify D2 receptor concentrations in vivo. Amongst other differences, competition of the radioligand with endogenous DA is expected to depend on affinity for the D2 receptor, so that changes in DA might confound estimates of Bmax. We examined the uptake and kinetics if C-11 raclopride (RAC; Kd = 1.2 nM) and C-11 N-methylspiperone (NMS); Kd = 75 pM in baboon striatum after pretreatment with 4HB (200 mg/Kg, i/v) which inhibits DA release by nigrostriatal nerve terminals. While 4HB diminished uptake (%ID/g) of NMS, it prolonged tissue retention of RAC, confirming previous observations in rodent models. Logan (for RAC) and Patlak (for NMS) plots gave changes of +24% and -20%, respectively, between control and 4HB treated animals. Since decreased competition with DA should increase uptake of NMS as well as RAC the paradoxical decrease in NMS uptake could be due to a second synaptic effect of DA, such as a decrease in agonist mediated internalization of NMS. Alternatively, it could result from an independent effect of 4HB, perhaps related to this drug`s ability to induce anesthesia and to depress cerebral glucose utilization. Although previous work in the rat suggests that 4HB does not alter brain blood flow, we found O-15 water that baboon striatal blood flow was decreased 22% and 42% at 30 and 60 minutes, respectively, after 4HB. Smaller changes were seen in cerebellar blood flow. Though a 4HB induced decrease in blood flow does not rule out a DA mediated alteration in D2 receptor Bmax or Kd for NMS, or other factor, it is unnecessary to invoke this to account for our results.

  2. RhHB1 mediates the antagonism of gibberellins to ABA and ethylene during rose (Rosa hybrida) petal senescence.

    PubMed

    Lü, Peitao; Zhang, Changqing; Liu, Jitao; Liu, Xiaowei; Jiang, Guimei; Jiang, Xinqiang; Khan, Muhammad Ali; Wang, Liangsheng; Hong, Bo; Gao, Junping

    2014-05-01

    Rose (Rosa hybrida) is one of the most important ornamental plants worldwide; however, senescence of its petals terminates the ornamental value of the flower, resulting in major economic loss. It is known that the hormones abscisic acid (ABA) and ethylene promote petal senescence, while gibberellins (GAs) delay the process. However, the molecular mechanisms underlying the antagonistic effects amongst plant hormones during petal senescence are still unclear. Here we isolated RhHB1, a homeodomain-leucine zipper I transcription factor gene, from rose flowers. Quantitative RT-PCR and GUS reporter analyses showed that RhHB1 was strongly expressed in senescing petals, and its expression was induced by ABA or ethylene in petals. ABA or ethylene treatment clearly accelerated rose petal senescence, while application of the gibberellin GA3 delayed the process. However, silencing of RhHB1 delayed the ABA- or ethylene-mediated senescence, and resulted in higher petal anthocyanin levels and lower expression of RhSAG12. Moreover, treatment with paclobutrazol, an inhibitor of GA biosynthesis, repressed these delays. In addition, silencing of RhHB1 blocked the ABA- or ethylene-induced reduction in expression of the GA20 oxidase encoded by RhGA20ox1, a gene in the GA biosynthetic pathway. Furthermore, RhHB1 directly binds to the RhGA20ox1 promoter, and silencing of RhGA20ox1 promoted petal senescence. Eight senescence-related genes showed substantial differences in expression in petals after treatment with GA3 or paclobutrazol. These results suggest that RhHB1 mediates the antagonistic effect of GAs on ABA and ethylene during rose petal senescence, and that the promotion of petal senescence by ABA or ethylene operates through an RhHB1-RhGA20ox1 regulatory checkpoint. PMID:24589134

  3. Suppression of tumorigenicity of rhabdoid tumor derived G401 cells by the multivalent HB-19 pseudopeptide that targets surface nucleolin.

    PubMed

    Krust, Bernard; El Khoury, Diala; Soundaramourty, Calaiselvy; Nondier, Isabelle; Hovanessian, Ara G

    2011-03-01

    Several studies have indicated that the cell-surface expressed nucleolin is implicated in tumorigenesis and angiogenesis, and represents an important target for cancer therapy. Here we show that treatment of rhabdoid tumor derived G401 cells with a nucleolin antagonist, the HB-19 pseudopeptide, could restore contact inhibition, impair anchorage-independent growth, and suppress tumor development in nude mice. G401 cells grow without contact inhibition, which is an in vitro characteristic property of malignant tumor cells. At concentrations of HB-19 that does not affect cell viability and multiplication index, there is restoration of contact inhibition thus suggesting that HB-19 treatment causes reversion of the malignant phenotype. Accordingly, HB-19 pretreated G401 cells lose the capacity to form colonies in soft agar. When assayed for tumorigenicity in nude mice, only 50% of mice injected with HB-19 pretreated G401 cells developed tumors with the mean tumor weight of 0.32 g, compared to 100% of mice injected with control G401 cells with the mean tumor weight of 2.36 g. Interestingly, the restoration of contact inhibition in HB-19 treated G401 cells is concomitant with marked reduction of transcripts coding the Wilms' tumor 1 gene, matrix metalloproteinase-2, epithelial isoform of CD44, and vascular endothelial growth factor, whereas no apparent modification is detected for transcripts coding the proto-oncogene c-Myc, anti-apoptotic Bcl-2, pro-apoptotic Bax, tissue inhibitor of metalloproteinase TIMP-1, angiogenesis inhibitor TSP-1, and growth factor Midkine. These findings indicate that the molecular mechanism of action of HB-19 on such highly malignant rhabdoid tumor cells is associated with a selective inhibitory effect on the expression of genes implicated in tumorigenesis and angiogenesis. PMID:21040752

  4. Features of the electronic structure of the active center of an HbS molecule

    NASA Astrophysics Data System (ADS)

    Novoselov, D. Yu.; Korotin, Dm. M.; Anisimov, V. I.

    2016-01-01

    Features of the electronic structure of the nonprotein part of the mutant form of the human hemoglobin molecule, HbS, are studied along with the magnetic state of the iron ion that is the "nucleus" of the active center of the molecule. It is found that the mutant form of the HbS molecule differs from a normal hemoglobin molecule by the distortion of the local environment of the iron ion, which changes the energy level splitting by a crystal field. As a result of ab initio calculations, the magnetic transition in the iron atom from the high-spin state to the low-spin state upon the addition of molecular oxygen to hemoglobin molecule is reproduced. It is established for the first time that a change in the crystal and electronic structure of the active center as a result of a mutation can lead to a substantial change in the energy of the bond between the active center of the hemoglobin molecule and an oxygen molecule.

  5. Quantification of tumour vasculature and hypoxia by immunohistochemical staining and HbO2 saturation measurements.

    PubMed

    Fenton, B M; Paoni, S F; Lee, J; Koch, C J; Lord, E M

    1999-02-01

    Despite the possibility that tumour hypoxia may limit radiotherapeutic response, the underlying mechanisms remain poorly understood. A new methodology has been developed in which information from several sophisticated techniques is combined and analysed at a microregional level. First, tumour oxygen availability is spatially defined by measuring intravascular blood oxygen saturations (HbO2) cryospectrophotometrically in frozen tumour blocks. Second, hypoxic development is quantified in adjacent sections using immunohistochemical detection of a fluorescently conjugated monoclonal antibody (ELK3-51) to a nitroheterocyclic hypoxia marker (EF5), thereby providing information relating to both the oxygen consumption rates and the effective oxygen diffusion distances. Third, a combination of fluorescent (Hoechst 33342 or DiOC7(3)) and immunohistological (PECAM-1/CD31) stains is used to define the anatomical vascular densities and the fraction of blood vessels containing flow. Using a computer-interfaced microscope stage, image analysis software and a 3-CCD colour video camera, multiple images are digitized, combined to form a photo-montage and revisited after each of the three staining protocols. By applying image registration techniques, the spatial distribution of HbO2 saturations is matched to corresponding hypoxic marker intensities in adjacent sections. This permits vascular configuration to be related to oxygen availability and allows the hypoxic marker intensities to be quantitated in situ. PMID:10027314

  6. Xanthochromia of the skull bone associated with HbA1c.

    PubMed

    Schäfer, T; Klintschar, M; Lichtinghagen, R; Plagemann, I; Smith, A; Budde, E; Hagemeier, L

    2016-03-01

    The color of the surface of 105 skull bones (part of the parietal bone) was determined using a portable spectral colorimeter (spectro color(®)). By this means it was possible to characterize the color objectively according to the L*a*b* color system defined by the "International Commission de l'Eclairage" (CIE). Biochemical markers of carbohydrate metabolism, HbA1c from venous blood, and glucose/lactate concentrations from vitreous humor, were also determined, for assessment of the ante-mortem plasma glucose concentration using Traub's sum formula. As biochemical markers for lipid metabolism disorder, cholesterol, triglycerides, high density lipoprotein (HDL), low density lipoprotein (LDL) and very low density lipoprotein (VLDL) were all determined from venous blood. There is a significant correlation of bone yellowing with HbA1c (p<0.001) and age (p<0.001). The literature asserts a significant correlation between diabetic condition and yellowing of the skull bone. Despite efforts to find the substance responsible for the yellowing of the bone in chronic metabolism disorder, no significant correlation was found between bone color and lipoproteins/bone extracted lipid acids. PMID:26799427

  7. Genomic characterization of Pasteurella multocida HB01, a serotype A bovine isolate from China.

    PubMed

    Peng, Zhong; Liang, Wan; Liu, Wenjing; Wu, Bin; Tang, Biao; Tan, Chen; Zhou, Rui; Chen, Huanchun

    2016-04-25

    Pasteurella multocida infects various domestic and feral animals, generally causing clinical disease. To investigate P. multocida disease in cattle, we sequenced the complete genome of P. multocida HB01 (GenBank accession CP006976), a serotype A organism isolated from a cow in China. The genome is composed of a single circular chromosome of 2,416,068 base pairs containing 2212 protein-coding sequences, 6 ribosomal rRNA operons, and 56 tRNA genes. The present study confirms that P. multocida HB01 possesses a more complete metabolic pathway with an intact trichloroacetic acid cycle for anabolism compared with A. pleuropneumoniae and Haemophilus parasuis. This is the first time that this metabolic mechanism of P. multocida has been described. We also identified a full spectrum of genes related to known virulence factors of P. multocida. The differences in virulence factors between strains of different serotypes and origins were also compared. This comprehensive comparative genome analysis will help in further studies of the metabolic pathways, genetic basis of serotype, and virulence of P. multocida. PMID:26827796

  8. Role of curcuminoids in ameliorating oxidative modification in β-thalassemia/Hb E plasma proteome.

    PubMed

    Weeraphan, Churat; Srisomsap, Chantragan; Chokchaichamnankit, Daranee; Subhasitanont, Pantipa; Hatairaktham, Suneerat; Charoensakdi, Ratiya; Panichkul, Narumol; Siritanaratkul, Noppadol; Fucharoen, Suthat; Svasti, Jisnuson; Kalpravidh, Ruchaneekorn W

    2013-03-01

    Thalassemic patients often exhibit high levels of oxidative stress and iron overload, which can lead to hazardous complications. Curcuminoids, extracted from the spice turmeric, are known to have antioxidant and iron-chelating properties and have been proposed as a potential upstream therapy of thalassemia. Here we have applied proteomic techniques to study the protein profile and oxidative damage in the plasma of β-thalassemia/Hb E patients before and after treatment with curcuminoids. In this study, 10 β-thalassemia/Hb E patients were treated with 500 mg curcuminoids daily for 12 months. The plasma protein profile and protein carbonyl content were determined at baseline, 6 and 12 months using two-dimensional fluorescence difference gel electrophoresis and carbonyl immunoblotting, respectively. Other hematological, clinical, and biochemical parameters were also analyzed. Twenty-six spots, identified as coagulation factors and proteins involved in iron homeostasis, showed significantly decreased intensity in thalassemic plasma, compared to those of normal subjects. Treatment with curcuminoids up-regulated the plasma levels of these proteins and reduced their oxidative damage. Serum non-transferrin bound iron, platelet factor-3 like activity, oxidative stress parameters and antioxidant enzymes were also improved after curcuminoids treatment. This study is the first proteomic study of plasma in the thalassemic state and also shows the ameliorating role of curcuminoids towards oxidative stress and iron overload in the plasma proteome. PMID:22818714

  9. Production of monoclonal antibodies for breast cancer by HB8696 hybridoma cells using novel perfusion system.

    PubMed

    Kamthan, Shweta; Gomes, James; Roychoudhury, Pradip K

    2014-10-01

    Perfusion culture using spinfilters have been used for the production of health-care products using mammalian cells culture. However, available spinfilters are either highly prone to clog and/or are disposable and hence affects product formation. To address these problems, a novel non-woven Bombyx mori silk screen based spinfilter module for clog-free extended perfusion culture of hybridoma cells has been designed. The module is versatile in nature and reusable, after autoclaving and replacement of used polymeric membrane. Its application for clog-free extended perfusion culture was demonstrated by comparative perfusion experiments of HB8696 cells with stainless-steel spinfilter. HB8696 cells produce monoclonal antibodies (MAbs) 520C9 active against breast cancer oncoprotein. Silk spinfilter was found to be less prone to clog with cells and debris owing to its negatively charged hydrophobic screen compared to the positively charged hydrophilic stainless-steel spinfilter. Therefore, it provides extended cell growth phase and production phase of up to 56 h and 40 h respectively and 57.4% increase in MAb productivity compared to the stainless-steel spinfilter. The effect of different perfusion rates on MAb production was studied and an optimal MAb productivity of 1.6 g L(-1) day(-1) was achieved. PMID:25152416

  10. Synthesis, Antimalarial, Antileishmanial, Antimicrobial, Cytotoxicity and Methemoglobin (MetHb) Formation Activities of New 8-Quinolinamines

    PubMed Central

    Kaur, Kirandeep; Jain, Meenakshi; Khan, Shabana I.; Jacob, Melissa R.; Tekwani, Babu L.; Jain, Rahul

    2014-01-01

    We report the synthesis, in vitro antiprotozoal (against Plasmodium and Leishmania), antimicrobial, cytotoxicity (Vero and MetHb-producing properties) and in vivo antimalarial activities of two series of 8-quinolinamines. N1-{4-[2-(tert-Butyl)-6-methoxy-8-quinolylamino]pentyl}-(2S/2R)-2-aminosubstitutedamides (21–33) and N1-[4-(4-ethyl-6-methoxy-5-pentyloxy-8-quinolylamino)pentyl]-(2S/2R)-2-aminosubstitutedamides (51–63) were synthesized in six steps from 6-methoxy-8-nitroquinoline and 4-methoxy-2-nitro-5-pentyloxyaniline, respectively. Several analogs displayed promising antimalarial activity in vitro against P. falciparum D6 (chloroquine-sensitive) and W2 (chloroquine-resistant) clones with high selectivity indices vs. mammalian cells. The most promising analogs (21–24) also displayed potent antimalarial activity in vivo in a P. berghei-infected mouse model. Most interestingly, many analogs exhibited promising in vitro antileishmanial activity against L. donovani promastigotes, and antimicrobial activities against a panel of pathogenic bacteria and fungi. Several analogs, notably 21–24, 26–32 and 60, showed less MetHb formation compared to primaquine indicating the potential of these compounds in 8-quinolinamine-based antimalarial drug development. PMID:17084633

  11. A Fetus with Hb Bart's Disease Due to Maternal Uniparental Disomy for Chromosome 16.

    PubMed

    Au, Patrick K C; Kan, Anita S Y; Tang, Mary H Y; Leung, Kwok Y; Chan, Kelvin Y K; Tang, Tommy W F; Lau, Elizabeth T

    2016-01-01

    We here report an unusual case of Hb Bart's (γ4) disease. Thalassemia screening of a couple showed that the wife was an α(0)-thalassemia (α(0)-thal) carrier and her husband's mean corpuscular volume (MCV) was normal. Chorionic villus sampling (CVS) was performed at 13 weeks' gestation for positive Down syndrome screening and chromosomal study of the cultured CVS showed a normal karyotype. Ultrasound examination at 22 weeks' gestation showed fetal cardiomegaly and raised middle cerebral artery peak systolic velocity. Cordocentesis confirmed fetal anemia and showed Hb Bart's disease. Multiplex gap-polymerase chain reaction (gap-PCR) for α-thal deletions on DNA extracted from the CVS showed the presence of a homozygous α(0)-thal - -(SEA) (Southeast Asian) deletion. The husband was found to be a carrier of the α(+)-thal -α(3.7) (rightward) deletion. Non paternity was excluded by fluorescent PCR using short tandem repeat (STR) markers on chromosomes 13, 18 and 21. A de novo terminal deletion of chromosome 16 was excluded by array comparative genomic hybridization (aCGH). Detection of uniparental disomy (UPD), using STR markers on chromosome 16 showed maternal uniparental isodisomy from 16pter to 16p13.2, and uniparental heterodisomy from 16p13.13 to 16qter. PMID:26574185

  12. Radio emission from the supernova remnant G160.9 + 2.6 (HB9)

    NASA Astrophysics Data System (ADS)

    Leahy, D. A.; Roger, R. S.

    1991-03-01

    High-resolution radio observations of the large-angular-diameter SNR HB9 are reported. Data obtained in the 408- and 1420-MHz continuum and in H I using the four 9-m paraboloid antennas of the Dominion Radio Astrophysical Observatory synthesis telescope during 1986-1989 are presented in graphs and grey-scale and contour maps and discussed in detail. It is shown that the emission is dominated by filamentary arcs extending across the SNR, often at locations where filaments are seen in H-alpha but at times displaced inward from the optical filaments. The mean spectral index derived from these observations is alpha = 0.61, with rms deviation 0.08 on scale sizes equal to about 15 percent of the SNR diameter. The distance of the SNR is estimated as 4 kpc or less, and it is suggested that HB9 may be associated with PSR 0458 + 46, at about 1.2 kpc. The H I observations show no evidence of interaction between the SNR and the atomic component of the surrounding gas.

  13. Femtosecond dynamics of decoupled superlattice zones in 4Hb-TaSe2 single crystals

    NASA Astrophysics Data System (ADS)

    Olaoye, O.; Erasmus, N.; Haupt, K.; Schwoerer, H.

    2016-03-01

    Strongly correlated electronic crystal systems marked by temperature-dependent phase transitions often feature an emergence of new structural periodicities, arising from an interplay between modulated electron density and periodic lattice distortion. We investigate the structural evolution of \\sqrt{13}a× \\sqrt{13}a× c superlattice clusters in 4Hb-TaSe2 single crystals on a subpicosecond and atomic resolution via femtosecond electron diffraction (FED). The superlattice clusters comprise of two six-member rings each, related by a rotational symmetry and held in position by Coulombic mode repulsion. The two six-member rings are decoupled into two possible zones, which are further decoupled into respective site-specific satellite reflections in the reciprocal space. Governed by the interlayer interactions and the electron diffraction simulation analysis, FED measurements are used to demonstrate the suppression and dynamics of the decoupled superlattice zones. The simultaneous temporal evolution of the two CDW reflection orders are assigned to the decoupled Raman-active A g and {E}2g soft phonon modes previously reported on an isomorphic crystal structure (4Hb-TaS2). It is found that the charge density wave amplitude mode dominates over the corresponding phase mode.

  14. An extended source of GeV gamma rays coincident with the supernova remnant HB 21

    NASA Astrophysics Data System (ADS)

    Reichardt, Ignasi; Oña-Wilhelmi, Emma De; Rico, Javier; Yang, Rui-zhi

    2012-12-01

    We analyze 3.5 years of public Fermi/LAT data around the position of the supernova remnant HB 21, where four point-like sources from the 2nd Fermi/LAT catalog are located. We determine that the gamma-ray source is produced by a single extended source. We model the observed morphology as a uniform circle. The spectral energy distribution is best described by a curved power law, with a maximum at 413+/-11 MeV. We divide the circle into three regions defined by previously identified shocked molecular clouds, and find that one of the se regions has a softer spectrum. The > 3GeV gamma-ray emission of the soft spectrum region is bow-shaped and coincident with the supernova remnant shell seen at radio wavelengths. We suggest that the gamma-ray emission from HB 21 can be understood as a combination of emission from shocked/illuminated molecular clouds, one of them coincident with the supernova remnant shell itself.

  15. A Lead Angle Control for HB-Type Stepping Motor in the Constant Voltage Range

    NASA Astrophysics Data System (ADS)

    Okumatsu, Yoshihiro; Kawamura, Atsuo

    Stepping motors are generally used as a positioning servo in the OA (Office Automation) and FA (Factory Automation) system because the construction cost is very low and the construction of system is very easy. Since they are generally driven by an open loop controller, the response of stepping motors is oscillatory and it is possible to be out of drive. Therefore they are driven by a closed loop controller in the special system, which requires the high reliability and stability. The lead angle control is used as a closed loop controller of stepping motors because an applied voltage amplitude is not able to be controlled. However a closed loop control of stepping motors is hardly used at present. This paper presents the lead angle control based on the vector control in the constant voltage drive range for 2 phases HB type stepping motors. In the constant voltage range, since the HB type stepping motor is modeled as a surface permanent magnet motor, the motor torque is controlled by the q-axis current. The d-axis current is calculated by the voltage limit condition because of the constant voltage amplitude operation. The control performances are examined by the simulations and experimental results.

  16. An extended source of GeV gamma rays coincident with the supernova remnant HB 21

    NASA Astrophysics Data System (ADS)

    Reichardt, I.; de Oña-Wilhelmi, E.; Rico, J.; Yang, R.

    2012-10-01

    We analyze 3.5 years of public Fermi/LAT data around the position of the supernova remnant HB 21, where four point-like sources from the 2nd Fermi/LAT catalog are located. We determine that the gamma-ray source is produced by a single extended source. We model the observed morphology as a uniform circle. The spectral energy distribution is best described by a curved power law, with a maximum at 413 ± 11 MeV. We divide the circle into three regions defined by previously identified shocked molecular clouds, and find that one of these regions has a softer spectrum. The >3 GeV gamma-ray emission of the soft spectrum region is bow-shaped and coincident with the supernova remnant shell seen at radio wavelengths. We suggest that the gamma-ray emission from HB 21 can be understood as a combination of emission from shocked/illuminated molecular clouds, one of them coincident with the supernova remnant shell itself.

  17. First Observation of the Hadronic Transition ϒ (4 S )→η hb(1 P ) and New Measurement of the hb(1 P ) and ηb(1 S ) Parameters

    NASA Astrophysics Data System (ADS)

    Tamponi, U.; Mussa, R.; Abdesselam, A.; Aihara, H.; Arinstein, K.; Asner, D. M.; Atmacan, H.; Aushev, T.; Ayad, R.; Badhrees, I.; Bakich, A. M.; Barberio, E.; Bhardwaj, V.; Bhuyan, B.; Biswal, J.; Bondar, A.; Bonvicini, G.; Bozek, A.; Bračko, M.; Browder, T. E.; Červenkov, D.; Chen, A.; Cheon, B. G.; Cho, K.; Chobanova, V.; Choi, S.-K.; Choi, Y.; Cinabro, D.; Danilov, M.; Doležal, Z.; Drásal, Z.; Drutskoy, A.; Eidelman, S.; Epifanov, D.; Farhat, H.; Fast, J. E.; Ferber, T.; Fulsom, B. G.; Gaur, V.; Gabyshev, N.; Garmash, A.; Getzkow, D.; Gillard, R.; Goh, Y. M.; Golob, B.; Haba, J.; Hayasaka, K.; Hayashii, H.; He, X. H.; Hedges, M. T.; Hou, W.-S.; Iijima, T.; Inami, K.; Ishikawa, A.; Jaegle, I.; Joffe, D.; Julius, T.; Kato, E.; Katrenko, P.; Kichimi, H.; Kiesling, C.; Kim, D. Y.; Kim, H. J.; Kim, J. H.; Kim, K. T.; Kim, S. H.; Kinoshita, K.; Kodyš, P.; Korpar, S.; Križan, P.; Krokovny, P.; Kumita, T.; Kuzmin, A.; Lange, J. S.; Lewis, P.; Libby, J.; Lukin, P.; Matvienko, D.; Miyabayashi, K.; Miyata, H.; Mizuk, R.; Mohanty, G. B.; Moll, A.; Mori, T.; Nakano, E.; Nakao, M.; Nanut, T.; Natkaniec, Z.; Nayak, M.; Nisar, N. K.; Nishida, S.; Ogawa, S.; Okuno, S.; Olsen, S. L.; Ostrowicz, W.; Oswald, C.; Pakhlova, G.; Pal, B.; Park, H.; Pedlar, T. K.; Pesántez, L.; Pestotnik, R.; Petrič, M.; Piilonen, L. E.; Ribežl, E.; Ritter, M.; Rostomyan, A.; Ryu, S.; Sakai, Y.; Sandilya, S.; Santelj, L.; Sanuki, T.; Sato, Y.; Savinov, V.; Schneider, O.; Schnell, G.; Schwanda, C.; Semmler, D.; Senyo, K.; Sevior, M. E.; Shapkin, M.; Shebalin, V.; Shen, C. P.; Shibata, T.-A.; Shiu, J.-G.; Shwartz, B.; Sibidanov, A.; Simon, F.; Sohn, Y.-S.; Sokolov, A.; Starič, M.; Steder, M.; Stypula, J.; Tanida, K.; Teramoto, Y.; Trabelsi, K.; Uchida, M.; Uglov, T.; Unno, Y.; Uno, S.; Urquijo, P.; Van Hulse, C.; Vanhoefer, P.; Varner, G.; Vinokurova, A.; Vossen, A.; Wagner, M. N.; Wang, M.-Z.; Wang, X. L.; Watanabe, Y.; Williams, K. M.; Won, E.; Yamaoka, J.; Yashchenko, S.; Zhang, Z. P.; Zhilich, V.; Zhulanov, V.; Zupanc, A.; Belle Collaboration

    2015-10-01

    Using a sample of 771.6 ×106 ϒ ϒ (4 S ) decays collected by the Belle experiment at the KEKB e+e- collider, we observe, for the first time, the transition ϒ (4 S )→η hb(1 P ) with the branching fraction B [ϒ (4 S )→η hb(1 P )]=(2.18 ±0.11 ±0.18 )×10-3 and we measure the hb(1 P ) mass Mhb(1P )=(9899.3 ±0.4 ±1.0 ) MeV /c2 , corresponding to the hyperfine (HF) splitting Δ MHF(1 P )=(0.6 ±0.4 ±1.0 ) MeV /c2 . Using the transition hb(1 P )→γ ηb(1 S ), we measure the ηb(1 S ) mass Mηb(1S )=(9400.7 ±1.7 ±1.6 ) MeV /c2 , corresponding to Δ MHF(1 S )=(59.6 ±1.7 ±1.6 ) MeV /c2 , the ηb(1 S ) width Γηb(1S )=(8-5+6±5 ) MeV /c2 and the branching fraction B [hb(1 P )→γ ηb(1 S )]=(56 ±8 ±4 )%.

  18. Comparison of the Current Diagnostic Criterion of HbA1c with Fasting and 2-Hour Plasma Glucose Concentration

    PubMed Central

    Karnchanasorn, Rudruidee; Huang, Jean; Feng, Wei; Chuang, Lee-Ming

    2016-01-01

    To determine the effectiveness of hemoglobin A1c (HbA1c) ≥ 6.5% in diagnosing diabetes compared to fasting plasma glucose (FPG) ≥ 126 mg/dL and 2-hour plasma glucose (2hPG) ≥ 200 mg/dL in a previously undiagnosed diabetic cohort, we included 5,764 adult subjects without established diabetes for whom HbA1c, FPG, 2hPG, and BMI measurements were collected. Compared to the FPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 43.3% (106 subjects). Compared to the 2hPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 28.1% (110 subjects). Patients who were diabetic using 2hPG criterion but had HbA1c < 6.5% were more likely to be older (64 ± 15 versus 60 ± 15 years old, P = 0.01, mean ± STD), female (53.2% versus 38.2%, P = 0.008), leaner (29.7 ± 6.1 versus 33.0 ± 6.6 kg/m2, P = 0.000005), and less likely to be current smokers (18.1% versus 29.1%, P = 0.02) as compared to those with HbA1c ≥ 6.5%. The diagnostic agreement in the clinical setting revealed the current HbA1c ≥ 6.5% is less likely to detect diabetes than those defined by FPG and 2hPG. HbA1c ≥ 6.5% detects less than 50% of diabetic patients defined by FPG and less than 30% of diabetic patients defined by 2hPG. When the diagnosis of diabetes is in doubt by HbA1c, FPG and/or 2hPG should be obtained. PMID:27597979

  19. Comparison of the Current Diagnostic Criterion of HbA1c with Fasting and 2-Hour Plasma Glucose Concentration.

    PubMed

    Karnchanasorn, Rudruidee; Huang, Jean; Ou, Horng-Yih; Feng, Wei; Chuang, Lee-Ming; Chiu, Ken C; Samoa, Raynald

    2016-01-01

    To determine the effectiveness of hemoglobin A1c (HbA1c) ≥ 6.5% in diagnosing diabetes compared to fasting plasma glucose (FPG) ≥ 126 mg/dL and 2-hour plasma glucose (2hPG) ≥ 200 mg/dL in a previously undiagnosed diabetic cohort, we included 5,764 adult subjects without established diabetes for whom HbA1c, FPG, 2hPG, and BMI measurements were collected. Compared to the FPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 43.3% (106 subjects). Compared to the 2hPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 28.1% (110 subjects). Patients who were diabetic using 2hPG criterion but had HbA1c < 6.5% were more likely to be older (64 ± 15 versus 60 ± 15 years old, P = 0.01, mean ± STD), female (53.2% versus 38.2%, P = 0.008), leaner (29.7 ± 6.1 versus 33.0 ± 6.6 kg/m(2), P = 0.000005), and less likely to be current smokers (18.1% versus 29.1%, P = 0.02) as compared to those with HbA1c ≥ 6.5%. The diagnostic agreement in the clinical setting revealed the current HbA1c ≥ 6.5% is less likely to detect diabetes than those defined by FPG and 2hPG. HbA1c ≥ 6.5% detects less than 50% of diabetic patients defined by FPG and less than 30% of diabetic patients defined by 2hPG. When the diagnosis of diabetes is in doubt by HbA1c, FPG and/or 2hPG should be obtained. PMID:27597979

  20. The correlation between the Glycated hemoglobin (HbA1c) in non-diabetics and cardiovascular risk factors.

    PubMed

    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 P<0.05. Hypertension, dyslipidemi, being overweight or obesity, age (male was over 45 years old and female was over 55 years old.), HbA1c 6.0% and fasting blood glucose (FBG) 6.1mmol/L were regarded as cardiovascular risk 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 (P<0.001) between groups. (3) The Regression analysis showed that there was a stronger correlation between HbA1c levels and impaired glucose tolerance (IGT), fasting blood glucose (FBG) rather than age. So Non-diabetics whose HbA1c levels ranged from 6.0% to 6.5% were at high risk of cardiovascular risk 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). PMID:27005508

  1. Relationship between HbA1c and Continuous Glucose Monitoring in Chinese Population: A Multicenter Study

    PubMed Central

    Li, Hong; Ran, Xingwu; Yang, Wenying; Li, Qiang; Peng, Yongde; Li, Yanbing; Gao, Xin; Luan, Xiaojun; Wang, Weiqing; Xie, Yun; Jia, Weiping

    2013-01-01

    Objective Since there is a paucity of reference data in the literature to indicate the relationship between HbA1c, and 24 h mean blood glucose (MBG) from continuous glucose monitoring (CGM) in Chinese populations, we described the above relationship in adult Chinese subjects with different glucose tolerance status. Methods Seven-hundred-and-forty-two individuals without history of diabetes were included to the study at 11 hospitals in urban areas across China from 2007–2009 and data of 673 subjects were included into the final analysis. Oral glucose tolerance test (OGTT) classified the participants as nondiabetic subjects, including those with normal glucose regulation (NGR; n = 121) and impaired glucose regulation (IGR; n = 209), or newly diagnosed type 2 diabetes (n = 343). All participants completed testing for HbA1c levels and wore a CGM system for three consecutive days. The 24 h MBG levels were calculated. Spearman correlations and linear regression analyses were applied to quantify the relationship between glucose markers. Results The levels of HbA1c and 24 h MBG significantly increased with presence of glucose intolerance (NGRHbA1c was strongly correlated with 24 h MBG (r = 0.735). The correlation was also found to be significant for the subgroup of participants with newly diagnosed type 2 diabetes (r = 0.694, P<0.001). Linear regression analysis of the total study population yielded the following equation: 24 h MBG mmol/L = 1.198×HbA1c–0.582 (24 h MBG mg/dL = 21.564×HbA1c–10.476) (R2 = 0.670, P<0.001). The model fit was not improved by application of exponential or quadratic modeling. When HbA1c was 6.5%, the calculated 24 h MBG was 7.2 (6.4–8.1) mmol/L (130 (115–146) mg/dL); and when HbA1c was 7.0%, the 24 h MBG was 7.8 (6.9–8.7) mmol/L (140 (124–157) mg/dL). Conclusions Our study provided the reference data of the

  2. Establishment of transgenic mice carrying the gene of human nuclear receptor NR5A2 (hB1F)

    PubMed Central

    Wang, Shui-Liang; Yang, Hua; Xie, You-Hua; Wang, Yuan; Li, Jian-Zhong; Wang, Long; Wang, Zhu-Gang; Fu, Ji-Liang

    2003-01-01

    AIM: Human hepatitis B virus enhancer II B1 binding factor (hB1F) was cloned and characterized as a novel member of the Ftz-F1 (NR5A) nuclear receptor subfamily. Although progresses have recently been made, its biological function remains largely unidentified. The aim of this study was to establish an hB1F transgenic mouse model to promote the functional study of hB1F. METHODS: Transgene fragments were microinjected into fertilized eggs of mice. The manipulated embryos were transferred into the oviducts of pseudopregnant female mice. The offsprings were identified by PCR and Southern blot analysis. Transgene expression was analyzed with RT-PCR and Western blot analysis. Transgenic founder mice were used to establish transgenic mouse lineages. The F1 and F2 mice were identified by PCR analysis. RESULTS: Seven mice were identified as carrying copies of transgene. RT-PCR and Western blotting results showed that the transgene was expressed in heart, liver, lung, kidney and stomach in one of the transgenic mouse lineages. Genetic analysis of the transgenic mice demonstrated that the transgene was integrated into the chromosome at a single site, and was transmitted stably. CONCLUSION: In this study we established an hB1F transgenic mouse model, which will facilitate the investigation of the biological function of hB1F in vivo. PMID:12800251

  3. Full-Length cDNA, Prokaryotic Expression, and Antimicrobial Activity of UuHb-F-I from Urechis unicinctus

    PubMed Central

    Niu, Rongli; Chen, Xiang

    2016-01-01

    Hemoglobin, which widely exists in all vertebrates and in some invertebrates, is possibly a precursor of antimicrobial peptides (AMPs). However, AMPs in the hemoglobin of invertebrates have been rarely investigated. This study is the first to report the full-length cDNA, prokaryotic expression, and antimicrobial activity of UuHb-F-I from Urechis unicinctus. The full-length cDNA sequence of UuHb-F-I was 780 bp with an open-reading frame of 429 bp encoding 142 amino acids. MALDI-TOF-MS suggested that the recombinant protein of UuHb-F-I (rUuHb-F-I) yielded a molecular weight of 15,168.01 Da, and its N-terminal amino acid sequence was MGLTGAQIDAIK. rUuHb-F-I exhibited different antimicrobial activities against microorganisms. The lowest minimum inhibitory concentration against Micrococcus luteus was 2.78–4.63 μM. Our results may help elucidate the immune defense mechanism of U. unicinctus and may provide insights into new AMPs in drug discovery. PMID:27471730

  4. Full-Length cDNA, Prokaryotic Expression, and Antimicrobial Activity of UuHb-F-I from Urechis unicinctus.

    PubMed

    Niu, Rongli; Chen, Xiang

    2016-01-01

    Hemoglobin, which widely exists in all vertebrates and in some invertebrates, is possibly a precursor of antimicrobial peptides (AMPs). However, AMPs in the hemoglobin of invertebrates have been rarely investigated. This study is the first to report the full-length cDNA, prokaryotic expression, and antimicrobial activity of UuHb-F-I from Urechis unicinctus. The full-length cDNA sequence of UuHb-F-I was 780 bp with an open-reading frame of 429 bp encoding 142 amino acids. MALDI-TOF-MS suggested that the recombinant protein of UuHb-F-I (rUuHb-F-I) yielded a molecular weight of 15,168.01 Da, and its N-terminal amino acid sequence was MGLTGAQIDAIK. rUuHb-F-I exhibited different antimicrobial activities against microorganisms. The lowest minimum inhibitory concentration against Micrococcus luteus was 2.78-4.63 μM. Our results may help elucidate the immune defense mechanism of U. unicinctus and may provide insights into new AMPs in drug discovery. PMID:27471730

  5. The sunflower transcription factor HaHB11 improves yield, biomass and tolerance to flooding in transgenic Arabidopsis plants.

    PubMed

    Cabello, Julieta V; Giacomelli, Jorge I; Piattoni, Claudia V; Iglesias, Alberto A; Chan, Raquel L

    2016-03-20

    HaHB11 is a member of the sunflower homeodomain-leucine zipper I subfamily of transcription factors. The analysis of a sunflower microarray hybridized with RNA from HaHB11-transformed leaf-disks indicated the regulation of many genes encoding enzymes from glycolisis and fermentative pathways. A 1300bp promoter sequence, fused to the GUS reporter gene, was used to transform Arabidopsis plants showing an induction of expression after flooding treatments, concurrently with HaHB11 regulation by submergence in sunflower. Arabidopsis transgenic plants expressing HaHB11 under the control of the CaMV 35S promoter and its own promoter were obtained and these plants exhibited significant increases in rosette and stem biomass. All the lines produced more seeds than controls and particularly, those of high expression level doubled seeds yield. Transgenic plants also showed tolerance to flooding stress, both to submergence and waterlogging. Carbohydrates contents were higher in the transgenics compared to wild type and decreased less after submergence treatments. Finally, transcript levels of selected genes involved in glycolisis and fermentative pathways as well as the corresponding enzymatic activities were assessed both, in sunflower and transgenic Arabidopsis plants, before and after submergence. Altogether, the present work leads us to propose HaHB11 as a biotechnological tool to improve crops yield, biomass and flooding tolerance. PMID:26876611

  6. CAPABILITY TO RECOVER PLUTONIUM-238 IN H-CANYON/HB-LINE

    SciTech Connect

    Fuller, Kenneth S. Jr.; Smith, Robert H. Jr.; Goergen, Charles R.

    2013-01-09

    Plutonium-238 is used in Radioisotope Thermoelectric Generators (RTGs) to generate electrical power and in Radioisotope Heater Units (RHUs) to produce heat for electronics and environmental control for deep space missions. The domestic supply of Pu-238 consists of scrap material from previous mission production or material purchased from Russia. Currently, the United States has no significant production scale operational capability to produce and separate new Pu-238 from irradiated neptunium-237 targets. The Department of Energy - Nuclear Energy is currently evaluating and developing plans to reconstitute the United States capability to produce Pu-238 from irradiated Np-237 targets. The Savannah River Site had previously produced and/or processed all the Pu-238 utilized in Radioisotope Thermoelectric Generators (RTGs) for deep space missions up to and including the majority of the plutonium for the Cassini Mission. The previous full production cycle capabilities included: Np-237 target fabrication, target irradiation, target dissolution and Np-237 and Pu-238 separation and purification, conversion of Np-237 and Pu-238 to oxide, scrap recovery, and Pu-238 encapsulation. The capability and equipment still exist and could be revitalized or put back into service to recover and purify Pu-238/Np-237 or broken General Purpose Heat Source (GPHS) pellets utilizing existing process equipment in HB-Line Scrap Recovery, and H-anyon Frame Waste Recovery processes. The conversion of Np-237 and Pu-238 to oxide can be performed in the existing HB-Line Phase-2 and Phase-3 Processes. Dissolution of irradiated Np-237 target material, and separation and purification of Np-237 and Pu-238 product streams would be possible at production rates of ~ 2 kg/month of Pu-238 if the existing H-Canyon Frames Process spare equipment were re-installed. Previously, the primary H-Canyon Frames equipment was removed to be replaced: however, the replacement project was stopped. The spare equipment is

  7. Capability to Recover Plutonium-238 in H-Canyon/HB-Line - 13248

    SciTech Connect

    Fuller, Kenneth S. Jr.; Smith, Robert H. Jr.; Goergen, Charles R.

    2013-07-01

    Plutonium-238 is used in Radioisotope Thermoelectric Generators (RTGs) to generate electrical power and in Radioisotope Heater Units (RHUs) to produce heat for electronics and environmental control for deep space missions. The domestic supply of Pu-238 consists of scrap material from previous mission production or material purchased from Russia. Currently, the United States has no significant production scale operational capability to produce and separate new Pu-238 from irradiated neptunium-237 targets. The Department of Energy - Nuclear Energy is currently evaluating and developing plans to reconstitute the United States capability to produce Pu-238 from irradiated Np-237 targets. The Savannah River Site had previously produced and/or processed all the Pu-238 utilized in Radioisotope Thermoelectric Generators (RTGs) for deep space missions up to and including the majority of the plutonium for the Cassini Mission. The previous full production cycle capabilities included: Np- 237 target fabrication, target irradiation, target dissolution and Np-237 and Pu-238 separation and purification, conversion of Np-237 and Pu-238 to oxide, scrap recovery, and Pu-238 encapsulation. The capability and equipment still exist and could be revitalized or put back into service to recover and purify Pu-238/Np-237 or broken General Purpose Heat Source (GPHS) pellets utilizing existing process equipment in HB-Line Scrap Recovery, and H-Canyon Frame Waste Recovery processes. The conversion of Np-237 and Pu-238 to oxide can be performed in the existing HB-Line Phase-2 and Phase- 3 Processes. Dissolution of irradiated Np-237 target material, and separation and purification of Np-237 and Pu-238 product streams would be possible at production rates of ∼2 kg/month of Pu-238 if the existing H-Canyon Frames Process spare equipment were re-installed. Previously, the primary H-Canyon Frames equipment was removed to be replaced: however, the replacement project was stopped. The spare equipment

  8. Growth of InGaAlP HB-LEDs in a large-scale-production reactor

    NASA Astrophysics Data System (ADS)

    Li, Sherman; Collins, D. A.; Vatanapradit, S.; Ferreira, M.; Zawadzki, Peter A.; Stall, Richard A.; Eliashevich, Ivan; Nering, J. E.

    1999-04-01

    The theory, structure, and current manufacturing technologies for InGaAlP high brightness light emitting diodes (HB-LED) emitting in the range of 650 to 585 nm are described in this paper. A state-of-the-art HB-LED MOCVD reactor designed for high volume manufacturing (42 - 2' or 16 - 3' wafers) is demonstrated. Data for thickness and compositional uniformity and reproducibility are presented showing the material quality and reactor stability that can currently be achieved. In addition, device data for InGaAlP HB-LEDs is reported, including brightness, forward voltage, and emission wavelength with excellent intra and inter wafer uniformity and run-to-run reproducibility.

  9. Catalysis of Dioxygen Reduction by Thermus thermophilus Strain HB27 Laccase on Ketjen Black Electrodes

    PubMed Central

    Agbo, Peter; Heath, James R.

    2012-01-01

    We present electrochemical analyses of the catalysis of dioxygen reduction by Thermus thermophilus strain HB27 laccase on ketjen black substrates. Our cathodes reliably produce 0.56 mA cm−2 at 0.0 V vs. Ag|AgCl reference at 30 °C in air-saturated buffer, under conditions of non-limiting O2 flux. We report the electrochemical activity of this laccase as a function of temperature, pH, time, and the efficiency of its conversion of dioxygen to water. We have measured the surface concentration of electrochemically active species, permitting the extraction of electron transfer rates at the enzyme-electrode interface: 1 s−1 for this process at zero driving force at 30 °C and a limiting rate of 23 s−1 at 240 mV overpotential at 50 °C. PMID:23163614

  10. Current meter data report, September 1980 - December 1980: mooring OTEC-HB

    SciTech Connect

    Roman, T M; Wang, D P

    1981-03-01

    Data tapes contained current meter records from instrumented mooring OTEC-HB near the OTEC-1 site approximately 14 nautical miles northwest of Keahole Point, Island of Hawaii. Deployed in 1345 m of water, the mooring had five Aanderaa RCM-5 current meters, one at each of the following depths: 47 m, 70m, 99m, 154m, and 829 m. Raw data consisted of east-west (U) velocity, north-south (V) velocity, temperature (T), and pressure (P) time series from September 23, 1980, through December 20, 1980, with a recording interval of 15 min. The series (U, V, T) were filtered into various frequency domains, thereby removing very high frequencies and separating tidal oscillations from very low frequencies. Spectral analyses were performed on the nontidal U and V time series.

  11. Quality of HbA1c Measurement in the Practice: The German Perspective.

    PubMed

    Heinemann, Lutz; Freckmann, Guido

    2015-05-01

    Hemoglobin A1c (HbA1c) measurement has come to be a cornerstone in modern diabetes therapy. However, the methodological aspects of this type of measurement have been given little attention lately due to its position as an established method of choice. Nevertheless, quite a number of issues face practical application, such as clinically relevant differences between different measurement methods--both lab-based and point-of-care (POCT) systems will show better or worse diabetes management results after switching methods; and there are a number of possible reasons that need to be known and observed in practice. The aim of this review is to draw attention to these problems from a German point of view and provide suggestions for appropriate measures to improve the situation. PMID:25691655

  12. Quality of HbA1c Measurement in the Practice

    PubMed Central

    Freckmann, Guido

    2015-01-01

    Hemoglobin A1c (HbA1c) measurement has come to be a cornerstone in modern diabetes therapy. However, the methodological aspects of this type of measurement have been given little attention lately due to its position as an established method of choice. Nevertheless, quite a number of issues face practical application, such as clinically relevant differences between different measurement methods—both lab-based and point-of-care (POCT) systems will show better or worse diabetes management results after switching methods; and there are a number of possible reasons that need to be known and observed in practice. The aim of this review is to draw attention to these problems from a German point of view and provide suggestions for appropriate measures to improve the situation. PMID:25691655

  13. Neutral hydrogen in the vicinity of the supernova remnant HB 9

    NASA Astrophysics Data System (ADS)

    Gosachinskii, I. V.

    2013-03-01

    The neutral hydrogen emission at 21 cm has been investigated with the RATAN-600 radio telescope in the vicinity of the supernova remnant HB9. A clumpyHI shell with radial motions surrounding the remnant has been detected. Its measured parameters contradict the connection with a shock wave from a supernova explosion. The shell formation under the action of a wind from a star that exploded as a supernova at the end of its evolution seems more realistic. The characteristics of the star obtained from the observed shell parameters are the following: a wind power of 0.5 × 1038 erg s-1, a mass-loss rate of 3.7 × 10-5 M ⊙ yr-1, and an age of 3 × 106 yr. Given the measurement errors, the mass of the star is estimated to be >8 M ⊙.

  14. Multiplexing of electronically scanned white-light interferometric strain sensors based on HB fibers

    NASA Astrophysics Data System (ADS)

    Urbanczyk, Waclaw; Bock, Wojtek J.; Zaremba, Marek B.

    1993-12-01

    Application of electronic scanning to a sequence of coherence-multiplexed strain sensors is proposed in this paper. The sensors consist of a cascade of HB fibers spliced with their polarization axes rotated by certain angles. We theoretically analyzed the behavior of such chains as a function of their alignment and found the optimal alignment ensuring readout of every sensor with the maximum S/N ratio. The performance of parallel and serial multiplexing configurations was experimentally studied. As a receiving interferometer we used a Wollaston prism followed by a CCD camera and an image processing system while a stepped delay line made of calcite and crystalline quartz was used to match the group delays between sensing and receiving interferometers.

  15. Best use of the recommended IFCC reference method, material and values in HbA1C analyses.

    PubMed

    Penttilä, I M; Halonen, T; Punnonen, K; Tiikkainen, U

    2005-01-01

    The results of Finnish HbA(1C) surveys (Labquality Ltd.) during the past 10 years have undergone continuous improvement with smaller overall coefficients of variation for the HbA(1C) mean values of all methods (from 7.5 to 5.4% for normal and from 8.9 to 4.7% for diabetic samples). Most of the HbA(1C) methods are certified for traceability to the Diabetes Control and Complication Trial (DCCT) designated comparison method, which originally was a high-performance liquid chromatography (HPLC) method (Bio-Rex 70, Bio-Rad) but is no longer in routine use. It was therefore important that the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) had prepared both reference preparations and method for the determination of HbA(1C). However, the very demanding reference method is not realistic for use in clinical laboratories. According to the present study, the mean HbA(1C) values of the Labquality Ltd. showed significant correlations to the HbA(1C) values of The European Reference Laboratory for Glycohemoglobin (r = 0.999) and to the values using the IFCC method (r = 0.999). The reference values of the IFCC method (mainly those of the manufacturer) range from 2.85 to 3.81%, being significantly lower than the present DCCT values (4.0-6.1%). Since it may take some time before consumers are ready to accept the new IFCC reference values for general use, we propose that the IFCC reference materials and method should be used for calibration of the present methods to the well-known DCCT levels. PMID:16179278

  16. Co-inheritance of compound heterozygous Hb Constant Spring and a single -alpha(3.7) gene deletion with heterozygous deltabeta thalassaemia: a diagnostic challenge.

    PubMed

    Azma, Raja Zahratul; Othman, Ainoon; Azman, Norazlina; Alauddin, Hafiza; Ithnin, Azlin; Yusof, Nurasyikin; Razak, Noor Farisah; Sardi, Nor Hidayati; Hussin, Noor Hamidah

    2012-06-01

    Haemoglobin Constant Spring (Hb CS) mutation and single gene deletions are common underlying genetic abnormalities for alpha thalassaemias. Co-inheritance of deletional and non-deletional alpha (alpha) thalassaemias may result in various thalassaemia syndromes. Concomitant co-inheritance with beta (beta) and delta (delta) gene abnormalities would result in improved clinical phenotype. We report here a 33-year-old male patient who was admitted with dengue haemorrhagic fever, with a background history of Grave's disease, incidentally noted to have mild hypochromic microcytic red cell indices. Physical examination revealed no thalassaemic features or hepatosplenomegaly. His full blood picture showed hypochromic microcytic red cells with normal haemoglobin (Hb) level. Quantitation of Hb using high performance liquid chromatography (HPLC) and capillary electrophoresis (CE) revealed raised Hb F, normal Hb A2 and Hb A levels. There was also small peak of Hb CS noted in CE. H inclusions was negative. Kleihauer test was positive with heterocellular distribution of Hb F among the red cells. DNA analysis for alpha globin gene mutations showed a single -alpha(-3.7) deletion and Hb CS mutation. These findings were suggestive of compound heterozygosity of Hb CS and a single -alpha(-3.7) deletion with a concomitant heterozygous deltabeta thalassaemia. Co-inheritance of Hb CS and a single -alpha(-3.7) deletion is expected to result at the very least in a clinical phenotype similar to that of two alpha genes deletion. However we demonstrate here a phenotypic modification of alpha thalassemia presumptively as a result of co-inheritance with deltabeta chain abnormality as suggested by the high Hb F level. PMID:22870600

  17. HB-LINE ANION EXCHANGE PURIFICATION OF AFS-2 PLUTONIUM FOR MOX

    SciTech Connect

    Kyser, E.; King, W.

    2012-04-25

    Non-radioactive cerium (Ce) and radioactive plutonium (Pu) anion exchange column experiments using scaled HB-Line designs were performed to investigate the feasibility of using either gadolinium nitrate (Gd) or boric acid (B as H{sub 3}BO{sub 3}) as a neutron poison in the H-Canyon dissolution process. Expected typical concentrations of probable impurities were tested and the removal of these impurities by a decontamination wash was measured. Impurity concentrations are compared to two specifications - designated as Column A or Column B (most restrictive) - proposed for plutonium oxide (PuO{sub 2}) product shipped to the Mixed Oxide (MOX) Fuel Fabrication Facility (MFFF). Use of Gd as a neutron poison requires a larger volume of wash for the proposed Column A specification. Since boron (B) has a higher proposed specification and is more easily removed by washing, it appears to be the better candidate for use in the H-Canyon dissolution process. Some difficulty was observed in achieving the Column A specification due to the limited effectiveness that the wash step has in removing the residual B after {approx}4 BV's wash. However a combination of the experimental 10 BV's wash results and a calculated DF from the oxalate precipitation process yields an overall DF sufficient to meet the Column A specification. For those impurities (other than B) not removed by 10 BV's of wash, the impurity is either not expected to be present in the feedstock or process, or recommendations have been provided for improvement in the analytical detection/method or validation of calculated results. In summary, boron is recommended as the appropriate neutron poison for H-Canyon dissolution and impurities are expected to meet the Column A specification limits for oxide production in HB-Line.

  18. HB-LINE ANION EXCHANGE PURIFICATION OF AFS-2 PLUTONIUM FOR MOX

    SciTech Connect

    Kyser, E. A.; King, W. D.

    2012-07-31

    Non-radioactive cerium (Ce) and radioactive plutonium (Pu) anion exchange column experiments using scaled HB-Line designs were performed to investigate the feasibility of using either gadolinium nitrate (Gd) or boric acid (B as H{sub 3}BO{sub 3}) as a neutron poison in the H-Canyon dissolution process. Expected typical concentrations of probable impurities were tested and the removal of these impurities by a decontamination wash was measured. Impurity concentrations are compared to two specifications - designated as Column A or Column B (most restrictive) - proposed for plutonium oxide (PuO{sub 2}) product shipped to the Mixed Oxide (MOX) Fuel Fabrication Facility (MFFF). Use of Gd as a neutron poison requires a larger volume of wash for the proposed Column A specification. Since boron (B) has a higher proposed specification and is more easily removed by washing, it appears to be the better candidate for use in the H-Canyon dissolution process. Some difficulty was observed in achieving the Column A specification due to the limited effectiveness that the wash step has in removing the residual B after ~4 BV's wash. However a combination of the experimental 10 BV's wash results and a calculated DF from the oxalate precipitation process yields an overall DF sufficient to meet the Column A specification. For those impurities (other than B) not removed by 10 BV's of wash, the impurity is either not expected to be present in the feedstock or process, or recommendations have been provided for improvement in the analytical detection/method or validation of calculated results. In summary, boron is recommended as the appropriate neutron poison for H-Canyon dissolution and impurities are expected to meet the Column A specification limits for oxide production in HB-Line.

  19. Structure of 3-oxoacyl-(acyl-carrier protein) synthase II from Thermus thermophilus HB8

    SciTech Connect

    Bagautdinov, Bagautdin Ukita, Yoko; Miyano, Masashi; Kunishima, Naoki

    2008-05-01

    The crystal structure of 3-oxoacyl-(acyl-carrier protein) synthase II from T. thermophilus HB8 has been determined at 2.0 Å resolution and compared with the structures of β-keto-ACP synthases from other sources. The β-ketoacyl-(acyl carrier protein) synthases (β-keto-ACP synthases; KAS) catalyse the addition of two-carbon units to the growing acyl chain during the elongation phase of fatty-acid synthesis. As key regulators of bacterial fatty-acid synthesis, they are promising targets for the development of new antibacterial agents. The crystal structure of 3-oxoacyl-ACP synthase II from Thermus thermophilus HB8 (TtKAS II) has been solved by molecular replacement and refined at 2.0 Å resolution. The crystal is orthorhombic, space group P2{sub 1}2{sub 1}2, with unit-cell parameters a = 72.07, b = 185.57, c = 62.52 Å, and contains one homodimer in the asymmetric unit. The subunits adopt the well known α-β-α-β-α thiolase fold that is common to ACP synthases. The structural and sequence similarities of TtKAS II to KAS I and KAS II enzymes of known structure from other sources support the hypothesis of comparable enzymatic activity. The dimeric state of TtKAS II is important to create each fatty-acid-binding pocket. Closer examination of KAS structures reveals that compared with other KAS structures in the apo form, the active site of TtKAS II is more accessible because of the ‘open’ conformation of the Phe396 side chain.

  20. The Haber Bosch-harmful algal bloom (HB-HAB) link

    NASA Astrophysics Data System (ADS)

    Glibert, Patricia M.; Maranger, Roxane; Sobota, Daniel J.; Bouwman, Lex

    2014-10-01

    Large-scale commercialization of the Haber-Bosch (HB) process is resulting in intensification of nitrogen (N) fertilizer use worldwide. Globally N fertilizer use is far outpacing that of phosphorus (P) fertilizer. Much of the increase in N fertilizers is also now in the form of urea, a reduced form of N. Incorporation of these fertilizers into agricultural products is inefficient leading to significant environmental pollution and aquatic eutrophication. Of particular concern is the increased occurrence of harmful algal blooms (HABs) in waters receiving nutrient enriched runoff. Many phytoplankton causing HABs have physiological adaptive strategies that make them favored under conditions of elevated N : P conditions and supply of chemically reduced N (ammonium, urea). We propose that the HB-HAB link is a function of (1) the inefficiency of incorporation of N fertilizers in the food supply chain, the leakiness of the N cycle from crop to table, and the fate of lost N relative to P to the environment; and (2) adaptive physiology of many HABs to thrive in environments in which there is excess N relative to classic nutrient stoichiometric proportions and where chemically reduced forms of N dominate. The rate of HAB expansion is particularly pronounced in China where N fertilizer use has escalated very rapidly, where soil retention is declining, and where blooms have had large economic and ecological impacts. There, in addition to increased use of urea and high N : P based fertilizers overall, escalating aquaculture production adds to the availability of reduced forms of N, as does atmospheric deposition of ammonia. HABs in both freshwaters and marginal seas in China are highly related to these overall changing N loads and ratios. Without more aggressive N control the future outlook in terms of HABs is likely to include more events, more often, and they may also be more toxic.

  1. Spectral analysis and abundances of the post-HB star HD 76431

    NASA Astrophysics Data System (ADS)

    Khalack, V.; Yameogo, B.; LeBlanc, F.; Fontaine, G.; Green, E.; Van Grootel, V.; Petit, P.

    2014-12-01

    HD 76431 is a slow rotating post-HB star that shows an underabundance of helium by 0.5 dex relative to the solar value. These observational facts suggest that atomic diffusion could be active in its atmosphere. We have used the MMT and Bok spectra to estimate the atmospheric parameters of the target star using the model atmospheres and synthetic spectra calculated with TLUSTY and SYNSPEC. The derived values of the effective temperature, surface gravity, and helium abundance are consistent with those obtained by Ramspeck et al. It appears that non-local thermodynamic equilibrium (NLTE) effects are not important for HD 76431. We have used Stokes I spectra from ESPaDOnS at CFHT to perform an abundance analysis and a search for observational evidence of vertical stratification of the abundance of certain elements. The results of our abundance analysis are in good agreement with previously published data with respect to average abundances. Our numerical simulations show that carbon and nitrogen reveal signatures of vertical abundance stratification in the atmosphere of HD 76431. It appears that the carbon abundance increases towards the deeper atmospheric layers. Nitrogen also shows a similar behaviour, but in deeper atmospheric layers we obtain a significant dispersion for the estimates of its abundance. To our knowledge, this is the first demonstration of vertical abundance stratification of metals in a post-HB star and up to now it is the hottest star to show such stratification features. We also report the detection of two Si III and one Ti III emission lines in the spectra of HD 76431 that were not detected in previous studies.

  2. Hb G-Waimanalo [A1] or α64(E13)Asp→Asn (α1) (HBA1: c.193G>A) Observed in a Bulgarian Family.

    PubMed

    Petkov, Georgi; Dimishkovska, Marija; Tsoneva Ivanova, Vanya; Yordanov, Georgi; Zdraveski, Alexandar; Plaseska-Karanfilska, Dijana

    2015-01-01

    The abnormal hemoglobin (Hb) with an aspartic acid to asparagine substitution at α64 has been found on both the α2- and α1-globin genes. It has been described in many different populations under different names, but never in Bulgaria. Using the recently proposed nomenclature, Hb G-Waimanalo [A1] refers to the HBA1: c.193G > A, while Hb G-Waimanalo [A2] refers to the HBA2: c.193G > A mutation. Here, we present the first family from Bulgaria with Hb G-Waimanalo [A1]. PMID:26212674

  3. A New δ-Globin Gene Variant: Hb A2-Fengshun [δ121(GH4)Glu→Lys (HBD: c.364G > A)].

    PubMed

    Yan, Jin-Mei; Zhou, Jian-Ying; Xie, Xing-Mei; Li, Jian; Li, Dong-Zhi

    2016-06-01

    An elevated Hb A2 (α2δ2 level) is a diagnostic marker for heterozygous β-thalassemia (β-thal). Mutations in the δ-globin gene can cause decreased expression of Hb A2, compromising screening for heterozygous β-thal. In this report, we describe a novel missense mutation of the δ-globin [Hb A2-Fengshun or δ121(GH4)Glu→Lys, HBD: c.364G > A] in a Chinese individual who had coinherited a heterozygous β-thal with a normal Hb A2 level. PMID:27117573

  4. A rare haemoglobin variant (Hb Phnom Penh) manifesting as a falsely high haemoglobin A1c value on ion-exchange chromatography.

    PubMed

    Chen, Chi-Fen; Tai, Yen-Kuang

    2014-08-01

    Most haemoglobin (Hb) variants are clinically silent. However, some Hb variants may interfere with the measurement of haemoglobin A1c (HbA1c), resulting in spurious values depending on the assays used. We herein report the case of a 53-year-old Taiwanese man with type 2 diabetes mellitus, who presented with an abnormal HbA1c peak on ion-exchange chromatography. Additional investigations, including intensified self-monitored blood glucose tests, an alternative HbA1c assay, and a glycaemic indicator based on a different method, revealed that the HbA1c values were falsely elevated. Subsequent DNA analysis confirmed that the patient was heterozygous for the insertion of an isoleucine residue at codons 117/118 of the a1-globin gene, Hb Phnom Penh. Clinical laboratorians should be aware of the interfering factors in their HbA1c analysis. Cautious inspection of the chromatogram may provide a valuable clue to the presence of an Hb variant. PMID:25189312

  5. Hb Chad or alpha 223(B4)Glu----Lys beta 2 observed in members of a Surinam family in association with alpha-thalassemia-2 and with Hb S.

    PubMed

    Codrington, J F; Codrington, F A; Wisse, J H; Wilson, J B; Webber, B B; Wong, S C; Huisman, T H

    1989-01-01

    Three different hemoglobinopathies, i.e. Hb S, Hb Chad [alpha 23 (B4)Glu----Lys], and alpha-thalassemia-2 (-3.7) have been observed in eight members of a family from Surinam. The proposita had all three abnormalities, while her mother and four of her half-brothers had Hb Chad together with an alpha-thalassemia-2 heterozygosity or homozygosity. Gene mapping and dot-blot analysis of amplified DNA identified a G----A mutation in codon 23 of the alpha 2 alpha 1 hybrid gene resulting in the Glu----Lys substitution. The quantity of the alpha-Chad chain averaged 31.5% in its carriers with an additional alpha-thalassemia-2 heterozygosity [-alpha Chad(-3.7 kb)/alpha alpha], and 43% in the two carriers with an additional alpha-thalassemia-2 homozygosity [-alpha Chad (-3.7 kb)/-alpha (3.7 kb)]. These quantities are considerably higher than those reported for families from Chad, China, and Japan; the low levels of 14.5-24% Hb Chad in members of previously reported cases suggest a mutation on a chromosome with two alpha-globin genes [alpha alpha Chad/alpha alpha or alpha Chad alpha/alpha alpha]. PMID:2606723

  6. Cloning and characterization of HbMT2a, a metallothionein gene from Hevea brasiliensis Muell. Arg differently responds to abiotic stress and heavy metals

    SciTech Connect

    Li, Yan; Chen, Yue Yi; Yang, Shu Guang; Tian, Wei Min

    2015-05-22

    Metallothioneins (MTs) are of low molecular mass, cysteine-rich proteins. They play an important role in the detoxification of heavy metals and homeostasis of intracellular metal ions, and protecting against intracellular oxidative damages. In this study a full-length cDNA of type 2 plant metallothioneins, HbMT2a, was isolated from 25 mM Polyethyleneglycol (PEG) stressed leaves of Hevea brasiliensis by RACE. The HbMT2a was 372 bp in length and had a 237 bp open reading frame (ORF) encoding for a protein of 78 amino acid residues with molecular mass of 7.772 kDa. The expression of HbMT2a in the detached leaves of rubber tree clone RY7-33-97 was up-regulated by Me-JA, ABA, PEG, H{sub 2}O{sub 2}, Cu{sup 2+} and Zn{sup 2+}, but down-regulated by water. The role of HbMT2a protein in protecting against metal toxicity was demonstrated in vitro. PET-28a-HbMT2-beared Escherichia coli. Differential expression of HbMT2a upon treatment with 10 °C was observed in the detached leaves of rubber tree clone 93-114 which is cold-resistant and Reken501 which is cold-sensitive. The expression patterns of HbMT2a in the two rubber tree clones may be ascribed to a change in the level of endogenous H{sub 2}O{sub 2}. - Highlights: • Cloning an HbMT2a gene from rubber tree. • Analyzing expression patterns of HbMT2a upon abiotic stress and heavy metal stress. • Finding different expression patterns of HbMT2a among two Hevea germplasm. • The expressed protein of HbMT2a enhances copper and zinc tolerance in Escherichia coli.

  7. The Change in HbA1c Associated with Initial Adherence and Subsequent Change in Adherence among Diabetes Patients Newly Initiating Metformin Therapy

    PubMed Central

    Rosales, A. Gabriela; Kimes, Teresa M.; Tunceli, Kaan; Kurtyka, Karen; Mavros, Panagiotis

    2016-01-01

    Introduction. Whether changes in adherence are associated with changes in HbA1c is assumed but not known. Methods. We conducted a observational study of 2,844 type 2 diabetes patients who initiated metformin as their first antihyperglycemic drug. Using HbA1c measures before, 6–12 months after, and up to 3 years after metformin initiation, we analyzed HbA1c change as a function of initial adherence and change in adherence. Results. Compared with no adherence, initial adherence of 50–79% was associated with an adjusted reduction in HbA1c of 0.45% while adherence ≥80% was associated with HbA1c reduction of 0.73%. Change from some initial adherence (1–79%) to total nonadherence was associated with 0.25% increase in HbA1c. Change from some to full adherence was associated with an HbA1c decrease of 0.15%. Those associations were accentuated among patients not in glycemic control: change from some to no adherence was associated with an HbA1c increase of 0.63% and change from some to full adherence was associated with an HbA1c decrease of 0.40%. Conclusions. Initial adherence to newly prescribed metformin therapy produces substantial HbA1c reduction. Among those with modest adherence but suboptimal glycemic control, the difference between moving to full adherence versus nonadherence results in lower HbA1c of one percentage point.

  8. The Change in HbA1c Associated with Initial Adherence and Subsequent Change in Adherence among Diabetes Patients Newly Initiating Metformin Therapy.

    PubMed

    Nichols, Gregory A; Rosales, A Gabriela; Kimes, Teresa M; Tunceli, Kaan; Kurtyka, Karen; Mavros, Panagiotis

    2016-01-01

    Introduction. Whether changes in adherence are associated with changes in HbA1c is assumed but not known. Methods. We conducted a observational study of 2,844 type 2 diabetes patients who initiated metformin as their first antihyperglycemic drug. Using HbA1c measures before, 6-12 months after, and up to 3 years after metformin initiation, we analyzed HbA1c change as a function of initial adherence and change in adherence. Results. Compared with no adherence, initial adherence of 50-79% was associated with an adjusted reduction in HbA1c of 0.45% while adherence ≥80% was associated with HbA1c reduction of 0.73%. Change from some initial adherence (1-79%) to total nonadherence was associated with 0.25% increase in HbA1c. Change from some to full adherence was associated with an HbA1c decrease of 0.15%. Those associations were accentuated among patients not in glycemic control: change from some to no adherence was associated with an HbA1c increase of 0.63% and change from some to full adherence was associated with an HbA1c decrease of 0.40%. Conclusions. Initial adherence to newly prescribed metformin therapy produces substantial HbA1c reduction. Among those with modest adherence but suboptimal glycemic control, the difference between moving to full adherence versus nonadherence results in lower HbA1c of one percentage point. PMID:27579326

  9. 75 FR 80545 - Carolina Power & Light Company; H.B. Robinson Steam Electric Plant, Unit No. 2; Environmental...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-22

    ... Register notice dated March 27, 2009 (74 FR 13967). There will be no change to radioactive effluents that... COMMISSION Carolina Power & Light Company; H.B. Robinson Steam Electric Plant, Unit No. 2; Environmental... Carolina Power & Light Company (the licensee), for operation of the H. B. Robinson Steam Electric...

  10. 76 FR 66333 - Carolina Power & Light Company, H.B. Robinson Steam Electric Plant, Unit No. 2; Environmental...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-26

    ... COMMISSION Carolina Power & Light Company, H.B. Robinson Steam Electric Plant, Unit No. 2; Environmental..., ``Acceptance criteria for emergency core cooling systems for light-water nuclear power reactors,'' and 10 CFR... Facility Operating License No. DPR-23, issued to Carolina Power & Light Company (the licensee),...

  11. Effect of drug therapy on HEDIS measurements of HbA1c control in diabetes patients.

    PubMed

    Bazalo, Gary; Weiss, Richard; Clark, Nathaniel; Alemayehu, Berhanu; Forma, Felicia; Ingram, Garrett

    2009-02-01

    The purpose of this study was to corroborate an earlier study that explored the relationship between a health plan's Health Plan Employer Data and Information Set (HEDIS) score for glycolated hemoglobin (HbA1c) control in diabetes patients and its utilization of insulin and oral diabetes products. Prescription volumes were tracked for four categories of diabetes drug therapy: analog insulin, human insulin, single-source brand oral products, and multisource generic oral products, for calendar years 2005 and 2006. The prescription shares of each of the four drug categories for each health plan were matched to the health plan's HEDIS measurements of HbA1c control for each year. Univariate and multivariate regression analysis was performed between the health plan's HbA1c -based HEDIS score and its prescription share of each drug category. A favorable and statistically significant (p < 0.01) relationship was found between plan HbA1c HEDIS score and plan prescription share of analog insulin in both 2005 and 2006. The correlation between HEDIS scores and human insulin was not statistically significant. Unfavorable relationships were found between HEDIS scores and both the single-source brand (statistically significant) and the multisource generic oral category prescription shares (not significant). These results corroborate the relationships found in our earlier study, although a cause and effect relationship cannot be confirmed. PMID:19264026

  12. Hot HB Stars in Globular Clusters: Physical Parameters and Consequences for Theory. 5; Radiative Levitation Versus Helium Mixing

    NASA Technical Reports Server (NTRS)

    Moehler, S.; Sweigart, A. V.; Landsman, W. B.; Heber, U.

    2000-01-01

    Atmospheric parameters (T(sub eff), log g), masses and helium abundances are derived for 42 hot horizontal branch (HB) stars in the globular cluster NGC6752. For 19 stars we derive magnesium and iron abundances as well and find that iron is enriched by a factor of 50 on average with respect to the cluster abundance whereas the magnesium abundances are consistent with the cluster abundance. Radiation pressure may levitate heavy elements like iron to the surface of the star in a diffusive process. Taking into account the enrichment of heavy elements in our spectroscopic analyses we find that high iron abundances can explain part, but not all, of the problem of anomalously low gravities along the blue HB. The blue HB stars cooler than about 15,100 K and the sdB stars (T(sub eff) greater than or = 20,000 K) agree well with canonical theory when analysed with metal-rich ([M/H] = +0.5) model atmospheres, but the stars in between these two groups remain offset towards lower gravities and masses. Deep Mixing in the red giant progenitor phase is discussed as another mechanism that may influence the position of the blue HB stars in the (T(sub eff), log g)-plane but not their masses.

  13. 76 FR 54261 - Carolina Power & Light; H.B. Robinson Steam Electric Plant, Unit No. 2; HBRSEP Independent Spent...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-31

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Carolina Power & Light; H.B. Robinson Steam Electric Plant, Unit No. 2; HBRSEP Independent Spent Fuel Storage Installations; Notice of Consideration of Approval of Application for Indirect License Transfer Resulting From the Proposed Merger...

  14. HB 2578--Relating to the School Meals Program. Testimony, 79th Texas State Legislature (April 26, 2005)

    ERIC Educational Resources Information Center

    Hagert, Celia

    2005-01-01

    The Center for Public Policy Priorities supports HB 2574. Why encourage school districts to offer free meals to all students? The link between adequate nutrition and improved academic performance creates a clear incentive for Texas to increase participation in the school breakfast and lunch programs, particularly among low-income children.…

  15. HB-EGF embedded in PGA/PLLA scaffolds via subcritical CO2 augments the production of tissue engineered intestine.

    PubMed

    Liu, Yanchun; Nelson, Tyler; Cromeens, Barrett; Rager, Terrence; Lannutti, John; Johnson, Jed; Besner, Gail E

    2016-10-01

    The ability to deliver sustained-release, biologically active growth factors through custom designed tissue engineering scaffolds at sites of tissue regeneration offers great therapeutic opportunity. Due to the short in vivo half-lives of most growth factors, it is challenging to deliver these proteins to sites of interest where they may be used before being degraded. The application of subcritical CO2 uses gas-phase CO2 at subcritical pressures ranging from 41 to 62 bar (595-913 PSI) which avoids foaming by reducing the amount of CO2 dissolved in the polymer and maintains completely reversible plasticization. In the current study, heparin-binding EGF-like growth factor (HB-EGF) was embedded into polyglycolic acid (PGA)/Poly-l-latic acid (PLLA) scaffolds via subcritical CO2 exposure for the production of tissue engineered intestine (TEI). PGA fiber morphology after subcritical CO2 exposure was examined by scanning electron microscopy (SEM) and the distribution of HB-EGF embedded in the scaffold fibers was detected by HB-EGF immunofluorescent staining. In vivo implantation of HB-EGF-embedded scaffolds confirmed significantly improved TEI structure as a result of local delivery of the trophic growth factor. These findings may be critical for the production of TEI in the treatment of patients with short bowel syndrome in the future. PMID:27380441

  16. HbA1c measured in stored erythrocytes and mortality rate among middle-aged and older women

    PubMed Central

    Liu, S.; Stampfer, M. J.; Cook, N. R.; Rexrode, K. M.; Ridker, P. M.; Buring, J. E.; Manson, J. E.

    2009-01-01

    Aims/hypothesis Diabetes is known to increase mortality rate, but the degree to which mild hyperglycaemia may be associated with the risk of death is uncertain. We examined the association between HbA1c measured in stored erythrocytes and mortality rate in women with and without diabetes. Methods We conducted a cohort study of 27,210 women ≥45 years old with no history of cardiovascular disease or cancer who participated in the Women’s Health Study, a randomised trial of vitamin E and aspirin. Results Over a median of 10 years of follow-up, 706 women died. Proportional hazards models adjusted for age, smoking, hypertension, blood lipids, exercise, postmenopausal hormone use, multivitamin use and C-reactive protein were used to estimate the relative risk of mortality. Among women without a diagnosis of diabetes and HbA1c <5.60%, those in the top quintile (HbA1c 5.19–5.59%) had a relative risk of mortality of 1.28 (95% CI 0.98–1.69, p value for linear trend=0.14) compared with those with HbA1c 2.27–4.79%. Women with HbA1c 5.60–5.99% and no diagnosis of diabetes had a 54% increased risk of mortality (95% CI 1–136%) compared with those with HbA1c 2.27–4.79%. HbA1c was significantly associated with mortality across the range 4.50–7.00% (p value for linear trend=0.02); a test of deviation from linearity was not statistically significant (p=0.67). Diabetic women had more than twice the mortality risk of non-diabetic women. Conclusions/interpretation This study provides further evidence that chronic mild hyperglycaemia, even in the absence of diagnosed diabetes, is associated with increased risk of mortality. PMID:18043905

  17. Bridging Theory and Experiment to Address Structural Properties of Truncated Haemoglobins: Insights from Thermobifida fusca HbO.

    PubMed

    Howes, Barry D; Boechi, Leonardo; Boffi, Alberto; Estrin, Dario E; Smulevich, Giulietta

    2015-01-01

    In this chapter, we will discuss the paradigmatic case of Thermobifida fusca (Tf-trHb) HbO in its ferrous and ferric states and its behaviour towards a battery of possible ligands. This choice was dictated by the fact that it has been one of the most extensively studied truncated haemoglobins, both in terms of spectroscopic and molecular dynamics studies. Tf-trHb typifies the structural properties of group II trHbs, as the active site is characterized by a highly polar distal environment in which TrpG8, TyrCD1, and TyrB10 provide three potential H-bond donors in the distal cavity capable of stabilizing the incoming ligands. The role of these residues in key topological positions, and their interplay with the iron-bound ligands, has been addressed in studies carried out on the CO, F(-), OH(-), CN(-), and HS(-) adducts formed with the wild-type protein and a combinatorial set of mutants, in which the distal polar residues, TrpG8, TyrCD1, and TyrB10, have been singly, doubly, or triply replaced by a Phe residue. In this context, such a complete analysis provides an excellent benchmark for the investigation of the relationship between protein structure and function, allowing one to translate physicochemical properties of the active site into the observed functional behaviour. Tf-trHb will be compared with other members of the group II trHbs and, more generally, with members of the other trHb subgroups. PMID:26616516

  18. HbA(1c) diagnostic categories and beta-cell function relative to insulin sensitivity in overweight/obese adolescents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The recommended HbA1c diagnostic categories remain controversial and their utility in doubt in pediatrics. We hypothesized that alterations in the pathophysiologic mechanisms of type 2 diabetes may be evident in the American Diabetes Association recommended at-risk/prediabetes category (HbA(1c) 5.7 ...

  19. Mechanism of Hb F stimulation by S-stage compounds. In vitro studies with bone marrow cells exposed to 5-azacytidine, Ara-C, or hydroxyurea.

    PubMed Central

    Galanello, R; Stamatoyannopoulos, G; Papayannopoulou, T

    1988-01-01

    The in vitro effect of S-stage-specific drugs on the fetal hemoglobin (Hb F) potential of erythroid precursors and progenitors was tested by exposing bone marrow cells to 5-aza-2'-deoxycytidine, Ara-C, or hydroxyurea in suspension cultures and reculturing the cells in drug-free clonal cultures. Analysis of Hb F in the erythroblasts present at the end of suspension cultures and in the erythroid colonies formed from treated progenitors showed that 1 X 10(-9)-5 X 10(-8) M 5-aza-2'-deoxycytidine produced a concentration-related increase in the proportion of Hb F-positive erythroblasts, of Hb F-positive erythroid CFU (CFUe) colonies, and at the higher doses used, an increased Hb F expression in erythroid burst-forming unit (BFUe)-derived colonies. Preincubation of bone marrow cells with Ara-C produced significant megaloblastic changes by the end of the 2-d incubation and increased the proportion of Hb F-positive erythroblasts, CFUe colonies, and e-clusters, but BFUe-derived progeny was unaffected. Hydroxyurea failed to produce significant changes in Hb F at the range of concentrations used. The data raise the possibility of more than one mechanism underlying the stimulation of Hb F by S-stage drugs. PMID:2450894

  20. Modelling the Relative Contribution of Fasting and Post-Prandial Plasma Glucose to HbA1c in Healthy and Type 2 Diabetic Subjects

    ERIC Educational Resources Information Center

    Ollerton, Richard L.; Luzio, Steven D.; Owens, David R.

    2004-01-01

    Glycated haemoglobin (HbA1c) is regarded as the gold standard of glucose homeostasis assessment in diabetes. There has been much discussion in recent medical literature of experimental results concerning the relative contribution of fasting and post-prandial glucose levels to the value of HbA1c. A mathematical model of haemoglobin glycation is…

  1. Functional characterization of the homeodomain leucine zipper I transcription factor AtHB13 reveals a crucial role in Arabidopsis development.

    PubMed

    Ribone, Pamela A; Capella, Matías; Chan, Raquel L

    2015-09-01

    AtHB13 is a homeodomain leucine zipper I transcription factor whose function in development is largely unknown. AtHB13 and AtHB23 mutant and silenced lines were characterized by expression studies, reciprocal crosses, complementation, molecular analyses, and developmental phenotypes. The athb13-1 and athb13-2 mutants, athb23 silenced, and athb13/athb23 double-silenced plants exhibited faster elongation rates of their inflorescence stems, whereas only athb13-1 and the double-knockdown athb13/athb23 exhibited shorter siliques, fewer seeds, and unfertilized ovules compared with the wild type (WT). The cell sizes of mutant and WT plants were similar, indicating that these transcription factors probably affect cell division. Reciprocal crosses between athb13-1 and the WT genotype indicated that the silique defect was male specific. Pollen hydration assays indicated that the pollen grains of the athb13-1 mutant were unable to germinate on stigmas. AtHB23-silenced plants exhibited normal siliques, whereas double-knockdown athb13/athb23 plants were similar to athb13-1 plants. Both AtHB13 and AtHB23 were able to rescue the abnormal silique phenotype. AtHB23 was upregulated in athb13-2 plants, whereas its transcript levels in athb13-1 mutants were not significantly increased. Transcriptome analysis comparing athb13-1 and WT inflorescences revealed that a large number of genes, including several involved in pollen coat formation, are regulated by AtHB13. Finally, athb13-1 complementation with mutated versions of AtHB13 confirmed that two different tryptophans in its C terminus are essential. We conclude that AtHB13 and AtHB23 play independent, negative developmental roles in stem elongation, whereas only AtHB13 is crucial for pollen germination. Furthermore, AtHB23, which does not normally exert a functional role in pollen, can act as a substitute for AtHB13. PMID:26136262

  2. Lipid fluidity at different regions in LDL and HDL of {beta}-thalassemia/Hb E patients

    SciTech Connect

    Morales, Noppawan Phumala . E-mail: scnpm@mahidol.ac.th; Charlermchoung, Chalermkhwan; Luechapudiporn, Rataya; Yamanont, Paveena; Fucharoen, Suthat; Chantharaksri, Udom

    2006-11-24

    Atherosclerosis-related vascular complications in {beta}-thalassemia/hemoglobin E ({beta}-thal/Hb E) patients may result from iron induced oxidation of lipoproteins. To identify the specific site of oxidative damage, changes in lipid fluidity at different regions in LDL and HDL particle were investigated using two fluorescence probes and two ESR spin probes. The magnitude of increased lipid fluidity in thalassemic lipoproteins was dependent on the location of the probes. In hydrophobic region, the rotational correlation times for 16-doxyl stearic acid and DPH anisotropy were markedly changed in LDL and HDL of the patients. In the surface region, there was only a slight change in the order parameter (S) for 5-doxyl stearic acid and TMA-DPH anisotropy. Lipid fluidity at the core of LDL and HDL showed good correlation with oxidative stress markers, the ratio of CL/CO, and the level of {alpha}-tocopherol, suggesting that hydrophobic region of thalassemic lipoprotein was a target site for oxidative damage.

  3. Transposon Mutagenesis of the Extremely Thermophilic Bacterium Thermus thermophilus HB27

    PubMed Central

    Carr, Jennifer F.; Gregory, Steven T.; Dahlberg, Albert E.

    2014-01-01

    Thermus thermophilus is an extremely thermophilic bacterium that grows between 50 °C and 80 °C and is an excellent model organism not only for understanding life at high temperature but also for its biotechnological and industrial applications. Multiple molecular capabilities are available including targeted gene inactivation and the use of shuttle plasmids that replicate in T. thermophilus and Escherichia coli; however the ability to disrupt gene function randomly by transposon insertion has not been developed. Here we report a detailed method of transposon mutagenesis of T. thermophilus HB27 based on the EZ-Tn5 system from Epicentre Biotechnologies. We were able to generate insertion mutations throughout the chromosome by in vitro transposition and transformation with mutagenized genomic DNA. We also report that an additional step, one that fills in single stranded gaps in donor DNA generated by the transposition reaction, was essential for successful mutagenesis. We anticipate that our method of transposon mutagenesis will enable further genetic development of T. thermophilus and may also be valuable for similar endeavors with other under-developed organisms. PMID:24948436

  4. Report on HbA1c Proficiency Testing in Asia in 2012

    PubMed Central

    Umemoto, Masao; Hoshino, Tadao; Miyashita, Tetsuo; Tani, Wataru

    2015-01-01

    In 2010, the Japan Diabetes Society decided to introduce the National Glycohemoglobin Standardization Program (NGSP) values into clinical practice. Accordingly, NGSP Certification of Japanese manufacturers of HbA1c-related diagnostic reagents and instruments was initiated in February, 2012, through an NGSP network laboratory, the Asian Secondary Reference Laboratory (ASRL) #1. Traceability to the NGSP reference system can be endorsed by manufacturer certification, as well as by the College of American Pathologists (CAP) survey. Nevertheless, only a few manufacturers participate in the CAP survey in Japan. Thus, proficiency testing (PT) was proposed and executed by ASRL #1. Single-donor whole-blood samples were used for the PT. The participated measurement systems were NGSP certified. Twenty-two laboratories obtained certification through ASRL #1; 2 through the Secondary Reference Laboratory (SRL) #8; and 9 through the SRL #9. The combination plots of the bias data in this PT and in the NGSP certification performed in March and May in 2012 were consistent with each other: mean NGSP values at each level agreed well with the target value. In conclusion, PT using whole blood is useful in endorsing NGSP certification. PMID:25932445

  5. Structure of putative 4-amino-4-deoxychorismate lyase from Thermus thermophilus HB8

    PubMed Central

    Padmanabhan, Balasundaram; Bessho, Yoshitaka; Ebihara, Akio; Antonyuk, Svetlana V.; Ellis, Mark J.; Strange, Richard W.; Kuramitsu, Seiki; Watanabe, Nobuhisa; Hasnain, S. Samar; Yokoyama, Shigeyuki

    2009-01-01

    The pyridoxal 5′-phosphate-dependent enzyme 4-amino-4-deoxychorismate lyase converts 4-amino-4-deoxychorismate to p-aminobenzoate and pyruvate in one of the crucial steps in the folate-biosynthesis pathway. The primary structure of the hypothetical protein TTHA0621 from Thermus thermophilus HB8 suggests that TTHA0621 is a putative 4-amino-4-deoxychorismate lyase. Here, the crystal structure of TTHA0621 is reported at 1.93 Å resolution. The asymmetric unit contained four NCS molecules related by 222 noncrystallographic symmetry, in which the formation of intact dimers may be functionally important. The cofactor pyridoxal 5′-phosphate (PLP) binds to the protein in the large cleft formed by the N-terminal and C-terminal domains of TTHA0621. The high structural similarity and the conservation of the functional residues in the catalytic region compared with 4-amino-4-deoxychorismate lyase (PabC; EC 4.1.3.38) from Escherichia coli suggest that the TTHA0621 protein may also possess 4-amino-4-deoxychorismate lyase activity. PMID:20054118

  6. Cloning, overexpression and characterization of a thermostable pullulanase from Thermus thermophilus HB27.

    PubMed

    Wu, Huawei; Yu, Xinxin; Chen, Libing; Wu, Guangxu

    2014-03-01

    A gene encoding a special type of pullulanase from Thermus thermophilus HB27 (TTHpu) was cloned. It has an open reading frame of 1428bp encoding a mature protein with a molecular mass of 52kDa. The gene was expressed in Escherichia coli using pHsh and pET28a vectors. The pHsh expression system produced a 3.6-fold higher recombinant pullulanase than pET28a. The recombinant TTHpu was purified to homogeneity by heat treatment and Ni-NTA affinity chromatography. The purified TTHpu exhibited highest activity at pH 6.5 and 70°C. More than 90% activity was retained after incubation at 60-70°C for 2h and the half-life was 2h at 80°C. The stability of the enzyme was in a pH range from 6.0 to 8.0. Manganese at 5mM enhanced its activity up to 298%. The Km and Vmax for the enzyme activity on pullulan were 0.0031mgmL(-1) and 23.8μmolmin(-1), respectively. Unlike the most of pullulan-hydrolyzing enzymes described to date, this enzyme can attack α-1,6- and α-1,4-glycosidic linkages in pullulan, and produce a mixture of maltotriose, maltose and glucose. The enzyme could be further employed for industrial saccharification of starch. PMID:24316447

  7. Sequences implicated in the processing of Thermus thermophilus HB8 23S rRNA.

    PubMed Central

    Hartmann, R K; Ulbrich, N; Erdmann, V A

    1987-01-01

    Nuclease S1 mapping analyses were performed in order to detect processing intermediates of pre-23S rRNA from Thermus thermophilus HB8. Two processing sites were identified downstream the start of transcription and several consecutive cleavage sites are associated with the mature 5'-end. In the 3'-flanking region one "primary" site and two cleavages which generate short-living intermediates were detected. A series of successive intermediates in the region of the mature 3'-end implies the existence of--in analogy to Escherichia coli--a 3'-exonucleolytic activity. The data were correlated with potential secondary structures within the pre-23S rRNA, which exhibit various repeated sequence elements. M13 sequencing data support the existence of one secondary structural element associated with the strong "primary" cleavage site in the 3'-flanking region. In T. thermophilus we can exclude the formation of an extended base-paired and precursor-specific stem enclosing the 23S rRNA which is inferred to mediate recognition by RNase III in E. coli. Images PMID:3313273

  8. Structure of indole-3-glycerol phosphate synthase from Thermus thermophilus HB8: implications for thermal stability.

    PubMed

    Bagautdinov, Bagautdin; Yutani, Katsuhide

    2011-12-01

    The three-dimensional structure of indole-3-glycerol phosphate synthase (IGPS) from the thermophilic bacterium Thermus thermophilus HB8 (TtIGPS) has been determined at 1.8 Å resolution. The structure adopts a typical (β/α)(8)-barrel fold with an additional N-terminal extension of 46 residues. A detailed comparison of the crystal structure of TtIGPS with available structures of IGPS from the archaeon Sulfolobus solfataricus (SsIGPS) and the bacteria Thermotoga maritima (TmIGPS) and Escherichia coli (EcIGPS) has been performed. Although the overall folds of the proteins are the same, there are differences in amino-acid composition, structural rigidity, ionic features and stability clusters which may account for the high thermostability of the hyperthermophilic (SsIGPS and TmIGPS) and thermophilic (TtIGPS) proteins when compared with the mesophilic EcIGPS. The thermostability of IGPS seems to be established mainly by favourable interactions of charged residues, salt bridges and the spatial distribution of relatively rigid clusters of extensively interacting residues. PMID:22120743

  9. Structure of 3-oxoacyl-(acyl-carrier protein) synthase II from Thermus thermophilus HB8

    PubMed Central

    Bagautdinov, Bagautdin; Ukita, Yoko; Miyano, Masashi; Kunishima, Naoki

    2008-01-01

    The β-ketoacyl-(acyl carrier protein) synthases (β-keto-ACP synthases; KAS) catalyse the addition of two-carbon units to the growing acyl chain during the elongation phase of fatty-acid synthesis. As key regulators of bacterial fatty-acid synthesis, they are promising targets for the development of new antibacterial agents. The crystal structure of 3-oxoacyl-ACP synthase II from Thermus thermophilus HB8 (TtKAS II) has been solved by molecular replacement and refined at 2.0 Å resolution. The crystal is orthorhombic, space group P21212, with unit-cell parameters a = 72.07, b = 185.57, c = 62.52 Å, and contains one homodimer in the asymmetric unit. The subunits adopt the well known α-β-α-β-α thiolase fold that is common to ACP synthases. The structural and sequence similarities of TtKAS II to KAS I and KAS II enzymes of known structure from other sources support the hypothesis of comparable enzymatic activity. The dimeric state of TtKAS II is important to create each fatty-acid-binding pocket. Closer examination of KAS structures reveals that compared with other KAS structures in the apo form, the active site of TtKAS II is more accessible because of the ‘open’ conformation of the Phe396 side chain. PMID:18453702

  10. Structure of 3-oxoacyl-(acyl-carrier protein) synthase II from Thermus thermophilus HB8.

    PubMed

    Bagautdinov, Bagautdin; Ukita, Yoko; Miyano, Masashi; Kunishima, Naoki

    2008-05-01

    The beta-ketoacyl-(acyl carrier protein) synthases (beta-keto-ACP synthases; KAS) catalyse the addition of two-carbon units to the growing acyl chain during the elongation phase of fatty-acid synthesis. As key regulators of bacterial fatty-acid synthesis, they are promising targets for the development of new antibacterial agents. The crystal structure of 3-oxoacyl-ACP synthase II from Thermus thermophilus HB8 (TtKAS II) has been solved by molecular replacement and refined at 2.0 A resolution. The crystal is orthorhombic, space group P2(1)2(1)2, with unit-cell parameters a = 72.07, b = 185.57, c = 62.52 A, and contains one homodimer in the asymmetric unit. The subunits adopt the well known alpha-beta-alpha-beta-alpha thiolase fold that is common to ACP synthases. The structural and sequence similarities of TtKAS II to KAS I and KAS II enzymes of known structure from other sources support the hypothesis of comparable enzymatic activity. The dimeric state of TtKAS II is important to create each fatty-acid-binding pocket. Closer examination of KAS structures reveals that compared with other KAS structures in the apo form, the active site of TtKAS II is more accessible because of the ;open' conformation of the Phe396 side chain. PMID:18453702

  11. Abnormal behavior of midgap electron trap in HB-GaAs during thermal annealing

    NASA Astrophysics Data System (ADS)

    Min, Suk-Ki; Kim, Eun Kyu; Cho, Hoon Young

    1988-05-01

    The behavior of the EL2 family in horizontal Bridgman-(HB) grown GaAs by two thermal annealing methods, furnace annealing and rapid thermal annealing, was studied through deep level transient spectroscopy (DLTS) measurements, and a similar behavior of another group of electron traps was observed. As the annealing time is increased, the EL2 trap (Ec-0.81 eV) is transformed to the new trap, EX2 (Ec-0.73 eV), and finally to the other new trap, EX1 (Ec-0.86 eV). Also the EL6 group (Ec-0.18, 0.22, 0.27, and 0.35 eV) varied similarly to the EL2 family as a trap (Ec-0.27 eV) is transformed to the first trap (Ec-0.18 eV) and then the second trap (Ec-0.22 eV). This result revealed that the EL2 family is related to the EL6 group. From the study of photocapacitance quenching, the existence of metastable states of the EL2 family is identified. These results suggest that the atomic structure of the EL2 trap may be an arsenic antisite with an interstitial arsenic and a double vacancy, such as VAsAsIVGaAsGa or its complex.

  12. Detailed Infrared views of the shock-cloud interactions in the supernova remnant HB 21

    NASA Astrophysics Data System (ADS)

    Shinn, Jong-Ho; Koo, Bon-Chul; Burton, Michael; Lee, Ho-Gyu; Moon, Dae-Sik

    HB 21 (G89.0+4.7) is a nearby (˜ 1 kpc), large (120 ×90 ), middle-aged (˜ 7000 yr) supernova remnant, whose interaction with nearby molecular clouds is known. We observed two specific regions (˜ 10 × 10 ), where the shock-cloud interactions are thought to be under way, with the Japanese infrared satellite AKARI. InfraRed Camera (IRC) onboard AKARI obtained several images at nearand mid-infrared wavebands (3, 4, 7, 11, 15, and 24 µm). Those images show diffuse filamentary features, together with some clumpy features, mainly in the 7, 11, and 15 µm bands. These features are generally consistent with those seen in H2 v = 1 → 0 S(1) 2.122 µm image. We analyzed the color ratios of the features in the IRC images using theoretically calculated emission lines from shocked H2 gas in local thermodynamic equilibrium and statistical equilibrium. The results show that the observed color-ratios are well described by power-law mixtures of H2 gas temperature, and that the degree of mixture varies from region to region (power-law index 4.0). Based on observations with AKARI, a JAXA project with the participation of ESA.

  13. HB-EGF-Promoted Airway Smooth Muscle Cells and Their Progenitor Migration Contribute to Airway Smooth Muscle Remodeling in Asthmatic Mouse.

    PubMed

    Wang, Qing; Li, Hequan; Yao, Yinan; Lu, Guohua; Wang, Yuehong; Xia, Dajing; Zhou, Jianying

    2016-03-01

    The airway smooth muscle (ASM) cells' proliferation, migration, and their progenitor's migration are currently regarded as causative factors for ASM remodeling in asthma. Heparin-binding epidermal growth factor (HB-EGF), a potent mitogen and chemotactic factor, could promote ASM cell proliferation through MAPK pathways. In this study, we obtained primary ASM cells and their progenitors from C57BL/6 mice and went on to explore the role of HB-EGF in these cells migration and the underlying mechanisms. We found that recombinant HB-EGF (rHB-EGF) intratracheal instillation accelerated ASM layer thickening in an OVA-induced asthmatic mouse. Modified Boyden chamber assay revealed that rHB-EGF facilitate ASM cell migration in a dose-dependent manner and ASM cells from asthmatic mice had a greater migration ability than that from normal counterparts. rHB-EGF could stimulate the phosphorylation of ERK1/2 and p38 in ASM cells but further migration assay showed that only epidermal growth factor receptor inhibitor (AG1478) or p38 inhibitor (SB203580), but not ERK1/2 inhibitor (PD98059), could inhibit rHB-EGF-mediated ASM cells migration. Actin cytoskeleton experiments exhibited that rHB-EGF could cause actin stress fibers disassembly and focal adhesions formation of ASM cells through the activation of p38. Finally, airway instillation of rHB-EGF promoted the recruitment of bone marrow-derived smooth muscle progenitor cells, which were transferred via caudal vein, migrating into the airway from the circulation. These observations demonstrated that ASM remodeling in asthma might have resulted from HB-EGF-mediated ASM cells and their progenitor cells migration, via p38 MAPK-dependent actin cytoskeleton remodeling. PMID:26826248

  14. Crystal structure of phenylacetic acid degradation protein PaaG from Thermus thermophilus HB8.

    PubMed

    Kichise, Tomoyasu; Hisano, Tamao; Takeda, Kazuki; Miki, Kunio

    2009-09-01

    Microbial degradation of phenylacetic acid proceeds via the hybrid pathway that includes formation of a coenzyme A thioester, ring hydroxylation, non-oxygenolytic ring opening, and beta-oxidation-like reactions. A phenylacetic acid degradation protein PaaG is a member of the crotonase superfamily, and is a candidate non-oxygenolytic ring-opening enzyme. The crystal structure of PaaG from Thermus thermophilus HB8 was determined at a resolution of 1.85 A. PaaG consists of three identical subunits related by local three-fold symmetry. The monomer is comprised of a spiral and a helical domain with a fold characteristic of the crotonase superfamily. A putative active site residue, Asp136, is situated in an active site cavity and surrounded by several hydrophobic and hydrophilic residues. The active site cavity is sufficiently large to accommodate a ring substrate. Two conformations are observed for helix H2 located adjacent to the active site. Helix H2 is kinked at Asn81 in two subunits, whereas it is kinked at Leu77 in the other subunit, and the side chain of Tyr80 is closer to Asp136. This indicates that catalytic reaction of PaaG may proceed with large conformational changes at the active site. Asp136 is the only conserved polar residue in the active site. It is located at the same position as those of 4-chlorobenzoyl-CoA dehalogenase and peroxisomal Delta(3),Delta(2)-enoyl-CoA isomerase, indicating that PaaG may undergo isomerization or a ring-opening reaction via a Delta(3),Delta(2)-enoyl-CoA isomerase-like mechanism. PMID:19452559

  15. Computational de novo design of a four-helix bundle protein—DND_4HB

    PubMed Central

    Murphy, Grant S; Sathyamoorthy, Bharatwaj; Der, Bryan S; Machius, Mischa C; Pulavarti, Surya V; Szyperski, Thomas; Kuhlman, Brian

    2015-01-01

    The de novo design of proteins is a rigorous test of our understanding of the key determinants of protein structure. The helix bundle is an interesting de novo design model system due to the diverse topologies that can be generated from a few simple α-helices. Previously, noncomputational studies demonstrated that connecting amphipathic helices together with short loops can sometimes generate helix bundle proteins, regardless of the bundle's exact sequence. However, using such methods, the precise positions of helices and side chains cannot be predetermined. Since protein function depends on exact positioning of residues, we examined if sequence design tools in the program Rosetta could be used to design a four-helix bundle with a predetermined structure. Helix position was specified using a folding procedure that constrained the design model to a defined topology, and iterative rounds of rotamer-based sequence design and backbone refinement were used to identify a low energy sequence for characterization. The designed protein, DND_4HB, unfolds cooperatively (Tm >90°C) and a NMR solution structure shows that it adopts the target helical bundle topology. Helices 2, 3, and 4 agree very closely with the design model (backbone RMSD = 1.11 Å) and >90% of the core side chain χ1 and χ2 angles are correctly predicted. Helix 1 lies in the target groove against the other helices, but is displaced 3 Å along the bundle axis. This result highlights the potential of computational design to create bundles with atomic-level precision, but also points at remaining challenges for achieving specific positioning between amphipathic helices. PMID:25287625

  16. A novel arsenate reductase from the bacterium Thermus thermophilus HB27: its role in arsenic detoxification.

    PubMed

    Del Giudice, Immacolata; Limauro, Danila; Pedone, Emilia; Bartolucci, Simonetta; Fiorentino, Gabriella

    2013-10-01

    Microorganisms living in arsenic-rich geothermal environments act on arsenic with different biochemical strategies, but the molecular mechanisms responsible for the resistance to the harmful effects of the metalloid have only partially been examined. In this study, we investigated the mechanisms of arsenic resistance in the thermophilic bacterium Thermus thermophilus HB27. This strain, originally isolated from a Japanese hot spring, exhibited tolerance to concentrations of arsenate and arsenite up to 20mM and 15mM, respectively; it owns in its genome a putative chromosomal arsenate reductase (TtarsC) gene encoding a protein homologous to the one well characterized from the plasmid pI258 of the Gram+bacterium Staphylococcus aureus. Differently from the majority of microorganisms, TtarsC is part of an operon including genes not related to arsenic resistance; qRT-PCR showed that its expression was four-fold increased when arsenate was added to the growth medium. The gene cloning and expression in Escherichia coli, followed by purification of the recombinant protein, proved that TtArsC was indeed a thioredoxin-coupled arsenate reductase with a kcat/KM value of 1.2×10(4)M(-1)s(-1). It also exhibited weak phosphatase activity with a kcat/KM value of 2.7×10(-4)M(-1)s(-1). The catalytic role of the first cysteine (Cys7) was ascertained by site-directed mutagenesis. These results identify TtArsC as an important component in the arsenic resistance in T. thermophilus giving the first structural-functional characterization of a thermophilic arsenate reductase. PMID:23800470

  17. Structural Basis of Free Reduced Flavin Generation by Flavin Reductase from Thermus thermophilus HB8*

    PubMed Central

    Imagawa, Takahito; Tsurumura, Toshiharu; Sugimoto, Yasushi; Aki, Kenji; Ishidoh, Kazumi; Kuramitsu, Seiki; Tsuge, Hideaki

    2011-01-01

    Free reduced flavins are involved in a variety of biological functions. They are generated from NAD(P)H by flavin reductase via co-factor flavin bound to the enzyme. Although recent findings on the structure and function of flavin reductase provide new information about co-factor FAD and substrate NAD, there have been no reports on the substrate flavin binding site. Here we report the structure of TTHA0420 from Thermus thermophilus HB8, which belongs to flavin reductase, and describe the dual binding mode of the substrate and co-factor flavins. We also report that TTHA0420 has not only the flavin reductase motif GDH but also a specific motif YGG in C terminus as well as Phe-41 and Arg-11, which are conserved in its subclass. From the structure, these motifs are important for the substrate flavin binding. On the contrary, the C terminus is stacked on the NADH binding site, apparently to block NADH binding to the active site. To identify the function of the C-terminal region, we designed and expressed a mutant TTHA0420 enzyme in which the C-terminal five residues were deleted (TTHA0420-ΔC5). Notably, the activity of TTHA0420-ΔC5 was about 10 times higher than that of the wild-type enzyme at 20–40 °C. Our findings suggest that the C-terminal region of TTHA0420 may regulate the alternative binding of NADH and substrate flavin to the enzyme. PMID:22052907

  18. Head-end reprocessing studies of H.B. Robinson-2 fuel: II. Parametric voloxidation studies

    SciTech Connect

    Goode, J.H.; Stacy, R.G.; Vaughen, V.C.A.

    1980-05-01

    A series of hot-cell tests was conducted with UO{sub 2} that had been irradiated to an average of 28,000 MWd/t in the H.B. Robinson-2 reactor of the Carolina Power and Light Company. The tests examined the effects of temperature and of the rate of oxygen supply on the release of gaseous and semivolatile fission products, while the fuel fragments were tumbled at 12 rpm during voloxidation - the high-temperature oxidation of UO{sub 2} to U{sub 3}O{sub 8}. The experiments showed that >99.9% of the tritium in the irradiated UO{sub 2} was released to the off-gas stream at temperatures of 480 and 550{sup 0}C and at oxygen feed rates ranging from 0.1 to 1.2 mol/h. The release of {sup 85}Kr varied from 2 to 7% of the fuel inventory. The U{sub 3}O{sub 8} product ({similar_to}99% smaller than 44 {mu}m) was easily dissolved in 7 M HNO{sub 3}. One 2-h leach in 7 M HNO{sub 3} dissolved {similar_to}99.5% of the heavy metals; a second 2-h leach in 7 M HNO{sub 3} brought the total to >99.98%. Voloxidation did not affect the final solubility of the uranium and plutonium but did increase the weight of the insoluble fission product residue from 0.18% of the irradiated UO{sub 2} to {similar_to}0.62%.

  19. A Detailed Study of the Structure of the Nested Planetary Nebula, Hb 12, the Matryoshka Nebula

    NASA Astrophysics Data System (ADS)

    Clark, D. M.; López, J. A.; Edwards, M. L.; Winge, C.

    2014-11-01

    We present near-IR, integral field spectroscopic observations of the planetary nebula (PN) Hb 12 using Near-infrared Integral Field Spectrograph (NIFS) on Gemini-North. Combining NIFS with the adaptive optics system Altair, we provide a detailed study of the core and inner structure of this PN. We focus the analysis in the prominent emission lines [Fe II] (1.6436 μm), He I (2.0585 μm), H2 (2.1214 μm), and Brγ (2.16553 μm). We find that the [Fe II] emission traces a tilted system of bipolar lobes, with the northern lobe being redshifted and the southern lobe blueshifted. The [Fe II] emission is very faint at the core and only present close to the systemic velocity. There is no H2 emission in the core, whereas the core is prominent in the He I and Brγ recombination lines. The H2 emission is concentrated in equatorial arcs of emission surrounding the core and expanding at ~30 km s-1. These arcs are compared with Hubble Space Telescope images and shown to represent nested loops belonging to the inner sections of a much larger bipolar structure that replicates the inner one. The He I and Brγ emission from the core clearly show a cylindrical central cavity that seems to represent the inner walls of an equatorial density enhancement or torus. The torus is 0.''2 wide (≡200 AU radius at a distance of 2000 pc) and expanding at <=30 km s-1. The eastern wall of the inner torus is consistently more intense than the western wall, which could indicate the presence of an off-center star, such as is observed in the similar hourglass PN, MyCn 18. A bipolar outflow is also detected in Brγ emerging within 0.''1 from the core at ~ ± 40 km s-1.

  20. Structural comparison between the open and closed forms of citrate synthase from Thermus thermophilus HB8

    PubMed Central

    Kanamori, Eiji; Kawaguchi, Shin-ichi; Kuramitsu, Seiki; Kouyama, Tsutomu; Murakami, Midori

    2015-01-01

    The crystal structures of citrate synthase from the thermophilic eubacteria Thermus thermophilus HB8 (TtCS) were determined for an open form at 1.5 Å resolution and for closed form at 2.3 Å resolution, respectively. In the absence of ligands TtCS in the open form was crystalized into a tetragonal form with a single subunit in the asymmetric unit. TtCS was also co-crystallized with citrate and coenzyme-A to form an orthorhombic crystal with two homodimers in the asymmetric unit. Citrate and CoA are found in the active site situated between the large domain and the small domain in all subunit whereas the complex shows two distinct closed conformations, the fully closed form and partially closed form. Structural comparisons are performed to describe conformational changes associated with binding of products of TtCS. Upon binding of citrate, basic residues in the active site move toward citrate and make a hydrogen bond network in the active site, inducing a large-scale rotation of the small domain relative to the large domain. CoA is sandwiched between the small and large domains and then the cysteamine tail is inserted into the active site with a cooperative rotation around mainchain dihedrals in the hinge region connecting helices M and N. According to this rotation these helices are extended to close the active site completely. The considerable flexibility and structural rearrangements in the hinge region are crucial for an ordered bibi reaction in catalysis for microbial CSs. PMID:27493854

  1. VizieR Online Data Catalog: Abundances of 9 HB stars in NGC 6352 (Feltzing+, 2009)

    NASA Astrophysics Data System (ADS)

    Feltzing, S.; Primas, F.; Johnson, R. A.

    2008-10-01

    Metal-rich globular clusters provide important tracers of the formation of our Galaxy. Moreover, and not less important, they are very important calibrators for the derivation of properties of extra-galactic metal-rich stellar populations. Nonetheless, only a few of the metal-rich globular clusters in the Milky Way have been studied using high-resolution stellar spectra to derive elemental abundances. Additionally, Rosenberg et al. identified a small group of metal-rich globular clusters that appeared to be about 2 billion years younger than the bulk of the Milky Way globular clusters. However, it is unclear if like is compared with like in this dataset as we do not know the enhancement of alpha-elements in the clusters and the amount of alpha-elements is well known to influence the derivation of ages for globular clusters. We present a study of elemental abundances for alpha and iron-peak elements for nine HB stars in the metal-rich globular cluster NGC 6352. The elemental abundances are based on high-resolution, high signal-to-noise spectra obtained with the UVES spectrograph on VLT. The elemental abundances have been derived using standard LTE calculations and stellar parameters have been derived from the spectra themselves by requiring ionizational as well as excitational equilibrium. We find that NGC 6352 has [Fe/H]=-0.55, is enhanced in the alpha-elements to about +0.2dex for Ca, Si, and Ti relative to Fe. For the iron-peak elements we find solar values. Based on the spectroscopically derived stellar parameters we find that an E(B-V)=0.24 and (m-M). (3 data files).

  2. Sickle cell anemia and α-thalassemia: a modulating factor in homozygous HbS/S patients in Oman.

    PubMed

    Hassan, S M; Al Muslahi, M; Al Riyami, M; Bakker, E; Harteveld, C L; Giordano, P C

    2014-01-01

    We report the general phenotype severity and the hematological presentation in a cohort of 125 sickle cell anemia (SCA) patients with identical homozygous HbS/S genotype and categorized by identical β(S) haplotype, both with and without alpha thalassemia. No clear general phenotype correlation was found when patients were compared regardless of the haplotype but overall, patients with homozygous alpha thalassemia (α-/α-) had the highest Hb, HCT, RBC and the lowest MCV, MCH and MCHC levels. When patients with identical haplotype were compared, the mildest hematological and clinical conditions were observed in patients of the Asian/Asian haplotype, also known as Arab-Indian haplotype, and carriers of α-thalassemia, suggesting an additional ameliorating effect of alpha thalassemia. In conclusion, our results show that alpha thalassemia improves the hematological conditions but amelioration of the general disease severity is only noticed when compared in cohorts of the same haplotype. PMID:25266642

  3. Enhanced recovery and purification of P(3HB-co-3HHx) from recombinant Cupriavidus necator using alkaline digestion method.

    PubMed

    Anis, Siti Nor Syairah; Nurhezreen, M I; Sudesh, K; Amirul, A A

    2012-06-01

    A simple, efficient and economical method for the recovery of P(3HB-co-3HHx) was developed using various chemicals and parameters. The initial content of P(3HB-co-3HHx) in bacterial cells was 50-60 wt%, whereas the monomer composition of 3HHx used in this experiments was 3-5 mol%. It was found that sodium hydroxide (NaOH) was the most effective chemical for the recovery of biodegradable polymer. High polyhydroxyalkanoate purity and recovery yield both in the range of 80-90 wt% were obtained when 10-30 mg/ml of cells were incubated in NaOH at the concentration of 0.1 M for 60-180 min at 30 °C and polished using 20 % (v/v) of ethanol. PMID:22569781

  4. Fermi LAT Discovery of Extended Gamma-Ray Emissions in the Vicinity of the HB 3 Supernova Remnant

    NASA Astrophysics Data System (ADS)

    Katagiri, H.; Yoshida, K.; Ballet, J.; Grondin, M.-H.; Hanabata, Y.; Hewitt, J. W.; Kubo, H.; Lemoine-Goumard, M.

    2016-02-01

    We report the discovery of extended gamma-ray emission measured by the Large Area Telescope (LAT) onboard the Fermi Gamma-ray Space Telescope in the region of the supernova remnant (SNR) HB 3 (G132.7+1.3) and the W3 II complex adjacent to the southeast of the remnant. W3 is spatially associated with bright 12CO (J = 1-0) emission. The gamma-ray emission is spatially correlated with this gas and the SNR. We discuss the possibility that gamma rays originate in interactions between particles accelerated in the SNR and interstellar gas or radiation fields. The decay of neutral pions produced in nucleon-nucleon interactions between accelerated hadrons and interstellar gas provides a reasonable explanation for the gamma-ray emission. The emission from W3 is consistent with irradiation of the CO clouds by the cosmic rays accelerated in HB 3.

  5. Modifying effects of maternal Hb concentration on infant birth weight in women receiving prenatal iron-containing supplements: a randomised controlled trial.

    PubMed

    Wang, Linlin; Mei, Zuguo; Li, Hongtian; Zhang, Yali; Liu, Jianmeng; Serdula, Mary K

    2016-02-28

    Concerns have been raised about the benefits of Fe-containing supplements on infant birth weight among women with normal/high Hb levels at baseline. Thus far, no clinical trials have examined whether the effects of prenatal Fe-containing supplements on birth weight vary by maternal Hb levels. We compared the effects of Fe-folic acid (IFA) or multiple micronutrients (MMN) with folic acid (FA) supplements on birth weight among pregnant women with mild/no anaemia or high Hb levels. A double-blind randomised controlled trial was conducted in 2006-2009. In total, 18 775 pregnant women with mild/no anaemia (145 g/l) baseline Hb levels, IFA and MMN supplements increased birth weight by 91·44 (95% CI 3·37, 179·51) g and 107·63 (95% CI 21·98, 193·28) g (P<0·05), respectively, compared with the FA group. No differences were found between the IFA and the MMN group, regardless of maternal Hb concentration. In conclusion, the effects of Fe-containing supplements on birth weight depended on baseline Hb concentrations. The Fe-containing supplements improved birth weight in women with very high Hb levels before 20 weeks of gestation. PMID:26824731

  6. A discrepancy between plasma glycated albumin and HbA1c levels in a patient with steroid-induced diabetes mellitus.

    PubMed

    Iizuka, Katsumi; Kato, Takehiro; Mizuno, Masami; Takeda, Jun

    2016-01-01

    A 57-year-old man was admitted for the treatment of steroid-induced diabetes mellitus (DM). He also had interstitial pneumonia and, to treat it, 20 mg prednisolone had been started in April 2014. Although glycated haemoglobin (HbA1c) level was 7.8% (62 mmol/mol), his glycated albumin (GA) level was normal (13.9%) and the ratio of GA to HbA1c (GA:HbA1c) was lower than that of normal participants and patients with type 2 DM. Plasma GA and GA:HbA1c levels became persistently lower. In September 2015, HbA1c levels measured by HPLC and immunoprecipitation methods were almost the same (6.8% (51 mmol/mol) and 6.7% (50 mmol/mol), respectively), but GA (10.2%) and GA:HbA1c (1.6) were much lower. We report the case of a patient with DM where steroid administration may have caused a decrease in plasma GA and GA:HbA1c levels via increased albumin turnover. PMID:26961565

  7. Visceral fat area is associated with HbA1c but not dialysate-related glucose load in nondiabetic PD patients

    PubMed Central

    Ho, Li-chun; Yen, Chung-Jen; Chao, Chia-Ter; Chiang, Chih-Kang; Huang, Jenq-Wen; Hung, Kuan-Yu

    2015-01-01

    Factors associated with increased visceral fat area (VFA) have been well documented in the general population but rarely explored in nondiabetic individuals on peritoneal dialysis (PD). As glycosylated hemoglobin (HbA1c) is positively correlated with VFA in diabetic patients, we hypothesized that the same correlation would exist in nondiabetic PD patients. We enrolled 105 nondiabetic patients who had undergone chronic PD for more than 3 months. Each subject underwent an abdominal computed tomography (CT) scan, and the umbilicus cut was analyzed for VFA. VFA values, corrected for body mass index and subjected to natural logarithm transformations, were examined to determine whether they were correlated with HbA1c and other parameters. PD dialysates prescribed at the time of enrollment were recorded to calculate glucose load. We found that when 105 nondiabetic PD patients were classified according to tertiles of HbA1c, higher HbA1c was associated with larger VFA. Multiple linear regression analysis revealed that HbA1c was an independent determinant of VFA, while glucose load and other PD-specific factors were not. In summary, HbA1c, but not PD-related glucose load, was positively correlated with VFA in nondiabetic PD patients, suggesting clinical utility of HbA1c in the PD population. PMID:26239161

  8. Efficacy of metabolic surgery on HbA1c decrease in type 2 diabetes mellitus patients with BMI <35 kg/m2--a review.

    PubMed

    Ngiam, Kee Yuan; Lee, Wei-Jei; Lee, Yi-Chih; Cheng, Anton

    2014-01-01

    High glycated hemoglobin A1c (HbA1c) is strongly correlated with developing type 2 diabetes mellitus (T2DM) complications; this study reviews the efficacy of various types of metabolic surgeries in reducing HbA1c levels in type 2 diabetics with BMI <35 kg/m(2). An electronic search of MEDLINE databases using terms 'metabolic surgery', type 2 diabetes mellitus, BMI <35 kg/m(2), and related keywords for studies published between 1987 and 2013. Data from 53 articles with 2,258 patients were selected for this review. The weighted mean change in HbA1c was -2.8 % (95 % CI -2.8 to -2.7, p < 0.01) and weighted mean BMI change was -5.5 kg/m(2) (95 % CI -5.6 to -5.4, p < 0.01). There was a strong correlation between weighted percentage mean change in HbA1c and BMI. Adjustable gastric banding and duodenal jejunal bypass were inferior to other surgeries in reducing BMI and HbA1c in BMI <35 kg/m(2). Metabolic surgery significantly decreases HbA1c in T2DM patients with BMI <35 kg/m(2) and that the magnitude of HbA1c change may be a useful surrogate of DM control. PMID:24242843

  9. Gq protein mediates UVB-induced cyclooxygenase-2 expression by stimulating HB-EGF secretion from HaCaT human keratinocytes

    SciTech Connect

    Seo, MiRan; Juhnn, Yong-Sung

    2010-03-05

    Ultraviolet (UV) radiation induces cyclooxygenase-2 expression to produce cellular responses including aging and carcinogenesis in skin. We hypothesised that heterotrimeric G proteins mediate UV-induced COX-2 expression by stimulating secretion of soluble HB-EGF (sHB-EGF). In this study, we aimed to elucidate the role and underlying mechanism of the {alpha} subunit of Gq protein (G{alpha}q) in UVB-induced HB-EGF secretion and COX-2 induction. We found that expression of constitutively active G{alpha}q (G{alpha}qQL) augmented UVB-induced HB-EGF secretion, which was abolished by knockdown of G{alpha}q with shRNA in HaCaT human keratinocytes. G{alpha}q was found to mediate the UVB-induced HB-EGF secretion by sequential activation of phospholipase C (PLC), protein kinase C{delta} (PKC{delta}), and matrix metaloprotease-2 (MMP-2). Moreover, G{alpha}qQL mediated UVB-induced COX-2 expression in an HB-EGF-, EGFR-, and p38-dependent manner. From these results, we concluded that G{alpha}q mediates UV-induced COX-2 expression through activation of EGFR by HB-EGF, of which ectodomain shedding was stimulated through sequential activation of PLC, PKC{delta} and MMP-2 in HaCaT cells.

  10. Visceral fat area is associated with HbA1c but not dialysate-related glucose load in nondiabetic PD patients

    NASA Astrophysics Data System (ADS)

    Ho, Li-Chun; Yen, Chung-Jen; Chao, Chia-Ter; Chiang, Chih-Kang; Huang, Jenq-Wen; Hung, Kuan-Yu

    2015-08-01

    Factors associated with increased visceral fat area (VFA) have been well documented in the general population but rarely explored in nondiabetic individuals on peritoneal dialysis (PD). As glycosylated hemoglobin (HbA1c) is positively correlated with VFA in diabetic patients, we hypothesized that the same correlation would exist in nondiabetic PD patients. We enrolled 105 nondiabetic patients who had undergone chronic PD for more than 3 months. Each subject underwent an abdominal computed tomography (CT) scan, and the umbilicus cut was analyzed for VFA. VFA values, corrected for body mass index and subjected to natural logarithm transformations, were examined to determine whether they were correlated with HbA1c and other parameters. PD dialysates prescribed at the time of enrollment were recorded to calculate glucose load. We found that when 105 nondiabetic PD patients were classified according to tertiles of HbA1c, higher HbA1c was associated with larger VFA. Multiple linear regression analysis revealed that HbA1c was an independent determinant of VFA, while glucose load and other PD-specific factors were not. In summary, HbA1c, but not PD-related glucose load, was positively correlated with VFA in nondiabetic PD patients, suggesting clinical utility of HbA1c in the PD population.

  11. Visceral fat area is associated with HbA1c but not dialysate-related glucose load in nondiabetic PD patients.

    PubMed

    Ho, Li-chun; Yen, Chung-Jen; Chao, Chia-Ter; Chiang, Chih-Kang; Huang, Jenq-Wen; Hung, Kuan-Yu

    2015-01-01

    Factors associated with increased visceral fat area (VFA) have been well documented in the general population but rarely explored in nondiabetic individuals on peritoneal dialysis (PD). As glycosylated hemoglobin (HbA1c) is positively correlated with VFA in diabetic patients, we hypothesized that the same correlation would exist in nondiabetic PD patients. We enrolled 105 nondiabetic patients who had undergone chronic PD for more than 3 months. Each subject underwent an abdominal computed tomography (CT) scan, and the umbilicus cut was analyzed for VFA. VFA values, corrected for body mass index and subjected to natural logarithm transformations, were examined to determine whether they were correlated with HbA1c and other parameters. PD dialysates prescribed at the time of enrollment were recorded to calculate glucose load. We found that when 105 nondiabetic PD patients were classified according to tertiles of HbA1c, higher HbA1c was associated with larger VFA. Multiple linear regression analysis revealed that HbA1c was an independent determinant of VFA, while glucose load and other PD-specific factors were not. In summary, HbA1c, but not PD-related glucose load, was positively correlated with VFA in nondiabetic PD patients, suggesting clinical utility of HbA1c in the PD population. PMID:26239161

  12. Toothbrushing, Blood Glucose and HbA1c: Findings from a Random Survey in Chinese Population.

    PubMed

    Su, Lingyu; Liu, Wenzhao; Xie, Bingwu; Dou, Lei; Sun, Jun; Wan, Wenjuan; Fu, Xiaoming; Li, Guangyue; Huang, Jiao; Xu, Ling

    2016-01-01

    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. PMID:27385509

  13. Evaluation of the relationship between corneal biomechanic and HbA1C levels in type 2 diabetes patients

    PubMed Central

    Yazgan, Serpil; Celik, Ugur; Kaldırım, Havva; Ayar, Orhan; Elbay, Ahmet; Aykut, Veysel; Celik, Burcu; Taş, Mehmet

    2014-01-01

    Purpose To evaluate the corneal biomechanical properties due to the glycosylated hemoglobin (HbA1C) levels using the ocular response analyzer (ORA) in the patients with type 2 diabetes mellitus (DM). Methods ORA values were obtained from 156 eyes of subjects with type 2 DM and 74 eyes of healthy control subjects with similar age and sex. Subjects were divided into three groups: Group 1, healthy control subjects; Group 2, diabetes patients with HbA1C <7%; and Group 3, diabetes patients with HbA1C ≥7%. Corneal biomechanical parameters: corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-correlated pressure (IOPg), and corneal-compensated intraocular pressure (IOPcc) measurements were obtained using ORA. Ultrasound pachymetry was used for measurement of central corneal thickness (CCT). Results CH and CRF were significantly different in each of the three groups (P-values for CH respectively; Groups 1 and 2=0.008, Groups 1 and 3, and Groups 2 and 3, <0.001, and for CRF respectively; =0.002, <0.001, <0.001). CCT was significantly different between Groups 1 and 3 and Groups 2 and 3 (P<0.001) but was insignificant between Groups 1 and 2 (P=0.965). IOPcc was not different between Groups 1 and 2 (P=0.524), and Groups 2 and 3 (P=0.115), but was significantly different between Groups 1 and 3 (P=0.003). IOPg was statistically different between each of the three groups (respectively; Groups 1 and 2, P=0.015, Groups 1 and 3, and Groups 2 and 3, P<0.001). Conclusion Both diabetes groups were affected in terms of corneal biomechanical properties when compared to healthy subjects, there was also a positive correlation between HbA1C level and intraocular pressure. PMID:25170249

  14. Radiolytic hydrogen production from process vessels in HB line - production rates compared to evolution rates and discussion of LASL reviews

    SciTech Connect

    Bibler, N.E.

    1992-11-12

    Hydrogen production from radiolysis of aqueous solutions can create a safety hazard since hydrogen is flammable. At times this production can be significant, especially in HB line where nitric acid solutions containing high concentrations of Pu-238, an intense alpha emitter, are processed. The hydrogen production rates from these solutions are necessary for safety analyses of these process systems. The methods and conclusions of hydrogen production rate tests are provided in this report.

  15. A Mouse Model of Otitis Media Identifies HB-EGF as a Mediator of Inflammation-Induced Mucosal Proliferation

    PubMed Central

    Pak, Kwang; Chavez, Eduardo; Kurabi, Arwa; Baird, Andrew; Wasserman, Stephen I.; Ryan, Allen F.

    2014-01-01

    Objective Otitis media is one of the most common pediatric infections. While it is usually treated without difficulty, up to 20% of children may progress to long-term complications that include hearing loss, impaired speech and language development, academic underachievement, and irreversible disease. Hyperplasia of middle ear mucosa contributes to the sequelae of acute otitis media and is of important clinical significance. Understanding the role of growth factors in the mediation of mucosal hyperplasia could lead to the development of new therapeutic interventions for this disease and its sequelae. Methods From a whole genome gene array analysis of mRNA expression during acute otitis media, we identified growth factors with expression kinetics temporally related to hyperplasia. We then tested these factors for their ability to stimulate mucosal epithelial growth in vitro, and determined protein levels and histological distribution in vivo for active factors. Results From the gene array, we identified seven candidate growth factors with upregulation of mRNA expression kinetics related to mucosal hyperplasia. Of the seven, only HB-EGF (heparin-binding-epidermal growth factor) induced significant mucosal epithelial hyperplasia in vitro. Subsequent quantification of HB-EGF protein expression in vivo via Western blot analysis confirmed that the protein is highly expressed from 6 hours to 24 hours after bacterial inoculation, while immunohistochemistry revealed production by middle ear epithelial cells and infiltrating lymphocytes. Conclusion Our data suggest an active role for HB-EGF in the hyperplasia of the middle ear mucosal epithelium during otitis media. These results imply that therapies targeting HB-EGF could ameliorate mucosal growth during otitis media, and thereby reduce detrimental sequelae of this childhood disease. PMID:25033458

  16. Toothbrushing, Blood Glucose and HbA1c: Findings from a Random Survey in Chinese Population

    PubMed Central

    Su, Lingyu; Liu, Wenzhao; Xie, Bingwu; Dou, Lei; Sun, Jun; Wan, Wenjuan; Fu, Xiaoming; Li, Guangyue; Huang, Jiao; Xu, Ling

    2016-01-01

    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. PMID:27385509

  17. An experimental study on aerodynamic characteristics of standard model HB-2 in high enthalpy shock tunnel HIEST

    NASA Astrophysics Data System (ADS)

    Sato, K.; Komuro, T.; Tanno, H.; Ueda, S.; Itoh, K.; Kuchiishi, S.; Watanabe, S.

    Force measurement of a standard model HB-2 was performed in high enthalpy shock tunnel HIEST to study its aerodynamic characteristics. The force measurement results were compared with that obtained in conventional 1.27m hypersonic wind tunnel HWT1. The comparison showed that HIEST results agreed well with that of HWT1 in case of low enthalpy condition. The real gas effect on aerodynamic characteristics was also studied in case of high enthalpy condition.

  18. UNC-4 represses CEH-12/HB9 to specify synaptic inputs to VA motor neurons in C. elegans.

    PubMed

    Von Stetina, Stephen E; Fox, Rebecca M; Watkins, Kathie L; Starich, Todd A; Shaw, Jocelyn E; Miller, David M

    2007-02-01

    In Caenorhabditis elegans, VA and VB motor neurons arise as lineal sisters but synapse with different interneurons to regulate locomotion. VA-specific inputs are defined by the UNC-4 homeoprotein and its transcriptional corepressor, UNC-37/Groucho, which function in the VAs to block the creation of chemical synapses and gap junctions with interneurons normally reserved for VBs. To reveal downstream genes that control this choice, we have employed a cell-specific microarray strategy that has now identified unc-4-regulated transcripts. One of these genes, ceh-12, a member of the HB9 family of homeoproteins, is normally restricted to VBs. We show that expression of CEH-12/HB9 in VA motor neurons in unc-4 mutants imposes VB-type inputs. Thus, this work reveals a developmental switch in which motor neuron input is defined by differential expression of transcription factors that select alternative presynaptic partners. The conservation of UNC-4, HB9, and Groucho expression in the vertebrate motor circuit argues that similar mechanisms may regulate synaptic specificity in the spinal cord. PMID:17289921

  19. VizieR Online Data Catalog: 2nd and 3d parameters of HB of globular clusters (Gratton+, 2010)

    NASA Astrophysics Data System (ADS)

    Gratton, R. G.; Carretta, E.; Bragaglia, A.; Lucatello, S.; S'orazii, V.

    2010-05-01

    The second parameter (the first being metallicity) defining the distribution of stars on the horizontal branch (HB) of globular clusters (GCs) has long been one of the major open issues in our understanding of the evolution of normal stars. Large photometric and spectroscopic databases are now available: they include large and homogeneous sets of colour-magnitude diagrams, cluster ages, and homogeneous data about chemical compositions from our FLAMES survey. We use these databases to re-examine this issue. Methods. We use the photometric data to derive median and extreme (i.e., the values including 90% of the distribution) colours and magnitudes of stars along the HB for about a hundred GCs. We transform these into median and extreme masses of stars on the HB, using the models developed by the Pisa group, and taking into account evolutionary effects. We compare these masses with those expected at the tip of the red giant branch (RGB) to derive the total mass lost by the stars. (11 data files).

  20. Implementation of the HbA1c IFCC unit --from the laboratory to the consumer: The New Zealand experience.

    PubMed

    Florkowski, Christopher; Crooke, Michael; Reed, Maxine

    2014-05-15

    In 2007, an international consensus statement recommended that HbA1c results should be reported world-wide in IFCC units (mmol/mol) and also the more familiar derived percentage units using a master equation. In New Zealand, the HbA1c IFCC units have been successfully implemented and used exclusively since 3rd October 2011 (following a 2 year period of reporting both units) for both patient monitoring and the diagnosis of diabetes, with a diagnostic cut-off of ≥50 mmol/mol. The consultation process in New Zealand dates back to 2003, well before the international recommendations were made. It reflects the close cooperation between the clinical and laboratory communities in New Zealand, particularly through the agency of the New Zealand Society for the Study of Diabetes (NZSSD), a key organisation in New Zealand open to all those involved in the care of people with diabetes and the national advisory body on scientific and clinical diabetes care and standards. There was a phased process of consultation designed to increase familiarity and comfort with the new units and the final step was coupled with the adoption of HbA1c as a diagnostic test with some evidence-based pragmatism around using the rounded cut-off. Genuine clinical engagement is vital in such a process. PMID:24148360

  1. Bio-plastic (P-3HB-co-3HV) from Bacillus circulans (MTCC 8167) and its biodegradation.

    PubMed

    Phukon, Pinkee; Saikia, Jyoti Prasad; Konwar, Bolin Kumar

    2012-04-01

    Polyhydroxyalkanoates (PHAs) are naturally occurring polyesters synthesized by bacteria for carbon and energy storage and it has commercial potential as bioplastic. The bacterial species Bacillus circulans MTCC 8167, isolated from crude oil contaminated soil, can efficiently produce medium chain length polyhydroxyalkanoates (P-3HB-co-3HV) from cheap carbon sources like dextrose. The molecular mass of P-3HB-co-3HV was reported as 5.1×10(4)Da with polydispersity index of 1.21 by gel permeation chromatography. In the present investigation different bacteria and fungi species were used for testing the biodegradability of the extracted polymer. The FTIR spectra of the biodegraded PHBV film showed a decrease in the peak from 1735 cm(-1) (untreated film) to 1675 cm(-1), and disappearance of a peak present in the control at 2922 cm(-1) indicating the breakdown of ester (>C=O) or O-R group and -C=H bond, respectively. From biodegradability testing, the tested microorganisms were found to have decisive contribution to the biodegradation of P-3HB-co-3HV polymer. PMID:22154099

  2. Contribution of transcription factor, SP1, to the promotion of HB-EGF expression in defense mechanism against the treatment of irinotecan in ovarian clear cell carcinoma

    PubMed Central

    Miyata, Kohei; Yotsumoto, Fusanori; Nam, Sung Ouk; Odawara, Takashi; Manabe, Sadao; Ishikawa, Toyokazu; Itamochi, Hiroaki; Kigawa, Junzo; Takada, Shuji; Asahara, Hiroshi; Kuroki, Masahide; Miyamoto, Shingo

    2014-01-01

    Ovarian clear cell carcinoma (OCCC) is a worst histological subtype than other ovarian malignant tumor. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a promising target for ovarian cancer therapy. The aims of this study were to validate the efficacy of HB-EGF–targeted therapy for OCCC and to identify the transcription factor that contributed to the induction of HB-EGF by SN38 treatment in OCCC cells. HB-EGF was highly expressed in OCCC cells, and an increase of HB-EGF was induced by SN38 which had only antitumor effect among conventional anticancer agents on OCCC. A specific inhibitor of HB-EGF, a cross-reacting material 197 (CRM197), led to a synergistic increase in the number of apoptotic OCCC cells with the treatment of SN38. The luciferase assay with 5′-deletion promoter constructs identified a GC-rich element between −125 and −178 (the distal transcription start site was denoted +1) as a cis-regulatory region, and the treatment of SN38 induced luciferase activity in this region. An in silico and chromatin immunoprecipitation analysis estimated that SP1 bound to the cis-regulatory region of HB-EGF in OCCC cells. Real-time PCR and cell viability assays showed that the transfection of a small interfering RNA targeting SP1 suppressed the expression of HB-EGF induced by SN38, resulting in the enhanced sensitivity of SN38. Taken together, these results indicate that induction of HB-EGF expression contributed to defense mechanism against treatment of SN38 through the transcriptional activity of SP1 in OCCC cells. PMID:25060396

  3. Are There Clinical Implications of Racial Differences in HbA1c? Yes, to Not Consider Can Do Great Harm!

    PubMed

    Herman, William H

    2016-08-01

    Studies that have compared HbA1c levels by race have consistently demonstrated higher HbA1c levels in African Americans than in whites. These racial differences in HbA1c have not been explained by measured differences in glycemia, sociodemographic factors, clinical factors, access to care, or quality of care. Recently, a number of nonglycemic factors and several genetic polymorphisms that operate through nonglycemic mechanisms have been associated with HbA1c Their distributions across racial groups and their impact on hemoglobin glycation need to be systematically explored. Thus, on the basis of evidence for racial differences in HbA1c, current clinical guidelines from the American Diabetes Association state: "It is important to take…race/ethnicity…into consideration when using the A1C to diagnose diabetes." However, it is not clear from the guidelines how this recommendation might be actualized. So, the critical question is not whether racial differences in HbA1c exist between African Americans and whites; the important question is whether the observed differences in HbA1c level are clinically meaningful. Therefore, given the current controversy, we provide a Point-Counterpoint debate on this issue. In the point narrative below, Dr. Herman provides his argument that the failure to acknowledge that HbA1c might be a biased measure of average glycemia and an unwillingness to rigorously investigate this hypothesis will slow scientific progress and has the potential to do great harm. In the counterpoint narrative that follows Dr. Herman's contribution, Dr. Selvin argues that there is no compelling evidence for racial differences in the validity of HbA1c as a measure of hyperglycemia and that race is a poor surrogate for differences in underlying causes of disease risk.-William T. CefaluEditor in Chief, Diabetes Care. PMID:27457636

  4. Are There Clinical Implications of Racial Differences in HbA1c? A Difference, to Be a Difference, Must Make a Difference.

    PubMed

    Selvin, Elizabeth

    2016-08-01

    Studies that have compared HbA1c levels by race have consistently demonstrated higher HbA1c levels in African Americans than in whites. These racial differences in HbA1c have not been explained by measured differences in glycemia, sociodemographic factors, clinical factors, access to care, or quality of care. Recently, a number of nonglycemic factors and several genetic polymorphisms that operate through nonglycemic mechanisms have been associated with HbA1c Their distributions across racial groups and their impact on hemoglobin glycation need to be systematically explored. Thus, on the basis of evidence for racial differences in HbA1c, current clinical guidelines from the American Diabetes Association state: "It is important to take…race/ethnicity…into consideration when using the A1C to diagnose diabetes." However, it is not clear from the guidelines how this recommendation might be actualized. So, the critical question is not whether racial differences in HbA1c exist between African Americans and whites; the important question is whether the observed differences in HbA1c level are clinically meaningful. Therefore, given the current controversy, we provide a Point-Counterpoint debate on this issue. In the preceding point narrative, Dr. Herman provides his argument that the failure to acknowledge that HbA1c might be a biased measure of average glycemia and an unwillingness to rigorously investigate this hypothesis will slow scientific progress and has the potential to do great harm. In the counterpoint narrative below, Dr. Selvin argues that there is no compelling evidence for racial differences in the validity of HbA1c as a measure of hyperglycemia and that race is a poor surrogate for differences in underlying causes of disease risk.-William T. CefaluEditor in Chief, Diabetes Care. PMID:27457637

  5. HbAHP-25, an In-Silico Designed Peptide, Inhibits HIV-1 Entry by Blocking gp120 Binding to CD4 Receptor

    PubMed Central

    Bashir, Tahir; Patgaonkar, Mandar; Kumar C, Selvaa; Pasi, Achhelal; Reddy, Kudumula Venkata Rami

    2015-01-01

    Human Immunodeficiency Virus (HIV-1) poses a serious threat to the developing world and sexual transmission continues to be the major source of new infections. Therefore, the development of molecules, which prevent new HIV-1 infections, is highly warranted. In the present study, a panel of human hemoglobin (Hb)-α subunit derived peptides and their analogues, with an ability to bind gp120, were designed in-silico and their anti-HIV-1 activity was evaluated. Of these peptides, HbAHP-25, an analogue of Hb-α derived peptide, demonstrated significant anti-HIV-1 activity. HbAHP-25 was found to be active against CCR5-tropic HIV-1 strains (ADA5 and BaL) and CXCR4-tropic HIV-1 strains (IIIB and NL4-3). Surface plasmon resonance (SPR) and ELISA revealed direct interaction between HbAHP-25 and HIV-1 envelope protein, gp120. The peptide prevented binding of CD4 to gp120 and blocked subsequent steps leading to entry and/or fusion or both. Anti-HIV activity of HbAHP-25 appeared to be specific as it failed to inhibit the entry of HIV-1 pseudotyped virus (HIV-1 VSV). Further, HbAHP-25 was found to be non-cytotoxic to TZM-bl cells, VK2/E6E7 cells, CEM-GFP cells and PBMCs, even at higher concentrations. Moreover, HbAHP-25 retained its anti-HIV activity in presence of seminal plasma and vaginal fluid. In brief, the study identified HbAHP-25, a novel anti-HIV peptide, which directly interacts with gp120 and thus has a potential to inhibit early stages of HIV-1 infection. PMID:25915507

  6. HbAHP-25, an In-Silico Designed Peptide, Inhibits HIV-1 Entry by Blocking gp120 Binding to CD4 Receptor.

    PubMed

    Bashir, Tahir; Patgaonkar, Mandar; Kumar, Selvaa C; Pasi, Achhelal; Reddy, Kudumula Venkata Rami

    2015-01-01

    Human Immunodeficiency Virus (HIV-1) poses a serious threat to the developing world and sexual transmission continues to be the major source of new infections. Therefore, the development of molecules, which prevent new HIV-1 infections, is highly warranted. In the present study, a panel of human hemoglobin (Hb)-α subunit derived peptides and their analogues, with an ability to bind gp120, were designed in-silico and their anti-HIV-1 activity was evaluated. Of these peptides, HbAHP-25, an analogue of Hb-α derived peptide, demonstrated significant anti-HIV-1 activity. HbAHP-25 was found to be active against CCR5-tropic HIV-1 strains (ADA5 and BaL) and CXCR4-tropic HIV-1 strains (IIIB and NL4-3). Surface plasmon resonance (SPR) and ELISA revealed direct interaction between HbAHP-25 and HIV-1 envelope protein, gp120. The peptide prevented binding of CD4 to gp120 and blocked subsequent steps leading to entry and/or fusion or both. Anti-HIV activity of HbAHP-25 appeared to be specific as it failed to inhibit the entry of HIV-1 pseudotyped virus (HIV-1 VSV). Further, HbAHP-25 was found to be non-cytotoxic to TZM-bl cells, VK2/E6E7 cells, CEM-GFP cells and PBMCs, even at higher concentrations. Moreover, HbAHP-25 retained its anti-HIV activity in presence of seminal plasma and vaginal fluid. In brief, the study identified HbAHP-25, a novel anti-HIV peptide, which directly interacts with gp120 and thus has a potential to inhibit early stages of HIV-1 infection. PMID:25915507

  7. Hb40-61a: Novel analogues help expanding the knowledge on chemistry, properties and candidacidal action of this bovine α-hemoglobin-derived peptide.

    PubMed

    Carvalho, L A C; Remuzgo, C; Perez, K R; Machini, M T

    2015-12-01

    This study expands the knowledge on chemical synthesis and properties of Hb40-61a as well as provides results of the first steps given towards knowing how it kills Candida cells. For the first time, this peptide, its all-D analogue (D-Hb40-61a) and its fluorescently labeled analogue (FAM-Hb40-61a) were successfully assembled on resin at 60°C using conventional heating in all steps. Purified and characterized, these peptides exhibited very low toxicity on human erythrocytes. Hb40-61a and D-Hb40-61a were equally active against Candida strains, ruling out sterically specific interactions on their working mechanism. Cell permeabilization assays confirmed progressive damage of the yeast plasma membrane with increasing concentrations of Hb40-61a. While experiment using the fluorescent probe DiBAC4(5) revealed that this synthetic hemocidin alters the yeast plasma membrane potential, test employing DPH indicated that Hb40-61a might affect its dynamics. Exposure of the yeast cells to FAM-Hb40-61a showed that the peptide accumulates in the cell membrane at the ½ MIC, but stains about 97% of the cells at the MIC. Such effect is salt-dependent and partially energy-dependent. These new findings indicate that the central target of Hb40-61a in Candida cells is the plasma membrane and that this synthetic hemocidin should be considered as a potential candidacidal for topic uses. PMID:26367061

  8. The Natural History of Hb S/Hereditary Persistence of Fetal Hemoglobin in 13 Children from the State of Minas Gerais, Brazil.

    PubMed

    Belisário, André R; Sales, Rahyssa R; Silva, Célia M; Velloso-Rodrigues, Cibele; Viana, Marcos Borato

    2016-06-01

    Children with Hb S (HBB: c.20A > T)/hereditary persistence of fetal hemoglobin (Hb S/HPFH) have a mild clinical phenotype, but some complications have been reported. The natural history of Hb S/HPFH in children from the State of Minas Gerais, Brazil newborn cohort is described. Clinical and hematological data regarding participants' phenotypes were retrieved from medical records. The HPFH-1, HPFH-2, and HPFH-3 and α-thalassemia (α-thal) deletions were detected by gap-polymerase chain reaction (gap-PCR). Thirteen children were included, nine (69.2%) had the Hb S/HPFH-2 deletion, and four (30.8%) had Hb S/HPFH-1 deletion; 11 children (84.6%) had αα/αα, and two (15.4%) carried the αα/-α(3.7) (rightward) deletion. The mean concentration of total hemoglobin (Hb) and Hb F was 12.52 ± 0.56 g/dL and 42.31% ± 1.97%, respectively. Mild microcytosis and hypochromia were observed. We found acute clinical manifestations of sickle cell disease, such as acute chest syndrome (ACS) and acute pain crisis in four children; nine (69.2%) children were completely asymptomatic during the follow-up period. All children were classified as having low-risk transcranial Doppler (TDC). In conclusion, children with Hb S/HPFH have a mild clinical phenotype of sickle cell disease, although acute clinical manifestations may occur. High Hb F levels and absence of anemia are common hematological characteristics. PMID:27117574

  9. Heterogeneous behavior of lipids according to HbA1c levels undermines the plausibility of metabolic syndrome in type 1 diabetes: data from a nationwide multicenter survey

    PubMed Central

    2012-01-01

    Background Cardiovascular risk factors (CVRF) may cluster in type 1 diabetes, analogously to the metabolic syndrome described in type 2 diabetes. The threshold of HbA1c above which lipid variables start changing behavior is unclear. This study aims to 1) assess the behavior of dyslipidemia according to HbA1c values; 2) detect a threshold of HbA1c beyond which lipids start to change and 3) compare the clustering of lipids and other non-lipid CVRF among strata of HbA1c individuals with type 1 diabetes. Methods Effects of HbA1c quintiles (1st: ≤7.4%; 2nd: 7.5-8.5%; 3rd: 8.6-9.6%; 4th: 9.7-11.3%; and 5th: >11.5%) and covariates (gender, BMI, blood pressure, insulin daily dose, lipids, statin use, diabetes duration) on dyslipidemia were studied in 1275 individuals from the Brazilian multi-centre type 1 diabetes study and 171 normal controls. Results Body size and blood pressure were not correlated to lipids and glycemic control. OR (99% CI) for high-LDL were 2.07 (1.21-3.54) and 2.51 (1.46-4.31), in the 4th and 5th HbA1c quintiles, respectively. Hypertriglyceridemia increased in the 5th quintile of HbA1c, OR 2.76 (1.20-6.37). OR of low-HDL-cholesterol were 0.48 (0.24-0.98) and 0.41 (0.19-0.85) in the 3rd and 4th HbA1c quintiles, respectively. HDL-cholesterol correlated positively (0.437) with HbA1c in the 3rd quintile. HDL-cholesterol and insulin dose correlated inversely in all levels of glycemic control. Conclusions Correlation of serum lipids with HbA1c is heterogeneous across the spectrum of glycemic control in type 1 diabetes individuals. LDL-cholesterol and triglycerides worsened alongside HbA1c with distinct thresholds. Association of lower HDL-cholesterol with higher daily insulin dose is consistent and it points out to a role of exogenous hyperinsulinemia in the pathophysiology of the CVRF clustering. These data suggest diverse pathophysiological processes depending on HbA1c, refuting a unified explanation for cardiovascular risk in type 1 diabetes. PMID

  10. Hb Belluno [β111(G13)Val→Gly;β133(H11)Val→Val (HBB: c.335T > G;402G > C)]: Incidental Detection of a New Clinically Silent β Chain Variant During Hb A1c Determination by High Performance Liquid Chromatography.

    PubMed

    Pianezze, Graziano; Toniolo, Manuele; Taddei Masieri, Marina; Dolcini, Bernardetta; Ravani, Anna

    2016-06-01

    A previously unreported β chain variant, Hb Belluno [β111(G13)Val→Gly;β133(H11)Val→Val (HBB: c.335T > G;402G > C)], was incidentally discovered in a woman suffering from diabetes, during glycated hemoglobin (Hb A1c) assay. Its presence was suspected because of a small abnormal peak with a retention time just shorter than that of normal Hb A1c. Standard high performance liquid chromatography (HPLC), capillary zone electrophoresis (CZE) and agarose gel electrophoresis did not allow to separate the variant from Hb A. The reversed phase HPLC of globin chains showed the presence of a heterozygous β-globin variant amounting to approximately 43.5% of the total β chains. Later, this variant was found in five other members of the same family and DNA sequencing analysis confirmed a β-globin gene mutation. The variant is clinically silent in all patients and showed a slight instability with both heat and isopropanol tests. The other three mutations at this locus also affect stability. Hemoglobin (Hb) variants may invalidate the results of Hb A1c analysis and could result in mismanagement of diabetes. A comment alerting the requesting clinician to the presence of the Hb variant must be appended to the Hb A1c result. Additionally, many Hb variants can be chromatographically and/or electrophoretically silent. Therefore, when the clinician suspects a variant Hb, it is not sufficient to get a negative response from an HPLC screening test to rule it out. A dialogue with the pathologist is essential, involving exchange of information and sharing a diagnostic work-up including surveys to assess Hb stability and oxygen affinity, as much as DNA sequencing. PMID:27032675

  11. NGF and HB-EGF: Potential Biomarkers that Reflect the Effects of Fesoterodine in Patients with Overactive Bladder Syndrome

    PubMed Central

    Kim, Soo Rim; Moon, Yeo Jung; Kim, Sei Kwang

    2015-01-01

    Purpose To determine whether levels of nerve growth factor (NGF) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) can be used to objectively assess overactive bladder syndrome (OAB) treatment outcome and to evaluate the effects of fixed-dose fesoterodine on OAB symptoms. Materials and Methods This study included 124 participants (62 patients with OAB and 62 controls) in Severance Hospital between 2010 and 2012. In patients with OAB, 4 mg fesoterodine was administered once daily. Repeated evaluations of putative biomarker levels, urine creatinine (Cr) levels, and questionnaire responses, including the Overactive Bladder Symptom Score (OABSS) and the Overactive Bladder Questionnaire (OAB q), were performed from baseline to 16 weeks. Results Urinary levels of NGF/Cr (OAB: 1.13±0.9 pg/mg; control: 0.5±0.29 pg/mg) and HB-EGF/Cr (OAB: 8.73±6.55 pg/mg; control: 4.45±2.93 pg/mg) were significantly higher in subjects with OAB than in controls (p<0.001). After 16 weeks of fixed-dose fesoterodine treatment, urinary NGF/Cr levels (baseline: 1.13±0.08 pg/mg; 16 weeks: 0.60±0.4 pg/mg; p=0.02) and HB-EGF/Cr levels significantly decreased (baseline: 8.73±6.55 pg/mg; 16 weeks: 4.72±2.69 pg/mg; p=0.03, respectively). Both the OABSS and OAB q scores improved (p<0.001). However, there were no a statistically significant correlations between these urinary markers and symptomatic scores. Conclusion Urinary levels of NGF and HB-EGF may be potential biomarkers for evaluating outcome of OAB treatment. Fixed-dose fesoterodine improved OAB symptoms. Future studies are needed to further examine the significance of urinary NGF and HB-EGF levels as therapeutic markers for OAB. PMID:25510766

  12. Modulating Distal Cavities in the α and β Subunits of Human HbA Reveals the Primary Ligand Migration Pathway†

    PubMed Central

    Birukou, Ivan; Maillett, David H.; Birukova, Anastasiya; Olson, John S.

    2011-01-01

    The free volume in the active site of human HbA plays a crucial role in governing the bimolecular rates of O2, CO, and NO binding, the fraction of geminate ligand recombination, and the rate of NO dioxygenation by the oxygenated complex. We have decreased the size of the distal pocket by mutating Leu(B10), Val(E11) and Leu(G8) to Phe and Trp and of other more internal cavities by filling them with Xe at high gas pressures. Increasing the size of the B10 side chain reduces bimolecular rates of ligand binding nearly 5,000-fold and inhibits CO geminate recombination due to both reduction of the capture volume in the distal pocket and direct steric hindrance of Fe-ligand bond formation. Phe and Trp(E11) mutations also cause a decrease in distal pocket volume but, at the same time, increase access to the Fe atom due to the loss of the γ2 CH3 group of the native Val(E11) side chain. The net result of these E11 substitutions is a dramatic increase in geminate recombination because dissociated CO is sequestered close to the Fe atom and can rapidly rebind without steric resistance. However, the bimolecular rate constants for ligand binding to the Phe and Trp(E11) mutants are decreased 5–30-fold, due to a smaller capture volume. Geminate and bimolecular kinetic parameters for Phe and Trp(G8) mutants are similar to those for the native HbA subunits because the aromatic rings at this position cause little change in distal pocket volume and because ligands do not move past this position into the globin interior of wild-type HbA subunits. The latter conclusion is verified by the observation that Xe binding to the α and β Hb subunits has little effect on either geminate or bimolecular ligand rebinding. All of these experimental results argue strongly against alternative ligand migration pathways that involve movements through the protein interior in HbA. Instead, ligands appear to enter through the His(E7) gate and are captured directly in the distal cavity. PMID:21793487

  13. A detailed study of the structure of the nested planetary nebula, Hb 12, the Matryoshka nebula

    SciTech Connect

    Clark, D. M.; López, J. A.; Edwards, M. L.; Winge, C. E-mail: jal@astrosen.unam.mx E-mail: cwinge@gemini.edu

    2014-11-01

    We present near-IR, integral field spectroscopic observations of the planetary nebula (PN) Hb 12 using Near-infrared Integral Field Spectrograph (NIFS) on Gemini-North. Combining NIFS with the adaptive optics system Altair, we provide a detailed study of the core and inner structure of this PN. We focus the analysis in the prominent emission lines [Fe II] (1.6436 μm), He I (2.0585 μm), H{sub 2} (2.1214 μm), and Br{sub γ} (2.16553 μm). We find that the [Fe II] emission traces a tilted system of bipolar lobes, with the northern lobe being redshifted and the southern lobe blueshifted. The [Fe II] emission is very faint at the core and only present close to the systemic velocity. There is no H{sub 2} emission in the core, whereas the core is prominent in the He I and Br{sub γ} recombination lines. The H{sub 2} emission is concentrated in equatorial arcs of emission surrounding the core and expanding at ∼30 km s{sup –1}. These arcs are compared with Hubble Space Telescope images and shown to represent nested loops belonging to the inner sections of a much larger bipolar structure that replicates the inner one. The He I and Br{sub γ} emission from the core clearly show a cylindrical central cavity that seems to represent the inner walls of an equatorial density enhancement or torus. The torus is 0.''2 wide (≡200 AU radius at a distance of 2000 pc) and expanding at ≤30 km s{sup –1}. The eastern wall of the inner torus is consistently more intense than the western wall, which could indicate the presence of an off-center star, such as is observed in the similar hourglass PN, MyCn 18. A bipolar outflow is also detected in Br{sub γ} emerging within 0.''1 from the core at ∼ ± 40 km s{sup –1}.

  14. Two new δ-globin gene variants: Hb A(2)-Saint-Etienne [δ14(A11)Leu→Pro (HBD: c.44T>C)] and Hb A(2)-Marseille [δ22(B4) Ala→Lys (HBD: c.67G>A;68C>A)].

    PubMed

    Joly, Philippe; Lacan, Philippe; Garcia, Caroline; Desbrée, Aurélie; Couprie, Nicole; Francina, Alain

    2013-01-01

    We report two new variants of the δ-globin gene: Hb A(2)-Saint-Etienne [δ14(A11)Leu→Pro] and Hb A(2)-Marseille [δ22(B4)Ala→Lys]. The first variant has a low rate of expression, the second results from a double nucleotide mutation on the same codon. PMID:23227922

  15. Co-Incidence or Co-Existence? Acute Lymphoblastic Leukaemia in HbE-alpha Thalassaemia: A Case Report with Review of Literature

    PubMed Central

    Rajendran, Rithika; Rajendran, Aruna; Scott, Julius Xavier

    2015-01-01

    Haemoglobin E (HbE) is a Haemoglobin variant that commonly occurs in many places in Asia. As β thalassaemia and α thalassaemia also occur in the same regions, the co-inheritance of these conditions leads to various phenotypic forms. HbE α thalassaemia is less common and of a milder phenotype than HbE β thalassaemia. Though malignancies are one of the complications in thalassaemia, occurrence of leukaemia is a rare event. Here we present a case of a two-year-old male child co-presenting with pre B acute lymphoblastic leukaemia (ALL) with MLL rearrangement and HbE alpha thalassaemia. The child is on remission 12 months post-therapy with standard ALL high risk protocol with no minimal residual disease (MRD). Haematological and oncological conditions coexisting at presentation is a challenge to therapy. This case is described for its rarity. Informed consent has been obtained from the parents. PMID:26672845

  16. Reduced rate of sickle-related complications in Brazilian patients carrying HbF-promoting alleles at the BCL11A and HMIP-2 loci.

    PubMed

    Leonardo, Flávia C; Brugnerotto, Ana F; Domingos, Igor F; Fertrin, Kleber Y; de Albuquerque, Dulcinéia M; Bezerra, Marcos A C; Araújo, Aderson S; Saad, Sara T O; Costa, Fernando F; Menzel, Stephan; Conran, Nicola; Thein, Swee Lay

    2016-05-01

    The presence of high levels of fetal haemoglobin (HbF) provides well-validated clinical benefits to patients with sickle cell anaemia (SCA). Nevertheless it has been difficult to show clear direct effects of the known genetic HbF modifiers, such as the enhancer polymorphisms for haematopoietic transcription factors BCL11A and MYB, on SCA severity. Investigating SCA patients from Brazil, with a high degree of European genetic admixture, we have detected strong effects of these variants on HbF levels. Critically, we have shown, for the first time, that the presence of such HbF-promoting variants leads to a reduced rate of SCA complications, especially stroke. PMID:26888013

  17. Effect of antigen-dependent clearance on pharmacokinetics of anti-heparin-binding EGF-like growth factor (HB-EGF) monoclonal antibody.

    PubMed

    Kasai, Noriyuki; Yoshikawa, Yukitaka; Enokizono, Junichi

    2014-01-01

    Heparin-binding EGF-like growth factor (HB-EGF) is a member of the EGF family and is an important therapeutic target in some types of human cancers. KM3566 is a mouse anti-HB-EGF monoclonal antibody that neutralizes HB-EGF activity by inhibiting the binding of HB-EGF to its receptors. Based on the results of our pharmacokinetics study, a humanized derivative antibody, KHK2866, is rapidly cleared from serum and shows nonlinear pharmacokinetics in cynomolgus monkeys. In this study, we examined the antigen-dependent clearance of an anti-HB-EGF monoclonal antibody in vivo and in vitro in order to pharmacokinetically explain the rapid elimination of KHK2866. We revealed tumor size-dependent clearance of KM3566 in in vivo studies and obtained good fits between the observed and simulated concentrations of KM3566 based on the two-compartment with a saturable route of clearance model. Furthermore, in vivo imaging analyses demonstrated tumor-specific distribution of KM3566. We then confirmed rapid internalization and distribution to lysosome of KM3566 at a cellular level. Moreover, we revealed that the amounts of HB-EGF on cell surface membrane were maintained even while HB-EGF was internalized with KM3566. Recycled or newly synthesized HB-EGF, therefore, may contribute to a consecutive clearance of KM3566, which could explain a rapid clearance from serum. These data suggested that the rapid elimination in pharmacokinetics of KM3566 is due to antigen-dependent clearance. Given that its antigen is expressed in a wide range of normal tissue, it is estimated that the rapid elimination of KHK2866 from cynomolgus monkey serum is caused by antigen-dependent clearance. PMID:25517307

  18. Single-Use Disposable Electrochemical Label-Free Immunosensor for Detection of Glycated Hemoglobin (HbA1c) Using Differential Pulse Voltammetry (DPV).

    PubMed

    Molazemhosseini, Alireza; Magagnin, Luca; Vena, Pasquale; Liu, Chung-Chiun

    2016-01-01

    A single-use disposable in vitro electrochemical immunosensor for the detection of HbA1c in undiluted human serum using differential pulse voltammetry (DPV) was developed. A three-electrode configuration electrochemical biosensor consisted of 10-nm-thin gold film working and counter electrodes and a thick-film printed Ag/AgCl reference electrode was fabricated on a polyethylene terephthalate (PET) substrate. Micro-fabrication techniques including sputtering vapor deposition and thick-film printing were used to fabricate the biosensor. This was a roll-to-roll cost-effective manufacturing process making the single-use disposable in vitro HbA1c biosensor a reality. Self-assembled monolayers of 3-Mercaptopropionic acid (MPA) were employed to covalently immobilize anti-HbA1c on the surface of gold electrodes. Electrochemical impedance spectroscopy (EIS) and X-ray photoelectron spectroscopy (XPS) confirmed the excellent coverage of MPA-SAM and the upward orientation of carboxylic groups. The hindering effect of HbA1c on the ferricyanide/ferrocyanide electron transfer reaction was exploited as the HbA1c detection mechanism. The biosensor showed a linear range of 7.5-20 µg/mL of HbA1c in 0.1 M PBS. Using undiluted human serum as the test medium, the biosensor presented an excellent linear behavior (R² = 0.999) in the range of 0.1-0.25 mg/mL of HbA1c. The potential application of this biosensor for in vitro measurement of HbA1c for diabetic management was demonstrated. PMID:27376299

  19. Single-Use Disposable Electrochemical Label-Free Immunosensor for Detection of Glycated Hemoglobin (HbA1c) Using Differential Pulse Voltammetry (DPV)

    PubMed Central

    Molazemhosseini, Alireza; Magagnin, Luca; Vena, Pasquale; Liu, Chung-Chiun

    2016-01-01

    A single-use disposable in vitro electrochemical immunosensor for the detection of HbA1c in undiluted human serum using differential pulse voltammetry (DPV) was developed. A three-electrode configuration electrochemical biosensor consisted of 10-nm-thin gold film working and counter electrodes and a thick-film printed Ag/AgCl reference electrode was fabricated on a polyethylene terephthalate (PET) substrate. Micro-fabrication techniques including sputtering vapor deposition and thick-film printing were used to fabricate the biosensor. This was a roll-to-roll cost-effective manufacturing process making the single-use disposable in vitro HbA1c biosensor a reality. Self-assembled monolayers of 3-Mercaptopropionic acid (MPA) were employed to covalently immobilize anti-HbA1c on the surface of gold electrodes. Electrochemical impedance spectroscopy (EIS) and X-ray photoelectron spectroscopy (XPS) confirmed the excellent coverage of MPA-SAM and the upward orientation of carboxylic groups. The hindering effect of HbA1c on the ferricyanide/ferrocyanide electron transfer reaction was exploited as the HbA1c detection mechanism. The biosensor showed a linear range of 7.5–20 µg/mL of HbA1c in 0.1 M PBS. Using undiluted human serum as the test medium, the biosensor presented an excellent linear behavior (R2 = 0.999) in the range of 0.1–0.25 mg/mL of HbA1c. The potential application of this biosensor for in vitro measurement of HbA1c for diabetic management was demonstrated. PMID:27376299

  20. HbNIN2, a cytosolic alkaline/neutral-invertase, is responsible for sucrose catabolism in rubber-producing laticifers of Hevea brasiliensis (para rubber tree).

    PubMed

    Liu, Shujin; Lan, Jixian; Zhou, Binhui; Qin, Yunxia; Zhou, Yihua; Xiao, Xiaohu; Yang, Jianghua; Gou, Jiqing; Qi, Jiyan; Huang, Yacheng; Tang, Chaorong

    2015-04-01

    In Hevea brasiliensis, an alkaline/neutral invertase (A/N-Inv) is responsible for sucrose catabolism in latex (essentially the cytoplasm of rubber-producing laticifers, the source of natural rubber) and implicated in rubber yield. However, neither the gene encoding this enzyme nor its molecular and biochemical properties have been well documented. Three Hevea A/N-Inv genes, namely HbNIN1, 2 and 3, were first cloned and characterized in planta and in Escherichia coli. Cellular localizations of HbNIN2 mRNA and protein were probed. From latex, active A/N-Inv proteins were purified, identified, and explored for enzymatic properties. HbNIN2 was identified as the major A/N-Inv gene functioning in latex based on its functionality in E. coli, its latex-predominant expression, the conspicuous localization of its mRNA and protein in the laticifers, and its expressional correlation with rubber yield. An active A/N-Inv protein was partially purified from latex, and determined as HbNIN2. The enhancement of HbNIN2 enzymatic activity by pyridoxal is peculiar to A/N-Invs in other plants. We conclude that HbNIN2, a cytosolic A/N-Inv, is responsible for sucrose catabolism in rubber laticifers. The results contribute to the studies of sucrose catabolism in plants as a whole and natural rubber synthesis in particular. PMID:25581169

  1. Pediatric Diabetes Consortium Type 1 Diabetes (T1D) New Onset (NeOn) Study: Factors Associated with HbA1c Levels One Year after Diagnosis

    PubMed Central

    Redondo, Maria J.; Connor, Crystal G.; Ruedy, Katrina J.; Beck, Roy W.; Kollman, Craig; Wood, Jamie R.; Buckingham, Bruce; Klingensmith, Georgeanna; Silverstein, Janet; Tamborlane, William V.

    2013-01-01

    Objective To identify determinants of HbA1c levels one year after the diagnosis of type 1 diabetes (T1D) in participants in the Pediatric Diabetes Consortium (PDC) T1D New Onset (NeOn) Study. Research Design and Methods Diabetes-specific as well as socioeconomic factors during the first year following diagnosis were analyzed in 857 participants (mean age 9.1 years, 51% female, 66% non-Hispanic White) not participating in an intervention study who had an HbA1c value at 12 months. Results Mean ± SD HbA1c at one year was 62 ± 16 mmol/mol (7.8% ± 1.5). In univariate and multivariate analyses, clinical center, non-Hispanic White race, private health insurance, living with both parents, higher frequency of self-monitoring of blood glucose (SMBG), and lower insulin requirements were associated with lower HbA1c concentrations at one year (p<0.01). No association was found with gender, age, Tanner stage, BMI, DKA at onset, number of positive autoantibodies or HbA1c at onset, or number of visits to diabetes physician during the first year. Conclusions White race, higher socioeconomic status, two-parent household, more frequent SMBG and low insulin requirements are associated with lower HbA1c concentration one year after the onset of T1D in children. PMID:23889707

  2. Hb San Cataldo [β144(HC1)Lys→Thr; HBB: C.434A > C]: A New Hemoglobin Variant with Increased Affinity for Oxygen.

    PubMed

    Vinciguerra, Margherita; Passarello, Cristina; Cassarà, Filippo; Leto, Filippo; Cannata, Monica; Crivello, Anna; Di Salvo, Veronica; Maggio, Aurelio; Giambona, Antonino

    2016-08-01

    A 59-year-old Italian woman came to our center for revaluation of a previous diagnosis of polycythemia vera. The patient presented with a lifelong history of polycythemia, no increase in white blood cells (WBCs) and platelets, and a negative bone marrow biopsy. Analysis of hemoglobin (Hb) fractions showed an abnormal fast moving Hb component. We aimed to determine if this variant was the cause of polycythemia in this patient. A complete blood count (CBC) was performed by an automated cell counter and Hb fractions were determined by high performance liquid chromatography (HPLC). Standard stability tests and oxygen affinity evaluation were also performed. Genomic DNA was extracted from peripheral blood leukocytes using the phenol chloroform method and the entire β-globin gene was analyzed by direct sequencing. At the hematological level, no anemia or hemolysis was observed but an abnormal Hb fraction was detected using cation exchange HPLC. Molecular analysis of the β-globin gene showed heterozygosity for an AAG > ACG substitution at codon 144, resulting in a Lys→Thr amino acid replacement. We demonstrated that this is a new Hb variant with increased oxygen affinity. Its altered physiology is caused by the reduction of 2,3-diphosphoglycerate (2,3-DPG) effects, due to an amino acid substitution in the central pocket near the C-terminal of the β chain. We called this new variant Hb San Cataldo for the native city of proband. PMID:27250824

  3. Diabetes case finding in the emergency department, using HbA1c: an opportunity to improve diabetes detection, prevention, and care

    PubMed Central

    Hng, Tien-Ming; Hor, Amanda; Ravi, Sumathy; Feng, Xiaoqi; Lin, Jaime; Astell-Burt, Thomas; Chipps, David; McLean, Mark; Maberly, Glen

    2016-01-01

    Objective We assessed the efficacy of routine glycated hemoglobin (HbA1c) testing to detect undiagnosed diabetes and prediabetes in an urban Australian public hospital emergency department (ED) located in an area of high diabetes prevalence. Methods Over 6 weeks, all patients undergoing blood sampling in the ED had their random blood glucose measured. If ≥5.5 mmol/L (99 mg/dL), HbA1c was measured on the same sample. HbA1c levels ≥6.5% (48 mmol/mol) and 5.7–6.4% (39–46 mmol/mol) were diagnostic of diabetes and prediabetes, respectively. Hospital records were reviewed to identify patients with previously diagnosed diabetes. Results Among 4580 presentations, 2652 had blood sampled of which 1267 samples had HbA1c measured. Of these, 487 (38.4%) had diabetes (either HbA1c≥6.5% or a prior diagnosis), and a further 347 (27.4%) had prediabetes. Among those with diabetes, 32.2% were previously undiagnosed. Conclusions Routine HbA1c testing in the ED identifies a large number of people with undiagnosed diabetes and prediabetes, and provides an opportunity to improve their care. PMID:27284456

  4. The Relation between Serum Uric Acid and HbA1c Is Dependent upon Hyperinsulinemia in Patients with Newly Diagnosed Type 2 Diabetes Mellitus

    PubMed Central

    Cui, Yuliang; Bu, Hemei; Zhao, Sha; Li, Xiaona; Lu, Shan

    2016-01-01

    Objective. The aim of our study was to explore the dependent condition of the relationship between uric acid and blood glucose in type 2 diabetes. Research Design and Methods. We measured the HbA1c, serum uric acid, creatinine, lipids profiles, and so forth of 605 newly diagnosed type 2 diabetes patients, and oral glucose tolerance tests (OGTTs) were performed on each patient. The population was divided into high and low insulin groups. Multiple linear regression analyses were conducted to assess the relationship between uric acid and HbA1c. Results. Serum uric acid and HbA1c levels were low in newly diagnosed type 2 diabetes patients. However, we found no significant relationship between uric acid and HbA1c by regression analysis after adjusting total insulin. The concentration of uric acid was inversely correlated with HbA1c in the high insulin group, regardless of patient sex. However, no associations were found in low insulin group. Conclusions. The negative correlation between uric acid and HbA1c is conditional in newly diagnosed type 2 diabetes patients and is related to hyperinsulinemia. Therefore, uric acid is likely only useful as a biomarker of blood glucose in patients exhibiting hyperinsulinemia. PMID:27403443

  5. The metalloendopeptidase nardilysin (NRDc) is potently inhibited by heparin-binding epidermal growth factor-like growth factor (HB-EGF).

    PubMed Central

    Hospital, Véronique; Nishi, Eiichiro; Klagsbrun, Michael; Cohen, Paul; Seidah, Nabil G; Prat, Annik

    2002-01-01

    Nardilysin (N-arginine dibasic convertase, or NRDc) is a cytosolic and cell-surface metalloendopeptidase that, in vitro, cleaves substrates upstream of Arg or Lys in basic pairs. NRDc differs from most of the other members of the M16 family of metalloendopeptidases by a 90 amino acid acidic domain (DAC) inserted close to its active site. At the cell surface, NRDc binds heparin-binding epidermal growth factor-like growth factor (HB-EGF) and enhances HB-EGF-induced cell migration. An active-site mutant of NRDc fulfills this function as well as wild-type NRDc, indicating that the enzyme activity is not required for this process. We now demonstrate that NRDc starts at Met(49). Furthermore, we show that HB-EGF not only binds to NRDc but also potently inhibits its enzymic activity. NRDc-HB-EGF interaction involves the 21 amino acid heparin-binding domain (P21) of the growth factor, the DAC of NRDc and most probably its active site. Only disulphide-bonded P21 dimers are inhibitory. We also show that Ca(2+), via the DAC, regulates both NRDc activity and HB-EGF binding. We conclude that the DAC is thus a key regulatory element for the two distinct functions that NRDc fulfills, i.e. as an HB-EGF modulator and a peptidase. PMID:12095415

  6. A 3-bp deletion in the HBS1L-MYB intergenic region on chromosome 6q23 is associated with HbF expression

    PubMed Central

    Farrell, John J.; Sherva, Richard M.; Chen, Zhi-yi; Luo, Hong-yuan; Chu, Benjamin F.; Ha, Shau Yin; Li, Chi Kong; Lee, Anselm C. W.; Li, Rever C. H.; Li, Chi Keung; Yuen, Hui Leung; So, Jason C. C.; Ma, Edmond S. K.; Chan, Li Chong; Chan, Vivian; Sebastiani, Paola; Farrer, Lindsay A.; Baldwin, Clinton T.; Steinberg, Martin H.

    2011-01-01

    Fetal hemoglobin (HbF) is regulated as a multigenic trait. By genome-wide association study, we confirmed that HBS1L-MYB intergenic polymorphisms (HMIP) and BCL11A polymorphisms are highly associated with HbF in Chinese β-thalassemia heterozygotes. In this population, the variance in HbF resulting from the HMIP is 13.5%; that resulting from the BCL11A polymorphism is 6.4%. To identify the functional variant in HMIP, we used 1000 Genomes Project data, single nucleotide polymorphism imputation, comparisons of association results across populations, potential transcription factor binding sites, and analysis of phylogenetic conservation. Based on these studies, a hitherto unreported association between HbF expression and a 3-bp deletion, between 135 460 326 and 135 460 328 bp on chromosome 6q23 was found. This 3-bp deletion is in complete linkage disequilibrium with rs9399137, which is the single nucleotide polymorphism in HMIP most significantly associated with HbF among Chinese, Europeans, and Africans. Chromatin immunoprecipitation assays confirmed erythropoiesis-related transcription factors binding to this region in K562 cells. Based on transient expression of a luciferase reporter plasmid, the DNA fragment encompassing the 3-bp deletion polymorphism has enhancer-like activity that is further augmented by the introduction of the 3-bp deletion. This 3-bp deletion polymorphism is probably the most significant functional motif accounting for HMIP modulation of HbF in all 3 populations. PMID:21385855

  7. Examining the relationship between HbA1c and diabetes risk models in a European population indicates a lower threshold to identify 'high risk' is required.

    PubMed

    Gray, Benjamin J; Bracken, Richard M; Turner, Daniel; Morgan, Kerry; Thomas, Michael; Williams, Sally P; Williams, Meurig; Rice, Sam; Stephens, Jeffrey W

    2016-05-01

    This study examined whether changes in HbA1c values are reflected in the risk scores and categories of four validated risk-assessment tools (QDiabetes, Leicester Risk Assessment, Finnish Diabetes Risk Score and Cambridge Risk Score). Retrospective analysis was performed on 651 individuals with no prior diagnosis of cardiovascular disease or diabetes who participated in a UK workplace-based risk-assessment initiative. There were significant positive correlations (p < 0.01) revealed between HbA1c values and predicted risk scores: QDiabetes (r = 0.362), Leicester Risk Assessment (r = 0.315), Finnish Diabetes Risk Score (r = 0.202) and Cambridge Risk Score (r = 0.335). HbA1c values increased within risk prediction categories, and at 'high-risk' categories, median HbA1c values were at least 39 mmol mol(-1) (5.7%) irrespective of gender or risk-assessment model. Overall, an association is present between increases in HbA1c scores and predicted risk of type 2 diabetes. Furthermore, the 'high-risk' median HbA1c values in each of the risk assessments are more akin to the lower American recommendations rather than those suggested by the UK expert group. PMID:26956443

  8. HbA1c Variability as an Independent Risk Factor for Diabetic Retinopathy in Type 1 Diabetes: A German/Austrian Multicenter Analysis on 35,891 Patients

    PubMed Central

    Hermann, Julia M.; Hammes, Hans-Peter; Rami-Merhar, Birgit; Rosenbauer, Joachim; Schütt, Morten; Siegel, Erhard; Holl, Reinhard W.

    2014-01-01

    Objective This study aimed to analyze the effect of HbA1c variability on the occurrence of diabetic retinopathy in type 1 diabetes patients. Patients and Methods 35,891 patients with childhood, adolescent or adult onset of type 1 diabetes from a large multicentre survey, the German/Austrian prospective documentation system (DPV), were analysed. Cox proportional hazard models were used to examine whether intra-individual HbA1c variability expressed as variation coefficient is an independent risk factor for the occurrence of diabetic retinopathy. Results Kaplan-Meier curves stratified by median HbA1c and variation coefficient revealed that retinopathy-free survival probability is lower when both median HbA1c and HbA1c variability are above the 50th percentile. Cox regression models confirmed this finding: After adjustment for age at diabetes onset, gender and median HbA1c, HbA1c variability was independently associated with the occurrence of diabetic retinopathy. Time-covariate interactions used to model non-proportionality indicated an effect decreasing with duration of diabetes for both median HbA1c and HbA1c variability. Predictive accuracy increased significantly when adding HbA1c variability to the Cox regression model. Conclusions In patients with type 1 diabetes, HbA1c variability adds to the risk of diabetic retinopathy independently of average metabolic control. PMID:24609115

  9. Prevalence of hemoglobin variants in a diabetic population at high risk of hemoglobinopathies and optimization of HbA1c monitoring by incorporating HPLC in the laboratory workup

    PubMed Central

    Bouzid, Kahena; Ahmed, Habib B.; Kalai, Eya; Blibeche, Salma; Couque, Nathalie; Khiari, Karima; Bahlous, Afef; Abdelmoula, Jaouida

    2014-01-01

    Background In Tunisia, diabetes mellitus and hemoglobinopathies are major public health problems. Glycated hemoglobin (HbA1c) is recommended for long-term monitoring of diabetes mellitus, but the presence of hemoglobin variants may interfere with HbA1c measurement. The aim was to determine the prevalence of hemoglobin variants in Tunisian diabetics and optimize the monitoring of diabetics using HbA1c. Methods The study enrolled 9,792 Tunisian diabetic patients. HbA1c was measured by cation-exchange high-pressure liquid chromatography (HPLC). All the chromatograms were analyzed for the presence of Hb variants. Results We identified 228 cases (2.33%) of Hb variants with D-10 HPLC (Bio-Rad): 191 with HbA/S trait, 27 with HbA/C trait, and 10 hemoglobin variants with the mention ‘Variant-Window’ on the chromatograms and subsequently identified as HbA/S on Variant I HPLC (Bio-Rad). Thus, the prevalence of HbS was 2.05%. We did not find any homozygous variant. All HbA1c results were reported to the treating physician. Conclusions To evaluate glycated hemoglobin in populations with a high prevalence of hemoglobinopathies, we should use the HPLC method, which is easy, economical, and reliable. Based on an algorithm, hemoglobin variants visualized on HPLC should be reported to the physician to improve the management of patients. PMID:25361891

  10. Meta-analysis of telemonitoring to improve HbA1c levels: promise for stroke survivors.

    PubMed

    Lieber, Bryan A; Taylor, Blake; Appelboom, Geoff; Prasad, Kiran; Bruce, Sam; Yang, Annie; Bruce, Eliza; Christophe, Brandon; Connolly, E Sander

    2015-05-01

    Monitoring glycemic control is useful not only in the primary prevention of stroke in diabetics, but also in the rehabilitation from and secondary prevention of stroke. In an often functionally and neurocognitively impaired population, however, poor compliance with treatment regimens is a major problem. Wireless, telemonitoring glucometers - often integrated into the patient's healthcare system - offer a solution to the compliance issue. We sought to evaluate the effectiveness of telemonitoring technologies in improving long-term glycemic control. A search on www.clinicaltrials.gov, using keywords such as "telemonitoring" and "self-care device" was performed, and five trials were identified that compared hemoglobin A1c (HbA1c) levels of a group receiving standard care (controls) to a group receiving a telemonitoring intervention. Four of the five studies showed a greater reduction in HbA1c in the intervention group compared to controls at 6 months, although only one was statistically significant. There was considerable heterogeneity between studies (I(2)=69.5%, p=0.02), and the random effects model estimated the aggregate effect size for mean difference in reduction of HbA1c levels to be 0.08% (95% confidence interval -0.12% to 0.28%), which was not statistically significant (p=0.42). The varying results may be due to specific factors in the trials that contributed to their large heterogeneity, and further trials are needed to support the role of telemonitoring in improving diabetes management in this population. Nonetheless, in the future telemonitoring may substantially help patients at risk of ischemic stroke and those who require close glucose monitoring. PMID:25791996

  11. Apolipoproteins and lipoproteins in children with type I diabetes: relation to glycosylated serum protein and HbA1.

    PubMed

    Strobl, W; Widhalm, K; Schober, E; Frisch, H; Pollak, A; Westphal, G

    1985-11-01

    Serum levels of cholesterol (C), triglycerides (TG), lipoprotein-C and apolipoproteins (apo) A-I, A-II and B were measured in 30 children with type I diabetes mellitus (16 boys, 14 girls, aged 11-14 years) and in 26 healthy controls (15 boys, 11 girls, aged 10-13 years). For 19 diabetics controls matched for age, sex and relative body weight were selected. The diabetic patients were considered to be in fair metabolic control according to HbA1 levels and glycosylated serum protein concentrations. Mean serum apo A-I, A-II and B, C, TG, low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) did not differ significantly between diabetic nondiabetic children. Very low density lipoprotein cholesterol (VLDL-C) was significantly higher in diabetic children than in controls. Serum C and LDL-C levels showed close univariate linear correlations with glycosylated serum protein (LDL-C: r = 0.53, p less than 0.01, C: r = 0.58, p less than 0.01) in diabetics. The ratio LDL/HDL-C was significantly correlated to HbA1 levels (r = 0.47, p less than 0.01). By canonical and multiple linear correlation analysis significant relations of a selected set of variables concerning the control and therapy of diabetes (serum glucose, HbA1, glycosylated serum protein, insulin dose) with a set of lipoprotein variables (C, TG, VLDL-C, HDL-C, LDL-C, apo A-I, A-II, B) could be demonstrated. From these data we conclude that significant relations between atherogenic serum lipids and lipoproteins (C, LDL-C) and the degree of metabolic control exist in diabetic children, even in the absence of marked dyslipoproteinemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:4090971

  12. Effect of biomimetic conditions on mechanical and structural integrity of PGA/P4HB and electrospun PCL scaffolds.

    PubMed

    Klouda, Leda; Vaz, Claudia M; Mol, Anita; Baaijens, Frank P T; Bouten, Carlijn V C

    2008-03-01

    The selection of an appropriate scaffold represents one major key to success in tissue engineering. In cardiovascular applications, where a load-bearing structure is required, scaffolds need to demonstrate sufficient mechanical properties and importantly, reliable retention of these properties during the developmental phase of the tissue engineered construct. The effect of in vitro culture conditions, time and mechanical loading on the retention of mechanical properties of two scaffold types was investigated. First candidate tested was a poly-glycolic acid non-woven fiber mesh, coated with poly-4-hydroxybutyrate (PGA/P4HB), the standard scaffold used successfully in cardiovascular tissue engineering applications. As an alternative, an electrospun poly-epsilon-caprolactone (PCL) scaffold was used. A 15-day dynamic loading protocol was applied to the scaffolds. Additionally, control scaffolds were incubated statically. All studies were performed in a simulated physiological environment (phosphate-buffered saline solution, T=37 degrees C). PGA/P4HB scaffolds showed a dramatic decrease in mechanical properties as a function of incubation time and straining. Mechanical loading had a significant effect on PCL scaffold properties. Degradation as well as fiber fatigue caused by loading promote loss of mechanical properties in PGA/P4HB scaffolds. For PCL, fiber reorganization due to straining seems to be the main reason behind the brittle behavior that was pronounced in these scaffolds. It is suggested that those changes in scaffolds' mechanical properties must be considered at the application of in vitro tissue engineering protocols and should ideally be taken over by tissue formation to maintain mechanically stable tissue constructs. PMID:17701317

  13. Salinomycin efficiency assessment in non-tumor (HB4a) and tumor (MCF-7) human breast cells.

    PubMed

    Niwa, Andressa Megumi; D Epiro, Gláucia Fernanda Rocha; Marques, Lilian Areal; Semprebon, Simone Cristine; Sartori, Daniele; Ribeiro, Lúcia Regina; Mantovani, Mário Sérgio

    2016-06-01

    The search for anticancer drugs has led researchers to study salinomycin, an ionophore antibiotic that selectively destroys cancer stem cells. In this study, salinomycin was assessed in two human cell lines, a breast adenocarcinoma (MCF-7) and a non-tumor breast cell line (HB4a), to verify its selective action against tumor cells. Real-time assessment of cell proliferation showed that HB4a cells are more resistant to salinomycin than MCF-7 tumor cell line, and these data were confirmed in a cytotoxicity assay. The half maximal inhibitory concentration (IC50) values show the increased sensitivity of MCF-7 cells to salinomycin. In the comet assay, only MCF-7 cells showed the induction of DNA damage. Flow cytometric analysis showed that cell death by apoptosis/necrosis was only induced in the MCF-7 cells. The increased expression of GADD45A and CDKN1A genes was observed in all cell lines. Decreased expression of CCNA2 and CCNB1 genes occurred only in tumor cells, suggesting G2/M cell cycle arrest. Consequently, cell death was activated in tumor cells through strong inhibition of the antiapoptotic genes BCL-2, BCL-XL, and BIRC5 genes in MCF-7 cells. These data demonstrate the selectivity of salinomycin in killing human mammary tumor cells. The cell death observed only in MCF-7 tumor cells was confirmed by gene expression analysis, where there was downregulation of antiapoptotic genes. These data contribute to clarifying the mechanism of action of salinomycin as a promising antitumor drug and, for the first time, we observed the higher resistance of HB4a non-tumor breast cells to salinomycin. PMID:26932586

  14. Biosynthesis and characterization of copolymer poly(3HB-co-3HV) from saponified Jatropha curcas oil by Pseudomonas oleovorans.

    PubMed

    Allen, Adrian D; Anderson, Winston A; Ayorinde, Folahan O; Eribo, Broderick E

    2010-08-01

    Polyhydroxyalkanoates (PHAs) are naturally occurring biodegradable polymers with promising application in the formulation of plastic materials. PHAs are produced by numerous bacteria as energy/carbon storage materials from various substrates, including sugars and plant oils. Since these substrates compete as food sources, their use as raw material for industrial-scale production of PHA is limited. Therefore, efforts have been focused on seeking alternative sources for bacterial production of PHA. One substrate that seems to have great potential is the seed oil of Jatropha curcas plant. Among other favorable properties, J. curcas seed oil is non-edible, widely available, and can be cheaply produced. In this study, Pseudomonas oleovorans (ATCC 29347) was grown in a mineral salt medium supplemented with saponified J. curcas seed oil as the only carbon source under batch fermentation. Optimum PHA yield of 26.06% cell dry weight was achieved after 72 h. The PHA had a melting point (T(m)) between 150 and 160 degrees C. Results of polymer analyses by gas chromatography/mass spectrometry (GC/MS) identified only the methyl 3-hydroxybutanoate monomeric unit. However, electrospray ionization-time of flight mass spectroscopy (ESI-TOF MS) confirmed that the PHA was a copolymer with the characteristic HB/HV peaks at m/z 1155.49 (HB) and 1,169, 1,184-1,194 (HV). The data were further supported by 1H and 13C NMR analysis. Polymer analysis by gel permeation chromatography (GPC) indicated a peak molecular weight (MP) of 179,797, molecular weight (M(W)) of 166,838, weight number average mass (M(n)) of 131,847, and polydispersity (M(w)/M (n)) of 1.3. The data from this study indicate that J. curcas seed oil can be used as a substrate to produce the copolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate), poly(3HB-co-3HV). PMID:20467780

  15. Identification of the Presence of Variant Hemoglobin Using a Measurement of the Labile HbA1c (#C) Fraction.

    PubMed

    Koga, Masafumi; Inada, Shinya; Miyazaki, Ayako

    2016-07-01

    Labile HbA1c migrates in the #C fraction together with modified hemoglobin (such as carbamylated hemoglobin, acetaldehyde hemoglobin, and acetylated hemoglobin) when HbA1c is measured by Arkray's high-performance liquid chromatography (HPLC). It is assumed that most of the labile glycation products of variant hemoglobin do not migrate in #C fraction; in addition, a part of the stable glycation products of variant hemoglobin migrates in #C fraction. We hypothesized that subjects with variant hemoglobin are likely to show abnormally low or high values of #C fraction. In this study, we investigated this hypothesis. Twenty-one non-diabetic subjects with nine types of variant hemoglobin, and 103 non-diabetic subjects without variant hemoglobin were used. HbA1c and #C fraction were measured by Arkray's HPLC (HA-8180) using standard mode. The values of #C fraction in the control group were 1.75 ± 0.15% (range: 1.5-2.1%). The variant hemoglobin group reported #C fraction values of ≤1.3% in twelve subjects, ≥2.3% in five subjects, and within the reference range (1.4-2.2%) in three subjects. When the cutoff values of #C fraction were set at ≤1.3% and ≥2.3%, sensitivity and specificity were 86% and 100%, respectively. Most non-diabetic subjects with variant hemoglobin showed abnormal values of #C fraction. Measurement of #C fraction is a useful screening test for variant hemoglobin in non-diabetic subjects. PMID:27466298

  16. Restraint Stress Inhibits Mouse Implantation: Temporal Window and the Involvement of HB-EGF, Estrogen and Progesterone

    PubMed Central

    Yuan, Hong-Jie; Liang, Bo; Zheng, Liang-Liang; Liu, Yu-Xiang; Luo, Ming-Jiu; Tan, Jing-He

    2013-01-01

    It is known that psychological stress affects reproduction in women, but it is unknown whether the effect is by impairing implantation. Although studies suggest that long periods of auditory or restraint stress may inhibit implantation in rats and mice, the exact stage of pregnancy at which stress impairs implantation is unclear. Furthermore, whether stress impairs implantation by decreasing the heparin-binding epidermal growth factor-like growth factor (HB-EGF), estrogen and/or progesterone and whether by acting on embryos or on the uterus need further investigations. In this study, a 24-h restraint stress was initiated at 15:30 of day 3 (regimen 1) or at 07:30 (regimen 2) or 15:30 of day 4 (regimen 3) of pregnancy (vaginal plug  =  day 1) to observe effects of restraint stress applied at different peri-implantation stages on implantation. Among the three regimens, whereas regimens 1 and 3 affected neither term pregnancy nor litter size, regimen 2 reduced both. Further observations indicated that regimen 2 of restraint stress also delayed blastocyst hatching and the attachment reaction, decreased serum concentrations of progesterone and estradiol, and down regulated the expression of HB-EGF in both the endometrium and blastocysts. Taken together, the results suggested that restraint stress inhibited mouse implantation in a temporal window-dependent manner and by impairing blastocyst activation and hatching and uterine receptivity via down-regulating HB-EGF, estrogen and progesterone. Thus, the stress applied within the implantation window impaired implantation by acting on both embryos and the uterus. PMID:24244689

  17. Prevalence of Hb S (HHB: c.20A > T) in a Honduran population of African descent.

    PubMed

    Erazo, Brian M; Ramírez, Gilberto A; Cerrato, Linda E; Pinto, Luis J; Castro, Edder J; Yanez, Néstor J; Montoya, Brayan; Fontecha, Gustavo A

    2015-01-01

    Sickle cell disease is the most common hemoglobinopathy worldwide, particularly in Africa and among people of African descent. Serious clinical consequences characterize the homozygous condition. To determine the prevalence of Hb S (HBB: c.20A > T) and anemia in a community of people of African descent from Honduras, 202 individuals were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The high prevalence found indicates that it is necessary to implement a program to prevent the consequences of this disease in vulnerable populations of Honduras. PMID:25707678

  18. A non-radioactive assay for selenophosphate synthetase activity using recombinant pyruvate pyrophosphate dikinase from Thermus thermophilus HB8.

    PubMed

    Kamada, Saho; Okugochi, Takahiro; Asano, Kaori; Tobe, Ryuta; Mihara, Hisaaki; Nemoto, Michiko; Inagaki, Kenji; Tamura, Takashi

    2016-10-01

    Biosynthesis of selenocysteine-containing proteins requires monoselenophosphate, a selenium-donor intermediate generated by selenophosphate synthetase (Sephs). A non-radioactive assay was developed as an alternative to the standard [8-(14)C] AMP-quantifying assay. The product, AMP, was measured using a recombinant pyruvate pyrophosphate dikinase from Thermus thermophilus HB8. The KM and kcat for Sephs2-Sec60Cys were determined to be 26 μM and 0.352 min(-1), respectively. PMID:27405844

  19. Oxidative instability of hemoglobin E (β26 Glu→Lys) is increased in the presence of free α subunits and reversed by α-hemoglobin stabilizing protein (AHSP): Relevance to HbE/β-thalassemia☆

    PubMed Central

    Strader, Michael Brad; Kassa, Tigist; Meng, Fantao; Wood, Francine B.; Hirsch, Rhoda Elison; Friedman, Joel M.; Alayash, Abdu I.

    2016-01-01

    When adding peroxide (H2O2), β subunits of hemoglobin (Hb) bear the burden of oxidative changes due in part to the direct oxidation of its Cys93. The presence of unpaired α subunits within red cells and/or co-inheritance of another β subunit mutant, HbE (β26 Glu→Lys) have been implicated in the pathogenesis and severity of β thalassemia. We have found that although both HbA and HbE autoxidize at initially comparable rates, HbE loses heme at a rate almost 2 fold higher than HbA due to unfolding of the protein. Using mass spectrometry and the spin trap, DMPO, we were able to quantify irreversible oxidization of βCys93 to reflect oxidative instability of β subunits. In the presence of free α subunits and H2O2, both HbA and HbE showed βCys93 oxidation which increased with higher H2O2 concentrations. In the presence of Alpha-hemoglobin stabilizing protein (AHSP), which stabilizes the α-subunit in a redox inactive hexacoordinate conformation (thus unable to undergo the redox ferric/ferryl transition), Cys93 oxidation was substantially reduced in both proteins. These experiments establish two important features that may have relevance to the mechanistic understanding of these two inherited hemoglobinopathies, i.e. HbE/β thalassemia: First, a persistent ferryl/ferryl radical in HbE is more damaging to its own β subunit (i.e., βCys93) than HbA. Secondly, in the presence of excess free α-subunit and under the same oxidative conditions, these events are substantially increased for HbE compared to HbA, and may therefore create an oxidative milieu affecting the already unstable HbE. PMID:26995402

  20. Oxidative instability of hemoglobin E (β26 Glu→Lys) is increased in the presence of free α subunits and reversed by α-hemoglobin stabilizing protein (AHSP): Relevance to HbE/β-thalassemia.

    PubMed

    Strader, Michael Brad; Kassa, Tigist; Meng, Fantao; Wood, Francine B; Hirsch, Rhoda Elison; Friedman, Joel M; Alayash, Abdu I

    2016-08-01

    When adding peroxide (H2O2), β subunits of hemoglobin (Hb) bear the burden of oxidative changes due in part to the direct oxidation of its Cys93. The presence of unpaired α subunits within red cells and/or co-inheritance of another β subunit mutant, HbE (β26 Glu→Lys) have been implicated in the pathogenesis and severity of β thalassemia. We have found that although both HbA and HbE autoxidize at initially comparable rates, HbE loses heme at a rate almost 2 fold higher than HbA due to unfolding of the protein. Using mass spectrometry and the spin trap, DMPO, we were able to quantify irreversible oxidization of βCys93 to reflect oxidative instability of β subunits. In the presence of free α subunits and H2O2, both HbA and HbE showed βCys93 oxidation which increased with higher H2O2 concentrations. In the presence of Alpha-hemoglobin stabilizing protein (AHSP), which stabilizes the α-subunit in a redox inactive hexacoordinate conformation (thus unable to undergo the redox ferric/ferryl transition), Cys93 oxidation was substantially reduced in both proteins. These experiments establish two important features that may have relevance to the mechanistic understanding of these two inherited hemoglobinopathies, i.e. HbE/β thalassemia: First, a persistent ferryl/ferryl radical in HbE is more damaging to its own β subunit (i.e., βCys93) than HbA. Secondly, in the presence of excess free α-subunit and under the same oxidative conditions, these events are substantially increased for HbE compared to HbA, and may therefore create an oxidative milieu affecting the already unstable HbE. PMID:26995402

  1. Production of poly-3-hydroxybutyrate (P3HB) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) P(3HB-co-3HV) from synthetic wastewater using Hydrogenophaga palleronii.

    PubMed

    Venkateswar Reddy, M; Mawatari, Yasuteru; Yajima, Yuka; Satoh, Kohki; Venkata Mohan, S; Chang, Young-Cheol

    2016-09-01

    In the present study, synthetic wastewater (SW) was used for production of poly-3-hydroxybutyrate (P3HB) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) P(3HB-co-3HV) using the bacteria Hydrogenophaga palleronii. SW at various volatile fatty acids concentrations (5-60g/l) was evaluated for the growth and biopolymer production using H. palleronii. Substrate degradation was analyzed using total organic carbon (TOC) analyzer and high pressure liquid chromatography (HPLC). H. palleronii showed highest and lowest removal of TOC at 5g/l (88±4%) and 60g/l (15±6%) respectively. Among all the concentrations evaluated, bacteria showed highest biopolymer production with 20g/l (63±5%), followed by 30g/l (58±3%) and 40g/l (56±2%). Lowest biopolymer production was observed at 5g/l concentration (21±3%). Structure, molecular weight, and thermal properties of the produced biopolymer were analyzed. These results denoted that the strain H. palleronii can be used for degradation of high concentration of volatile fatty acids persistent in wastewaters and their subsequent conversion into useable biopolymers. PMID:26995321

  2. HbA1c as a Predictor of Diabetes and as an Outcome in the Diabetes Prevention Program: A Randomized Clinical Trial

    PubMed Central

    2015-01-01

    OBJECTIVE Glycated hemoglobin (HbA1c), a standard measure of chronic glycemia for managing diabetes, has been proposed to diagnose diabetes and identify people at risk. The Diabetes Prevention Program (DPP) was a 3.2-year randomized clinical trial of preventing type 2 diabetes with a 10-year follow-up study, the DPP Outcomes Study (DPPOS). We evaluated baseline HbA1c as a predictor of diabetes and determined the effects of treatments on diabetes defined by an HbA1c ≥6.5% (48 mmol/mol). RESEARCH DESIGN AND METHODS We randomized 3,234 nondiabetic adults at high risk of diabetes to placebo, metformin, or intensive lifestyle intervention and followed them for the development of diabetes as diagnosed by fasting plasma glucose (FPG) and 2-h postload glucose (2hPG) concentrations (1997 American Diabetes Association [ADA] criteria). HbA1c was measured but not used for study eligibility or outcomes. We now evaluate treatment effects in the 2,765 participants who did not have diabetes at baseline according to FPG, 2hPG, or HbA1c (2010 ADA criteria). RESULTS Baseline HbA1c predicted incident diabetes in all treatment groups. Diabetes incidence defined by HbA1c ≥6.5% was reduced by 44% by metformin and 49% by lifestyle during the DPP and by 38% by metformin and 29% by lifestyle throughout follow-up. Unlike the primary DPP and DPPOS findings based on glucose criteria, metformin and lifestyle were similarly effective in preventing diabetes defined by HbA1c. CONCLUSIONS HbA1c predicted incident diabetes. In contrast to the superiority of the lifestyle intervention on glucose-defined diabetes, metformin and lifestyle interventions had similar effects in preventing HbA1c-defined diabetes. The long-term implications for other health outcomes remain to be determined. PMID:25336746

  3. The Association between HbA1c and Cardiovascular Disease Markers in a Remote Indigenous Australian Community with and without Diagnosed Diabetes

    PubMed Central

    Arnold, Luke W.; Hoy, Wendy E.; Sharma, Suresh K.; Wang, Zhiqiang

    2016-01-01

    Objectives. This study investigates the burden of cardiovascular risk markers in people with and without diabetes in a remote Indigenous Australian community, based on their HbA1c concentration. Methods. This study included health screening exams of 1187 remote Indigenous residents over 15 years old who represented 70% of the age-eligible community. The participants were stratified by HbA1c into 5 groups using cut-off points recommended by international organisations. The associations of traditional cardiovascular risk markers with HbA1c groups were assessed using logistic and linear regressions and ANOVA models. Results. Of the 1187 participants, 158 (13%) had a previous diabetes diagnosis, up to 568 (48%) were at high risk (5.7–6.4% (39–46 mmol/mol) HbA1c), and 67 (6%) potential new cases of diabetes (≥6.5% (48 mmol/mol)) were identified. Individuals with higher HbA1c levels were more likely to have albuminuria (OR 3.14, 95% CI 1.26–7.82) and dyslipidaemia (OR 2.37, 95% CI 1.29–4.34) and visited the clinic more often (OR 2.52, 95% CI 1.26–4.99). Almost all traditional CVD risk factors showed a positive association with HbA1c. Conclusions. Screening in this remote Indigenous Australian community highlights the high proportion of individuals who are at high risk of diabetes as indicated by HbA1c and who also had an accentuated cardiovascular risk profile. PMID:26989697

  4. Characterization of the genomic structure and tissue-specific promoter of the human nuclear receptor NR5A2 (hB1F) gene.

    PubMed

    Zhang, C K; Lin, W; Cai, Y N; Xu, P L; Dong, H; Li, M; Kong, Y Y; Fu, G; Xie, Y H; Huang, G M; Wang, Y

    2001-08-01

    The human homologue of the Drosophila melanogaster orphan nuclear receptor fushi tarazu factor 1 (Ftz-F1), NR5A2 (hB1F), was initially identified as a regulatory factor that binds and activates enhancer II of hepatitis B virus. NR5A2 (hB1F) is expressed specifically in pancreas and liver, playing important roles in the regulation of several liver-specific genes. A detailed analysis on the genomic structure and promoter activity will greatly promote future studies on the function of the NR5A2 (hB1F) gene. In this report, a bacterial artificial chromosome clone and several phage clones covering the NR5A2 (hB1F) gene were isolated and the complete genomic sequence was obtained. Alignment of different cDNAs of the NR5A2 (hB1F) gene with the genomic sequence facilitated the delineation of its structural organization, which spans over 150 kb and consists of eight exons interrupted by seven introns. RT-PCR and 3'-RACE revealed that utilization of two polyadenylation signals results in the 3.8 and 5.2 kb transcripts that were observed previously. The transcription start site of the NR5A2 (hB1F) gene was mapped downstream of a canonical TATA box. An upstream fragment containing binding sites for several liver-specific and ubiquitous transcription factors exhibits hepatocyte-specific promoter activity. Transient transfections indicated that hepatocyte nuclear factors HNF1 and HNF3beta could activate NR5A2 (hB1F) promoter. PMID:11595170

  5. Cloning and characterization of HbMT2a, a metallothionein gene from Hevea brasiliensis Muell. Arg differently responds to abiotic stress and heavy metals.

    PubMed

    Li, Yan; Chen, Yue Yi; Yang, Shu Guang; Tian, Wei Min

    2015-05-22

    Metallothioneins (MTs) are of low molecular mass, cysteine-rich proteins. They play an important role in the detoxification of heavy metals and homeostasis of intracellular metal ions, and protecting against intracellular oxidative damages. In this study a full-length cDNA of type 2 plant metallothioneins, HbMT2a, was isolated from 25 mM Polyethyleneglycol (PEG) stressed leaves of Hevea brasiliensis by RACE. The HbMT2a was 372bp in length and had a 237bp open reading frame (ORF) encoding for a protein of 78 amino acid residues with molecular mass of 7.772 kDa. The expression of HbMT2a in the detached leaves of rubber tree clone RY7-33-97 was up-regulated by Me-JA, ABA, PEG, H2O2, Cu(2+) and Zn(2+), but down-regulated by water. The role of HbMT2a protein in protecting against metal toxicity was demonstrated in vitro. PET-28a-HbMT2-beared Escherichia coli. Differential expression of HbMT2a upon treatment with 10 °C was observed in the detached leaves of rubber tree clone 93-114 which is cold-resistant and Reken501 which is cold-sensitive. The expression patterns of HbMT2a in the two rubber tree clones may be ascribed to a change in the level of endogenous H2O2. PMID:25858315

  6. Quantitative classification of HbA1C and blood glucose level for diabetes diagnosis using neural networks.

    PubMed

    Saraoğlu, Hamdi Melih; Temurtas, Feyzullah; Altıkat, Sayit

    2013-12-01

    In this study, artificial neural network structures were used for the quantitative classification of Haemoglobin A1C and blood glucose level for diabetes diagnosis as a non-invasive measurement technique. The neural network structures make inferences from the relationship between the palm perspiration and blood data values. For this purpose, feed forward multilayer, Elman, and radial basis neural network structures were used. The quartz crystal microbalance type and humidity sensors were used for the detection of palm perspiration rates. Total 297 volunteer's data is used in this study. Three quarters of the data was used to train the neural networks. The remaining data were used as test data. The best results for the quantitative classification were obtained from the feed forward NN structure for the detection of the glucose and HbA1C level quantities. And, the performances of all neural networks for the HbA1C value were better than the performances of these neural networks for the glucose level. PMID:23975344

  7. Electroenzymatic oxidation of bisphenol A (BPA) based on the hemoglobin (Hb) film in a membraneless electrochemical reactor.

    PubMed

    Tang, Tiantian; Hou, Juying; Ai, Shiyun; Qiu, Yanyan; Ma, Qiang; Han, Ruixia

    2010-09-15

    This paper presents a novel electroenzymatic method for the treatment of bisphenol A (BPA) in a membraneless electrochemical reactor. The electrochemical reactor was arranged with a stainless steel and an enzymatic film as anode and cathode, respectively. The enzymatic film was formed by immobilizing hemoglobin (Hb) on carbon fiber. In the membraneless electrochemical reactor, hydrogen peroxide (H(2)O(2)) was generated in situ in cathode and BPA was oxidated and removed by the combining Hb with H(2)O(2). The experimental conditions for electrogeneration of H(2)O(2) and electroremoval of BPA were optimized. Experimental results showed that in supplied voltage 2.4 V, pH 5.0 and oxygen flow rate 25 mL/min, the electrogeneration of H(2)O(2) and the electroenzymatic removal of BPA were highest. Under optimal operation conditions, the removal efficiency of BPA reached 50.7% in 120 min and then kept constant when further prolonging the period of reaction. Compared with electrochemical and biochemical methods, the removal of BPA through electroenzymatic method was comparatively favorable. PMID:20605681

  8. Weight-HbA1c-insulin-glucose model for describing disease progression of type 2 diabetes.

    PubMed

    Choy, S; Kjellsson, M C; Karlsson, M O; de Winter, W

    2016-01-01

    A previous semi-mechanistic model described changes in fasting serum insulin (FSI), fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) in patients with type 2 diabetic mellitus (T2DM) by modeling insulin sensitivity and β-cell function. It was later suggested that change in body weight could affect insulin sensitivity, which this study evaluated in a population model to describe the disease progression of T2DM. Nonlinear mixed effects modeling was performed on data from 181 obese patients with newly diagnosed T2DM managed with diet and exercise for 67 weeks. Baseline β-cell function and insulin sensitivity were 61% and 25% of normal, respectively. Management with diet and exercise (mean change in body weight = -4.1 kg) was associated with an increase of insulin sensitivity (30.1%) at the end of the study. Changes in insulin sensitivity were associated with a decrease of FPG (range, 7.8-7.3 mmol/L) and HbA1c (6.7-6.4%). Weight change as an effector on insulin sensitivity was successfully evaluated in a semi-mechanistic population model. PMID:26844011

  9. Secondary Sea-Blue Histiocytosis in a Patient with Transfusion Dependent HbE-Beta Thalassaemia and Osteosarcoma.

    PubMed

    Saad Eldeen Bakheet, Omayma; Yusof, Nurasyikin; Raja Zahratul, Azma; Ithnin, Azlin; Abdul Aziz, Suria; Alias, Hamidah

    2016-06-01

    Secondary sea-blue histiocytosis occurs more frequently than the primary form and occurs consequent to a wide range of metabolic and haematologic disorders including thalassaemia. We report an 18-year-old Chinese boy with transfusion-dependent HbE-beta thalassaemia who complained of pain and swelling at the left iliac crest region for 2 months duration. Physical examination revealed pallor with hepatosplenomegaly. Local examination revealed a huge swelling 12 cm × 12 cm in diameter, firm in consistency and tender. Histopathological examination of the mass revealed an osteosarcoma. His bone marrow aspirate showed numerous sea-blue histiocytes, the cytoplasm of which was closely packed with fine granules that stained blue with May-Grunwald-Giemsa. The nuclei were centrally located in some cells and displaced towards the periphery in other cells. There was no malignant cell infiltration in the marrow. The case is reported due to the co-incidental dual pathology in our patient (HbE-beta thalassaemia and osteosarcoma) and the unusual bone marrow finding of numerous sea-blue histiocytes. PMID:27408409

  10. Synthesis, Antiprotozoal, Antimicrobial, β-Hematin Inhibition, Cytotoxicity and Methemoglobin (MetHb) Formation Activities of Bis(8-aminoquinolines)

    PubMed Central

    Kaur, Kirandeep; Jain, Meenakshi; Khan, Shabana I.; Jacob, Melissa R.; Tekwani, Babu L.; Singh, Savita; Singh, Prati Pal; Jain, Rahul

    2011-01-01

    In continuing our search of potent antimalarials based on 8-aminoquinoline structural framework, three series of novel bis(8-aminoquinolines) using convenient one to four steps synthetic procedures were synthesized. The bisquinolines were evaluated for in vitro antimalarial (P. falciparum), antileishmanial (L. donovani), antimicrobial (a panel of pathogenic bacteria and fungi), cytotoxicity, β-hematin inhibitory and methemoglobin (MetHb) formation activities. Several compounds exhibited superior antimalarial activities compared to parent drug primaquine. Selected compounds (41, 61 and 79) when tested for in vivo blood-schizontocidal antimalarial activity (P. berghei) displayed potent blood-schizontocial activities. The bisquinolines showed negligible MetHb formation (0.2 – 1.2%) underlining their potential in the treatment of glucose-6-phosphate dehydrogenase deficient patients. The bisquinoline analogues (36, 73 and 79) also exhibited promising in vitro antileishmanial activity, and antimicrobial activities (43, 44 and 76) against a panel of pathogenic bacteria and fungi. The results of this study provide evidence that bis(8-aminoquinolines), like their bis(4-aminoquinolines) and artemisinin dimers counterparts, are a promising class of antimalarial agents. PMID:21172735

  11. A FACS Based Case Study on Two HbE-β Thalassaemia Members of a Family, Having Similar Mutational Background.

    PubMed

    Chatterjee, Tridip; Halder, Suchismita; Chakravarty, Amit; Chakravarty, Sudipa; Chakrabarti, Abhijit

    2016-01-01

    In this report we have tried to explain the reasons behind the difference in the pattern of transfusion requirement between two members of a family with similar β-globin mutation. The father and younger son both are HbE-β, but the father never had transfusion, whereas the younger son takes transfusion monthly. Mother and the elder son are HbEE without any history of transfusion. β-globin mutations of all family members were determined by ARMS-PCR. These were reconfirmed by direct sequencing of β-globin gene. Father and younger son were found to be Cod 26 (G-A)/IVS 1-5 (G-C), whereas mother and elder son were found to be Cod 26 (G-A)/Cod 26 (G-A). XmnI sequencing also revealed that all members of the family were CC. Then, flow cytometry study of red blood cells (RBCs) was performed to measure the oxidative stress of the RBCs. This study was also done on the light and dense fractions of the RBC population of the father and younger son. It was seen that the younger son suffers severe oxidative stress, which can be explained by his higher transfusion requirement. From our work, we have established the importance of taking oxidative stress of RBCs into consideration to explain the clinical manifestation and progression of haemoglobin related diseases like thalassaemia. PMID:27195173

  12. A FACS Based Case Study on Two HbE-β Thalassaemia Members of a Family, Having Similar Mutational Background

    PubMed Central

    Chatterjee, Tridip; Halder, Suchismita; Chakravarty, Amit; Chakravarty, Sudipa; Chakrabarti, Abhijit

    2016-01-01

    In this report we have tried to explain the reasons behind the difference in the pattern of transfusion requirement between two members of a family with similar β-globin mutation. The father and younger son both are HbE-β, but the father never had transfusion, whereas the younger son takes transfusion monthly. Mother and the elder son are HbEE without any history of transfusion. β-globin mutations of all family members were determined by ARMS-PCR. These were reconfirmed by direct sequencing of β-globin gene. Father and younger son were found to be Cod 26 (G-A)/IVS 1-5 (G-C), whereas mother and elder son were found to be Cod 26 (G-A)/Cod 26 (G-A). XmnI sequencing also revealed that all members of the family were CC. Then, flow cytometry study of red blood cells (RBCs) was performed to measure the oxidative stress of the RBCs. This study was also done on the light and dense fractions of the RBC population of the father and younger son. It was seen that the younger son suffers severe oxidative stress, which can be explained by his higher transfusion requirement. From our work, we have established the importance of taking oxidative stress of RBCs into consideration to explain the clinical manifestation and progression of haemoglobin related diseases like thalassaemia. PMID:27195173

  13. Paenibacillus larvae-Directed Bacteriophage HB10c2 and Its Application in American Foulbrood-Affected Honey Bee Larvae

    PubMed Central

    Beims, Hannes; Wittmann, Johannes; Bunk, Boyke; Spröer, Cathrin; Rohde, Christine; Günther, Gabi; Rohde, Manfred; von der Ohe, Werner

    2015-01-01

    Paenibacillus larvae is the causative agent of American foulbrood (AFB), the most serious honey bee brood bacterial disease. We isolated and characterized P. larvae-directed bacteriophages and developed criteria for safe phage therapy. Whole-genome analysis of a highly lytic virus of the family Siphoviridae (HB10c2) provided a detailed safety profile and uncovered its lysogenic nature and a putative beta-lactamase-like protein. To rate its antagonistic activity against the pathogens targeted and to specify potentially harmful effects on the bee population and the environment, P. larvae genotypes ERIC I to IV, representatives of the bee gut microbiota, and a broad panel of members of the order Bacillales were analyzed for phage HB10c2-induced lysis. Breeding assays with infected bee larvae revealed that the in vitro phage activity observed was not predictive of the real-life scenario and therapeutic efficacy. On the basis of the disclosed P. larvae-bacteriophage coevolution, we discuss the future prospects of AFB phage therapy. PMID:26048941

  14. Paenibacillus larvae-Directed Bacteriophage HB10c2 and Its Application in American Foulbrood-Affected Honey Bee Larvae.

    PubMed

    Beims, Hannes; Wittmann, Johannes; Bunk, Boyke; Spröer, Cathrin; Rohde, Christine; Günther, Gabi; Rohde, Manfred; von der Ohe, Werner; Steinert, Michael

    2015-08-15

    Paenibacillus larvae is the causative agent of American foulbrood (AFB), the most serious honey bee brood bacterial disease. We isolated and characterized P. larvae-directed bacteriophages and developed criteria for safe phage therapy. Whole-genome analysis of a highly lytic virus of the family Siphoviridae (HB10c2) provided a detailed safety profile and uncovered its lysogenic nature and a putative beta-lactamase-like protein. To rate its antagonistic activity against the pathogens targeted and to specify potentially harmful effects on the bee population and the environment, P. larvae genotypes ERIC I to IV, representatives of the bee gut microbiota, and a broad panel of members of the order Bacillales were analyzed for phage HB10c2-induced lysis. Breeding assays with infected bee larvae revealed that the in vitro phage activity observed was not predictive of the real-life scenario and therapeutic efficacy. On the basis of the disclosed P. larvae-bacteriophage coevolution, we discuss the future prospects of AFB phage therapy. PMID:26048941

  15. Hb Oegstgeest [alpha104(G11)Cys-->Ser (alpha1)]. A new hemoglobin variant associated with a mild alpha-thalassemia phenotype.

    PubMed

    Harteveld, Cornelis L; Rozendaal, Lieke; Blom, Nico A; Lo-A-Njoe, Shirley; Akkerman, Nicole; Arkestijn, Sandra; Van Delft, Peter; Giordano, Piero C

    2005-01-01

    A microcytic hypochromic anemic state was observed in an 8-year old Black female of Surinam origin during pre-operative Hb S [beta6(A3)Glu-->Val] screening. Her high zinc protoporphyrin (ZPP) level suggested a chronic iron depletion but, in contrast, the high red blood cell (RBC) count (5.85 x 10(12)/L) was indicative of a possible coexisting thalassemia. No abnormal hemoglobin (Hb) bands were present on high performance liquid chromatography (HPLC) or alkaline electrophoresis and the Hb A2 level was normal. Break point polymerase chain reaction (PCR) failed to reveal any of the common alpha-thalassemia (thal) mutations but selective DNA sequencing of both alpha-globin genes disclosed a TGC-->AGC transversion at codon 104 of the alpha1 gene. Cystine at codon 104 is involved in alpha/beta globin contact and has been described to be a critical amino acid of the alpha2 chain when substituted by a tyrosine (Hb Sallanches), inducing Hb H (beta4) disease in the homozygous state. Our heterozygous patient had a moderate anemia of 12.2 g/dL and a borderline haptoglobin suggesting some degree of hemolysis. PMID:16114179

  16. Use of an oral stable isotope label to confirm variation in red blood cell mean age that influences HbA1c interpretation

    PubMed Central

    Lindsell, Christopher J.; Rogge, Mary Colleen; Haggerty, Shannon; Wagner, David A.; Palascak, Mary B.; Mehta, Shilpa; Hibbert, Jacqueline M.; Joiner, Clinton H.; Franco, Robert S.; Cohen, Robert M.

    2014-01-01

    HbA1c is commonly used to monitor glycemic control. However, there is growing evidence that the relationship between HbA1c and mean blood glucose (MBG) is influenced by variation in red blood cell (RBC) lifespan in hematologically normal individuals. Correction of HbA1c for mean RBC age (MRBC) requires a noninvasive, accurate, and affordable method to measure RBC survival. In this study, we evaluated whether a stable isotope approach would satisfy these requirements. RBC lifespan and MRBC were determined in a group of nine hematologically normal diabetic and nondiabetic subjects using oral 15N-glycine to label heme in an age cohort of RBC. The MRBC was 58.7 ± 9.1 (2SD) days and RBC lifespan was 106 ± 21 (2SD) days. This degree of variation (±15 - 20%) is consistent with previous studies using other techniques. In a subset of seven subjects, MRBC determined with the biotin label technique were available from approximately five years prior, and strongly correlated with the stable isotope values (R2 = 0.79). This study suggests that the MRBC is stable over time but varies substantially among individuals, and supports the importance of its variation in HbA1c interpretation. The characteristics of the stable isotope method support its suitability for studies to directly evaluate the impact of variation in MRBC on the interpretation of HbA1c. PMID:25293624

  17. Interaction between Mean Arterial Pressure and HbA1c in Prediction of Cardiovascular Disease Hospitalisation: A Population-Based Case-Control Study

    PubMed Central

    Yu, Dahai; Zhao, Zhanzheng; Simmons, David

    2016-01-01

    Objective. To explore the relationship between mean arterial pressure (MAP), HbA1c, and cardiovascular (CV) hospitalisation risk in type 2 diabetes. Design. Population-based case-control study. Settings. Primary and secondary care level in Cambridgeshire, United Kingdom. Participants. 588 patients with type 2 diabetes from 18 English general practices recording a CV hospitalisation in 2009–2011 were included. Risk-set sampling was used to select 2920 gender, age, and practice matched control type 2 diabetes patients. Main Outcome Measure. Conditional logistic regression was used to explore further dose-response relationships between MAP, HbA1c, and CV hospitalisation risk. Results. The relationship between MAP and CV hospitalisation was nonlinear (P < 0.001 for linearity test). The MAP associated with the lowest CV hospitalisation risk was 97 (95% CI: 93–101) mmHg. An interaction between MAP and HbA1c for increased risk of cardiovascular hospitalisation was observed among those with HbA1c < 7% (53 mmol/mol) and MAP < 97 mmHg. Conclusions. In type 2 diabetes, MAP is a good predictor of CV hospitalisation risk. CV hospitalisation is lowest with a MAP between 93 and 101 mmHg. CV hospitalisation was particularly high among those with both a low MAP and a lower HbA1c. PMID:27382575

  18. Study of three families with Hb Agrinio [α29(B10)Leu→Pro, CTG>CCG (α2)] in the Spanish population: three homozygous cases.

    PubMed

    de la Fuente-Gonzalo, Felix; Baiget, Montserrat; Badell, Isabel; Ricard, Pilar; Vinuesa, Lara; Martínez-Nieto, Jorge; Ropero, Paloma; Villegas, Ana; González, Fernando A; Díaz-Mediavilla, Joaquin; Erythropathology Spanish Group

    2012-01-01

    Most α-thalassemia (α-thal) mechanisms are deletions of one or both α-globin genes and less than 5.0-10.0% are point mutations. Hb Agrinio [α29(B10)Leu→Pro, CTG>CCG (α2)] is a hyperunstable α chain structural variant in which the thalassemic phenotype is determined by a post translational precipitation of the structurally anomalous chain in erythroid precursors. This study involved 14 cases with Hb Agrinio from three families. Selective sequencing of the α2 gene showed a CTG(Leu)>CCG(Pro) mutation at codon 29. The mutation was found in a heterozygous state in 11 cases and in a homozygous state in three cases. These are the first cases with Hb Agrinio described in Spain. In all cases where a leucine is exchanged for a proline, an unstable hemoglobin (Hb) will occur both in the α and the β chain. Some of these are as unstable as Hb Agrinio and their presence is difficult to detect except by DNA sequencing. PMID:23094635

  19. Cloning and Expression Analysis of One Gamma-Glutamylcysteine Synthetase Gene (Hbγ-ECS1) in Latex Production in Hevea brasiliensis

    PubMed Central

    Fang, Wei; Qiao, Luo Shi; Ming, Wu; Jian, Qiu; Feng, Yang Wen; Hua, Gao Hong; Zhou, Xiao Xian

    2016-01-01

    Rubber tree is a major commercial source of natural rubber. Latex coagulation is delayed by thiols, which belong to the important type of antioxidants in laticifer submembrane, and is composed of glutathione (GSH), cysteine, and methionine. The rate-limiting enzyme, γ-ECS, plays an important role in regulating the biosynthesis of glutathione under any environment conditions. To understand the relation between γ-ECS and thiols and to correlate latex flow with one-time tapping and continuous tapping, we cloned and derived the full length of one γ-ECS from rubber tree latex (Hbγ-ECS1). According to qPCR analysis, the expression levels of Hbγ-ECS1 were induced by tapping and Ethrel stimulation, and the expression was related to thiols content in the latex. Continuous tapping induced injury, and the expression of HbγECS1 increased with routine tapping and Ethrel-stimulation tapping (more intensive tapping). According to expression in long-term flowing latex, the gene was related to the duration of latex flow. HbγECS1 was expressed in E. coli Rosetta using pET-sumo as an expression vector and the recombinant enzyme was purified; then we achieved 0.827 U/mg specific activity and about 66 kDa molecular weight. The present study can help us understand the complex role of Hbγ-ECS in thiols biosynthesis, which is influenced by tapping. PMID:27419133

  20. Cloning and Expression Analysis of One Gamma-Glutamylcysteine Synthetase Gene (Hbγ-ECS1) in Latex Production in Hevea brasiliensis.

    PubMed

    Fang, Wei; Qiao, Luo Shi; Ming, Wu; Jian, Qiu; Feng, Yang Wen; Hua, Gao Hong; Zhou, Xiao Xian

    2016-01-01

    Rubber tree is a major commercial source of natural rubber. Latex coagulation is delayed by thiols, which belong to the important type of antioxidants in laticifer submembrane, and is composed of glutathione (GSH), cysteine, and methionine. The rate-limiting enzyme, γ-ECS, plays an important role in regulating the biosynthesis of glutathione under any environment conditions. To understand the relation between γ-ECS and thiols and to correlate latex flow with one-time tapping and continuous tapping, we cloned and derived the full length of one γ-ECS from rubber tree latex (Hbγ-ECS1). According to qPCR analysis, the expression levels of Hbγ-ECS1 were induced by tapping and Ethrel stimulation, and the expression was related to thiols content in the latex. Continuous tapping induced injury, and the expression of HbγECS1 increased with routine tapping and Ethrel-stimulation tapping (more intensive tapping). According to expression in long-term flowing latex, the gene was related to the duration of latex flow. HbγECS1 was expressed in E. coli Rosetta using pET-sumo as an expression vector and the recombinant enzyme was purified; then we achieved 0.827 U/mg specific activity and about 66 kDa molecular weight. The present study can help us understand the complex role of Hbγ-ECS in thiols biosynthesis, which is influenced by tapping. PMID:27419133

  1. Genetic mechanisms for dominant V[sub H] gene expression: The V[sub H]B512 gene

    SciTech Connect

    Fernandez, C. )

    1992-10-01

    A total of 37 mAb with reactivity for dextran B512 have been studied; 30 of them were products of independent rearrangements and 21 made use of the same V[sub H] gene, the V[sub H]B512 gene. These results unambiguously established that the immune response to dextran in the high responder mouse strain C57BL/6 was restricted. Idiotypic determinants are located all over the Ig V region. Many but not all Id described so far can be ascribed to protein structures encoded by V[sub H] or V[sub L] gene segments. The expression of the major Id, 17-9 Id, in C57BL/6 was not absolutely correlated with the expression of the dominant V[sub H]B512 gene in the same mouse strain. Inspection of amino acid sequences of the CDR3 of idiotypic positive and negative clones suggested idiotypic structures may be associated with the expression of Tyr at position 95 and Phe or Leu at position 96 in the H and L chains, respectively. Therefore the indiscriminate use of idiotypic markers to characterize V[sub H] genes and the relevance of idiotypic regulation in V[sub H] gene expression are questioned. Id-positive and Id-negative clones displayed similar affinity values for dextran, indicating that idiotypic and binding structures were probably separated. The exchange of Asp65 for Gly65 in one of the clones reduced affinity for dextran, suggesting the involvement of CDR2 in dextran binding. The dominant expression of V[sub H] genes can be explained by somatic and/or genetic mechanisms. Because somatic mechanisms such as idiotypic regulation or selection based on affinity for dextran did not seem to influence the expression of the V[sub H]B512 gene, the authors favor a genetic alternative. They discuss a model based on the distance between V[sub H] genes and D and J[sub H] elements. This model is compatible with somatic and genetic regulation in other systems and provides a new theoretical approach to the understanding of immune V[sub H] dominance and low responsiveness. 43 refs., 3 figs., 4 tabs.

  2. Description of the phenotypes of 63 heterozygous, homozygous and compound heterozygous patients carrying the Hb Groene Hart [α119(H2)Pro→Ser; HBA1: c.358C>T] variant.

    PubMed

    Joly, Philippe; Lacan, Philippe; Garcia, Caroline; Francina, Alain

    2014-01-01

    We here report the phenotypes and genotypes of 63 patients of North African origin, carriers of Hb Groene Hart [Hb GH, α119(H2)Pro → Ser; HBA1: c.358C>T], an α(+)-thalassemia (α(+)-thal) hemoglobin (Hb) variant. Fifty patients were heterozygous, five were homozygous and eight also carried the common -α(3.7) (rightward) deletion in compound heterozygosity. The expression of the α(GH)-globin chain is increased in the following order: heterozygous, compound heterozygous and homozygous. Parallel significant changes of mean corpuscular Hb (MCH) and mean corpuscular volume (MCV) were also observed. Our large cohort of Hb GH carriers could have been obtained by the systematic realization of globin chain separation by reversed phase liquid chromatography (RP-LC) in our routine Hb testing. PMID:24111644

  3. Adsorption of Two Dyes by Mg(OH)2: Procion Blue HB and Remazol Brilliant Blue R

    NASA Astrophysics Data System (ADS)

    Bouberka, Zohra; Bentaleb, Kahina; Benabbou, Khalil A.; Maschke, Ulrich

    The use of low-cost and ecofriendly adsorbents has been investigated as an ideal alternative to the current expensive methods of removing dyes from wastewater. Mg(OH)2 sludge was produced from precipitation of magnesium ions (Mg2+) with NaOH in pH = 10 and investigated as a low-cost adsorbent. This paper deals with the removal of textile dyes from aqueous solutions by Mg(OH)2. Reactive Procion blue HB (PR) and Acid Remazol brilliant blue R (RB) were used as model compounds. The adsorption capacity was found as 43.47 and 26.89 mg/g at initial pH 6.5.

  4. Update of HB-line consequences based on new meteorological and population databases in AXAIR89Q

    SciTech Connect

    DelGenio, M.E.

    1994-03-01

    Additional analyses and upgrading of the Safety Analysis Report (SAR) and Justification for Continued Operation (JCO) is needed for an Environmental Assessment (EA) currently being prepared for HB-Line. Since the JCO and SAR do not include population doses for two accidents; a propagated fire and a ground level release for an earthquake, this analysis will provide these doses. Population distribution information has been updated to 1992. This analysis will analyze the onsite worker at a distance of 640 meters from the release point using 50% meteorology in accordance with more recent DOE guidance. The doses will be calculated for all the accidents reported in the JCO. This analysis will update maximum offsite individual doses using a new meteorological database based on more recent data collected from 1987-1991. The new meteorological database results in a decrease in the dose from a release from H-Area.

  5. STS-56 ATLAS-2 pallet is lowered into OV-103's payload bay at KSC's OPF HB-3

    NASA Technical Reports Server (NTRS)

    1993-01-01

    STS-56 Atmospheric Laboratory for Applications and Science 2 (ATLAS-2) unpressurized spacelab pallet and the mission peculiar support structure (MPESS)-mounted Shuttle Pointed Autonomous Research Tool for Astronomy 201 (SPARTAN-201) are lowered into the payload bay (PLB) of Discovery, Orbiter Vehicle (OV) 103, at the Kennedy Space Center's (KSC's) Orbiter Processing Facility (OPF) High Bay 3 (HB-3) during preflight integration. Clean-suited technicians monitor the progress and operation of the overhead crane from which the ATLAS-2 pallet/SPARTAN MPESS are suspended. ATLAS-2 equipment and instruments include: the igloo (cylindrical tank - front and center); the inverters and pump package (far right); port conical scan sensor (next to pump package at far right); the millimeter-wave atmospheric sounder (MAS) antenna (pallet center, just above igloo); the starboard conical scan sensor (small cylinder at far left); and the atmospheric trace module spectroscopy (ATMOS) (box behind conical se

  6. Ultrafast heme-ligand recombination in truncated hemoglobin HbO from Mycobacterium tuberculosis: A ligand cage

    NASA Astrophysics Data System (ADS)

    Jasaitis, Audrius; Ouellet, Hugues; Lambry, Jean-Christophe; Martin, Jean-Louis; Friedman, Joel M.; Guertin, Michel; Vos, Marten H.

    2012-03-01

    Truncated hemoglobin HbO from Mycobacterium tuberculosis displays very slow exchange of diatomic ligands with its environment. Using femtosecond spectroscopy, we show that upon photoexcitation, ligands rebind with unusual speed and efficiency. Only ˜1% O2 can escape from the heme pocket and less than 1% NO. Most remarkably, CO rebinding occurs for 95%, predominantly in 1.2 ns. The general CO rebinding properties are unexpectedly robust against changes in the interactions with close by aromatic residues Trp88 (G8) and Tyr36 (CD1). Molecular dynamics simulations of the CO complex suggest that interactions of the ligand with structural water molecules as well as its rotational freedom play a role in the high reactivity of the ligand and the heme. The slow exchange of ligands between heme and environment may result from a combination of hindered ligand access to the heme pocket by the network of distal aromatic residues, and low escape probability from the pocket.

  7. Investigation Of In-Line Monitoring Options At H Canyon/HB Line For Plutonium Oxide Production

    SciTech Connect

    Sexton, L.

    2015-10-14

    H Canyon and HB Line have a production goal of 1 MT per year of plutonium oxide feedstock for the MOX facility by FY17 (AFS-2 mission). In order to meet this goal, steps will need to be taken to improve processing efficiency. One concept for achieving this goal is to implement in-line process monitoring at key measurement points within the facilities. In-line monitoring during operations has the potential to increase throughput and efficiency while reducing costs associated with laboratory sample analysis. In the work reported here, we mapped the plutonium oxide process, identified key measurement points, investigated alternate technologies that could be used for in-line analysis, and initiated a throughput benefit analysis.

  8. Cloning and characterization of a novel human hepatocyte transcription factor, hB1F, which binds and activates enhancer II of hepatitis B virus.

    PubMed

    Li, M; Xie, Y H; Kong, Y Y; Wu, X; Zhu, L; Wang, Y

    1998-10-30

    Enhancer II (ENII) of hepatitis B virus (HBV) is one of the essential cis-elements for the transcriptional regulation of HBV gene expression. Its function is highly liver-specific, suggesting that liver-enriched transcriptional factors play critical roles in regulating the activity of ENII. In this report, a novel hepatocyte transcription factor, which binds specifically to the B1 region (AACGACCGACCTTGAG) within the major functional unit (B unit) of ENII, has been cloned from a human liver cDNA library by yeast one-hybrid screening, and demonstrated to trans-activate ENII via the B1 region. We named this factor hB1F, for human B1-binding factor. Amino acid analysis revealed this factor structurally belongs to nuclear receptor superfamily. Based on the sequence similarities, hB1F is characterized to be a novel human homolog of the orphan receptor fushi tarazu factor I (FTZ-F1). Using reverse transcription-polymerase chain reaction, a splicing isoform of hB1F (hB1F-2) was identified, which has an extra 46 amino acid residues in the A/B region. Examination of the tissue distribution has revealed an abundant 5.2-kilobase transcript of hB1F is present specifically in human pancreas and liver. Interestingly, an additional transcript of 3.8 kilobases was found to be present in hepatoma cells HepG2. Fluorescent in situ hybridization has mapped the gene locus of hB1F to the region q31-32.1 of human chromosome 1. Altogether, this study provides the first report that a novel human homolog of FTZ-F1 binds and regulates ENII of HBV. The potential roles of this FTZ-F1 homolog in tissue-specific gene regulation, in embryonic development, as well as in liver carcinogenesis are discussed. PMID:9786908

  9. Elevated HbA1c Levels Are Associated with the Blunted Autonomic Response Assessed by Heart Rate Variability during Blood Volume Reduction.

    PubMed

    Kamakura, Miho; Maruyama, Ryoko

    2016-01-01

    A high glycemic status increases the risk for autonomic dysfunction and cardiovascular failure. The aim of this study was to investigate time-dependent changes in the autonomic response and cardiovascular dynamics and the association between the level of hemoglobin A1c (HbA1c) and autonomic response during blood volume reduction. The study population consisted of 26 preoperative participants who were scheduled for autologous blood donation (200-400 mL of whole blood) for intraoperative or postoperative use. These participants without circulatory, respiratory, or brain disease and diabetes mellitus were grouped according to their HbA1c levels: < 6.5% (n = 18) and ≥ 6.5% (n = 8). We measured blood pressure (BP) and analyzed heart rate variability (HRV) to quantify cardiac autonomic regulation throughout blood donation. During blood volume reduction, which was about 10% of the circulating blood volume, the BP and heart rate varied within normal ranges in both groups. The high-frequency (HF) component, an index of parasympathetic nerve activity, and the ratio of low-frequency (LF) to HF components (LF/HF), an index of sympathetic nerve activity, significantly decreased and increased with the progression of blood volume reduction, respectively, in the HbA1c < 6.5% group. In contrast, in the HbA1c ≥ 6.5% group, the HF component did not significantly change, and the increase in the LF/HF ratio was delayed. Time-dependent changes in HRV were related to blood volume reduction only in the HbA1c < 6.5% group. Thus, elevated HbA1c levels are associated with the decrease in the autonomic response induced by blood volume reduction. PMID:27615262

  10. Incidence of the Hb E [β26(B8)Glu→Lys, GAG>AAG] variant in Totos, one of the smallest primitive tribes in the world.

    PubMed

    Bhattacharyya, Deboshree; Mukhopadhyay, Ashis; Chakraborty, Abhijit; Dasgupta, Swati; Mukhopadhyay, Soma; Pal, Nabamita; Basak, Jayasri

    2013-01-01

    Toto is one of the smallest tribes in the world. This primitive sub Himalayan, endogamous tribe lives in a small, isolated village called Totopara in the Jalpaiguri district of West Bengal in India. The tribal communities of West Bengal are vulnerable to various genetic disorders such as β-thalassemia (β-thal). We have studied 443 Totos to define their Hb E [β26(B8)Glu→Lys, GAG>AAG] status. Awareness and screening camps have been organized in various parts of Totopara during the last 2 years. We collected 3 mL peripheral blood from each individual aseptically on which to use the naked eye single tube red cell osmotic fragility test (NESTROFT); complete hemogram and high performance liquid chromatography (HPLC) were done to detect their carrier status. The Hb E variant had been found to be prevalent among the Totos. To confirm the codon 26 (GAG>AAG) mutation in the β-globin gene, amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) was performed. Restriction fragment length polymorphism (RFLP)-PCR was carried out with 44 Hb E alleles to construct the haplotype(s) of the Totos. Our extensive studies have revealed that 49.21% of Totos are Hb E heterozygotes and 19.19% Totos are Hb E homozygotes. The most prevalent haplotype linked with the codon 26 mutation in the Totos is [+ - - - - -] (HincII 5'ϵ, HindIII (G)γ, HindIII (A)γ, HincII 5'ψβ, HincII 3'ψβ and HinfI 3'β). Consanguineous marriages have resulted in a significant increase of the percentages of heterozygotes and homozygotes of Hb E in the Totos. Genetic counseling is essential and important to prevent the spread of this mutation and hence to save them from having any kind of clinically significant hemoglobinopathy in the future. PMID:23215760

  11. Efficacy of Rapamycin as Inducer of Hb F in Primary Erythroid Cultures from Sickle Cell Disease and β-Thalassemia Patients.

    PubMed

    Pecoraro, Alice; Troia, Antonio; Calzolari, Roberta; Scazzone, Concetta; Rigano, Paolo; Martorana, Adriana; Sacco, Massimiliano; Maggio, Aurelio; Di Marzo, Rosalba

    2015-01-01

    Phenotypic improvement of hemoglobinopathies such as sickle cell disease and β-thalassemia (β-thal) has been shown in patients with high levels of Hb F. Among the drugs proposed to increase Hb F production, hydroxyurea (HU) is currently the only one proven to improve the clinical course of these diseases. However, Hb F increase and patient's response are highly variable, indicating that new pharmacological agents could be useful for patients not responding to HU or showing a reduction of response during long-term therapy. In this study we evaluated the efficacy of rapamycin, a lypophilic macrolide used for the prevention of acute rejection in renal transplant recipients, as an inducer of Hb F production. The analyses were performed in cultured erythroid progenitors from 25 sickle cell disease and 25 β-thal intermedia (β-TI) patients. The use of a quantitative Real-Time-polymerase chain reaction ReTi-PCR technique and high performance liquid chromatography (HPLC) allowed us to determine the increase in γ-globin mRNA expression and Hb F production in human erythroid cells treated with rapamycin. The results of our study demonstrated an increase in vitro of γ-globin mRNA expression in 15 sickle cell disease and 14 β-TI patients and a corresponding Hb F increase. The induction by rapamycin, even if lower or similar in most of samples analyzed, in some cases was higher than HU. These data suggest that rapamycin could be a good candidate to be used in vivo for the treatment of hemoglobinopathies. PMID:26016899

  12. Transformation with TT8 and HB12 RNAi Constructs in Model Forage (Medicago sativa, Alfalfa) Affects Carbohydrate Structure and Metabolic Characteristics in Ruminant Livestock Systems.

    PubMed

    Li, Xinxin; Zhang, Yonggen; Hannoufa, Abdelali; Yu, Peiqiang

    2015-11-01

    Lignin, a phenylpropanoid polymer present in secondary cell walls, has a negative impact on feed digestibility. TT8 and HB12 genes were shown to have low expression levels in low-lignin tissues of alfalfa, but to date, there has been no study on the effect of down-regulation of these two genes in alfalfa on nutrient chemical profiles and availability in ruminant livestock systems. The objectives of this study were to investigate the effect of transformation of alfalfa with TT8 and HB12 RNAi constructs on carbohydrate (CHO) structure and CHO nutritive value in ruminant livestock systems. The results showed that transformation with TT8 and HB12 RNAi constructs reduced rumen, rapidly degraded CHO fractions (RDCA4, P = 0.06; RDCB1, P < 0.01) and totally degraded CHO fraction (TRDCHO, P = 0.08). Both HB12 and TT8 populations had significantly higher in vitro digestibility of neutral detergent fiber (NDF) at 30 h of incubation (ivNDF30) compared to the control (P < 0.01). The TT8 populations had highest ivDM30 and ivNDF240. Transformation of alfalfa with TT8 and HB12 RNAi constructs induced molecular structure changes. Different CHO functional groups had different sensitivities and different responses to the transformation. The CHO molecular structure changes induced by the transformation were associated with predicted CHO availability. Compared with HB12 RNAi, transformation with TT8 RNAi could improve forage quality by increasing the availability of both NDF and DM. Further study is needed on the relationship between the transformation-induced structure changes at a molecular level and nutrient utilization in ruminant livestock systems when lignification is much higher. PMID:26492548

  13. Genetic modifiers of Hb E/β0 thalassemia identified by a two-stage genome-wide association study

    PubMed Central

    2010-01-01

    Background Patients with Hb E/β0 thalassemia display remarkable variability in disease severity. To identify genetic modifiers influencing disease severity, we conducted a two-stage genome scan in groups of 207 mild and 305 severe unrelated patients from Thailand with Hb E/β0 thalassemia and normal α-globin genes. Methods First, we estimated and compared the allele frequencies of approximately 110,000 gene-based single nucleotide polymorphisms (SNPs) in pooled DNAs from different severity groups. The 756 SNPs that showed reproducible allelic differences at P < 0.02 by pooling were selected for individual genotyping. Results After adjustment for age, gender and geographic region, logistic regression models showed 50 SNPs significantly associated with disease severity (P < 0.05) after Bonferroni adjustment for multiple testing. Forty-one SNPs in a large LD block within the β-globin gene cluster had major alleles associated with severe disease. The most significant was bthal_bg200 (odds ratio (OR) = 5.56, P = 2.6 × 10-13). Seven SNPs in two distinct LD blocks within a region centromeric to the β-globin gene cluster that contains many olfactory receptor genes were also associated with disease severity; rs3886223 had the strongest association (OR = 3.03, P = 3.7 × 10-11). Several previously unreported SNPs were also significantly associated with disease severity. Conclusions These results suggest that there may be an additional regulatory region centromeric to the β-globin gene cluster that affects disease severity by modulating fetal hemoglobin expression. PMID:20353593

  14. Prevalence of comorbidity in primary care patients with type 2 diabetes and its association with elevated HbA1c: A cross-sectional study in Croatia

    PubMed Central

    Bralić Lang, Valerija; Bergman Marković, Biserka

    2016-01-01

    Objective To the authors’ knowledge, there are few valid data that describe the prevalence of comorbidity in type 2 diabetes mellitus (T2DM) patients seen in family practice. This study aimed to investigate the prevalence of comorbidities and their association with elevated (≥ 7.0%) haemoglobin A1c (HbA1c) using a large sample of T2DM patients from primary care practices. Design A cross-sectional study in which multivariate logistic regression was applied to explore the association of comorbidities with elevated HbA1c. Setting Primary care practices in Croatia. Subjects Altogether, 10 264 patients with diabetes in 449 practices. Main outcome measures Comorbidities and elevated HbA1c. Results In total 7979 (77.7%) participants had comorbidity. The mean number of comorbidities was 1.6 (SD 1.28). Diseases of the circulatory system were the most common (7157, 69.7%), followed by endocrine and metabolic diseases (3093, 30.1%), and diseases of the musculoskeletal system and connective tissue (1437, 14.0%). After adjustment for age and sex, the number of comorbidities was significantly associated with HbA1c. The higher the number of comorbidities, the lower the HbA1c. The prevalence of physicians’ inertia was statistically significantly and negatively associated with the number of comorbidities (Mann–Whitney U test, Z = –12.34; p < 0.001; r = –0.12). Conclusion There is a high prevalence of comorbidity among T2DM patients in primary care. A negative association of number of comorbidities and HbA1c is probably moderated by physicians’ inertia in treatment of T2DM strictly according to guidelines. Key pointsThere is a high prevalence of comorbidity among T2DM patients in primary care.Patients with breast cancer, obese patients, and those with dyslipidaemia and ischaemic heart disease were more likely to have increased HbA1c.The higher the number of comorbidities, the lower the HbA1c. PMID:26853192

  15. HbA1c Levels Are Associated with Chronic Kidney Disease in a Non-Diabetic Adult Population: A Nationwide Survey (KNHANES 2011–2013)

    PubMed Central

    Kang, Seok Hui; Jung, Da Jung; Choi, Eun Woo; Cho, Kyu Hyang; Park, Jong Won; Do, Jun Young

    2015-01-01

    Background Many studies have reported an association between glycated hemoglobin A1c (HbA1c) and metabolic syndrome (MetS) in non-diabetes patients. Each component of MetS is in fact related to chronic kidney disease (CKD) incidence and progression. Therefore, HbA1c in non-diabetic mellitus (DM) may be intrinsically associated with the prevalence of CKD. The hypothesis of the present study was that high HbA1c in non-DM patients is associated with CKD. Patients and Methods The total number of participants in this study was 24,594. The participants were divided into three groups according to their HbA1c levels: a Low group (<5.7% or <39 mmol/mol), a Middle group (5.7–6.0% or 39–42 mmol/mol), and a High group (>6.0% or >42 mmol/mol). The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Results The number of participants allocated to the Low, Middle, and High groups was 8,651, 4,634, and 1,387, respectively. Linear regression analyses were performed to evaluate the association between variables. Standardized β ± standard error was 0.25 ± 0.22 for waist circumference, 0.44 ± 0.20 for fasting glucose, –0.14 ± 0.30 for high-density lipoprotein cholesterol levels, 0.15 ± 2.31 for triglyceride levels, 0.21 ± 0.00 for systolic blood pressure, 0.10 ± 0.00 for diastolic blood pressure, and –0.22 ± 0.42 for eGFR (P < 0.001 for all variables). eGFR in non-diabetes participants was inversely associated with the HbA1c level, where eGFR decreased as HbA1c levels increased. Standardized βs were –0.04 ± 0.42 in multivariable analysis (P < 0.001). The proportion of participants with only MetS, only CKD, or both MetS and CKD was higher in the High group than in the Low and Middle groups. Conclusion High HbA1c in non-DM patients may be associated with CKD. Renal function in patients with high HbA1c levels may need to be monitored. PMID:26716684

  16. HbA1c overtesting and overtreatment among US adults with controlled type 2 diabetes, 2001-13: observational population based study

    PubMed Central

    Van Houten, Holly K; Ross, Joseph S; Montori, Victor M; Shah, Nilay D

    2015-01-01

    Study question What is the extent and effect of excessive testing for glycated hemoglobin (HbA1c) among adults with controlled type 2 diabetes? Methods A retrospective analysis of data from a national administrative claims database included commercially insured individuals in the USA, 2001-13. Study patients were aged 18 years or older, had type 2 diabetes with stable glycemic control (two consecutive tests showing HbA1c<7.0% within 24 months), did not use insulin, had no history of severe hypoglycemia or hyperglycemia, and were not pregnant. HbA1c testing frequency was measured within 24 months after the second (index) HbA1c test, and classified as guideline recommended (≤2 times/year), frequent (3-4 times/year), and excessive (≥5 times/year). Changes in treatment regimen were ascertained within three months of the index test. Study answer and limitations Of 31 545 patients in the study cohort (mean age 58 years; mean index HbA1c 6.2%), HbA1c testing frequency was excessive in 6% and frequent in 55%. Despite good glycemic control at baseline, treatment was further intensified by addition of glucose lowering drugs or insulin in 8.4% of patients (comprising 13%, 9%, and 7% of those tested excessively, frequently, and per guidelines, respectively; P<0.001). Compared with guideline recommended testing, excessive testing was associated with treatment intensification (odds ratio 1.35 (95% confidence interval 1.22 to 1.50)). Excessive testing rates remained unchanged in 2001-08, but fell significantly after 2009. The odds of excessive testing was 46% lower in 2011 than in 2001-02. The study population is not representative of all US patients with type 2 diabetes because it was restricted to commercially insured adults with stable and controlled diabetes not receiving insulin treatment. The study design did not capture the underuse of HbA1c testing. What this study adds In this US cohort of adults with stable and controlled type 2 diabetes, more than 60% received

  17. Diagnostic Dilemma of Hb Perth [β32(B14)Leu→Pro; HBB: c.98T > C] in Mainland China.

    PubMed

    Jiang, Hua; Yan, Jin-Mei; Li, Jian; Xie, Xing-Mei; Li, Dong-Zhi

    2016-06-01

    Unstable hemoglobin (Hb) variants represent a rare etiology of congenital hemolytic anemia. Correct diagnosis can be a challenge due to the relative rarity or lack of awareness of this disorder. We report an 18-month-old girl, who presented with a long-standing hemolytic anemia. Her diagnosis of unstable Hb Perth [β32(B14)Leu→Pro, HBB: c.98T > C] had not been made until gene sequencing of the β-globin gene was performed. PMID:27117570

  18. Association of pre-pregnancy BMI and postpartum weight retention with postpartum HbA1c among women with Type 1 diabetes

    PubMed Central

    Huang, T.; Brown, F. M.; Curran, A.; James-Todd, T.

    2015-01-01

    Aim To examine the association of pre-pregnancy BMI and postpartum weight retention with postpartum HbA1c levels in women with Type 1 diabetes. Methods We longitudinally evaluated 136 women with Type 1 diabetes who received prenatal and postpartum care through the Joslin Diabetes Center’s Diabetes and Pregnancy Program between 2004 and 2009. Weight, BMI and HbA1c concentration were assessed before the index pregnancy and repeatedly monitored after delivery until 12 months postpartum. We used a linear mixed model to assess the association of postpartum HbA1c with pre-pregnancy BMI and postpartum weight retention. Results The mean HbA1c concentration increased from 49 mmol/mol (6.6%) at 6 weeks postpartum to 58 mmol/mol (7.5%) by 10 months postpartum, a level similar to the mean pre-pregnancy HbA1c concentration. Postpartum weight retention showed a linearly decreasing trend of 0.06 kg/week (P<0.0001), with −0.1 kg average postpartum weight retention by 1 year postpartum. Compared with women with a pre-pregnancy BMI≥25 kg/m2, women with a lower pre-pregnancy BMI maintained a 3.4 mmol/mol (0.31%) lower HbA1c concentration, after adjusting for several sociodemographic, reproductive and diabetes-related factors (P=0.03). There was a suggestion of a time-varying positive association between HbA1c and postpartum weight retention, with the most significant difference of 3.7 mmol/mol (0.34%; P=0.05) at 30 weeks postpartum among women with postpartum weight retention ≥5 kg vs those with postpartum weight retention <5 kg. Conclusions Pre-pregnancy BMI and postpartum weight retention were positively associated with HbA1c during the first postpartum year in women with Type 1 diabetes. Interventions to modify the behaviours associated with these body weight factors before pregnancy and after delivery may help women with Type 1 diabetes maintain good glycaemic control after pregnancy. PMID:25346003

  19. Extreme Levels of HbA1c Increase Incident ESRD Risk in Chinese Patients with Type 2 Diabetes: Competing Risk Analysis in National Cohort of Taiwan Diabetes Study

    PubMed Central

    Liu, Chiu-Shong; Huang, Chiu-Ching; Lin, Wen-Yuan; Chiang, Jen-Huai; Lin, Cheng-Chieh; Li, Tsai-Chung

    2015-01-01

    Background Whether HbA1c is a predictor of end-stage renal disease (ESRD) in type 2 diabetes patients remains unclear. This study evaluated relationship between HbA1c and ESRD in Chinese patients with type 2 diabetes. Methods Patients aged ≥ 30 years who were free of ESRD (n = 51 681) were included from National Diabetes Care Management Program from 2002–2003. Extended Cox proportional hazard model with competing risk of death served to evaluate association between HbA1c level and ESRD. Results A total of 2613 (5.06%) people developed ESRD during a follow-up period of 8.1 years. Overall incidence rate of ESRD was 6.26 per 1000 person-years. Patients with high levels of HbA1c had a high incidence rate of ESRD, from 4.29 for HbA1c of  6.0%–6.9% to 10.33 for HbA1c ≥ 10.0% per 1000 person-years. Patients with HbA1c < 6.0% particularly had a slightly higher ESRD incidence (4.34 per 1000 person-years) than those with HbA1c  of 6.0%–6.9%. A J-shaped relationship between HbA1c level and ESRD risk was observed. After adjustment, patients with HbA1c < 6.0% and ≥ 10.0% exhibited an increased risk of ESRD (HR: 1.99, 95% CI: 1.62–2.44; HR: 4.42, 95% CI: 3.80–5.14, respectively) compared with those with HbA1c of 6.0%–6.9%. Conclusions Diabetes care has focused on preventing hyperglycemia, but not hypoglycemia. Our study revealed that HbA1c level ≥ 7.0% was linked with increased ESRD risk in type 2 diabetes patients, and that HbA1c < 6.0% also had the potential to increase ESRD risk. Our study provides epidemiological evidence that appropriate glycemic control is essential for diabetes care to meet HbA1c targets and improve outcomes without increasing the risk to this population. Clinicians need to pay attention to HbA1c results on diabetic nephropathy. PMID:26098901

  20. Hot HB Stars in Globular Clusters - Physical Parameters and Consequences for Theory. VI. The Second Parameter Pair M3 and M13

    NASA Technical Reports Server (NTRS)

    Moehler, S.; Landsman, W. B.; Sweigart, A. V.; Grundahl, F.

    2002-01-01

    We present the results of spectroscopic analyses of hot horizontal branch (HB) stars in M13 and M3, which form a famous second parameter pair. From the spectra we derived - for the first time in M13 - atmospheric parameters (effective temperature and surface gravity) as well as abundances of helium, magnesium, and iron. Consistent with analyses of hot HB stars in other globular clusters we find evidence for helium depletion and iron enrichment in stars hotter than about 12,000 K in both M3 and M13. Accounting for the iron enrichment substantially improves the agreement with canonical evolutionary models, although the derived gravities and masses are still somewhat too low. This remaining discrepancy may be an indication that scaled-solar metal-rich model atmospheres do not adequately represent the highly non-solar abundance ratios found in blue HB stars with radiative levitation. We discuss the effects of an enhancement in the envelope helium abundance on the atmospheric parameters of the blue HB stars, as might be caused by deep mixing on the red giant branch or primordial pollution from an earlier generation of intermediate mass asymptotic giant branch stars.

  1. Pediatric diabetes consortium type 1 diabetes new onset (NeOn) study: Factors associated with HbA1c levels one year after diagnosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To identify determinants of hemoglobin A1c (HbA1c) levels 1 yr after the diagnosis of type 1 diabetes (T1D) in participants in the Pediatric Diabetes Consortium (PDC) T1D New Onset (NeOn) Study. Diabetes-specific as well as socioeconomic factors during the first year following diagnosis were analyze...

  2. 75 FR 1650 - Notice of Intent To Prepare an Environmental Impact Statement for the Proposed HB Potash, LLC-“In...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-12

    ... subsidence, hydrology, air quality, water quality and quantity, underground mine workings, socioeconomics... Leasing and Development Within the Designated Potash Area of Eddy and Lea Counties, New Mexico, 51 FR 39425 (October 28, 1986), as corrected at 52 FR 32171 (August 26, 1987). The proposed HB...

  3. 76 FR 77022 - In the Matter of Carolina Power & Light Company, H.B. Robinson Steam Electric Plant, Unit No. 2...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-09

    ... the Federal Register on August 31, 2011 (76 FR 54261). No comments or hearing requests were received... Control of Licenses I. Carolina Power & Light Company (CP&L, the licensee) is the owner of the H.B... and materials license authorize CP&L to possess, use, and operate the Robinson facility. II....

  4. 77 FR 5566 - Notice of Availability of the Final EIS for the HB In-Situ Solution Mine Project, Eddy County...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-03

    ...In accordance with the National Environmental Policy Act of 1969, as amended, and the Federal Land Policy and Management Act of 1976, as amended, the Bureau of Land Management (BLM) has prepared a Final Environmental Impact Statement (Final EIS) for the HB In-Situ Solution Mine Project, and by this notice is announcing its...

  5. Adherence to oral glucose lowering therapies and associations with one year HbA1c: a retrospective cohort analysis in a large primary care database

    PubMed Central

    Shields, Beverley; Weedon, Michael N.; Donnelly, Louise; Holman, Rury R.; Pearson, Ewan R.; Hattersley, Andrew T

    2016-01-01

    Objectives The impact of taking oral glucose-lowering medicines intermittently, rather than as recommended, is unclear. We conducted a retrospective cohort study using community-acquired United Kingdom clinical data (CPRD and GoDARTS databases) to examine the prevalence of non-adherence to treatment for type 2 diabetes, and investigate its potential impact on HbA1c reduction stratified by type of glucose-lowering medication. Research design and methods Data for patients treated between 2004 and 2014 were extracted for those newly-prescribed metformin, sulfonylurea, thiazolidinedione or dipeptidyl peptidase-4 inhibitors who continued to obtain prescriptions over one year, were extracted. Cohorts were defined by prescribed medication type, and good adherence as a medication possession ratio ≥0.8. Linear regression was used to determine potential associations between adherence and one-year baseline-adjusted HbA1c reduction. Results In CPRD and GoDARTS, 13% and 15% of patients respectively were non-adherent. Proportions of non-adherent patients varied by the oral glucose-lowering treatment prescribed (range 8.6% (thiazolidinedione) to 18.8% (metformin)). Non-adherent, compared with adherent, patients had a smaller HbA1c reduction (0.4%[4.4mmmol/mol] and 0.46%[5.0mmol/mol] for CPRD and GoDARTs respectively). Difference in HbA1c response for adherent compared with non-adherent patients varied by drug (range: 0.38%[4.1mmol/mol] to 0.75%[8.2mmol/mol] lower in adherent group). Decreasing levels of adherence were consistently associated with a smaller reduction in HbA1c. Conclusions Reduced medication adherence for commonly used glucose lowering therapies among patients persisting with treatment is associated with smaller HbA1c reductions, compared with those taking treatment as recommended. Differences observed in HbA1c responses to glucose lowering-treatments may be explained in part by their intermittent use. PMID:26681714

  6. Seed-specific elevation of non-symbiotic hemoglobin AtHb1: beneficial effects and underlying molecular networks in Arabidopsis thaliana

    PubMed Central

    2011-01-01

    Background Seed metabolism is dynamically adjusted to oxygen availability. Processes underlying this auto-regulatory mechanism control the metabolic efficiency under changing environmental conditions/stress and thus, are of relevance for biotechnology. Non-symbiotic hemoglobins have been shown to be involved in scavenging of nitric oxide (NO) molecules, which play a key role in oxygen sensing/balancing in plants and animals. Steady state levels of NO are suggested to act as an integrator of energy and carbon metabolism and subsequently, influence energy-demanding growth processes in plants. Results We aimed to manipulate oxygen stress perception in Arabidopsis seeds by overexpression of the non-symbiotic hemoglobin AtHb1 under the control of the seed-specific LeB4 promoter. Seeds of transgenic AtHb1 plants did not accumulate NO under transient hypoxic stress treatment, showed higher respiratory activity and energy status compared to the wild type. Global transcript profiling of seeds/siliques from wild type and transgenic plants under transient hypoxic and standard conditions using Affymetrix ATH1 chips revealed a rearrangement of transcriptional networks by AtHb1 overexpression under non-stress conditions, which included the induction of transcripts related to ABA synthesis and signaling, receptor-like kinase- and MAP kinase-mediated signaling pathways, WRKY transcription factors and ROS metabolism. Overexpression of AtHb1 shifted seed metabolism to an energy-saving mode with the most prominent alterations occurring in cell wall metabolism. In combination with metabolite and physiological measurements, these data demonstrate that AtHb1 overexpression improves oxidative stress tolerance compared to the wild type where a strong transcriptional and metabolic reconfiguration was observed in the hypoxic response. Conclusions AtHb1 overexpression mediates a pre-adaptation to hypoxic stress. Under transient stress conditions transgenic seeds were able to keep low levels

  7. Universal HbA1c Measurement in Early Pregnancy to Detect Type 2 Diabetes Reduces Ethnic Disparities in Antenatal Diabetes Screening: A Population-Based Observational Study

    PubMed Central

    2016-01-01

    In response to the type 2 diabetes epidemic, measuring HbA1c with the first-antenatal blood screen was recently recommended in NZ. This would enable prompt treatment of women with unrecognised type 2 diabetes, who may otherwise go undetected until the gestational diabetes (GDM) screen. We compare inter-ethnic antenatal screening practices to examine whether the HbA1c test would be accessed by ethnicities most at risk of diabetes, and we determined the prevalence of unrecognised type 2 diabetes and prediabetes in our pregnant population. This is an observational study of pregnancies in Christchurch NZ during 2008–2010. Utilising electronic databases, we matched maternal characteristics to first-antenatal bloods, HbA1c, and GDM screens (glucose challenge tests and oral glucose tolerance tests). Overall uptake of the first-antenatal bloods versus GDM screening was 83.1% and 53.8% respectively in 11,580 pregnancies. GDM screening was lowest in Māori 39.3%, incidence proportion ratio (IPR) 0.77 (0.71, 0.84) compared with Europeans. By including HbA1c with the first-antenatal bloods, the number screened for diabetes increases by 28.5% in Europeans, 40.0% in Māori, 28.1% in Pacific People, and 26.7% in ‘Others’ (majority of Asian descent). The combined prevalence of unrecognised type 2 diabetes and prediabetes by NZ criteria, HbA1c ≥5.9% (41mmol/mol), was 2.1% in Europeans, Māori 4.7% IPR 2.59 (1.71, 3.93), Pacific People 9.5% IPR 4.76 (3.10, 7.30), and ‘Others’ 6.2% IPR 2.99 (2.19, 4.07). Applying these prevalence data to 2013 NZ national births data, routine antenatal HbA1c testing could have identified type 2 diabetes in 0.44% and prediabetes in 3.96% of women. Routine HbA1c measurement in early pregnancy is an ideal screening opportunity, particularly benefitting vulnerable groups, reducing ethnic disparities in antenatal diabetes screening. This approach is likely to have world-wide relevance and applicability. Further research is underway to establish

  8. Characterization of a strong repression domain in the hinge region of orphan nuclear receptor hB1F/hLRH-1.

    PubMed

    Xu, Ping-Long; Shan, Shi-Fang; Kong, Yu-Ying; Xie, You-Hua; Wang, Yuan

    2003-10-01

    Human hepatitis B virus enhancer II B1 binding factor (hB1F also known as NR5A2, LRH-1, FTF or CPF) is an orphan nuclear receptor and belongs to the fushi tarazu factor I (FTZ-F1) subfamily. It plays important roles in the transcriptional regulation of a number of genes involved in bile acid biosynthesis pathway, hepatitis B virus (HBV) replication and liver specific regulatory network. Like other nuclear receptors, hB1F is composed of modular functional domains. We characterized a domain in its hinge region that imposes a strong repression on the transcriptional activity of hB1F, which is important for the function of hB1F on regulating the activity of HBV enhancer II/core promoter. Mutations of the core residues in this domain abrogate the repression. Bioinformatic analysis reveals that the amino acid sequence of this region is highly conserved only among members of the FTZ-F1 subfamily. The repression is observed in five cell lines tested, while the degree of the repression varies greatly, which does not parallel with the expression level of the DEAD box protein of 130 kD (DP103), a potential interacting protein of a homologous domain in the steroidogenic factor 1 (SF-1). Moreover, the repression is not affected by the silencing mediator for retinoic acid receptor and thyroid hormone receptor (SMRT) and steroid receptor coactivator 1 (SRC-1). Collectively, these data suggest a novel regulatory mechanism for the transcriptional activity of hB1F. PMID:14515208

  9. Interaction of cationic dodecyl-trimethyl-ammonium bromide with oxy-HbGp by isothermal titration and differential scanning calorimetric studies: Effect of proximity of isoelectric point.

    PubMed

    Alves, Fernanda Rosa; Carvalho, Francisco Adriano O; Carvalho, José Wilson P; Tabak, Marcel

    2016-04-01

    In this work, isothermal titration and differential scanning calorimetric methods, in combination with pyrene fluorescence emission and dynamic light scattering have been used to investigate the interaction of dodecyltrimethylammonium bromide (DTAB) with the giant extracellular Glossoscolex paulistus hemoglobin (HbGp) in the oxy-form, at pH values around the isoelectric point (pI ≈ 5.5). Our ITC results have shown that the interaction of DTAB with the hemoglobin is more intense at pH 7.0, with a smaller cac (critical aggregation concentration) value. The increase of protein concentration does not influence the cac value of the interaction, at both pH values. Therefore, the beginning of the DTAB-oxy-HbGp premicellar aggregates formation, in the cac region, is not affected by the increase of protein concentration. HSDSC studies show higher Tm values at pH 5.0, in the absence and presence of DTAB, when compared with pH 7.0. Furthermore, at pH 7.0, an aggregation process is observed with DTAB in the range from 0.75 to 1.5 mmol/L, noticed by the exothermic peak, and similar to that observed for pure oxy-HbGp, at pH 5.0, and in the presence of DTAB. DLS melting curves show a decrease on the hemoglobin thermal stability for the oxy-HbGp-DTAB mixtures and formation of larger aggregates, at pH 7.0. Our present data, together with previous results, support the observation that the protein structural changes, at pH 7.0, occur at smaller DTAB concentrations, as compared with pH 5.0, due to the acidic pI of protein that favors the oxy-HbGp-cationic surfactant interaction at neutral pH. PMID:26574155

  10. Trypanosoma brucei gambiense Group 1 Is Distinguished by a Unique Amino Acid Substitution in the HpHb Receptor Implicated in Human Serum Resistance

    PubMed Central

    Sistrom, Mark; Agbebakun, Kehinde; Balmer, Oliver; Gibson, Wendy; Aksoy, Serap; Caccone, Adalgisa

    2012-01-01

    Trypanosoma brucei rhodesiense (Tbr) and T. b. gambiense (Tbg), causative agents of Human African Trypanosomiasis (sleeping sickness) in Africa, have evolved alternative mechanisms of resisting the activity of trypanosome lytic factors (TLFs), components of innate immunity in human serum that protect against infection by other African trypanosomes. In Tbr, lytic activity is suppressed by the Tbr-specific serum-resistance associated (SRA) protein. The mechanism in Tbg is less well understood but has been hypothesized to involve altered activity and expression of haptoglobin haemoglobin receptor (HpHbR). HpHbR has been shown to facilitate internalization of TLF-1 in T.b. brucei (Tbb), a member of the T. brucei species complex that is susceptible to human serum. By evaluating the genetic variability of HpHbR in a comprehensive geographical and taxonomic context, we show that a single substitution that replaces leucine with serine at position 210 is conserved in the most widespread form of Tbg (Tbg group 1) and not found in related taxa, which are either human serum susceptible (Tbb) or known to resist lysis via an alternative mechanism (Tbr and Tbg group 2). We hypothesize that this single substitution contributes to reduced uptake of TLF and thus may play a key role in conferring serum resistance to Tbg group 1. In contrast, similarity in HpHbR sequence among isolates of Tbg group 2 and Tbb/Tbr provides further evidence that human serum resistance in Tbg group 2 is likely independent of HpHbR function. PMID:22802982

  11. A Comparison of hs-CRP Levels in New Diabetes Groups Diagnosed Based on FPG, 2-hPG, or HbA1c Criteria

    PubMed Central

    Tutuncu, Yildiz; Satman, Ilhan; Celik, Selda; Dinccag, Nevin; Karsidag, Kubilay; Telci, Aysegul; Genc, Sema; Issever, Halim; Tuomilehto, Jaakko; Omer, Beyhan

    2016-01-01

    Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) have been used to diagnose new-onset diabetes mellitus (DM) in order to simplify the diagnostic tests compared with the 2-hour oral glucose tolerance test (OGTT; 2-hPG). We aimed to identify optimal cut-off points of high sensitive C-reactive protein (hs-CRP) in new-onset DM people based on FPG, 2-hPG, or HbA1c methods. Data derived from recent population-based survey in Turkey (TURDEP-II). The study included 26,499 adult people (63% women, response rate 85%). The mean serum concentration of hs-CRP in women was higher than in men (p < 0.001). The people with new-onset DM based on HbA1c had higher mean hs-CRP level than FPG based and 2-hPG based DM cases. In HbA1c, 2-hPG, and FPG based new-onset DM people, cut-off levels of hs-CRP in women were 2.9, 2.1, and 2.5 mg/L [27.5, 19.7, and 23.5 nmol/L] and corresponding values in men were 2.0, 1.8, and 1.8 mg/L (19.0, 16.9, and 16.9 nmol/L), respectively (sensitivity 60–65% and specificity 54–64%). Our results revealed that hs-CRP may not further strengthen the diagnosis of new-onset DM. Nevertheless, the highest hs-CRP level observed in new-onset DM people diagnosed with HbA1c criterion supports the general assumption that this method might recognize people in more advanced diabetic stage compared with other diagnostic methods. PMID:26824043

  12. Functional expression of a penicillin acylase from the extreme thermophile Thermus thermophilus HB27 in Escherichia coli

    PubMed Central

    2012-01-01

    Background Penicillin acylases (PACs) are enzymes of industrial relevance in the manufacture of β-lactam antibiotics. Development of a PAC with a longer half-life under the reaction conditions used is essential for the improvement of the operational stability of the process. A gene encoding a homologue to Escherichia coli PAC was found in the genome of the thermophilic bacterium Thermus thermophilus (Tth) HB27. Because of the nature of this PAC and its complex maturation that is crucial to reach its functional heterodimeric final conformation, the overexpression of this enzyme in a heterologous mesophilic host was a challenge. Here we describe the purification and characterization of the PAC protein from Tth HB27 overexpressed in Escherichia coli. Results Fusions to a superfolder green fluorescent protein and differential membrane solubilization assays indicated that the native enzyme remains attached through its amino-terminal end to the outer side of the cytoplasmic membrane of Tth cells. In order to overexpress this PAC in E. coli cells, a variant of the protein devoid of its membrane anchoring segment was constructed. The effect of the co-expression of chaperones and calcium supplementation of the culture medium was investigated. The total production of PAC was enhanced by the presence of DnaK/J and GrpE and even more by trigger factor and GroEL/ES. In addition, 10 mM calcium markedly improved both PAC specific and volumetric activities. Recombinant PAC was affinity-purified and proper maturation of the protein was confirmed by SDS-PAGE and MALDI-TOF analysis of the subunits. The recombinant protein was tested for activity towards several penicillins, cephalosporins and homoserine lactones. Hydrophobic acyl-chain penicillins were preferred over the rest of the substrates. Penicillin K (octanoyl penicillin) was the best substrate, with the highest specificity constant value (16.12 mM-1.seg-1). The optimum pH was aprox. 4 and the optimum temperature was 75

  13. The role of ribonucleases in regulating global mRNA levels in the model organism Thermus thermophilus HB8

    PubMed Central

    2014-01-01

    Background RNA metabolism, including RNA synthesis and RNA degradation, is one of the most conserved biological systems and has been intensively studied; however, the degradation network of ribonucleases (RNases) and RNA substrates is not fully understood. Results The genome of the extreme thermophile, Thermus thermophilus HB8 includes 15 genes that encode RNases or putative RNases. Using DNA microarray analyses, we examined the effects of disruption of each RNase on mRNA abundance. Disruption of the genes encoding RNase J, RecJ-like protein and RNase P could not be isolated, indicating that these RNases are essential for cell viability. Disruption of the TTHA0252 gene, which was not previously considered to be involved in mRNA degradation, affected mRNA abundance, as did disruption of the putative RNases, YbeY and PhoH-like proteins, suggesting that they have RNase activity. The effects on mRNA abundance of disruption of several RNase genes were dependent on the phase of cell growth. Disruption of the RNase Y and RNase HII genes affected mRNA levels only during the log phase, whereas disruption of the PhoH-like gene affected mRNA levels only during the stationary phase. Moreover, disruption of the RNase R and PNPase genes had a greater impact on mRNA abundance during the stationary phase than the log phase, whereas the opposite was true for the TTHA0252 gene disruptant. Similar changes in mRNA levels were observed after disruption of YbeY or PhoH-like genes. The changes in mRNA levels in the bacterial Argonaute disruptant were similar to those in the RNase HI and RNase HII gene disruptants, suggesting that bacterial Argonaute is a functional homolog of RNase H. Conclusion This study suggests that T. thermophilus HB8 has 13 functional RNases and that each RNase has a different function in the cell. The putative RNases, TTHA0252, YbeY and PhoH-like proteins, are suggested to have RNase activity and to be involved in mRNA degradation. In addition, PhoH-like and Ybe

  14. RESULTS OF EXPERIMENT TO DETERMINE CORROSION RATES FOR 304L IN HB-LINE DISSOLVER VESSEL VENTILATION SYSTEM

    SciTech Connect

    Mickalonis, J; Kathryn Counts, K

    2008-02-22

    Radioactive material being processed as part of the DE3013 program for HB-Line will result in the presence of chlorides, and in some cases fluorides, in the dissolver. Material Science and Technology developed an experimental plan to evaluate the impact of chloride on corrosion of the dissolver vessel ventilation system. The plan set test variables from the proposed operating parameters, previous test results, and a desired maximum chloride concentration for processing. The test variables included concentrations of nitric acid, fluorides and chlorides, and the presence of a welded and stressed metal coupon. Table 1 contains expected general corrosion rates in the HB-Line vessel vent system from dissolution of 3013 contents of varying nitric acid and chloride content. These general corrosion rates were measured upstream of the condenser in the experiment's offgas system near the entrance to the dissolver. However, they could apply elsewhere in the offgas system, depending on factors not simulated in the testing, including offgas system temperatures and airflow. Localized corrosion was significant in Tests One, Two, and Three. This corrosion is significant because it will probably be the first mode of penetration of the 304L steel in several places in the system. See Table 2. For Tests One and Three, the penetration rate of localized corrosion was much higher than that for general corrosion. It was approximately four times higher in Test One and at least 45 times higher in Test Three, penetrating an entire coupon thickness of 54 mils in 186 hours or less. There was no significant difference in corrosion between welded areas and un-welded areas on coupons. There was also no significant attack on stressed portions of coupons. It is probable that the lack of corrosion was because the stressed areas were facing downwards and offered no place for condensation or deposits to form. Had deposits formed, pitting may have occurred and led to stress corrosion cracking. The

  15. Low oxygen affinity in reptilian hemoglobin D: prediction of residue interactions in Geochelone carbonaria HbD by homology modeling.

    PubMed

    Lutfullah, Ghosia; Khalil, Hilal Shahid; Amin, Farhat; Azhar, Noreen

    2008-04-01

    The homology model of hemoglobin D from Geochelone carbonaria, the red-footed tortoise was predicted using the 3D structure coordinates of Geochelone gigantea hemoglobin D as the template. The model was built using the program, MODELLER (8v1) and evaluated with PROCHECK and PROSA. The present study features an in-depth analysis of the 3D model and its conformational changes brought about with variations in its environment. These structural changes are correlated with its ability to adapt to different environmental constraints enabling the organism to better suit to its natural habitat. The model shows additional contacts between amino acid pairs of alpha-119 and beta-55, alpha-35 and beta-124, alpha-103 and beta-112, alpha-115 and beta-116, alpha-120 and beta-52, alpha-120 and beta-55, alpha-36 and beta-127 which are not found in human hemoglobin. It is predicted that these contacts may result in T-state stabilization thus lowering oxygen affinity. Furthermore, decrease in the interaction of phosphate heteroatoms with the amino acid residues of G. carbonaria Hb was also predicted in this study. PMID:18085430

  16. Inactivation and unfolding of protein tyrosine phosphatase from Thermus thermophilus HB27 during urea and guanidine hydrochloride denaturation.

    PubMed

    Wang, Yejing; He, Huawei; Liu, Lina; Gao, Chunyan; Xu, Shui; Zhao, Ping; Xia, Qingyou

    2014-01-01

    The effects of urea and guanidine hydrochloride (GdnHCl) on the activity, conformation and unfolding process of protein tyrosine phosphatase (PTPase), a thermostable low molecular weight protein from Thermus thermophilus HB27, have been studied. Enzymatic activity assays showed both urea and GdnHCl resulted in the inactivation of PTPase in a concentration and time-dependent manner. Inactivation kinetics analysis suggested that the inactivation of PTPase induced by urea and GdnHCl were both monophasic and reversible processes, and the effects of urea and GdnHCl on PTPase were similar to that of mixed-type reversible inhibitors. Far-ultraviolet (UV) circular dichroism (CD), Tryptophan and 1-anilinonaphthalene -8-sulfonic acid (ANS) fluorescence spectral analyses indicated the existence of a partially active and an inactive molten globule-like intermediate during the unfolding processes induced by urea and GdnHCl, respectively. Based on the sequence alignment and the homolog Tt1001 protein structure, we discussed the possible conformational transitions of PTPase induced by urea and GdnHCl and compared the conformations of these unfolding intermediates with the transient states in bovine PTPase and its complex structures in detail. Our results may be able to provide some valuable clues to reveal the relationship between the structure and enzymatic activity, and the unfolding pathway and mechanism of PTPase. PMID:25255086

  17. Crystallization and preliminary X-ray analysis of peptidyl-tRNA hydrolase from Thermus thermophilus HB8

    PubMed Central

    Matsumoto, Ami; Shimizu, Yoshihiro; Takemoto, Chie; Ueda, Takuya; Uchiumi, Toshio; Ito, Kosuke

    2013-01-01

    Peptidyl-tRNA is produced from the ribosome as a result of aborted translation. Peptidyl-tRNA hydrolase cleaves the ester bond between the peptide and the tRNA of peptidyl-tRNA molecules, to recycle tRNA for further rounds of protein synthesis. In this study, peptidyl-tRNA hydrolase from Thermus thermophilus HB8 (TthPth) was crystallized using 2-methyl-2,4-pentanediol as a precipitant. The crystals belonged to the orthorhombic space group P212121, with unit-cell parameters a = 47.45, b = 53.92, c = 58.67 Å, and diffracted X-rays to atomic resolution (beyond 1.0 Å resolution). The asymmetric unit is expected to contain one TthPth molecule, with a solvent content of 27.13% (V M = 1.69 Å3 Da−1). The structure is being solved by molecular replacement. PMID:23519816

  18. Single Stage Single Switch Power Supply (S4PS)Design for Low Power HB-LED Lighting

    NASA Astrophysics Data System (ADS)

    Shrivastava, Ashish; Singh, Bhim

    2013-05-01

    This paper presents an improved power quality converter (IPQC)-based power supply design for high brightness light emitting diode (HB-LED) low power lighting. The IPQC circuit uses a Cuk buck-boost converter to operate it in a discontinuous conduction mode (DCM) using the voltage follower technique for the mitigation of harmonic contents present in the AC mains current. Subsequently, reduction in harmonic contents results in improving the power quality indices at the AC mains. Single-stage single switch converter topology is used, which has less component count, size and cost as compared to the two-stage converter topology. DCM operation has an advantage that only output voltage control loop is required as compared to three control loops required in the continuous conduction mode operation. An 18-W LED driver is designed, modeled and simulated using MATLAB/Simulink software for 220 V, 50 Hz AC mains. The performance of the proposed LED driver is observed in terms of total harmonic distortion of the input current (THDi), input power factor (PF) and crest factor (CF) taking into account the strict international standard of IEC 61000-3-2 for class C equipments.

  19. Biofilm growth and hydrodynamic behaviour in the biological plate tower (BPT) with and without hanging biomass (BPT-HB).

    PubMed

    Peixoto, João Monteiro; Pinto, João Carlos Ribeiro

    2012-01-01

    Deodorization and volatile organic compound abatement from polluted air streams can be accomplished with the biological plate tower (BPT), which has proved to be a reliable alternative to biofilters and biotrickling filters. Unlike those, the BPT is a non-clogging device, with constant active surface, and steady performance, making it ideal for scale-up and modelling. The initial BPT design needed improvement for better performance. The cylindrical body (circular plates) was replaced by a rectangular cuboid (rectangular plates). Holes in the plates did augment the amount of active biomass (hanging from the holes and under the plates), without reducing the transfer of toluene from the gaseous to the liquid phase. The diminished distance between plates was well tolerated in co-current flow, allowing much higher quantities of biomass in the same reactor volume. With 18 and 14 mm spacing between adjacent plates, the BPT, with and without holes, was tested for flooding, holdup and pressure drop. Several gas and liquid flows were tested, both in co-current and counter-current. In hydrodynamic terms, the BPT-HB with co-current flow was clearly the best option. Higher stability with higher flow rates, and lower pressure drops were observed. The inoculum was obtained from wastewater plant activated sludge (petrochemical industry). PMID:22907451

  20. Mechanism of Hbγ-35-induced an increase in the activation of the human immune system by endotoxins.

    PubMed

    Heinbockel, Lena; Palacios-Chaves, Leyre; Alexander, Christian; Rietschel, Ernst; Behrends, Jochen; Correa, Wilmar; Fukuoka, Satoshi; Gutsmann, Thomas; Ulmer, Artur J; Brandenburg, Klaus

    2015-04-01

    Endotoxins (LPS) are highly potent immune stimulatory molecules and are mainly known for triggering Gram-negative sepsis. However, besides their toxic effects, this stimulatory function may be advantageous, for example when used as an adjuvant during vaccination. Thus, there is always a narrow range between the useful wake-up of the immune system and its overwhelming reaction, which can lead to diseases like sepsis. This raises the question of which conformational properties are responsible for making the LPS aggregates more or less potent. As described previously, the size, type and form of LPS aggregates play a major role in their immune stimulatory activity. In this study we investigate the role of these parameters. On the one hand, we use a peptide (Pep19-2.5; Aspidasept) that causes a change of the LPS aggregate structure into a less toxic state; on the other hand, we use a potent immune stimulating peptide (Hbγ-35), leading to higher toxicity. We have found opposing effects on LPS aggregate conformations allowing a better understanding of the processes of immune stimulation. PMID:25034969

  1. HbVar: A relational database of human hemoglobin variants and thalassemia mutations at the globin gene server.

    PubMed

    Hardison, Ross C; Chui, David H K; Giardine, Belinda; Riemer, Cathy; Patrinos, George P; Anagnou, Nicholas; Miller, Webb; Wajcman, Henri

    2002-03-01

    We have constructed a relational database of hemoglobin variants and thalassemia mutations, called HbVar, which can be accessed on the web at http://globin.cse.psu.edu. Extensive information is recorded for each variant and mutation, including a description of the variant and associated pathology, hematology, electrophoretic mobility, methods of isolation, stability information, ethnic occurrence, structure studies, functional studies, and references. The initial information was derived from books by Dr. Titus Huisman and colleagues [Huisman et al., 1996, 1997, 1998]. The current database is updated regularly with the addition of new data and corrections to previous data. Queries can be formulated based on fields in the database. Tables of common categories of variants, such as all those involving the alpha1-globin gene (HBA1) or all those that result in high oxygen affinity, are maintained by automated queries on the database. Users can formulate more precise queries, such as identifying "all beta-globin variants associated with instability and found in Scottish populations." This new database should be useful for clinical diagnosis as well as in fundamental studies of hemoglobin biochemistry, globin gene regulation, and human sequence variation at these loci. PMID:11857738

  2. Evaluation of the effects of nano-TiO2 on bioactivity and mechanical properties of nano bioglass-P3HB composite scaffold for bone tissue engineering.

    PubMed

    Bakhtiyari, Sanaz Soleymani Eil; Karbasi, Saeed; Monshi, Ahmad; Montazeri, Mahbobeh

    2016-01-01

    To emulate bone structure, porous composite scaffold with suitable mechanical properties should be designed. In this research the effects of nano-titania (nTiO2) on the bioactivity and mechanical properties of nano-bioglass-poly-3-hydroxybutyrate (nBG/P3HB)-composite scaffold were evaluated. First, nBG powder was prepared by melting method of pure raw materials at a temperature of 1400 °C and then the porous ceramic scaffold of nBG/nTiO2 with 30 wt% of nBG containing different weight ratios of nTiO2 (3, 6, and 9 wt% of nTiO2 with grain size of 35-37 nm) was prepared by using polyurethane sponge replication method. Then the scaffolds were coated with P3HB in order to increase the scaffold's mechanical properties. Mechanical strength and modulus of scaffolds were improved by adding nTiO2 to nBG scaffold and adding P3HB to nBG/nTiO2 composite scaffold. The results of the compressive strength and porosity tests showed that the best scaffold is 30 wt% of nBG with 6 wt% of nTiO2 composite scaffold immersed for 30 s in P3HB with 79.5-80 % of porosity in 200-600 μm, with a compressive strength of 0.15 MPa and a compressive modulus of 30 MPa, which is a good candidate for bone tissue engineering. To evaluate the bioactivity of the scaffold, the simulated body fluid (SBF) solution was used. The best scaffold with 30 wt% of nBG, 6 wt% of P3HB and 6 wt% of nTiO2 was immersed in SBF for 4 weeks at an incubation temperature of 37 °C. The bioactivity of the scaffolds was characterized by AAS, SEM, EDXA and XRD. The results of bioactivity showed that bone-like apatite layer formed well at scaffold surface and adding nTiO2 to nBG/P3HB composite scaffold helped increase the bioactivity rate. PMID:26610925

  3. Study on Diastolic Dysfunction in Newly Diagnosed Type 2 Diabetes Mellitus and its Correlation with Glycosylated Haemoglobin (HbA1C)

    PubMed Central

    Aneja, Girish Kumar; Shukla, Shubhra; Razi, Syed Mohd

    2015-01-01

    Introduction Left ventricular diastolic dysfunction (LVDD) represents the first stage of diabetic cardiomyopathy preceding changes in systolic function, reinforcing the importance of early examination of ventricular function in individuals with diabetes mellitus (DM). This cross-sectional study was conducted to determine the incidence of asymptomatic LVDD in newly diagnosed normotensive cases of type 2 diabetes subjects, and its relation to glycosylated haemoglobin (HbA1C), age at the time of diagnosis, body mass index (BMI) and serum total cholesterol. Aim and Objective To study the incidence of left ventricular diastolic dysfunction (LVDD) and its correlation with HbA1C in normotensive, newly diagnosed type 2 diabetic patients. Materials and Methods This cross-sectional study was done in western U.P. on 100 patients of newly diagnosed (within 1 month) type 2 DM between patients 30 and 60 years of age, visiting the Medicine and Endocrinology outpatient Department of LLRM Medical College, Meerut. Patients with established type 2 diabetes and already taking antidiabetic treatment, cardiac diseases like valvular heart disease, ischemic and hypertensive heart disease, congestive heart failure, cardiomyopathy, renal failure, chronic pulmonary disease, severe anaemia and haemoglobinopathies were excluded from the study. These patients were informed about the study and informed consent was obtained before proceeding with the investigations. Patients selected were evaluated with relevant investigations like fasting and post prandial blood sugar, HbA1C level, lipid profile and 2D echocardiography to assess LVDD. These selected patients were divided in 2 groups; one with left ventricular diastolic dysfunction (LVDD) and second group of subjects without LVDD. Various parameters like HbA1C, age, body mass index and serum cholesterol were evaluated between these 2 groups. Statistical analysis was performed using Student t-test, Chi-square and Fisher Exact-test. Results Out of

  4. Driving Down HB-LED Costs. Implementation of Process Simulation Tools and Temperature Control Methods of High Yield MOCVD Growth

    SciTech Connect

    Quinn, William

    2012-04-30

    The overall objective of this multi-faceted program is to develop epitaxial growth systems that meet a goal of 75% (4X) cost reduction in the epitaxy phase of HB-LED manufacture. A 75% reduction in yielded epitaxy cost is necessary in order to achieve the cost goals for widespread penetration of HB-LED's into back-lighting units (BLU) for LCD panels and ultimately for solid-state lighting (SSL). To do this, the program will address significant improvements in overall equipment Cost of Ownership, or CoO. CoO is a model that includes all costs associated with the epitaxy portion of production. These aspects include cost of yield, capital cost, operational costs, and maintenance costs. We divide the program into three phases where later phases will incorporate the gains of prior phases. Phase one activities are enabling technologies. In collaboration with Sandia National Laboratories we develop a Fluent-compatible chemistry predictive model and a set of mid-infrared and near-ultraviolet pyrometer monitoring tools. Where previously the modeling of the reactor dynamics were studied within FLUENT alone, here, FLUENT and Chemkin are integrated into a comprehensive model of fluid dynamics and the most advanced transport equations developed for Chemkin. Specifically, the Chemkin model offered the key reaction terms for gas-phase nucleation, a key consideration in the optimization of the MOCVD process. This new predictive model is used to design new MOCVD reactors with optimized growth conditions and the newly developed pyrometers are used monitor and control the MOCVD process temperature to within 0.5°C run-to-run and within each wafer. This portion of the grant is in collaboration with partners at Sandia National Laboratories. Phase two activities are continuous improvement projects which extend the current reactor platform along the lines of improved operational efficiency, improved systems control for throughput, and carrier modifications for increased yield

  5. Combined FISH, anti-γ-Hb and DAPI for detection of fetal nucleated RBCs in maternal blood

    NASA Astrophysics Data System (ADS)

    Farhad, Mona; Price, Jeffrey H.

    2002-05-01

    Since the 1970s, extensive research has been devoted to the development of a standard procedure for the isolation of fetal nucleated red cells (fnRBCs) from maternal blood. Since these cells are sources of fetal DNA, cytogenetic analysis would lead to a minimally-invasive method for the prenatal diagnosis of chromosomal and genetic disorders early in gestation. FnRBCs constitute a significant portion of the fetal blood, have a short and finite life span, and are rare in peripheral adult blood. They have been reported to exist in the maternal circulation at frequencies as low as 1:105 - 1:109 maternal nucleated cells. Due to these ultra-rare frequencies, isolation with minimal loss has been a time and labor-intensive process. To overcome this problem, a fully automated scanning cytometer that incorporates high-performance autofocus and image segmentation has been built and shown higher rate, quantity, sensitivity (true positive rate) and specificity (true negative rate) in a model cell preparation. For detecting fnRBCs, two discriminating characteristics may suffice: (1) the presence of fetal hemoglobin, which is the major intracytoplasmic protein found in fetal red cells from 5 to 35 weeks gestation, and (2) the presence of a nucleus. In clinical trials, the fetal origin of the isolated cells will be confirmed by fluorescence in situ hybridization (FISH) on the X and Y chromosomes in male pregnancies. The aim of the present study was to develop a reliable and reproducible staining method for combined immunofluorescence and FISH analysis for these clinical trials. This staining technique was developed using fnRBCs extracted from fetal liver blood and a human erythroleukemia cell line (HEL) that expresses fetal hemoglobin. The resulting method for four-color X- and Y-FISH , anti-(gamma) -Hb fluorescence and DAPI staining was consistent and bright.

  6. Physiological Properties and Genome Structure of the Hyperthermophilic Filamentous Phage φOH3 Which Infects Thermus thermophilus HB8

    PubMed Central

    Nagayoshi, Yuko; Kumagae, Kenta; Mori, Kazuki; Tashiro, Kosuke; Nakamura, Ayano; Fujino, Yasuhiro; Hiromasa, Yasuaki; Iwamoto, Takeo; Kuhara, Satoru; Ohshima, Toshihisa; Doi, Katsumi

    2016-01-01

    A filamentous bacteriophage, φOH3, was isolated from hot spring sediment in Obama hot spring in Japan with the hyperthermophilic bacterium Thermus thermophilus HB8 as its host. Phage φOH3, which was classified into the Inoviridae family, consists of a flexible filamentous particle 830 nm long and 8 nm wide. φOH3 was stable at temperatures ranging from 70 to 90°C and at pHs ranging from 6 to 9. A one-step growth curve of the phage showed a 60-min latent period beginning immediately postinfection, followed by intracellular virus particle production during the subsequent 40 min. The released virion number of φOH3 was 109. During the latent period, both single stranded DNA (ssDNA) and the replicative form (RF) of phage DNA were multiplied from min 40 onward. During the release period, the copy numbers of both ssDNA and RF DNA increased sharply. The size of the φOH3 genome is 5688 bp, and eight putative open reading frames (ORFs) were annotated. These ORFs were encoded on the plus strand of RF DNA and showed no significant homology with any known phage genes, except ORF 5, which showed 60% identity with the gene VIII product of the Thermus filamentous phage PH75. All the ORFs were similar to predicted genes annotated in the Thermus aquaticus Y51MC23 and Meiothermus timidus DSM 17022 genomes at the amino acid sequence level. This is the first report of the whole genome structure and DNA multiplication of a filamentous T. thermophilus phage within its host cell. PMID:26941711

  7. Physiological Properties and Genome Structure of the Hyperthermophilic Filamentous Phage φOH3 Which Infects Thermus thermophilus HB8.

    PubMed

    Nagayoshi, Yuko; Kumagae, Kenta; Mori, Kazuki; Tashiro, Kosuke; Nakamura, Ayano; Fujino, Yasuhiro; Hiromasa, Yasuaki; Iwamoto, Takeo; Kuhara, Satoru; Ohshima, Toshihisa; Doi, Katsumi

    2016-01-01

    A filamentous bacteriophage, φOH3, was isolated from hot spring sediment in Obama hot spring in Japan with the hyperthermophilic bacterium Thermus thermophilus HB8 as its host. Phage φOH3, which was classified into the Inoviridae family, consists of a flexible filamentous particle 830 nm long and 8 nm wide. φOH3 was stable at temperatures ranging from 70 to 90°C and at pHs ranging from 6 to 9. A one-step growth curve of the phage showed a 60-min latent period beginning immediately postinfection, followed by intracellular virus particle production during the subsequent 40 min. The released virion number of φOH3 was 109. During the latent period, both single stranded DNA (ssDNA) and the replicative form (RF) of phage DNA were multiplied from min 40 onward. During the release period, the copy numbers of both ssDNA and RF DNA increased sharply. The size of the φOH3 genome is 5688 bp, and eight putative open reading frames (ORFs) were annotated. These ORFs were encoded on the plus strand of RF DNA and showed no significant homology with any known phage genes, except ORF 5, which showed 60% identity with the gene VIII product of the Thermus filamentous phage PH75. All the ORFs were similar to predicted genes annotated in the Thermus aquaticus Y51MC23 and Meiothermus timidus DSM 17022 genomes at the amino acid sequence level. This is the first report of the whole genome structure and DNA multiplication of a filamentous T. thermophilus phage within its host cell. PMID:26941711

  8. Isolation and characterization of Bacteroides host strain HB-73 used to detect sewage specific phages in Hawaii.

    PubMed

    Vijayavel, Kannappan; Fujioka, Roger; Ebdon, James; Taylor, Huw

    2010-06-01

    Previous studies have shown that Escherichia coli and enterococci are unreliable indicators of fecal contamination in Hawaii because of their ability to multiply in environmental soils. In this study, the method of detecting Bacteroides phages as specific markers of sewage contamination in Hawaii's recreational waters was evaluated because these sewage specific phages cannot multiply under environmental conditions. Bacteroides hosts (GB-124, GA-17), were recovered from sewage samples in Europe and were reported to be effective in detecting phages from sewage samples obtained in certain geographical areas. However, GB-124 and GA-17 hosts were ineffective in detecting phages from sewage samples obtained in Hawaii. Bacteroides host HB-73 was isolated from a sewage sample in Hawaii, confirmed as a Bacteroides sp. and shown to recover phages from multiple sources of sewage produced in Hawaii at high concentrations (5.2-7.3 x 10(5) PFU/100 mL). These Bacteroides phages were considered as potential markers of sewage because they also survived for three days in fresh stream water and two days in marine water. Water samples from Hawaii's coastal swimming beaches and harbors, which were known to be contaminated with discharges from streams, were shown to contain moderate (20-187 CFU/100 mL) to elevated (173-816 CFU/100 mL) concentrations of enterococci. These same samples contained undetectable levels (<10 PFU/100 mL) of F+ coliphage and Bacteroides phages and provided evidence to suggest that these enterococci may not necessarily be associated with the presence of raw sewage. These results support previous conclusions that discharges from streams are the major sources of enterococci in coastal waters of Hawaii and the most likely source of these enterococci is from environmental soil rather than from sewage. PMID:20451947

  9. Crystal structure analysis of ornithine transcarbamylase from Thermus thermophilus --HB8 provides insights on the plasticity of the active site.

    PubMed

    Sundaresan, Ramya; Ebihara, Akio; Kuramitsu, Seiki; Yokoyama, Shigeyuki; Kumarevel, Thirumananseri; Ponnuraj, Karthe

    2015-09-18

    The enzymatic biosynthesis of L-arginine involves complex, sequential action of many enzymes and ornithine transcarbamylase (OTCase) is one of the essential enzymes in the pathway. In mammals OTCase is part of the urea cycle. Arginine is used in a variety of pharmaceutical and industrial applications and therefore engineering arginine biosynthesis pathway for overproduction of arginine has gained importance. On the other hand, it was found that detrimental mutations in the human OTCase gene resulted clinical hyperammonemia, with subsequent neurological damage. Therefore a better understanding of the structure-function relationship of this enzyme from various sources could be useful for modifying its enzymatic action. Here we report the structure of ornithine transcarbamylase of Thermus thermophilus HB8 (aTtOTCase) at 2.0 Å resolution. On comparison with its homologs, aTtOTCase showed maximum variation at the substrate binding loops namely 80s and SMG/240s loops. The active site geometry of aTtOTCase is unique among its homologs where the side chain of certain residues (Leu57, Arg58 and Arg288) is oriented differently. To study the structural insights of substrate binding in aTtOTCase, docking of carbamoyl phosphate (CP) and ornithine (Orn) was carried out sequentially. Both substrates were unable to bind in a proper orientation in the active site pocket and this could be due to the differently oriented side chains. This suggests that the active site geometry should also undergo fine tuning besides the large structural changes as the enzyme switches from completely open to a substrate bound closed state. PMID:26210451

  10. Comparison of Massimo Pronto-7 and HemoCue Hb 201+ with laboratory haemoglobin estimation: a clinical study.

    PubMed

    Hiscock, R; Simmons, Sw; Carstensen, B; Gurrin, Lc

    2014-09-01

    We prospectively studied agreement in haemoglobin estimation between two point-of-care devices (Pronto-7(®) Pulse CO-Oximetry(™), Masimo Corporation, Irvine, California, USA and HemoCue(®) Hb 201 +, HemoCue, Angelholm, Sweden) and an automated laboratory analyser (Sysmex XE5000, Sysmex Corporation, Kobe, Japan). Venous blood sampling and finger co-oximeter readings were performed on 141 pregnant women undergoing routine mid-trimester haemoglobin assessment. Three replicate measures were performed and analysis used Bayesian-based variance component modelling to provide estimates of repeatability, between person within method bias and precision. Repeatability, assessed by coefficient of variation, was higher for Pronto-7(®) (2.3%) compared to HemoCue(®) (5.2%). Fixed bias (mean difference, device - laboratory) was +1.18 (standard deviation 1.19) g/dl and - 0.01 (standard deviation 1.34) g/dl for Pronto-7(®) and HemoCue(®) respectively, with no statistical evidence of proportional bias. Based upon a single device reading, the 95% prediction limits for Pronto-7(®) were -1.2 to 3.6 g.dl-1 and HemoCue(®) were -2.7 to 2.7 g/dl. For both devices precision was not meaningfully improved by averaging replicate readings. However, repeated readings may allow detection of aberrant results. Overall both devices are imprecise and 95% prediction limits wide. We present further prediction limits, derived from the posterior distribution and adjusted for any fixed bias for set levels of probability (certainty). These may be used to support clinical decisions when using these point-of-care devices. PMID:25233174

  11. Complete genome sequence of Thermovibrio ammonificans HB-1T, a thermophilic, chemolithoautotrophic bacterium isolated from a deep-sea hydrothermal vent

    SciTech Connect

    Giovannelli, Donato; Ricci, Jessica; Perez-Rodriguez, Ileana; Hugler, Michael; O'Brien, Charles; Keddis, Ramaydalis; Grosche, Ashley; Goodwin, Lynne A.; Bruce, David; Davenport, Karen W.; Detter, J. Chris; Han, James; Han, Cliff; Ivanova, N; Land, Miriam L; Mikhailova, Natalia; Nolan, Matt; Pitluck, Sam; Tapia, Roxanne; Woyke, Tanja; Vetriani, Costantino

    2012-01-01

    Thermovibrio ammonificans type strain HB-1T is a thermophilic (Topt: 75 C), strictly anaero- bic, chemolithoautotrophic bacterium that was isolated from an active, high temperature deep-sea hydrothermal vent on the East Pacific Rise. This organism grows on mineral salts medium in the presence of CO2/H2, using NO3- or S0 as electron acceptors, which are re- duced to ammonium or hydrogen sulfide, respectively. T. ammonificans is one of only three species within the genus Thermovibrio, a member of the family Desulfurobacteriaceae, and it forms a deep branch within the phylum Aquificae. Here we report the main features of the genome of T. ammonificans strain HB-1T (DSM 15698T).

  12. Hb Sallanches [alpha104(G11)Cys-->Tyr, TGC-->TAC (alpha2)]: an unstable hemoglobin variant found in an Indian child.

    PubMed

    Dash, Sumitra; Harano, Keiko; Menon, Santosh

    2006-01-01

    We report the fourth observation of Hb Sallanches [alpha104(G11)Cys-->Tyr, TGC-->TAC (alpha2)], an unstable alpha chain variant of intermediate severity in the homozygous state. Heterozygosity occasionally produces mild hypochromia and microcytosis in some patients. A balanced beta/alpha ratio, found in previously reported cases, points to unstable alphabeta dimers formed as a result of the Cys-->Tyr substitution at the alpha1beta1 contact site in this hemoglobin (Hb) variant. Our patient, and the previous two of the three cases reported in patients of Pakistani origin, points to a common population stock, separated by the mass population migration which occurred during the partition of Pakistan and India in 1947. PMID:16840231

  13. The relationship between HbA1c & atrial fibrillation after off-pump coronary artery bypass surgery in diabetic patients

    PubMed Central

    Surer, Suleyman; Seren, Mustafa; Saydam, Onur; Bulut, Ali; Kiziltepe, Ugursay

    2016-01-01

    Objective: Diabetes mellitus is recognized as a risk factor for mortality and morbidity after coronary bypass grafting. We aimed to determine the association between preoperative hemoglobin HbA1c and AF after isolated off-pump coronary bypass grafting (OPCAB). Methods: The seventy-two diabetic patients undergoing isolated off-pump coronary bypass grafting were retrospectively analyzed for AF. They were divided into; Low (4.8–5.4%), Medium (5.5–8%) and High (8.1–11.5%) groups. The three groups were compared with respect to demographic, echocardiographic, intraoperative and postoperative clinical characteristics correlation. Results: Three patients died during postoperative period. AF occurred in 12 patients (16.6%) after surgery. The incidence of postoperative AF was 15.3% in the lower, 4.4% middle and 57.1% upper group. There was statistically significant correlation between preoperative HbA1C and preoperative stroke, preoperative MI history, Left atrial (LA) size, preoperative levosimendan, preoperative clopidogrel, postoperative AF, postoperative dopamine and dobutamine use, IABP, duration of extubation time, 24-hour chest tube drainage, duration of ICU and hospital mortality. Univariate logistic regression analysis showed significant correlation between postoperative AF and variables like preoperative HbA1c levels, LVEF<30%, history of preoperative MI, preoperative use of levosimendan, preoperative use of clopidogrel, postoperative dopamine, dobutamine adrenaline use, left atrium size, 24-hour chest tube drainage and length of stay in the intensive care unit. Conclusion: Preoperative HbA1c levels could predict the occurrence of postoperative AF in diabetic patients and may entail to administer protective strategies. PMID:27022346

  14. Group Medical Visits (GMVs) in primary care: an RCT of group-based versus individual appointments to reduce HbA1c in older people

    PubMed Central

    Khan, Karim M; Windt, Adriaan; Davis, Jennifer C; Dawes, Martin; Liu-Ambrose, Teresa; Madden, Ken; Marra, Carlo A; Housden, Laura; Hoppmann, Christiane; Adams, David J

    2015-01-01

    Introduction Type 2 diabetes mellitus (T2DM) affects more than 1.1 million Canadians aged ≥65 years. Group Medical Visits are an emerging health service delivery method. Recent systematic reviews show that they can significantly reduce glycated haemoglobin (HbA1c) levels, but Group Visits have not been evaluated within primary care. We intend to determine the clinical effectiveness, quality of life and economic implications of Group Medical Visits within a primary care setting for older people with T2DM. Methods and analysis A 2-year proof-of-concept, single-blinded (measurement team) randomised control trial to test the efficacy of Group Medical Visits in an urban Canadian primary care setting. Participants ≥65 years old with T2DM (N=128) will be equally randomised to either eight groups of eight patients each (Group Medical Visits; Intervention) or to Individual visits (Standard Care; Controls). Those administering cointerventions are not blinded to group assignment. Our sample size is based on estimates of variance (±1.4% for HbA1c) and effect size (0.9/1.4=0.6) from the literature and from our own preliminary data. Forty participants per group will provide a β likelihood of 0.80, assuming an α of 0.05. A conservative estimation of an effect size of 0.7/1.4 changes the N in the power calculation to 59 per group. Hence, we aim to enrol 64 participants in each study arm. We will use intention-to-treat analysis and compare mean HbA1c (% glycosylated HbA1c) (primary outcome) of Intervention/Control participants at 12 months, 24 months and 1 year postintervention on selected clinical, patient-rated and economic measures. Trial registration number NCT02002143. PMID:26169803

  15. Comparability of HbA1c and lipids measured with dried blood spot versus venous samples: a systematic review and meta-analysis

    PubMed Central

    2014-01-01

    Background Levels of haemoglobin A1c (HbA1c) and blood lipids are important determinants of risk in patients with diabetes. Standard analysis methods based upon venous blood samples can be logistically challenging in resource-poor settings where much of the diabetes epidemic is occurring. Dried blood spots (DBS) provide a simple alternative method for sample collection but the comparability of data from analyses based on DBS is not well established. Methods We conducted a systematic review and meta-analysis to define the association of findings for HbA1c and blood lipids for analyses based upon standard methods compared to DBS. The Cochrane, Embase and Medline databases were searched for relevant reports and summary regression lines were estimated. Results 705 abstracts were found by the initial electronic search with 6 further reports identified by manual review of the full papers. 16 studies provided data for one or more outcomes of interest. There was a close agreement between the results for HbA1c assays based on venous and DBS samples (DBS = 0.9858venous + 0.3809), except for assays based upon affinity chromatography. Significant adjustment was required for assays of total cholesterol (DBS = 0.6807venous + 1.151) but results for triglycerides (DBS = 0.9557venous + 0.1427) were directly comparable. Conclusions For HbA1c and selected blood lipids, assays based on DBS samples are clearly associated with assays based on standard venous samples. There are, however, significant uncertainties about the nature of these associations and there is a need for standardisation of the sample collection, transportation, storage and analysis methods before the technique can be considered mainstream. This should be a research priority because better elucidation of metabolic risks in resource poor settings, where venous sampling is infeasible, will be key to addressing the global epidemic of cardiovascular diseases. PMID:25045323

  16. Activation of mitochondrial function and Hb expression in non-haematopoietic cells by an EPO inducer ameliorates ischaemic diseases in mice

    PubMed Central

    Hsu, Pei-Lun; Horng, Lin-Yea; Peng, Kang-Yung; Wu, Chia-Ling; Sung, Hui-Ching; Wu, Rong-Tsun

    2013-01-01

    Background and Purpose Many organs suffer from ischaemic injuries that reduce their ability to generate sufficient energy, which is required for functional maintenance and repair. Erythropoietin (EPO) ameliorates ischaemic injuries by pleiotropic effects. The aim of this study was to investigate the effect and mechanism of a small molecule EH-201, and found it as a potent EPO inducer and its effect in non-haematopoietic cells for therapeutic potential in ischemic disorders. Experimental Approach Mice kidney slices, primary hepatocytes, primary cardiomyocytes and C2C12 myoblasts were treated with EH-201. The effects of this treatment on EPO, Hb expression and mitochondrial biogenesis were analysed. In vivo, doxorubicin-induced cardiomyopathic mice were treated with EH-201. The mice were subjected to an endurance test, electrocardiography and echocardiography, and a histological examination of the isolated hearts was performed. EH-201 was also administered to cisplatin-induced nephropathic mice. Key Results In non-haematopoietic cells, EH-201 was potent at inducing EPO. EH-201 also stimulated mitochondrial biogenesis and enhanced the expression of Hb by a mechanism dependent on EPO-mediated signalling. In mechanistic studies, using EPO and EPO receptor-neutralizing antibodies, we confirmed that EH-201 enhances EPO-EPOR autocrine activity. EH-201 robustly increased the endurance performance activity of healthy and cardiomyopathic mice during hypoxic stress, enhanced myocardial mitochondrial biogenesis and Hb expression, and also improved cardiac function. EH-201 ameliorated anaemia and renal dysfunction in nephropathic mice. Conclusions and Implications The enhancement and recovery of cellular functions through the stimulation of mitochondrial activity and Hb production in non-haematopoietic cells by an inducer of endogenous EPO has potential as a therapeutic strategy for ischaemic diseases. PMID:23530756

  17. Integrative health coaching: a behavior skills approach that improves HbA1c and pharmacy claims-derived medication adherence

    PubMed Central

    Wolever, Ruth Q; Dreusicke, Mark H

    2016-01-01

    Objective Medication adherence requires underlying behavior skills and a supporting mindset that may not be addressed with education or reminders. Founded in the study of internal motivation and health psychology, integrative health coaching (IHC) helps patients gain insight into their behaviors and make long-term, sustainable lifestyle changes. The purpose of the study is to determine whether IHC improves oral medication adherence, glycated hemoglobin (HbA1c), and psychosocial measures, and to assess whether adherence changes are sustained after the intervention. Methods Using a prospective observational design, participants (n=56) received 14 coaching calls by telephone over 6 months. Medication possession ratio (MPR) was calculated for time intervals before, during, and after the intervention. HbA1c and patient-reported psychosocial outcomes were obtained to test interactions with MPR. Results Medication adherence (MPR) increased from 0.74±0.197 to 0.85±0.155 during coaching, and was sustained at 0.82±0.175 during a 6-month period after the study. Better adherence correlated with a greater decrease in HbA1c. HbA1c decreased from 8.0±1.92% to 7.7±1.70% over the 6-month intervention. All psychosocial measures showed significant improvement. In addition to discussing medication adherence strategies with their coach, patients discussed nutrition and exercise (86.9% of calls), stress management (39.8%), and social support and relationships (15.4%). Conclusions IHC targets internal motivation and supports behavior change by facilitating patients’ insight into their own behaviors, and it uses this insight to foster self-efficacy. This approach may yield sustainable results for medication adherence and warrants further exploration for health-related behavior change. PMID:27239318

  18. Effect of Long-Term Dietary Arginyl-Fructose (AF) on Hyperglycemia and HbA1c in Diabetic db/db Mice

    PubMed Central

    Lee, Kwang-Hyoung; Ha, Kyoung-Soo; Jo, Sung-Hoon; Lee, Chong M.; Kim, Young-Cheul; Chung, Kwang-Hoe; Kwon, Young-In

    2014-01-01

    We have previously reported that Amadori compounds exert anti-diabetic effects by lowering sucrose-induced hyperglycemia in normal Sprague-Dawley rats. In the present study we extended our recent findings to evaluate whether α-glucosidase inhibitor arginyl-fructose (AF) lowers blood glucose level in diabetic db/db mice, a genetic model for type 2 diabetes. The db/db mice were randomly assigned to high-carbohydrate diets (66.1% corn starch) with and without AF (4% in the diet) for 6 weeks. Changes in body weight, blood glucose level, and food intake were measured daily for 42 days. Dietary supplementation of AF resulted in a significant decrease of blood glucose level (p < 0.001) and body weight (p < 0.001). The level of HbA1c, a better indicator of plasma glucose concentration over prolonged periods of time, was also significantly decreased for 6-week period (p < 0.001). Dietary treatment of acarbose® (0.04% in diet), a positive control, also significantly alleviated the level of blood glucose, HbA1c, and body weight. These results indicate that AF Maillard reaction product improves postprandial hyperglycemia by suppressing glucose absorption as well as decreasing HbA1c level. PMID:24823880

  19. Hot HB Stars in Globular Clusters: Physical Parameters and Consequences for Theory. VI; The Second Parameter Pair M 3 and M 13

    NASA Technical Reports Server (NTRS)

    Moehler, S.; Landsman, W. B.; Sweigart, A. V.; Grundahl, F.

    2003-01-01

    We present the results of spectroscopic analyses of hot horizontal branch (HB) stars in M 13 and M 3, which form a famous "second parameter" pair. F rom the spectra and Stromgren photometry we derived - for the first time in M 13 - atmospheric parameters (effective temperature and surface gravity). For stars with Stromgren temperatures between 10,000 and 12,000 K we found excellent agreement between the atmospheric parameters derived from Stromgren photometry and those derived from Balmer line profile fits. However, for cooler stars there is a disagreement in the parameters derived by the two methods, for which we have no satisfactory explanation. Stars hotter than 12,000 K show evidence for helium depletion and iron enrichment, both in M 3 and M 13. Accounting for the iron enrichment substantially improves the agreement with canonical evolutionary models, although the derived gravities and masses are still somewhat too low. This remaining discrepancy may be an indication that scaled-solar metal-rich model atmospheres do not adequately represent the highly non-solar abundance ratios found in blue HB stars affected by diffusion. We discuss the effects of an enhancement in the envelope helium abundance on the atmospheric parameters of the blue HB stars, as might be caused by deep mixing on the red giant branch or primordial pollution from an earlier generation of intermediate mass asymptotic giant branch stars. Key words. Stars: atmospheres - Stars: evolution - Stars: horizontal branch - Globular clusters: individual: M 3 - Globular clusters: individual: M 13

  20. Interaction of Hb Adana (HBA2: c.179G>A) with Deletional and Nondeletional α +-Thalassemia Mutations: Diverse Hematological and Clinical Features

    PubMed Central

    2013-01-01

    We describe 27 cases of mild-to-severe α-thalassemia (α-thal) syndrome caused by interaction of Hb Adana [α59(E8)Gly→Asp, GGC>GAC (α2)] with deletional and nondeletional α+-thal mutations in Indonesian patients. Hematological profiles and clinical manifestations of all patients were assessed by routine procedures. The genotypes were generated by a multiplex-polymerase chain reaction (m-PCR), PCR-RFLP (restriction fragment length polymorphism)-based method, and DNA sequencing. The α-thal patients who had Hb Adana in combination with the 3.7 kb deletion mostly have mild-to-moderate anemia. In contrast, patients who were compound heterozygotes for Hb Adana and nondeletional mutations, generally showed a more severe anemia and it mostly presented in childhood. Thus, accurate diagnosis of α-thal disorders is not only important for future management of these patients but also for providing proper genetic counseling to the family. PMID:23614625

  1. MORPHO-KINEMATIC ANALYSIS OF THE POINT-SYMMETRIC, BIPOLAR PLANETARY NEBULAE Hb 5 AND K 3-17, A PATHWAY TO POLY-POLARITY

    SciTech Connect

    Lopez, J. A.; Garcia-Diaz, Ma. T.; Steffen, W.; Riesgo, H.; Richer, M. G. E-mail: tere@astrosen.unam.mx E-mail: hriesgo@astrosen.unam.mx

    2012-05-10

    The kinematics of the bipolar planetary nebulae Hb 5 and K 3-17 are investigated in detail by means of a comprehensive set of spatially resolved high spectral resolution, long-slit spectra. Both objects share particularly interesting characteristics, such as a complex filamentary, rosette-type nucleus, axial point-symmetry, and very fast bipolar outflows. The kinematic information of Hb 5 is combined with Hubble Space Telescope imagery to construct a detailed three-dimensional model of the nebula using the code SHAPE. The model shows that the large-scale lobes are growing in a non-homologous way. The filamentary loops in the core are proven to actually be secondary lobes emerging from what appears to be a randomly punctured, dense, gaseous core and the material that forms the point-symmetric structure flows within the lobes with a distinct kinematic pattern and its interaction with the lobes has had a shaping effect on them. Hb 5 and K 3-17 may represent a class of fast evolving planetary nebulae that will develop poly-polar characteristics once the nebular core evolves and expands.

  2. Morpho-kinematic Analysis of the Point-symmetric, Bipolar Planetary Nebulae Hb 5 and K 3-17, A Pathway to Poly-polarity

    NASA Astrophysics Data System (ADS)

    López, J. A.; García-Díaz, Ma. T.; Steffen, W.; Riesgo, H.; Richer, M. G.

    2012-05-01

    The kinematics of the bipolar planetary nebulae Hb 5 and K 3-17 are investigated in detail by means of a comprehensive set of spatially resolved high spectral resolution, long-slit spectra. Both objects share particularly interesting characteristics, such as a complex filamentary, rosette-type nucleus, axial point-symmetry, and very fast bipolar outflows. The kinematic information of Hb 5 is combined with Hubble Space Telescope imagery to construct a detailed three-dimensional model of the nebula using the code SHAPE. The model shows that the large-scale lobes are growing in a non-homologous way. The filamentary loops in the core are proven to actually be secondary lobes emerging from what appears to be a randomly punctured, dense, gaseous core and the material that forms the point-symmetric structure flows within the lobes with a distinct kinematic pattern and its interaction with the lobes has had a shaping effect on them. Hb 5 and K 3-17 may represent a class of fast evolving planetary nebulae that will develop poly-polar characteristics once the nebular core evolves and expands.

  3. Protic anions [H(B12X12)]- (X = F, Cl, Br, I) that act as Brønsted acids in the gas phase.

    PubMed

    Jenne, Carsten; Keßler, Mathias; Warneke, Jonas

    2015-04-01

    The acidity of protic cations and neutral molecules has been studied extensively in the gas phase, and the gas-phase acidity has been established previously as a very useful measure of the intrinsic acidity of neutral and cationic compounds. However, no data for any anionic acids were available prior to this study. The protic anions [H(B12X12)](-) (X = F, Cl, Br, I) are expected to be the most acidic anions known to date. Therefore, they were investigated in this study with respect to their ability to protonate neutral molecules in the gas phase by using a combination of mass spectrometry and quantum-chemical calculations. For the first time it was shown that in the gas phase protic anions are also able to protonate neutral molecules and thus act as Brønsted acids. According to theoretical calculations, [H(B12I12)](-) is the most acidic gas-phase anion, whereas in actual protonation experiments [H(B12Cl12)](-) is the most potent gas-phase acidic anion for the protonation of neutral molecules. This discrepancy is explained by ion pairing and kinetic effects. PMID:25735766

  4. The Prediction of Clinical Outcome Using HbA1c in Acute Ischemic Stroke of the Deep Branch of Middle Cerebral Artery

    PubMed Central

    Shin, Sung Bong; Kim, Tae Uk; Hyun, Jung Keun

    2015-01-01

    Objective To elucidate the association between glycemic control status and clinical outcomes in patients with acute ischemic stroke limited to the deep branch of the middle cerebral artery (MCA). Methods We evaluated 65 subjects with first-ever ischemic stroke of the deep branches of the MCA, which was confirmed by magnetic resonance angiography. All subjects had blood hemoglobin A1c (HbA1c) measured at admission. They were classified into two groups according to the level of HbA1c (low <7.0% or high ≥7.0%). Neurological impairment and functional status were evaluated using the National Institutes of Health Stroke Scale (NIHSS), Functional Independence Measure (FIM), Korean version of Modified Barthel Index (K-MBI), Korean version of Mini-Mental State Examination (MMSE-K), and the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) at admission and discharge. Body mass index, serum glucose, homocysteine and cholesterol levels were also measured at admission. Results The two groups did not show any difference in the NIHSS, FIM, K-MBI, MMSE-K, and LOTCA scores at any time point. Body mass index and levels of blood homocysteine and cholesterol were not different between the two groups. The serum blood glucose level at admission was negatively correlated with all outcome measures. Conclusion We found that HbA1c cannot be used for predication of clinical outcome in patients with ischemic stroke of the deep branch of the middle cerebral artery. PMID:26798617

  5. [HbA1c is not enough in screening for impaired glucose metabolism. Glucose tolerance tests are also needed, as shown in Swedish prospective epidemiological study].

    PubMed

    Hellgren, Margareta; Daka, Bledar; Larsson, Charlotte

    2015-01-01

    An HbA1c threshold of ≥ 42 mmol/mol has been proposed to diagnose prediabetes. The sensitivity, specificity and positive predictive value of the proposed threshold for detection of individuals with prediabetes was examined in a study of 573 randomly selected individuals from Vara and Skövde. In addition, the utility of the FINDRISC questionnaire and of a fasting glucose test in combination with three short questions concerning BMI, heredity for type 2 diabetes and known hypertension was examined. Results from an oral glucose tolerance test were used as reference. The sensitivity of HbA1c and FINDRISC to detect individuals with IGT was 16 and 26 per cent respectively. Questions regarding BMI, heredity and hypertension together with a fasting glucose test yielded a sensitivity of 50%, but a lower specificity and positive predictive value. We conclude that HbA1c inefficiently detected individuals with impaired glucose tolerance and that oral glucose tolerance tests can still preferably be recommended. PMID:26418933

  6. Effectiveness of HB2 (anti-CD7)--saporin immunotoxin in an in vivo model of human T-cell leukaemia developed in severe combined immunodeficient mice.

    PubMed Central

    Morland, B. J.; Barley, J.; Boehm, D.; Flavell, S. U.; Ghaleb, N.; Kohler, J. A.; Okayama, K.; Wilkins, B.; Flavell, D. J.

    1994-01-01

    The transplantation of the human T-cell acute lymphoblastic leukaemia (T-ALL) cell line HSB-2 into severe combined immunodeficient (SCID) mice was found to produce a disseminated pattern of leukaemia similar to that seen in man. The intravenous injection of 10(7) HSB-2 cells was associated with a universally fatal leukaemia. Histopathological examination of animals revealed the spread of leukaemia initially from bone marrow to involve all major organs including the meninges. An immunotoxin (HB2-Sap) was constructed by conjugating the anti-CD7 MAb HB2 to the ribosome-inactivating protein saporin. An in vitro protein synthesis inhibition assay revealed specific delivery of HB2-Sap immunotoxin (IT) to CD7+ HSB-2 target cells with an IC50 of 4.5 pM. When SCID mice were injected with 10(6) HSB-2 cells and then treated 8 days later with a single intravenous dose of 10 micrograms of immunotoxin there was a significant therapeutic effect evidenced by the numbers of animals surviving in the therapy group compared with untreated controls (chi 2 = 5.348, P = 0.021). These results demonstrate the useful application of human leukaemia xenografts in SCID mice and the potential therapeutic effect of an anti-CD7 immunotoxin in human T-ALL. Images Figure 1 PMID:7507691

  7. Comparison of the potency and therapeutic efficacy of the anti-CD7 immunotoxin HB2-saporin constructed with one or two saporin moieties per immunotoxin molecule.

    PubMed Central

    Flavell, D. J.; Boehm, D. A.; Noss, A.; Flavell, S. U.

    1997-01-01

    Immunotoxins that carry two toxin molecules to the target cell should in theory have a greater anti-tumour effect than those that carry just one. We have investigated the therapeutic efficacy of two anti-CD7-saporin immunotoxins constructed with one saporin (HB2-Sap 1-mer) or two saporin molecules (HB2-Sap 2-mer) per immunotoxin molecule. In vitro, the 2-mer immunotoxin was 5.6 times more effective than the 1-mer immunotoxin at inhibiting protein synthesis in the CD7+ human T-cell acute lymphoblastic leukaemia (T-ALL) cell line HSB-2 and was also more effective at inhibiting HSB-2 cell proliferation. Flow cytometry revealed that the 2-mer immunotoxin had a reduced binding capacity to HSB-2 cells compared with the 1-mer immunotoxin or native HB2 antibody. In therapy studies in SCID mice with disseminated HSB-2 human leukaemia, the 2-mer immunotoxin performed marginally better than the 1-mer immunotoxin, but log-rank analysis did not reveal any significant differences between the two therapy groups. We therefore conclude that, although the 2-mer immunotoxin performed better than the 1-mer immunotoxin against target HSB-2 cells in vitro, this improved performance was not reflected as an improved in vivo therapeutic outcome in the SCID mouse model. Images Figure 2 PMID:9083340

  8. Antibody response to Engerix-B and Recombivax-HB hepatitis B vaccination in end-stage renal disease.

    PubMed

    Lacson, Eduardo; Teng, Ming; Ong, Janus; Vienneau, Lori; Ofsthun, Norma; Lazarus, J Michael

    2005-10-01

    Recombivax-HB (REC) and Engerix-B (ENG) are FDA-approved vaccines for hepatitis B virus (HBV) in end-stage renal disease (ESRD). This study compares antibody response rates between them in routine clinical practice. Patients completing the recommended 40 mug dose of REC (3 doses) or ENG (4 doses) between January 1, 2000 to April 30, 2003 were eligible. Patients with prior positive HBV surface antigen (HBsAg) or antibody (HBsAb) test results were excluded. The conversion rate and persistence of protective titer (HBsAb titer>or=10 IU/mL) were tracked for 1 year. A supplemental analysis of a one-to-one matched patient sample was also performed. REC patients (N=885) were older, had longer dialysis vintage, and had a larger proportion of whites than ENG patients (N=13,661). Cumulative conversion response was greater in ENG (58%) than REC (40%) at 1 year (p<0.0001). The odds ratio for response to ENG compared with REC was 1.96 (95% limits: 1.56, 2.45; p<0.0001) adjusted for age, gender, race, diabetes, vintage, BSA, hemoglobin, and eKt/V. Persistent protective HBsAb after 1 year was 77% (ENG) vs. 53% (REC). HBsAg was positive in 208 ENG patients (1.5%) with all but 1 because of transient, vaccine-related antigenemia. The difference in conversion response favoring ENG persisted in a one-to-one sample matched for age, gender, race, modality, and dialysis vintage. The study found higher seroconversion response to ENG compared with REC at several time points up to 1 year. Protective HBsAb disappeared in 23-47% of patients 1 year later, validating CDC recommendations to re-test HBsAb yearly. The observed difference in response rates may be related to the extra ENG dose given at the second month (0, 1, 2, 6 regimen). The study raises a hypothesis that requires confirmation in a prospective clinical trial. PMID:16219057

  9. Molecular Dynamics of a Thermostable Multicopper Oxidase from Thermus thermophilus HB27: Structural Differences between the Apo and Holo Forms

    PubMed Central

    Bello, Martiniano; Valderrama, Brenda; Serrano-Posada, Hugo; Rudiño-Piñera, Enrique

    2012-01-01

    Molecular dynamic (MD) simulations have been performed on Tth-MCO, a hyperthermophilic multicopper oxidase from thermus thermophilus HB27, in the apo as well as the holo form, with the aim of exploring the structural dynamic properties common to the two conformational states. According to structural comparison between this enzyme and other MCOs, the substrate in process to electron transfer in an outer-sphere event seems to transiently occupy a shallow and overall hydrophobic cavity near the Cu type 1 (T1Cu). The linker connecting the β-strands 21 and 24 of the second domain (loop (β21–β24)D2) has the same conformation in both states, forming a flexible lid at the entrance of the electron-transfer cavity. Loop (β21–β24)D2 has been tentatively assigned a role occluding the access to the electron-transfer site. The dynamic of the loop (β21–β24)D2 has been investigated by MD simulation, and results show that the structures of both species have the same secondary and tertiary structure during almost all the MD simulations. In the simulation, loop (β21–β24)D2 of the holo form undergoes a higher mobility than in the apo form. In fact, loop (β21–β24)D2 of the holo form experiences a conformational change which enables exposure to the electron-transfer site (open conformation), while in the apo form the opposite effect takes place (closed conformation). To confirm the hypothesis that the open conformation might facilitate the transient electron-donor molecule occupation of the site, the simulation was extended another 40 ns with the electron-donor molecule docked into the protein cavity. Upon electron-donor molecule stabilization, loops near the cavity reduce their mobility. These findings show that coordination between the copper and the protein might play an important role in the general mobility of the enzyme, and that the open conformation seems to be required for the electron transfer process to T1Cu. PMID:22808237

  10. Does the treatment of type 2 diabetes mellitus with the DPP-4 inhibitor vildagliptin reduce HbA1c to a greater extent in Japanese patients than in Caucasian patients?

    PubMed Central

    Foley, James E; Bhosekar, Vaishali; Kawamori, Ryuzo

    2016-01-01

    Background Previous work suggests that Japanese patients with type 2 diabetes mellitus (T2DM) may respond more favorably to a DPP-4 (dipeptidyl peptidase-4) inhibitor than Caucasians. We aimed to compare the efficacy of the DPP-4 inhibitor vildagliptin (50 mg twice daily [bid]) between Japanese and Caucasian populations. Methods This analysis pooled data from 19 studies of drug-naïve patients with T2DM who were treated for 12 weeks with vildagliptin 50 mg bid as monotherapy. The pool comprised Japanese patients (n=338) who had been treated in Japan and Caucasian patients (n=1,275) who were treated elsewhere. Change from baseline (Δ) in glycated hemoglobin (HbA1c) at 12 weeks (in millimoles per mole) versus baseline HbA1c (both in percentage National Glycohemoglobin Standardization Program units [NGSP%] and millimoles per mole) for each population was reported. Universal HbA1c in millimoles per mole was calculated from either the Japanese Diabetes Society or the NGSP% HbA1c standards. Results At baseline, mean values for Japanese and Caucasian patients, respectively, were as follows: age, 59 years and 56 years; % male, 69% and 57%. The average HbA1c was reduced from 7.90% to 6.96% (Japanese Diabetes Society) and from 8.57% to 7.50% (United States National Glycohemoglobin Standardization Program), while HbA1c was reduced from 63 mmol/mol to 53 mmol/mol and from 70 mmol/mol to 58 mmol/mol in Japanese and Caucasians, respectively. ΔHbA1c increased with increasing baseline in both populations. The slopes were the same (0.41, r2=0.36; and 0.41, r2=0.15), and the intercepts were 15.4 mmol/mol and 17.2 mmol/mol, respectively. In Japanese patients, mean ΔHbA1c was greater by 1.7 mmol/mol (0.2% NGSP HbA1c) at any given baseline HbA1c than in Caucasians (P=0.01). Conclusion The present pooled analysis suggests that Japanese patients respond better to vildagliptin treatment compared with Caucasians. However, when glycemic control was corrected by using the same glycemic

  11. Single, community-based blood glucose readings may be a viable alternative for community surveillance of HbA1c and poor glycaemic control in people with known diabetes in resource-poor settings

    PubMed Central

    Reidpath, Daniel D.; Jahan, Nowrozy K.; Mohan, Devi; Allotey, Pascale

    2016-01-01

    Background The term HbA1c (glycated haemoglobin) is commonly used in relation to diabetes mellitus. The measure gives an indication of the average blood sugar levels over a period of weeks or months prior to testing. For most low- and middle-income countries HbA1c measurement in community surveillance is prohibitively expensive. A question arises about the possibility of using a single blood glucose measure for estimating HbA1c and therefore identifying poor glycaemic control in resource-poor settings. Design Using data from the 2011–2012 US National Health and Nutrition Examination Surveys, we examined the relationship between HbA1c and a single fasting measure of blood glucose in a non-clinical population of people with known diabetes (n=333). A linear equation for estimating HbA1c from blood glucose was developed. Appropriate blood glucose cut-off values were set for poor glycaemic control (HbA1c≥69.4 mmol/mol). Results The HbA1c and blood glucose measures were well correlated (r=0.7). Three blood glucose cut-off values were considered for classifying poor glycaemic control: 8.0, 8.9, and 11.4 mmol/L. A blood glucose of 11.4 had a specificity of 1, but poor sensitivity (0.37); 8.9 had high specificity (0.94) and moderate sensitivity (0.7); 8.0 was associated with good specificity (0.81) and sensitivity (0.75). Conclusions Where HbA1c measurement is too expensive for community surveillance, a single blood glucose measure may be a reasonable alternative. Generalising the specific results from these US data to low resource settings may not be appropriate, but the general approach is worthy of further investigation. PMID:27511810

  12. Regulation of HbPIP2;3, a Latex-Abundant Water Transporter, Is Associated with Latex Dilution and Yield in the Rubber Tree (Hevea brasiliensis Muell. Arg.).

    PubMed

    An, Feng; Zou, Zhi; Cai, Xiuqing; Wang, Jin; Rookes, James; Lin, Weifu; Cahill, David; Kong, Lingxue

    2015-01-01

    Rubber tree (Hevea brasiliensis) latex, the source of natural rubber, is synthesised in the cytoplasm of laticifers. Efficient water inflow into laticifers is crucial for latex flow and production since it is the determinant of the total solid content of latex and its fluidity after tapping. As the mature laticifer vessel rings are devoid of plasmodesmata, water exchange between laticifers and surrounding cells is believed to be governed by plasma membrane intrinsic proteins (PIPs). To identify the most important PIP aquaporin in the water balance of laticifers, the transcriptional profiles of ten-latex-expressed PIPs were analysed. One of the most abundant transcripts, designated HbPIP2;3, was characterised in this study. When tested in Xenopus laevis oocytes HbPIP2;3 showed a high efficiency in increasing plasmalemma water conductance. Expression analysis indicated that the HbPIP2;3 gene was preferentially expressed in latex, and the transcripts were up-regulated by both wounding and exogenously applied Ethrel (a commonly-used ethylene releaser). Although regular tapping up-regulated the expression of HbPIP2;3 during the first few tappings of the virginal rubber trees, the transcriptional kinetics of HbPIP2;3 to Ethrel stimulation in the regularly tapped tree exhibited a similar pattern to that of the previously reported HbPIP2;1 in the virginal rubber trees. Furthermore, the mRNA level of HbPIP2;3 was associated with clonal yield potential and the Ethrel stimulation response. Together, these results have revealed the central regulatory role of HbPIP2;3 in laticifer water balance and ethylene stimulation of latex production in Hevea. PMID:25927524

  13. Regulation of HbPIP2;3, a Latex-Abundant Water Transporter, Is Associated with Latex Dilution and Yield in the Rubber Tree (Hevea brasiliensis Muell. Arg.)

    PubMed Central

    Cai, Xiuqing; Wang, Jin; Rookes, James; Lin, Weifu; Cahill, David; Kong, Lingxue

    2015-01-01

    Rubber tree (Hevea brasiliensis) latex, the source of natural rubber, is synthesised in the cytoplasm of laticifers. Efficient water inflow into laticifers is crucial for latex flow and production since it is the determinant of the total solid content of latex and its fluidity after tapping. As the mature laticifer vessel rings are devoid of plasmodesmata, water exchange between laticifers and surrounding cells is believed to be governed by plasma membrane intrinsic proteins (PIPs). To identify the most important PIP aquaporin in the water balance of laticifers, the transcriptional profiles of ten-latex-expressed PIPs were analysed. One of the most abundant transcripts, designated HbPIP2;3, was characterised in this study. When tested in Xenopus laevis oocytes HbPIP2;3 showed a high efficiency in increasing plasmalemma water conductance. Expression analysis indicated that the HbPIP2;3 gene was preferentially expressed in latex, and the transcripts were up-regulated by both wounding and exogenously applied Ethrel (a commonly-used ethylene releaser). Although regular tapping up-regulated the expression of HbPIP2;3 during the first few tappings of the virginal rubber trees, the transcriptional kinetics of HbPIP2;3 to Ethrel stimulation in the regularly tapped tree exhibited a similar pattern to that of the previously reported HbPIP2;1 in the virginal rubber trees. Furthermore, the mRNA level of HbPIP2;3 was associated with clonal yield potential and the Ethrel stimulation response. Together, these results have revealed the central regulatory role of HbPIP2;3 in laticifer water balance and ethylene stimulation of latex production in Hevea. PMID:25927524

  14. Health Coaching Reduces HbA1c in Type 2 Diabetic Patients From a Lower-Socioeconomic Status Community: A Randomized Controlled Trial

    PubMed Central

    Wayne, Noah; Perez, Daniel F; Kaplan, David M

    2015-01-01

    Background Adoptions of health behaviors are crucial for maintaining good health after type 2 diabetes mellitus (T2DM) diagnoses. However, adherence to glucoregulating behaviors like regular exercise and balanced diet can be challenging, especially for people living in lower-socioeconomic status (SES) communities. Providing cost-effective interventions that improve self-management is important for improving quality of life and the sustainability of health care systems. Objective To evaluate a health coach intervention with and without the use of mobile phones to support health behavior change in patients with type 2 diabetes. Methods In this noninferiority, pragmatic randomized controlled trial (RCT), patients from two primary care health centers in Toronto, Canada, with type 2 diabetes and a glycated hemoglobin/hemoglobin A1c (HbA1c) level of ≥7.3% (56.3 mmol/mol) were randomized to receive 6 months of health coaching with or without mobile phone monitoring support. We hypothesized that both approaches would result in significant HbA1c reductions, although health coaching with mobile phone monitoring would result in significantly larger effects. Participants were evaluated at baseline, 3 months, and 6 months. The primary outcome was the change in HbA1c from baseline to 6 months (difference between and within groups). Other outcomes included weight, waist circumference, body mass index (BMI), satisfaction with life, depression and anxiety (Hospital Anxiety and Depression Scale [HADS]), positive and negative affect (Positive and Negative Affect Schedule [PANAS]), and quality of life (Short Form Health Survey-12 [SF-12]). Results A total of 138 patients were randomized and 7 were excluded for a substudy; of the remaining 131, 67 were allocated to the intervention group and 64 to the control group. Primary outcome data were available for 97 participants (74.0%). While both groups reduced their HbA1c levels, there were no significant between-group differences in

  15. Nano/micro hybrid scaffold of PCL or P3HB nanofibers combined with silk fibroin for tendon and ligament tissue engineering.

    PubMed

    Naghashzargar, Elham; Farè, Silvia; Catto, Valentina; Bertoldi, Serena; Semnani, Dariush; Karbasi, Saeed; Tanzi, Maria Cristina

    2015-01-01

    A novel biodegradable nano/micro hybrid structure was obtained by electrospinning P3HB or PCL nanofibers onto a twisted silk fibroin (SF) structure, with the aim of fabricating a suitable scaffold for tendon and ligament tissue engineering. The electrospinning (ES) processing parameters for P3HB and PCL were optimized on 2D samples, and applied to produce two different nano/micro hybrid constructs (SF/ES-PCL and SF/ES-P3HB).Morphological, chemico-physical and mechanical properties of the novel hybrid scaffolds were evaluated by SEM, ATR FT-IR, DSC, tensile and thermodynamic mechanical tests. The results demonstrated that the nanofibers were tightly wrapped around the silk filaments, and the crystallinity of the SF twisted yarns was not influenced by the presence of the electrospun polymers. The slightly higher mechanical properties of the hybrid constructs confirmed an increase of internal forces due to the interaction between nano and micro components. Cell culture tests with L929 fibroblasts, in the presence of the sample eluates or in direct contact with the hybrid structures, showed no cytotoxic effects and a good level of cytocompatibility of the nano/micro hybrid structures in term of cell viability, particularly at day 1. Cell viability onto the nano/micro hybrid structures decreased from the first to the third day of culture when compared with the control culture plastic, but appeared to be higher when compared with the uncoated SF yarns. Although additional in vitro and in vivo tests are needed, the original fabrication method here described appears promising for scaffolds suitable for tendon and ligament tissue engineering. PMID:25589157

  16. Depth profiling of the elemental surface composition of the oral microorganism S. salivarius HB and fibrillar mutants by X-ray photoelectron spectroscopy.

    PubMed

    van der Mei, H C; Handley, P S; Busscher, H J

    1992-02-01

    X-ray photoelectron spectroscopy (XPS) on microbial cell surfaces requires freeze-drying of cells, and as a result, the cell surface appendages flatten out on the cell surface and form a collapsed fibrillar mass. At present, it is unclear how the density, length and composition of these fibrils influence the elemental surface composition as probed by XPS. The sampling depth of XPS can be varied by changing the electron take-off angle. In this article, we made a depth profiling of the collapsed fibrillar mass of Streptococcus salivarius HB and fibril-deficient mutants by angle-dependent XPS. Methylamine tungstate negative staining and ruthenium red staining followed by sectioning revealed distinct classes of fibrils with various lengths on each of the strains. Interpretation of the angle dependence of the oxygen/carbon (O/C) and phosphorus/carbon (P/C) surface concentration ratios of these strains was difficult. However, the angle dependence of the nitrogen/carbon (N/C) surface concentration ratio could be fully interpreted: N/C did not vary with sampling depth on a bald strain, S. salivarius HBC12 and on S. salivarius HB7, a strain with a dense array of fibrils of uniform length. N/C decreased with sampling depth in case of a sparsely fibrillated strain, S. salivarius HBV51 and eventually reached the value observed for the bald strain, HBC12. A high N/C at small sampling depth was observed for S. salivarius HB with protruding, protein rich fibrils. We conclude that elemental depth profiling of microbial cell surfaces by XPS can be interpreted to coincide with structural and biochemical information on the cell surface as obtained by electron microscopy and can therefore be considered as a useful technique to study structural features of cell surfaces in combination with electron microscopy. PMID:1284785

  17. Genistein at maximal physiologic serum levels induces G0/G1 arrest in MCF-7 and HB4a cells, but not apoptosis.

    PubMed

    Tsuboy, Marcela S; Marcarini, Juliana C; de Souza, Alecsandra O; de Paula, Natália A; Dorta, Daniel J; Mantovani, Mário S; Ribeiro, Lucia R

    2014-02-01

    Several studies have demonstrated that a balanced diet can contribute to better human health. For this reason, soy-based food and pure isoflavones (pills) are one of the most consumed. The association of this consumption and lower risks of chronic diseases and cancer is well established for the Asian population and has been attracting the attention of people worldwide, especially women at menopause who seek to alleviate the symptoms associated with the lack of estrogen. Despite positive epidemiological data, concerns still exist because of conflicting results found in scientific literature with relation to the role of isoflavones in breast and hormone-related cancers. The aim of our study was to investigate the cytotoxicity, induction of apoptosis, and changes in apoptosis-related genes of maximal physiological serum levels of the isoflavone genistein (Gen) in MCF-7 tumoral cells and in HB4a non-tumoral cells. In addition, induction of cell cycle arrest was also investigated. Only supraphysiological levels of Gen (50 and 100 μM) were cytotoxic to these cell lines. Concentrations of 10 and 25 μM did not induce apoptosis and significant changes in expression of the studied genes. Positive results were found only in cell cycle analysis: G0/G1 delay of MCF-7 cells in both concentrations of Gen and at 25 μM in HB4a cells. It is the first study investigating effects of Gen in the HB4a cell line. Thus, despite the lack of apoptosis induction (generally found with high concentrations), Gen at physiologically relevant serum levels still exerts chemopreventive effects through the modulation of cell cycle. PMID:24325455

  18. Dietary Pattern Trajectories during 15 Years of Follow-up and HbA1c, Insulin Resistance, and Diabetes Prevalence among Chinese Adults

    PubMed Central

    Batis, Carolina; Mendez, Michelle A.; Sotres-Alvarez, Daniela; Gordon-Larsen, Penny; Popkin, Barry

    2014-01-01

    Background Most research on dietary patterns and health outcomes does not include longitudinal exposure data. We used an innovative technique to capture dietary pattern trajectories and their association with hemoglobin A1c (HbA1c), homeostasis model of insulin resistance (HOMA-IR), and prevalence of newly diagnosed diabetes. Methods We included 4,096 adults with three to six waves of diet data (1991–2006) and biomarkers measured in 2009 from the China Health and Nutrition Survey. Diet was assessed with three 24-hour recalls and a household food inventory. We used a dietary pattern previously identified with reduced rank regression that positively predicted diabetes in 2006 (high in wheat products and soy milk and low in rice, legumes, poultry, eggs, and fish). We estimated a score for this dietary pattern for each subject at each wave. Using latent class trajectory analysis, we grouped subjects with similar dietary pattern score trajectories over time into five classes. Results Three trajectory classes were stable over time, and in two classes the diet became unhealthier over time (upward trend in dietary pattern score). Among two classes with similar scores in 2006, the one with the lower (healthier) initial score had an HbA1c 1.64% lower (−1.64 [95% confidence interval= −3.17, −0.11]) and nonsignificantly a HOMA-IR 6.47% lower (−6.47 [−17.37, 4.42]) and lower odds of diabetes (0.86 [0.44, 1.67]). Conclusions Our findings suggest that dietary pattern trajectories with healthier scores longitudinally had a lower HbA1c compared to those with unhealthier scores, even when the trajectories had similar scores in the end point. PMID:24729424

  19. Real-time evaluation of tissue vitality by monitoring of microcirculatory blood flow, HbO2, and mitochondrial NADH redox state

    NASA Astrophysics Data System (ADS)

    Deutsch, Assaf; Pevzner, Eliyahu; Jaronkin, Alex; Mayevsky, Avraham

    2004-06-01

    Monitoring of tissue vitality (oxygen supply/demand) in real time is very rare in clinical practice although its use as an early warning alarming system, for clinical care medicine, is very practical. In our previous communication (SPIE 2003) we described the Tissue Spectroscope - TiSpec02, by which tissue microcirculatory blood flow (TBF) and mitochondrial NADH fluorescence were measured using a single light source (390nm). In order to improve the measurement capabilities as well as to decrease dramatically the size and cost of this clinical device, we have changed the TiSpec02 into a multi-wavelength illumination system in the new TiSpec03. In order to measure microcirculatory blood flow by laser Doppler flowmetry we used a 785nm laser diode. For mitochondrial NADH fluorescence measurement we adopted the 370nm LED. For the determination of the oxygenation level of hemoglobin (HbO2) we used the 2-wavelength reflectance technique. This new monitored parameter that was added to the TiSpec03 increases the accuracy of the diagnosis of tissue vitality. The bundle of optical fibers used to connect the tissue to the TiSpec03, was integrated into a special anchoring methodology depending on the monitored tissue or organ. In order to test the performance of the improved TiSpec we have used it in experimental animals brain models exposed to various pathophysiological conditions. Rats and gerbils were anesthetized and the fiber optic probe was located epidurally used dental acrylic cement. During anoxia and ischemia the lack of O2 led to a clear decrease in TBF and HbO2 while NADH shows a large elevation. When brain activation was induced by cortical spreading depression (SD), the elevated O2 consumption was recorded as a large oxidation (decrease) of mitochondrial NADH while TBF increase dramatically. Blood HbO2 was not affected significantly by the SD wave.

  20. Ortho-to-para Ratio Studies of Shocked H2 Gas in the Two Supernova Remnants IC 443 and HB 21

    NASA Astrophysics Data System (ADS)

    Shinn, Jong-Ho; Lee, Ho-Gyu; Moon, Dae-Sik

    2012-11-01

    We present near-infrared (2.5-5.0 μm) spectral studies of shocked H2 gas in two supernova remnants, IC 443 and HB 21, which are well known for their interactions with nearby molecular clouds. The observations were performed with the Infrared Camera aboard the AKARI satellite. At the energy range 7000 K lsim E(\\upsilon,J) lsim 20,000 K, the shocked H2 gas in IC 443 shows an ortho-to-para ratio (OPR) of 2.4+0.3 - 0.2, which is significantly lower than the equilibrium value 3, suggesting the existence of non-equilibrium OPR. The shocked gas in HB 21 also indicates a potential non-equilibrium OPR in the range of 1.8-2.0. The level populations are well described by the power-law thermal admixture model with a single OPR, where the temperature integration range is 1000-4000 K. We conclude that the obtained non-equilibrium OPR probably originates from the reformed H2 gas of dissociative J-shocks, considering several factors such as the shock combination requirement, the line ratios, and the possibility that H2 gas can form on grains with a non-equilibrium OPR. We also investigate C-shocks and partially dissociative J-shocks as the origin of the non-equilibrium OPR. However, we find that they are incompatible with the observed ionic emission lines for which dissociative J-shocks are required to explain. The difference in the collision energy of H atoms on grain surfaces would give rise to the observed difference between the OPRs of IC 443 and HB 21, if dissociative J-shocks are responsible for the H2 emission. Our study suggests that dissociative J-shocks can produce shocked H2 gas with a non-equilibrium OPR.

  1. TECHNICAL BASIS FOR DOE STANDARD 3013 EQUIVALENCY SUPPORTING REDUCED TEMPERATURE STABILIZATION OF OXALATE-DERIVED PLUTONIUM DIOXIDE PRODUCED BY THE HB-LINE FACILITY AT SAVANNAH RIVER SITE

    SciTech Connect

    Duffey, J. M.; Livingston, R. R.; Berg, J. M.; Veirs, D. K.

    2013-02-06

    This report documents the technical basis for determining that stabilizing highpurity PuO{sub 2} derived from oxalate precipitation at the SRS HB-Line facility at a minimum of 625 {degree}C for at least four hours in an oxidizing atmosphere is equivalent to stabilizing at a minimum of 950 {degree}C for at least two hours as regards meeting the objectives of stabilization defined by DOE-STD-3013 if the material is handled in a way to prevent excessive absorption of water.

  2. Environmental assessment operation of the HB-Line facility and frame waste recovery process for production of Pu-238 oxide at the Savannah River Site

    SciTech Connect

    1995-04-01

    The Department of Energy (DOE) has prepared an environmental assessment (EA), DOE/EA-0948, addressing future operations of the HB-Line facility and the Frame Waste Recovery process at the Savannah River Site (SRS), near Aiken, South Carolina. Based on the analyses in the EA, DOE has determined that the proposed action is not a major Federal action significantly affecting the quality of the human environment within the meaning of the National Environmental Policy Act (NEPA) of 1969. Therefore, DOE has concluded that, the preparation of an environmental impact statement is not required, and is issuing this Finding of No Significant Impact.

  3. Longitudinal relationship between diabetes-specific emotional distress and follow-up HbA1c in adults with Type 1 diabetes mellitus

    PubMed Central

    Strandberg, R B; Graue, M; Wentzel-Larsen, T; Peyrot, M; Thordarson, H B; Rokne, B

    2015-01-01

    Aim To examine whether diabetes-specific emotional distress was related to follow-up glycaemic control in adults with Type 1 diabetes mellitus. Methods Adults with Type 1 diabetes mellitus completed the Diabetes Distress Scale and reported sociodemographic information when attending a clinical consultation at a university endocrinology unit. Blood samples to determine baseline HbA1c were taken during consultations. All respondents’ HbA1c measurements registered from January 2009 to December 2011 were collected from medical records. The relationship between baseline diabetes-specific emotional distress and HbA1c was examined with linear mixed-effects models in 175 patients with complete data. Results After controlling for confounders, baseline diabetes-specific emotional distress and glycaemic control were significantly associated (fixed-effect coefficient 0.40, P < 0.001) and the regimen-related distress subscale had the strongest association with glycaemic control (fixed-effect coefficient 0.47, P < 0.001). The two-item measure of diabetes-specific distress had a weaker but still significant association with glycaemic control (fixed-effect coefficient 0.31, P < 0.001). None of these relationships was significant after adjusting for the baseline HbA1c. Conclusions People with elevated baseline diabetes-specific emotional distress are at risk of prolonged suboptimum glycaemic control; therefore, elevated diabetes-specific emotional distress, especially regimen-related distress, might be an important marker for prolonged suboptimum glycaemic control, and might indicate a need for special attention regarding patient self-management. What’s new? In adults with Type 1 diabetes, elevated baseline diabetes-specific emotional distress is associated with worse glycaemic control over a 1–3-year period and regimen-related distress had the strongest association with subsequent glycaemic control. Baseline diabetes-specific emotional distress is associated with the

  4. An indirect comparison of HbA1c treatment effect with albiglutide and exenatide 2.0 mg QW using the Bucher method

    PubMed Central

    Martin, Alan A; Parks, Daniel

    2016-01-01

    No head-to-head comparisons exist between once-weekly (QW) glucagon-like peptide-1 receptor agonists; accordingly, this indirect comparison was conducted to evaluate the comparative efficacy of QW albiglutide vs QW exenatide. Following a systematic literature search, it was determined that HARMONY 7 and DURATION 6, Phase III trials for albiglutide and exenatide, respectively, were similar in study design and baseline characteristics and included a common comparator arm, making them suitable for an indirect comparison using the Bucher method. The primary endpoint of change from baseline in glycated hemoglobin (HbA1c) with albiglutide 50 mg QW and exenatide 2.0 mg QW was compared and tested for noninferiority. The indirect comparison showed a treatment difference of 0.0% (95% confidence interval: −0.189% to 0.189%) in mean change in HbA1c from baseline, and albiglutide 50 mg was noninferior to exenatide 2.0 mg QW at the noninferiority margin of 0.3%. In the absence of a head-to-head trial, these results can be used in pharmacoeconomic analysis and to inform health technology assessment and clinical decision making. PMID:27274297

  5. Phosphoproteomic Analysis Reveals the Effects of PilF Phosphorylation on Type IV Pilus and Biofilm Formation in Thermus thermophilus HB27*

    PubMed Central

    Wu, Wan-Ling; Liao, Jiahn-Haur; Lin, Guang-Huey; Lin, Miao-Hsia; Chang, Ying-Che; Liang, Suh-Yuen; Yang, Feng-Ling; Khoo, Kay-Hooi; Wu, Shih-Hsiung

    2013-01-01

    Thermus thermophilus HB27 is an extremely thermophilic eubacteria with a high frequency of natural competence. This organism is therefore often used as a thermophilic model to investigate the molecular basis of type IV pili–mediated functions, such as the uptake of free DNA, adhesion, twitching motility, and biofilm formation, in hot environments. In this study, the phosphoproteome of T. thermophilus HB27 was analyzed via a shotgun approach and high-accuracy mass spectrometry. Ninety-three unique phosphopeptides, including 67 in vivo phosphorylated sites on 53 phosphoproteins, were identified. The distribution of Ser/Thr/Tyr phosphorylation sites was 57%/36%/7%. The phosphoproteins were mostly involved in central metabolic pathways and protein/cell envelope biosynthesis. According to this analysis, the ATPase motor PilF, a type IV pili–related component, was first found to be phosphorylated on Thr-368 and Ser-372. Through the point mutation of PilF, mimic phosphorylated mutants T368D and S372E resulted in nonpiliated and nontwitching phenotypes, whereas nonphosphorylated mutants T368V and S372A displayed piliation and twitching motility. In addition, mimic phosphorylated mutants showed elevated biofilm-forming abilities with a higher initial attachment rate, caused by increasing exopolysaccharide production. In summary, the phosphorylation of PilF might regulate the pili and biofilm formation associated with exopolysaccharide production. PMID:23828892

  6. Surface properties of Streptococcus salivarius HB and nonfibrillar mutants: measurement of zeta potential and elemental composition with X-ray photoelectron spectroscopy.

    PubMed Central

    van der Mei, H C; Léonard, A J; Weerkamp, A H; Rouxhet, P G; Busscher, H J

    1988-01-01

    To characterize the functional cell surface, the zeta potentials and elemental surface composition of Streptococcus salivarius HB and a range of mutants with known molecular surface structures were determined. Zeta potentials of fully hydrated cells were measured as a function of pH in dilute potassium phosphate solutions, yielding isoelectric points of the strains. Elemental composition (O, C, N, and P) of the outer 2 to 5 nm of the freeze-dried cell surfaces were measured by X-ray photoelectron spectroscopy. An increasing loss of proteinaceous fibrillar surface antigens of the mutants was found to be accompanied by a progressive decrease in the N/C ratio from 0.104 in the parent strain HB to 0.053 in mutant HBC12. Simultaneously, the value of the isoelectric point shifted from 3.0 to 1.3. In a previous study (A.H. Weerkamp, H.C. van der Mei, and J. W. Slot, Infect. Immun. 55:438-455, 1987) on the cell surfaces of the same strains, it was shown that removal of fibrils led to increased exposure of (lipo)teichoic acid at the surface, which explains the low isoelectric point caused by the low pKa of the phosphate groups. PMID:3372474

  7. C-Peptide Level in Fasting Plasma and Pooled Urine Predicts HbA1c after Hospitalization in Patients with Type 2 Diabetes Mellitus.

    PubMed

    Sonoda, Remi; Tanaka, Kentaro; Kikuchi, Takako; Onishi, Yukiko; Takao, Toshiko; Tahara, Tazu; Yoshida, Yoko; Suzawa, Naoki; Kawazu, Shoji; Iwamoto, Yasuhiko; Kushiyama, Akifumi

    2016-01-01

    In this study, we investigate how measures of insulin secretion and other clinical information affect long-term glycemic control in patients with type 2 diabetes mellitus. Between October 2012 and June 2014, we monitored 202 diabetes patients who were admitted to the hospital of Asahi Life Foundation for glycemic control, as well as for training and education in diabetes management. We measured glycated hemoglobin (HbA1c) six months after discharge to assess disease management. In univariate analysis, fasting plasma C-peptide immunoreactivity (F-CPR) and pooled urine CPR (U-CPR) were significantly associated with HbA1c, in contrast to ΔCPR and C-peptide index (CPI). This association was strongly independent of most other patient variables. In exploratory factor analysis, five underlying factors, namely insulin resistance, aging, sex differences, insulin secretion, and glycemic control, represented patient characteristics. In particular, insulin secretion and resistance strongly influenced F-CPR, while insulin secretion affected U-CPR. In conclusion, the data indicate that among patients with type 2 diabetes mellitus, F-CPR and U-CPR may predict improved glycemic control six months after hospitalization. PMID:26849676

  8. The Analysis of the Possible Thermal Emission at Radio Frequencies from an Evolved Supernova Remnant HB 3 (G132.7+1.3): Revisited

    NASA Astrophysics Data System (ADS)

    Onic, D.; Urosevic, D.

    2008-12-01

    It has recently been reported that some of the flux density values for an evolved supernova remnant (SNR) HB 3 (G132.7+1.3) are not accurate enough. In this work we therefore revised the analysis of the possible thermal emission at radio frequencies from this SNR using the recently published, corrected flux density values. A model including the sum of non-thermal (purely synchrotron) and thermal (bremsstrahlung) components is applied to fit the integrated radio spectrum of this SNR. The contribution of thermal component to the total volume emissivity at 1 GHz is estimated to be ≈37 %. The ambient density is also estimated to be n≈ 9 {cm}^{-3} for {T}=10^{4} {K}. Again we obtained a relatively significant presence of thermal emission at radio frequencies from the SNR, which can support interaction between SNR HB 3 and adjacent molecular cloud associated with the H II region W3. Our model estimates for thermal component contribution to total volume emissivity at 1 {GHz} and ambient density are similar to those obtained earlier (≈40 %, ≈10 {cm^{-3}}). It is thus obvious that the corrected flux density values do not affect the basic conclusions.

  9. Burden of Diabetes and First Evidence for the Utility of HbA1c for Diagnosis and Detection of Diabetes in Urban Black South Africans: The Durban Diabetes Study

    PubMed Central

    Hird, Thomas R.; Pirie, Fraser J.; Esterhuizen, Tonya M.; O’Leary, Brian; McCarthy, Mark I.; Young, Elizabeth H.; Sandhu, Manjinder S.; Motala, Ayesha A.

    2016-01-01

    Objective Glycated haemoglobin (HbA1c) is recommended as an additional tool to glucose-based measures (fasting plasma glucose [FPG] and 2-hour plasma glucose [2PG] during oral glucose tolerance test [OGTT]) for the diagnosis of diabetes; however, its use in sub-Saharan African populations is not established. We assessed prevalence estimates and the diagnosis and detection of diabetes based on OGTT, FPG, and HbA1c in an urban black South African population. Research Design and Methods We conducted a population-based cross-sectional survey using multistage cluster sampling of adults aged ≥18 years in Durban (eThekwini municipality), KwaZulu-Natal. All participants had a 75-g OGTT and HbA1c measurements. Receiver operating characteristic (ROC) analysis was used to assess the overall diagnostic accuracy of HbA1c, using OGTT as the reference, and to determine optimal HbA1c cut-offs. Results Among 1190 participants (851 women, 92.6% response rate), the age-standardised prevalence of diabetes was 12.9% based on OGTT, 11.9% based on FPG, and 13.1% based on HbA1c. In participants without a previous history of diabetes (n = 1077), using OGTT as the reference, an HbA1c ≥48 mmol/mol (6.5%) detected diabetes with 70.3% sensitivity (95%CI 52.7–87.8) and 98.7% specificity (95%CI 97.9–99.4) (AUC 0.94 [95%CI 0.89–1.00]). Additional analyses suggested the optimal HbA1c cut-off for detection of diabetes in this population was 42 mmol/mol (6.0%) (sensitivity 89.2% [95%CI 78.6–99.8], specificity 92.0% [95%CI: 90.3–93.7]). Conclusions In an urban black South African population, we found a high prevalence of diabetes and provide the first evidence for the utility of HbA1c for the diagnosis and detection of diabetes in black Africans in sub-Saharan Africa. PMID:27560687

  10. HbA1c Alone Is a Poor Indicator of Cardiometabolic Risk in Middle-Aged Subjects with Pre-Diabetes but Is Suitable for Type 2 Diabetes Diagnosis: A Cross-Sectional Study

    PubMed Central

    Millar, Seán R.; Perry, Ivan J.; Phillips, Catherine M.

    2015-01-01

    Objectives Glycated haemoglobin A1c (HbA1c) measurement is recommended as an alternative to fasting plasma glucose (FPG) for the diagnosis of pre-diabetes and type 2 diabetes. However, evidence suggests discordance between HbA1c and FPG. In this study we examine a range of metabolic risk features, pro-inflammatory cytokines, acute-phase response proteins, coagulation factors and white blood cell counts to determine which assay more accurately identifies individuals at increased cardiometabolic risk. Materials and Methods This was a cross-sectional study involving a random sample of 2,047 men and women aged 46-73 years. Binary and multinomial logistic regression were employed to examine risk feature associations with pre-diabetes [either HbA1c levels 5.7-6.4% (39-46 mmol/mol) or impaired FPG levels 5.6-6.9 mmol/l] and type 2 diabetes [either HbA1c levels >6.5% (>48 mmol/mol) or FPG levels >7.0 mmol/l]. Receiver operating characteristic curve analysis was used to evaluate the ability of HbA1c to discriminate pre-diabetes and diabetes defined by FPG. Results Stronger associations with diabetes-related phenotypes were observed in pre-diabetic subjects diagnosed by FPG compared to those detected by HbA1c. Individuals with type 2 diabetes exhibited cardiometabolic profiles that were broadly similar according to diagnosis by either assay. Pre-diabetic participants classified by both assays displayed a more pro-inflammatory, pro-atherogenic, hypertensive and insulin resistant profile. Odds ratios of having three or more metabolic syndrome features were also noticeably increased (OR: 4.0, 95% CI: 2.8-5.8) when compared to subjects diagnosed by either HbA1c (OR: 1.4, 95% CI: 1.2-1.8) or FPG (OR: 3.0, 95% CI: 1.7-5.1) separately. Conclusions In middle-aged Caucasian-Europeans, HbA1c alone is a poor indicator of cardiometabolic risk but is suitable for diagnosing diabetes. Combined use of HbA1c and FPG may be of additional benefit for detecting individuals at highest odds of

  11. Ligand Migration and Cavities within Scapharca Dimeric HbI: Studies by Time-Resolved Crystallo- graphy, Xe Binding, and Computational Analysis

    SciTech Connect

    Knapp, James E.; Pahl, Reinhard; Cohen, Jordi; Nichols, Jeffry C.; Schulten, Klaus; Gibson, Quentin H.; Šrajer, Vukica; Royer, Jr., William E.; (UC_

    2009-12-01

    As in many other hemoglobins, no direct route for migration of ligands between solvent and active site is evident from crystal structures of Scapharca inaequivalvis dimeric HbI. Xenon (Xe) and organic halide binding experiments, along with computational analysis presented here, reveal protein cavities as potential ligand migration routes. Time-resolved crystallographic experiments show that photodissociated carbon monoxide (CO) docks within 5 ns at the distal pocket B site and at more remote Xe4 and Xe2 cavities. CO rebinding is not affected by the presence of dichloroethane within the major Xe4 protein cavity, demonstrating that this cavity is not on the major exit pathway. The crystal lattice has a substantial influence on ligand migration, suggesting that significant conformational rearrangements may be required for ligand exit. Taken together, these results are consistent with a distal histidine gate as one important ligand entry and exit route, despite its participation in the dimeric interface.

  12. Cloning, expression, purification, crystallization and preliminary crystallographic analysis of the putative NlpC/P60 endopeptidase, TTHA0266, from Thermus thermophilus HB8

    PubMed Central

    Wong, Jaslyn E. M. M.; Blaise, Mickael

    2013-01-01

    Autolysins belong to a protein family involved in peptidoglycan degradation and remodelling. Within this family, NlpC/P60 endopeptidases are involved in the hydrolysis of the peptide arm of peptidoglycan. In this work, the putative NlpC/P60 endopeptidase TTHA0266 from Thermus thermophilus HB8 was overexpressed, purified and crystallized. The crystals diffracted to 2.4 Å resolution and belonged to the hexagonal space group P61, with unit-cell parameters a = b = 71.19, c = 198.68 Å, γ = 120°. Selenomethionine-substituted protein was crystallized and the structure was solved by single-wavelength anomalous dispersion. PMID:24192372

  13. Gapless quantum spin liquid ground state in the spin-1 antiferromagnet 6HB-Ba3NiSb2O9

    NASA Astrophysics Data System (ADS)

    Quilliam, J. A.; Bert, F.; Manseau, A.; Darie, C.; Guillot-Deudon, C.; Payen, C.; Baines, C.; Amato, A.; Mendels, P.

    2016-06-01

    We present an in-depth study of the magnetic properties of the spin-1 antiferromagnet 6HB-Ba3NiSb2O9 . μ SR measurements demonstrate that this material shows no static magnetism down to temperatures as low as 20 mK, making it a likely candidate for a quantum spin liquid state. 121Sb NMR shift measurements show that the local, intrinsic susceptibility levels off at temperatures below ˜60 K. The NMR spin-lattice relaxation rate 1 /T1 is essentially constant in temperature and the muon relaxation rate exhibits a low-temperature relaxation plateau, all indications of gapless spin excitations. Our local probe measurements are discussed in the context of several theories proposed for this material.

  14. Ligand migration and cavities within Scapharca dimeric HbI: Studies by time-resolved crystallography, Xe binding and computational analysis

    PubMed Central

    Knapp, James E.; Pahl, Reinhard; Cohen, Jordi; Nichols, Jeffry C.; Schulten, Klaus; Gibson, Quentin H.; Šrajer, Vukica; Royer, William E.

    2009-01-01

    Summary As in many other hemoglobins, no direct route for migration of ligands between solvent and active site is evident from crystal structures of Scapharca inaequivalvis dimeric HbI. Xenon (Xe) and organic halide binding experiments along with computational analysis presented here reveal protein cavities as potential ligand migration routes. Time-resolved crystallographic experiments show that photodissociated carbon monoxide (CO) docks within 5ns at the distal pocket B-site and at more remote Xe4 and Xe2 cavities. CO rebinding is not affected by the presence of dichloroethane within the major Xe4 protein cavity, demonstrating that this cavity is not on the major exit pathway. The crystal lattice has a substantial influence on ligand migration, suggesting that significant conformational rearrangements may be required for ligand exit. Taken together, these results are consistent with a distal histidine gate as one important ligand entry and exit route, despite its participation in the dimeric interface. PMID:19913484

  15. MIXED-MORPHOLOGY SUPERNOVA REMNANTS IN X-RAYS: ISOTHERMAL PLASMA IN HB21 AND PROBABLE OXYGEN-RICH EJECTA IN CTB 1

    SciTech Connect

    Pannuti, Thomas G.; Rho, Jeonghee; Borkowski, Kazimierz J.; Brian Cameron, P. E-mail: pbc@astro.caltech.ed E-mail: jrho@sofia.usra.ed

    2010-12-15

    We present an analysis of X-ray observations of the Galactic supernova remnants (SNRs) HB21 (G89.0+4.7) and CTB 1 (G116.9+0.2), two well-known members of the class of mixed-morphology (MM) SNRs. Our analysis draws upon observations of both SNRs made with the Advanced Satellite for Cosmology and Astrophysics (ASCA): we have also used an archived Chandra observation of CTB 1 as part of this effort. We find a marked contrast between the X-ray properties of HB21 and CTB 1: in the case of HB21, the extracted spectra of the northwest and southeast regions of the X-ray-emitting plasma associated with the SNR can be fit with a single thermal model with marginally enhanced silicon and sulfur abundances. For both of these regions, the derived column density and temperature are N{sub H} {approx} 0.3 x 10{sup 22} cm{sup -2} and kT {approx} 0.7 keV, respectively. No significant spatial differences in temperature or elemental abundances between the two regions are detected and the X-ray-emitting plasma for both regions is close to ionization equilibrium. Our Chandra spectral analysis of CTB 1 reveals that this source is likely an oxygen-rich SNR with enhanced abundances of oxygen and neon: this result is quite surprising for an evolved SNR like CTB 1. The high angular resolution Chandra observation of CTB 1 reveals spectral variations across this SNR: in particular, we have detected localized hard emission with an angular extent of {approx}1'. The extracted ASCA spectra for both the southwest and northeastern regions of CTB 1 cannot be fit with a single thermal component and instead an additional component is required to account for the presence of excess emission seen at higher energies. Based on our fits to the extracted ASCA spectra, we derive a column density N{sub H} {approx} 0.6 x 10{sup 22} cm{sup -2} and a temperature for the soft thermal component of kT{sub soft} {approx} 0.28 keV for both regions. The hard emission from the southwest region may be modeled with either a

  16. Excimer-laser-induced oxidation of diborane: Formation and isolation of HBO, HB 18O AND H 3B 3O 3 in argon matrices

    NASA Astrophysics Data System (ADS)

    Ault, Bruce S.

    1989-05-01

    An excimer laser operating at 193 nm has been employed in conjunction with the matrix isolation technique to study the reaction of B 2H 6 with oxygen atoms. N 2O and O 2 were used as photolytic oxygen atom sources, and a number of oxidation products were detected. Absorptions near 750 and 1813 cm -1 were assigned to H 11BO; experiments with 18O led to production of HB 18O for the first time, and the identification of two of the fundamentals of this species. Also, H 3B 3O 3 was detected near 910, 1380 and 2610 cm -1. In addition, the most intense fundamental of BH 3 was tentatively identified at 1138 cm -1. These observations support the most recently postulated mechanism for the oxidation of diborane, and the suggested intermediacy of HBO in the process.

  17. Cypermethrin Stimulates GSK3β-Dependent Aβ and p-tau Proteins and Cognitive Loss in Young Rats: Reduced HB-EGF Signaling and Downstream Neuroinflammation as Critical Regulators.

    PubMed

    Maurya, Shailendra Kumar; Mishra, Juhi; Abbas, Sabiya; Bandyopadhyay, Sanghamitra

    2016-03-01

    Pesticide exposure is recognized as a risk factor for Alzheimer's disease (AD). We investigated early signs of AD-like pathology upon exposure to a pyrethroid pesticide, cypermethrin, reported to impair neurodevelopment. We treated weanling rats with cypermethrin (10 and 25 mg/kg) and detected dose-dependent increase in the key proteins of AD, amyloid beta (Aβ), and phospho-tau, in frontal cortex and hippocampus as early as postnatal day 45. Upregulation of Aβ pathway involved an increase in amyloid precursor protein (APP) and its pro-amyloidogenic processing through beta-secretase (BACE) and gamma-secretase. Tau pathway entailed elevation in tau and glycogen-synthase kinase-3-beta (GSK3β)-dependent, phospho-tau. GSK3β emerged as a molecular link between the two pathways, evident from reduction in phospho-tau as well as BACE upon treating GSK3β inhibitor, lithium chloride. Exploring the mechanism revealed an attenuated heparin-binding epidermal growth factor (HB-EGF) signaling and downstream astrogliosis-mediated neuroinflammation to be responsible for inducing Aβ and phospho-tau. Cypermethrin caused a proximal reduction in HB-EGF, which promoted astrocytic nuclear factor kappa B signaling and astroglial activation close to Aβ and phospho-tau. Glial activation stimulated generation of interleukin-1 (IL-1), which upregulated GSK3β, and APP and tau as well, resulting in co-localization of Aβ and phospho-tau with IL-1 receptor. Intracerebral insertion of exogenous HB-EGF restored its own signaling and suppressed neuroinflammation and thereby Aβ and phospho-tau in cypermethrin-exposed rats, proving a central role of reduced HB-EGF signaling in cypermethrin-mediated neurodegeneration. Furthermore, cypermethrin stimulated cognitive impairments, which could be prevented by exogenous HB-EGF. Our data demonstrate that cypermethrin induces premature upregulation of GSK3β-dependent Aβ and tau pathways, where HB-EGF signaling and neuroinflammation serve as

  18. The Impact of XmnI-HBG2, BCL11A and HBS1L-MYB Single Nucleotide Polymorphisms on Hb F Variation of Hematologically Normal Iranian Individuals.

    PubMed

    Keyhani, Elaheh; Jafari Vesiehsari, Mahjoobeh; Talebi Kakroodi, Setareh; Darabi, Elham; Zamani, Fahimeh; Karimlou, Masoud; Kamali, Koorosh; Neishabury, Maryam

    2016-06-01

    The impact of Hb F on severity of sickle cell disease and β-thalassemia (β-thal) is well documented. The XmnI-HBG2, BCL11A and HBS1L-MYB single nucleotide polymorphisms (SNPs) have been introduced as the most important factors causing variation in fetal hemoglobin (Hb F) levels in different population studies. However, the extent of their effect could be population-specific. In this study, multivariate linear regression analysis was used to evaluate the association of Hb F with age, sex, and eight SNPs, including XmnI-HBG2, four BCL11A, two HBS1L-MYB SNPs and the polymorphic palindromic 5' hypersensitive 4-locus control region (5'HS4-LCR). One hundred and twenty-two hematologically normal individuals, from a previous study cohort, constituted our study population. In multivariate regression analyses, no association of Hb F was observed with age or sex of the individuals and SNPs in this study. We conducted a univariate regression analysis to further investigate the results, which among all the factors only detected XmnI-HBG2 and 5'HS4 SNPs as significant modifiers of Hb F. The significance of these two factors disappeared in a bivariate analysis. These results suggest that either XmnI-HBG2 or 5'HS4-LCR have a stronger contribution in Hb F variations of the Iranian population than BCL11A and HBS1L-MYB SNPs. Furthermore, the effect of low population size and technical limitations on obtained results could not be ruled out. PMID:27117569

  19. Energy balance and macronutrient distribution in relation to C-reactive protein and HbA1c levels among patients with type 2 diabetes

    PubMed Central

    Bawadi, Hiba; Katkhouda, Rami; Al-Haifi, Ahmad; Tayyem, Reema; Elkhoury, Cosette Fakih; Jamal, Zeina

    2016-01-01

    Background Recently growing evidence indicates that obesity and diabetes are states of inflammation associated with elevated circulation of inflammatory mediators. Excess adiposity and oxidative stress, induced by feeding, may also lead to a state of low-grade inflammation. Objective This study aimed at investigating energy balance and distribution in relation to low-grade inflammation among patients with type 2 diabetes. Design A cross-sectional study included 198 male and female patients with type 2 diabetes. Patients’ weight, height, waist circumference, total body fat and truncal fat percent, energy, and macronutrient intake were measured. Venous blood specimens were collected, and levels of HbA1c and serum levels of high-sensitivity C-reactive protein (hs-CRP) were determined. Results After adjusting for covariates (body mass index, total body fat, and truncal fat), energy balance was positively correlated with hs-CRP and HbA1c. A positive energy balance was also associated with increased waist circumference and truncal fat percent (p<0.05). Total energy intake, percent energy from fat (p=0.04), and percent energy from proteins (p=0.03), but not percent energy from carbohydrates (p=0.12), were also correlated with higher hs-CRP levels among poorly glycemic-controlled patients. Conclusion Positive energy balance is associated with elevations in hs-CRP. Increased energy intake and increased percentages of energy from fat and protein are associated with elevated hs-CRP among patients with poor glycemic control. PMID:27238554

  20. Characterization of three putative Lon proteases of Thermus thermophilus HB27 and use of their defective mutants as hosts for production of heterologous proteins.

    PubMed

    Maehara, Tomoko; Hoshino, Takayuki; Nakamura, Akira

    2008-03-01

    In the genome of a thermophilic bacterium, Thermus thermophilus HB27, three genes, TTC0418, TTC0746 and TTC1975, were annotated as ATP-dependent protease La (Lon). Sequence comparisons indicated that TTC0418 and TTC0746 showed significant similarities to bacterial LonA-type proteases, such as Escherichia coli Lon protease, especially in regions corresponding to domains for ATP-binding and hydrolysis, and for proteolysis, but TTC1975 exhibited a similarity only at the C-terminal proteolytic domain. The enzymatic analyses, using purified recombinant proteins produced by E. coli, revealed that TTC0418 and TTC0746 exhibited peptidase and protease activities against two synthetic peptides and casein, respectively, in an ATP-dependent manner, and at the same time, both the enzymes had significant ATPase activities in the presence of substrates. On the other hand, TTC1975 possessed a protease activity against casein, but addition of ATP did not enhance this activity. Moreover, a T. thermophilus mutant deficient in both TTC0418 and TTC0746 showed a similar growth characteristic to an E. coli lon mutant, i.e., a growth defect lag after a nutritional downshift. These results indicate that TTC0418 and TTC0746 are actually members of bacterial LonA-type proteases with different substrate specificities, whereas TTC1975 should not be classified as a Lon protease. Finally, the effects of mutations deficient in these proteases were assessed on production of several heterologous gene products from Pyrococcus horikoshii and Geobacillus stearothermophilus. It was shown that TTC0746 mutation was more effective in improving production than the other two mutations, especially for production of P. horikoshii alpha-mannosidase and G. stearothermophilus alpha-amylase, indicating that the TTC0746 mutant of T. thermophilus HB27 may be useful for production of heterologous proteins from thermophiles and hyperthermophiles. PMID:18157502

  1. Mobilization of the genetically engineered plasmid pHSV106 from Escherichia coli HB101(pHSV106) to Enterobacter cloacae in drinking water.

    PubMed Central

    Sandt, C H; Herson, D S

    1991-01-01

    We have used triparental matings to demonstrate transfer (mobilization) of the nonconjugative genetically engineered plasmid pHSV106, which contains the thymidine kinase gene of herpes simplex virus cloned into pBR322, from Escherichia coli HB101 to an environmental isolate of Enterobacter cloacae in sterile drinking water. This is the first demonstration of a two-step mobilization of a genetically engineered plasmid in any type of fresh water, including drinking water. Transfer was mediated by R plasmid R100-1 of E. coli ED2149(R100-1). Matings in drinking water at 15, 25, and 35 degrees C yielded recombinants, the number of which increased with increasing temperature. Numbers of recombinants obtained were 2 orders of magnitude lower than those obtained from matings in Trypticase soy broth. High concentrations of parental organisms (2.6 x 10(8) to 2.0 x 10(9) CFU/ml) were required. During 1 week of incubation in drinking water, number of parental organisms and recombinants resulting from mobilization remained constant in the absence of indigenous organisms and declined in their presence. Using oligonucleotide probes for the cloned foreign DNA (thymidine kinase gene) and plasmid vector DNA (ampicillin resistance gene), we demonstrated that both genes were transferred to E. cloacae in the mobilization process. In one recombinant selected for detailed study, the plasmids containing these genes differed in size from all forms of pHSV106 present in E. coli HB101(pHSV106), indicating that DNA rearrangement had occurred. This recombinant maintained its plasmids in unchanged form for 15 days in drinking water. A second rearrangement occurred during serial passage of this recombinant on selective media.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:2036007

  2. Curing the Megaplasmid pTT27 from Thermus thermophilus HB27 and Maintaining Exogenous Plasmids in the Plasmid-Free Strain

    PubMed Central

    Tomita, Masaru; Itaya, Mitsuhiro

    2015-01-01

    Stepwise deletions in the only plasmid in Thermus thermophilus HB27, megaplasmid pTT27, showed that two distantly located loci were important for maintenance of the plasmid. One is a minimum replicon including one gene, repT, coding a replication initiator, and the other encodes subunits of class I ribonucleotide reductase (RNR) for deoxynucleoside triphosphate (dNTP) synthesis. Since the initiator protein, RepT, bound to direct repeats downstream from its own gene, it was speculated that a more-downstream A+T-rich region, which was critical for replication ability, could be unwound for replication initiation. On the other hand, the class I RNR is not necessarily essential for cell growth, as evidenced by the generation of the plasmid-free strain by the loss of pTT27. However, the plasmid-free strain culture has fewer viable cells than the wild-type culture, probably due to a dNTP pool imbalance in the cell. This is because of the introduction of the class I RNR genes or the supplementation of 5′-deoxyadenosylcobalamin, which stimulated class II RNR encoded in the chromosome, resolved the decrease in the number of viable cells in the plasmid-free strain. Likewise, these treatments dramatically enhanced the efficiency of transformation by exogenous plasmids and the stability of the plasmids in the strain. Therefore, the class I RNR would enable the stable maintenance of plasmids, including pTT27, as a result of genome replication normalized by reversing the dNTP pool imbalance. The generation of this plasmid-free strain with great natural competence and its analysis in regard to exogenous plasmid maintenance will expand the availability of HB27 for thermophilic cell factories. PMID:26712540

  3. First report on rapid screening of nanomaterial-based antimicrobial agents against β-lactamase resistance using pGLO plasmid transformed Escherichia coli HB 101 K-12

    NASA Astrophysics Data System (ADS)

    Raj, M. Alpha; Muralidhar, Y.; Sravanthi, M.; Prasad, T. N. V. K. V.; Nissipriya, M.; Reddy, P. Sirisha; Neelima, T. Shoba; Reddy, G. Dilip; Adilaxmamma, K.; Kumar, P. Anand; Krishna, T. Giridhara

    2016-08-01

    Combating antibiotic resistance requires discovery of novel antimicrobials effective against resistant bacteria. Herein, we present for the first time, pGLO plasmid transformed Escherichia coli HB 101 K 12 as novel model for screening of nanomaterial-based antimicrobial agents against β-lactamase resistance. E. coli HB 101 was transformed by pGLO plasmid in the presence of calcium chloride (50 mM; pH 6.1) aided by heat shock (0-42-0 °C). The transformed bacteria were grown on Luria-Bertani agar containing ampicillin (amp) and arabinose (ara). The transformed culture was able to grow in the presence of ampicillin and also exhibited fluorescence under UV light. Both untransformed and transformed bacteria were used for screening citrate-mediated nanosilver (CNS), aloin-mediated nanosilver (ANS), 11-α-keto-boswellic acid (AKBA)-mediated nanosilver (BNS); nanozinc oxide, nanomanganese oxide (NMO) and phytochemicals such as aloin and AKBA. Minimum inhibitory concentrations (MIC) were obtained by microplate method using ρ-iodo nitro tetrazolium indicator. All the compounds were effective against transformed bacteria except NMO and AKBA. Transformed bacteria exhibited reverse cross resistance against aloin. ANS showed the highest antibacterial activity with a MIC of 0.32 ppm followed by BNS (10.32 ppm), CNS (20.64 ppm) and NZO (34.83 ppm). Thus, pGLO plasmid can be used to induce resistance against β-lactam antibiotics and the model can be used for rapid screening of new antibacterial agents effective against resistant bacteria.

  4. First report on rapid screening of nanomaterial-based antimicrobial agents against β-lactamase resistance using pGLO plasmid transformed Escherichia coli HB 101 K-12

    NASA Astrophysics Data System (ADS)

    Raj, M. Alpha; Muralidhar, Y.; Sravanthi, M.; Prasad, T. N. V. K. V.; Nissipriya, M.; Reddy, P. Sirisha; Neelima, T. Shoba; Reddy, G. Dilip; Adilaxmamma, K.; Kumar, P. Anand; Krishna, T. Giridhara

    2015-10-01

    Combating antibiotic resistance requires discovery of novel antimicrobials effective against resistant bacteria. Herein, we present for the first time, pGLO plasmid transformed Escherichia coli HB 101 K 12 as novel model for screening of nanomaterial-based antimicrobial agents against β-lactamase resistance. E. coli HB 101 was transformed by pGLO plasmid in the presence of calcium chloride (50 mM; pH 6.1) aided by heat shock (0-42-0 °C). The transformed bacteria were grown on Luria-Bertani agar containing ampicillin (amp) and arabinose (ara). The transformed culture was able to grow in the presence of ampicillin and also exhibited fluorescence under UV light. Both untransformed and transformed bacteria were used for screening citrate-mediated nanosilver (CNS), aloin-mediated nanosilver (ANS), 11-α-keto-boswellic acid (AKBA)-mediated nanosilver (BNS); nanozinc oxide, nanomanganese oxide (NMO) and phytochemicals such as aloin and AKBA. Minimum inhibitory concentrations (MIC) were obtained by microplate method using ρ-iodo nitro tetrazolium indicator. All the compounds were effective against transformed bacteria except NMO and AKBA. Transformed bacteria exhibited reverse cross resistance against aloin. ANS showed the highest antibacterial activity with a MIC of 0.32 ppm followed by BNS (10.32 ppm), CNS (20.64 ppm) and NZO (34.83 ppm). Thus, pGLO plasmid can be used to induce resistance against β-lactam antibiotics and the model can be used for rapid screening of new antibacterial agents effective against resistant bacteria.

  5. Crystallization and preliminary X-ray analysis of the oxygenase component (HpaB) of 4-hydroxyphenylacetate 3-monooxygenase from Thermus thermophilus HB8

    SciTech Connect

    Kim, Seong-Hoon; Miyatake, Hideyuki; Hisano, Tamao; Iwasaki, Wakana; Ebihara, Akio; Miki, Kunio

    2007-07-01

    Crystals of the oxygenase component (HpaB) of 4-hydroxyphenylacetate 3-monooxygenase from T. thermophilus HB8 were obtained which diffracted synchrotron X-rays to a resolution of 1.6 Å. The 4-hydroxyphenylacetate (4HPA) 3-monooxygenase enzyme catalyzes the hydroxylation of 4HPA to 3,4-dihydroxyphenylacetate in the initial step of the degradation pathway of 4HPA. This enzyme consists of two components: an oxygenase (HpaB) and a reductase (HpaC). HpaB hydroxylates 4HPA using an oxygen molecule and a reduced flavin, which is supplied by HpaC. HpaB from Thermus thermophilus HB8 was overexpressed in Escherichia coli and crystallized. Crystals of HpaB were grown in 0.4 M 1,6-hexanediol, 0.1 M sodium acetate pH 5.0 and 25%(v/v) glycerol and diffracted X-rays to a resolution of 1.60 Å. The crystals belong to the orthorhombic space group I222, with unit-cell parameters a = 91.8, b = 99.6, c = 131.1 Å. The asymmetric unit volume provides space for only one subunit of the tetrameric HpaB molecule, giving a Matthews coefficient V{sub M} of 2.8 Å{sup 3} Da{sup −1} and a solvent content of 55.1%. Platinum-derivatized crystals of HpaB were prepared by soaking native crystals in a solution containing 1 mM ammonium tetrachloroplatinate(II) for 1 d and diffracted X-rays to a resolution of 2.50 Å. MAD data were successfully collected for structural determination using these crystals.

  6. Effects of in vivo exposure to UV filters (4-MBC, OMC, BP-3, 4-HB, OC, OD-PABA) on endocrine signaling genes in the insect Chironomus riparius.

    PubMed

    Ozáez, Irene; Martínez-Guitarte, José Luis; Morcillo, Gloria

    2013-07-01

    There is increasing evidence indicating that several UV filters might have endocrine disruptive effects. Numerous studies have evaluated hormonal effects in vertebrates, mainly reporting estrogenic and androgenic activities in mammals and fishes. There is only limited knowledge about potential endocrine activity in invertebrate hormonal systems. In this work, the effects on endocrine signaling genes of six frequently used UV filters were investigated in Chironomus riparius, a reference organism in aquatic toxicology. The UV filters studied were: octyl-p-methoxycinnamate (OMC) also called 2-ethylhexyl-4-methoxycinnamate (EHMC); 4-methylbenzylidene camphor (4-MBC); benzophenone-3 (BP-3); 4-hidroxybenzophenone (4-HB); octocrylene (OC); and octyldimethyl-p-aminobenzoate (OD-PABA). After in vivo exposure at different dosages, expression levels of the genes coding for the ecdysone receptor (EcR), the ultraspiracle (usp, ortholog of the RXR) and the estrogen-related receptor (ERR) were quantified by Real Time PCR. The EcR gene was significantly upregulated by 4-MBC, OMC/EHMC and OD-PABA, with a dose-related response following 24h exposure. In contrast, the benzophenones, BP-3 and 4-HB, as well as OC did not alter this gene at the same exposure conditions. The transcription profiles of the usp and ERR genes were not significantly affected, except for BP-3 that inhibited the usp gene at the highest concentration. To our knowledge, this is the first experimental evidence in invertebrates of a direct effect of UV filters on endocrine-related genes, and is consistent with the known effects on vertebrate hormonal receptor genes. The capability of 4-MBC, OMC/EHMC and OD-PABA to stimulate the expression of the ecdysone receptor, a key transcription factor for the ecdysone-genomic response in arthropods, suggests the possibility of a broad and long-term effect on this hormonal pathway. These findings strengthen the need for further research about the ecotoxicological implications

  7. Three-dimensional structure of mannosyl-3-phosphoglycerate phosphatase from Thermus thermophilus HB27: a new member of the haloalcanoic acid dehalogenase superfamily.

    PubMed

    Gonçalves, Susana; Esteves, Ana M; Santos, Helena; Borges, Nuno; Matias, Pedro M

    2011-11-01

    Mannosyl-3-phosphoglycerate phosphatase (MpgP) is a key mediator in the physiological response to thermal and osmotic stresses, catalyzing the hydrolysis of mannosyl-3-phosphoglycerate (MPG) to the final product, α-mannosylglycerate. MpgP is a metal-dependent haloalcanoic acid dehalogenase-like (HAD-like) phosphatase, preserving the catalytic motifs I-IV of the HAD core domain, and classified as a Cof-type MPGP (HAD-IIB-MPGP family; SCOP [117505]) on the basis of its C2B cap insertion module. Herein, the crystallographic structures of Thermus thermophilus HB27 MpgP in its apo form and in complex with substrates, substrate analogues, and inhibitors are reported. Two distinct enzyme conformations, open and closed, are catalytically relevant. Apo-MpgP is primarily found in the open state, while holo-MpgP, in complex with the reaction products, is found in the closed state. Enzyme activation entails a structural rearrangement of motifs I and IV with concomitant binding of the cocatalytic Mg(2+) ion. The closure motion of the C2B domain is subsequently triggered by the anchoring of the phosphoryl group to the cocatalytic metal center, and by Arg167 fixing the mannosyl moiety inside the catalytic pocket. The results led to the proposal that in T. thermophilus HB27 MpgP the phosphoryl transfer employs a concerted D(N)S(N) mechanism with assistance of proton transfer from the general acid Asp8, forming a short-lived PO(3)(-) intermediate that is attacked by a nucleophilic water molecule. These results provide new insights into a possible continuum of phosphoryl transfer mechanisms, ranging between those purely associative and dissociative, as well as a picture of the main mechanistic aspects of phosphoryl monoester transfer catalysis, common to other members of the HAD superfamily. PMID:21961705

  8. Can Trimodal Distribution of HbS Levels in Sickle Cell Traits Be Used To Predict the Associated Alpha-Thalassemia For Screening Cases in Central India?

    PubMed Central

    WARPE, BM; SHRIKHANDE, AV; POFLEE, SV

    2016-01-01

    Background: Until now, trimodal distribution of HbS has been seen by six different studies in the world when associated with alpha-thalassemia with confirmation by corresponding alpha-genotyping studies. The RBC indices reduce as alpha-globin genes reduce in sickle cell trait (SCT) patients, which decreases the extent of intra-vascular sickling and thus betters the clinical course of the patients. This is a pioneer study conducted on Central Indian poor population to use the already proven six studies to screen associated alpha-thalassemia in SCT patients thus, circumventing the much costlier alpha-genotyping studies. Moreover, it aimed to study the haematological parameters in such cases. Methods: The study was performed at RHDMC, IGGMC, Nagpur, India from 2003 to 2012. The sample population was suspected cases of haemolytic anaemia. CBC and RBC indices were obtained by a cell analyzer. The sickle solubility test positively screened cases were confirmed by agar-gel haemoglobin electrophoresis at pH 8.6. Finally, quantitative assessment of haemoglobin variants was performed by HPLC. Results: Out of total 5819 cases over ten years, 933 cases were sickle heterozygotes. Overall, 180/933 subjects were predicted to be homozygous alpha-thalassemia and 338/933 were heterozygous alpha-thalassemia, based on trimodal distribution of HbS. Conclusion: Genotyping is costlier for majority of the poor non-affording patients in Indian government set-ups, so this study is suitable to screen for associated alpha-thalassemia in SCT patients. PMID:27499774

  9. Infrared studies of molecular shocks in the supernova remnant HB 21: II. Thermal admixture of shocked H2 gas in the south

    NASA Astrophysics Data System (ADS)

    Shinn, Jong-Ho; Koo, Bon-Chul; Burton, Michael; Lee, Ho-Gyu; Moon, Dae-Sik

    2010-02-01

    We present near- and mid-infrared observations on the shock-cloud interaction region in the southern part of the supernova remnant HB 21, performed with the InfraRed Camera (IRC) aboard AKARI satellite and the Wide InfraRed Camera (WIRC) at the Palomar 5 m telescope. The IRC 4 μm (N4), 7 μm (S7), and 11 μm (S11) band images and the WIRC Hυ=1→0S(1) 2.12 μm image show similar diffuse features, around a shocked CO cloud. We analyzed the emission through comparison with the H2 line emission of several shock models. The IRC colors are well explained by the thermal admixture model of H2 gas - whose infinitesimal H2 column density has a power-law relation with the temperature T, dN˜T-dT - with n(H)˜3.9×104cm-3,b˜4.2, and N(H;T>100K)˜2.8×1021cm-2. We interpreted these parameters with several different pictures of the shock-cloud interactions - multiple planar C-shocks, bow shocks, and shocked clumps - and discussed their weaknesses and strengths. The observed Hυ=1→0S(1) intensity is four times greater than the prediction from the power-law admixture model, the same tendency as found in the northern part of HB 21 (Paper I). We also explored the limitation of the thermal admixture model with respect to the derived model parameters.

  10. Hb F-Avellino [(G)γ41(C7)Phe → Leu; HBG2: c.124 T > C]: A New Hemoglobin Variant Observed In A Healthy Newborn.

    PubMed

    Pirastru, Monica; Mereu, Paolo; Trova, Sandro; Masala, Bruno; Manca, Laura

    2016-01-01

    Here we describe Hb F-Avellino [(G)γ41(C7)Phe → Leu; HBG2: c.124 T > C], a new hemoglobin (Hb) variant observed in a healthy newborn. The proband's hemolysate was found to be mildly unstable by the isopropanol test. The occurrence of the variant was assessed by both chromatographic and electrophoretic methods. DNA sequencing analysis of the (G)γ gene showed a T to C transition at codon 41 (TTC > CTC) corresponding to the Phe → Leu substitution. Normal functional properties have been hypothesized. PMID:26573261

  11. Hb Cambridge-MA [β144(HC1)-β146(HC3)Lys-Tyr-His→0 (HBB c.433 A>T)]: a new high oxygen affinity variant.

    PubMed

    Oliveira, Jennifer L; Swanson, Kenneth; Wendt, Patricia; Caughey, Thomas D; Hoyer, James D

    2010-01-01

    A new β hemoglobin (Hb) variant, Hb Cambridge-MA [β144(HC1)β146(HC3)Lys-Tyr-His→0 (AAG>TAG) (HGVS: HBB c.433 A>T] is described. The variant was characterized by high performance liquid chromatography (HPLC), alkaline, acid, globin chain and capillary electrophoresis, isoelectric focusing (IEF), heat and isopropanol stability, p50 analyses, intact globin mass spectrometry (MS) and DNA sequencing. The new variant shows high oxygen (O₂) affinity and is associated with mild polycythemia. PMID:21077764

  12. Ethnic differences in cross-sectional associations between impaired glucose regulation, identified by oral glucose tolerance test or HbA1c values, and cardiovascular disease in a cohort of European and South Asian origin

    PubMed Central

    Eastwood, S. V.; Tillin, T.; Mayet, J.; Shibata, D. K.; Wright, A.; Heasman, J.; Beauchamp, N.; Forouhi, N. G.; Hughes, A. D.; Chaturvedi, N.

    2015-01-01

    Aims We contrasted impaired glucose regulation (prediabetes) prevalence, defined according to oral glucose tolerance test or HbA1c values, and studied cross-sectional associations between prediabetes and subclinical/clinical cardiovascular disease (CVD) in a cohort of European and South-Asian origin. Methods For 682 European and 520 South-Asian men and women, aged 58–85 years, glycaemic status was determined by oral glucose tolerance test or HbA1c thresholds. Questionnaires, record review, coronary artery calcification scores and cerebral magnetic resonance imaging established clinical plus subclinical coronary heart and cerebrovascular disease. Results Prediabetes was more prevalent in South Asian participants when defined by HbA1c rather than by oral glucose tolerance test criteria. Accounting for age, sex, smoking, systolic blood pressure, triglycerides and waist–hip ratio, prediabetes was associated with coronary heart disease and cerebrovascular disease in European participants, most obviously when defined by HbA1c rather than by oral glucose tolerance test [odds ratios for HbA1c-defined prediabetes 1.60 (95% CI 1.07, 2.39) for coronary heart disease and 1.57 (95% CI 1.00, 2.51) for cerebrovascular disease]. By contrast, non-significant associations were present between oral glucose tolerance test-defined prediabetes only and coronary heart disease [odds ratio 1.41 (95% CI 0.84, 2.36)] and HbA1c-defined prediabetes only and cerebrovascular disease [odds ratio 1.39 (95% CI 0.69, 2.78)] in South Asian participants. Prediabetes defined by HbA1c or oral glucose tolerance test criteria was associated with cardiovascular disease (defined as coronary heart and/or cerebrovascular disease) in Europeans [odds ratio 1.95 (95% CI 1.31, 2.91) for HbA1c prediabetes criteria] but not in South Asian participants [odds ratio 1.00 (95% CI 0.62, 2.66); ethnicity interaction P=0.04]. Conclusions Prediabetes appeared to be less associated with cardiovascular disease in the

  13. The Complete Sequences and Ecological Roles of Two IncP-1β Plasmids, pHB44 and pBS64, Isolated from the Mycosphere of Laccaria proxima

    PubMed Central

    Zhang, Miaozhi; Brons, Jolanda K.; van Elsas, Jan Dirk

    2016-01-01

    Two novel plasmids, coined pHB44 and pBS64, were recently found in Variovorax paradoxus strains HB44 and BS64 isolated from the mycosphere of Laccaria proxima, on two different sampling occasions. We here describe the full sequences of pHB44 and pBS64 and establish their evolutionary placement and ecological function. Both plasmids, unique for mycospheric V. paradoxus, were around 58 kb in size. They possessed, in a very similar fashion, three main plasmid backbone regions, which were predicted to be involved in plasmid replication, central control of maintenance, and conjugational transfer. Phylogenetic inference on the basis of seven selected and concatenated plasmid backbone genes provided solid evidence for the placement of the two plasmids in the IncP-1β1 group, with the recently isolated IncP-1β1 plasmid pMBUI8 as the closest relative. A comparative analysis of the sequences present in each of the recombinational hot spots (RHS) I to III across plasmids pHB44, pBS64, and pMBUI8 revealed the insertions found in plasmids pHB44 and pBS64 to be different from those of pMBUI8. Whereas, in the former two plasmids, RHS I and III were devoid of any major inserts, their RHS II regions contained inserts of 15,043 (pHB44) and 16,406 kb (pBS64), against about 9,3 kb for pMBUI8. Interestingly, these regions were highly similar across plasmids pHB44 and pBS64, and differed from that of pMBUI8. Closer inspection revealed the insert in the former plasmids to contain, next to transposases, an “mmf” gene cassette previously reported to encode metal “responsiveness” in the PromA plasmid pMOL98. Whereas the plasmid pHB44 RHS II contained the canonical mmf sequence, that in pBS64 contained, in addition, a “two-gene duplicated region” flanking the mmf C2 gene. In vitro experiments on the growth and survival of strains with or without plasmid pHB44 suggested this plasmid was involved in the binding and import of Fe3+ as well as V3+ ions into the host cells, thus

  14. A Novel Heme Pocket Hemoglobin Variant Associated with Normal Hematology: Hb Zara or α91(FG3)Leu→Ile (α2) (HBA2: c.274C > A).

    PubMed

    Trova, Sandro; Mereu, Paolo; Decandia, Luca; Cocco, Elena; Masala, Bruno; Manca, Laura; Pirastru, Monica

    2015-01-01

    We report a new hemoglobin (Hb) variant on the HBA2 gene, Hb Zara [α91(FG3)Leu→Ile (α2); HBA2: c.274C > A], which was found in a Caucasian man from Croatia. It was observed by routine cation exchange chromatography as an abnormal 21.8% fraction overlapping Hb A2, and associated with normal hematology. It was slightly unstable by the standard isopropanol precipitation test. DNA analysis revealed the CTT > ATT mutation at codon 91 on an α2 gene of a normal α-globin gene arrangement. This new variant represents the sixth described mutation at codon α91 and fourth on the α2 locus. As a result of the slight instability due to the significant role of the α91 residue in the α1β2 contact, the level of the Hb Zara variant was lower than levels observed for several stable variants codified by the α2 locus. PMID:26291971

  15. Synthesis, characterizations, and biocompatibility of block poly(ester-urethane)s based on biodegradable poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P3/4HB) and poly(ε-caprolactone).

    PubMed

    Qiu, Handi; Li, Dandan; Chen, Xi; Fan, Kaiyan; Ou, Wenfeng; Chen, Kevin C; Xu, Kaitian

    2013-01-01

    A type of block poly(ester-urethane)s (abbreviated as PUBC) based on bacterial copolyester poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P3/4HB) and biodegradable poly(ε-caprolactone) (PCL) was synthesized by melting polymerization using 1,6-hexamethylene diisocyanate (HDI) as the coupling agent, with different 3HB, 4HB and PCL contents and segment lengths. Stannous octanoate (Sn(Oct)(2)) was used as catalyst. The chemical structure, molecular weight and thermal property were characterized by (1)H NMR, FTIR GPC, DSC and TGA. DSC analysis revealed that the PUBC polyurethanes exhibit amorphous to semi-crystalline (20.9% crystallinity degree) with T(g) range from -39.7 to -21.5 °C. The hydrophilicity was investigated by static contact angle of deionized water and CH(2)I(2). The obtained PUBCs are hydrophobic (water contact angle 73.7-90.2°). Platelet adhesion study and plasma recalcification time revealed that the block polyurethanes possess hemastasis ability. CCK-8 assay illuminated that the no cytotoxic polyurethanes maintain rat aortic smooth muscle cells (RaSMCs) good viability. It was found that the 4HB content in the materials is an important factor to affect the sustainable cell viability. PMID:22826204

  16. A new hemoglobin variant: Hb Meylan [β73(E17)Asp → Phe; HBB: c.220G>T; c.221A>T] with a double base mutation at the same codon.

    PubMed

    Renoux, Céline; Feray, Cécile; Joly, Philippe; Zanella-Cleon, Isabelle; Garcia, Caroline; Lacan, Philippe; Couprie, Nicole; Francina, Alain

    2015-01-01

    We report a new β-globin chain variant: Hb Meylan [β73(E17)Asp → Phe; HBB: c.220G>T; c.221A>T]. The new variant results from a double nucleotide mutation at the same codon. The possible molecular mechanisms are discussed. PMID:25476778

  17. Serous carcinomatous component championed by heparin-binding EGF-like growth factor (HB-EGF) predisposing to metastasis and recurrence in stage I uterine malignant mixed mullerian tumor.

    PubMed

    Zhang, Lei; Shimizu, David; Killeen, Jeffrey L; Honda, Stacey A; Lu, Di; Stanoyevitch, Alexander; Lin, Fritz; Wang, Beverly; Monuki, Edwin S; Carbone, Michele

    2016-07-01

    The stage I uterine malignant mixed mullerian tumor (MMMT) shows different potential for progression. We reason that MMMTs with high-grade carcinomatous component and positivity for HB-EGF are prone to recurrence/metastasis in the early stage. A retrospective clinical and histopathologic review with immunohistochemical staining for HB-EGF, EGFR, and integrin-α5 was performed for 62 surgically staged MMMT cases. Recurrence/metastasis (RM) is 6/18 (33%) in stage I disease. Of all the clinicopathologic variables and biomarkers analyzed for stage I MMMT, serous carcinomatous component (83% [5/6] versus 17% [1/12], P = .0015) and HB-EGF expression (100% [6/6] versus 50% [6/12], P=.0339) were significantly different between groups with RM and without RM. The presence of serous carcinoma in all stages was 83% (5/6) in stage I with RM, 8% (1/12) in stage I without RM, 20% (1/5) in stage II, 36.4% (8/22) in stage III and 64.7% (11/17) in stage IV; this was paralleled by HB-EGF expression of 100% (6/6), 50% (6/12), 40% (2/5), 50% (11/22) and 71% (12/17) with a correlation coefficient r=0.9131 (P=.027). HB-EGF and integrin-α5 were highly expressed in MMMTs bearing serous carcinoma component, compared to endometrioid and unclassifiable/miscellaneous subtypes (84.6%/47.6%/33.3%, P=.025 for HB-EGF; and 61.5%/42.9%/20.0%, P=.021 for integrin-α5). The EGFR positivity was comparable among the three subtypes (48.1%, 47.6% and 26.7%, P=.326). This study indicates that serous carcinomatous component championed by expression of HB-EGF predisposes to recurrence/metastasis in stage I MMMT. This process might involve integrin-α5 and does not seem to require overexpression of EGFR. Further study is required. PMID:26980026

  18. Identification of heparin-binding EGF-like growth factor (HB-EGF) as a biomarker for lysophosphatidic acid receptor type 1 (LPA1) activation in human breast and prostate cancers.

    PubMed

    David, Marion; Sahay, Debashish; Mege, Florence; Descotes, Françoise; Leblanc, Raphaël; Ribeiro, Johnny; Clézardin, Philippe; Peyruchaud, Olivier

    2014-01-01

    Lysophosphatidic acid (LPA) is a natural bioactive lipid with growth factor-like functions due to activation of a series of six G protein-coupled receptors (LPA₁₋₆). LPA receptor type 1 (LPA₁) signaling influences the pathophysiology of many diseases including cancer, obesity, rheumatoid arthritis, as well as lung, liver and kidney fibrosis. Therefore, LPA₁ is an attractive therapeutic target. However, most mammalian cells co-express multiple LPA receptors whose co-activation impairs the validation of target inhibition in patients because of missing LPA receptor-specific biomarkers. LPA₁ is known to induce IL-6 and IL-8 secretion, as also do LPA₂ and LPA₃. In this work, we first determined the LPA induced early-gene expression profile in three unrelated human cancer cell lines expressing different patterns of LPA receptors (PC3: LPA₁,₂,₆; MDA-MB-231: LPA1,2; MCF-7: LPA₂,₆). Among the set of genes upregulated by LPA only in LPA₁-expressing cells, we validated by QPCR and ELISA that upregulation of heparin-binding EGF-like growth factor (HB-EGF) was inhibited by LPA₁-₃ antagonists (Ki16425, Debio0719). Upregulation and downregulation of HB-EGF mRNA was confirmed in vitro in human MDA-B02 breast cancer cells stably overexpressing LPA₁ (MDA-B02/LPA₁) and downregulated for LPA₁ (MDA-B02/shLPA1), respectively. At a clinical level, we quantified the expression of LPA₁ and HB-EGF by QPCR in primary tumors of a cohort of 234 breast cancer patients and found a significantly higher expression of HB-EGF in breast tumors expressing high levels of LPA₁. We also generated human xenograph prostate tumors in mice injected with PC3 cells and found that a five-day treatment with Ki16425 significantly decreased both HB-EGF mRNA expression at the primary tumor site and circulating human HB-EGF concentrations in serum. All together our results demonstrate that HB-EGF is a new and relevant biomarker with potentially high value in quantifying LPA

  19. Gene-Silencing-Induced Changes in Carbohydrate Conformation in Relation to Bioenergy Value and Carbohydrate Subfractions in Modeled Plant (Medicago sativa) with Down-Regulation of HB12 and TT8 Transcription Factors.

    PubMed

    Li, Xinxin; Hannoufa, Abdelali; Zhang, Yonggen; Yu, Peiqiang

    2016-01-01

    Gene silencing with RNA interference (RNAi) technology may be capable of modifying internal structure at a molecular level. This structural modification could affect biofunctions in terms of biodegradation, biochemical metabolism, and bioactive compound availability. The objectives of this study were to (1) Detect gene silencing-induced changes in carbohydrate molecular structure in an alfalfa forage (Medicago sativa spp. sativa: alfalfa) with down-regulation of genes that encode transcription factors TT8 and HB12; (2) Determine gene silencing-induced changes in nutrient bioutilization and bioavailability in the alfalfa forage (Medicago sativa); and (3) Quantify the correlation between gene silencing-induced molecular structure changes and the nutrient bioutilization and bioavailability in animals of ruminants. The experimental treatments included: T1 = Non-transgenic and no-gene silenced alfalfa forage (code "NT"); T2 = HB12-RNAi forage with HB12 gene down regulation (code "HB12"); T3 = TT8-RNAi forage with TT8 gene down regulation (code "TT8"). The HB12 and TT8 gene silencing-induced molecular structure changes were determined by non-invasive and non-destructive advanced molecular spectroscopy in a middle infrared radiation region that focused on structural, non-structural and total carbohydrate compounds. The nutrient bioutilization and bioavailability of the modified forage were determined using NRC-2001 system in terms of total digestive nutrient (TDN), truly digestible fiber (tdNDF), non-fiber carbohydrate (tdNDF), fatty acid (tdFA), crude protein (tdCP) and bioenergy profiles (digestible energy, metabolizable energy, net energy) for ruminants. The carbohydrate subfractions were evaluated using the updated CNCPS 6.0 system. The results showed that gene silencing significantly affected tdNFC (42.3 (NT) vs. 38.7 (HB12) vs. 37.4% Dry Matter (TT8); p = 0.016) and tdCP (20.8 (NT) vs. 19.4 (HB12) vs. 22.3% DM (TT8); p = 0.009). The gene-silencing also affected

  20. Gene-Silencing-Induced Changes in Carbohydrate Conformation in Relation to Bioenergy Value and Carbohydrate Subfractions in Modeled Plant (Medicago sativa) with Down-Regulation of HB12 and TT8 Transcription Factors

    PubMed Central

    Li, Xinxin; Hannoufa, Abdelali; Zhang, Yonggen; Yu, Peiqiang

    2016-01-01

    Gene silencing with RNA interference (RNAi) technology may be capable of modifying internal structure at a molecular level. This structural modification could affect biofunctions in terms of biodegradation, biochemical metabolism, and bioactive compound availability. The objectives of this study were to (1) Detect gene silencing-induced changes in carbohydrate molecular structure in an alfalfa forage (Medicago sativa spp. sativa: alfalfa) with down-regulation of genes that encode transcription factors TT8 and HB12; (2) Determine gene silencing-induced changes in nutrient bioutilization and bioavailability in the alfalfa forage (Medicago sativa); and (3) Quantify the correlation between gene silencing-induced molecular structure changes and the nutrient bioutilization and bioavailability in animals of ruminants. The experimental treatments included: T1 = Non-transgenic and no-gene silenced alfalfa forage (code “NT”); T2 = HB12-RNAi forage with HB12 gene down regulation (code “HB12”); T3 = TT8-RNAi forage with TT8 gene down regulation (code “TT8”). The HB12 and TT8 gene silencing-induced molecular structure changes were determined by non-invasive and non-destructive advanced molecular spectroscopy in a middle infrared radiation region that focused on structural, non-structural and total carbohydrate compounds. The nutrient bioutilization and bioavailability of the modified forage were determined using NRC-2001 system in terms of total digestive nutrient (TDN), truly digestible fiber (tdNDF), non-fiber carbohydrate (tdNDF), fatty acid (tdFA), crude protein (tdCP) and bioenergy profiles (digestible energy, metabolizable energy, net energy) for ruminants. The carbohydrate subfractions were evaluated using the updated CNCPS 6.0 system. The results showed that gene silencing significantly affected tdNFC (42.3 (NT) vs. 38.7 (HB12) vs. 37.4% Dry Matter (TT8); p = 0.016) and tdCP (20.8 (NT) vs. 19.4 (HB12) vs. 22.3% DM (TT8); p = 0.009). The gene-silencing also

  1. Hb St. Jozef, A Val-->Leu N-terminal mutation leading to retention of the methionine, and partial acetylation found in the globin gene in Cis with a -alpha3.7 thalassemia deletion.

    PubMed

    Harteveld, Cornelis L; Versteegh, Florens G A; van Leer, Eduard H G; Starreveld, Jaap S; Kok, Peter J M J; van Rooijen-Nijdam, Irene; van Delft, Peter; Zanella-Cleon, Isabelle; Becchi, Michel; Wajcman, Henri; Giordano, Piero C

    2007-01-01

    We report a new hemoglobin (Hb) variant found in a 6-year-old girl of Moroccan origin, living in the Dutch city of Gouda. The child was referred because of microcytic and hypochromic parameters. A normal zinc protoporphyirin (ZPP) value excluded iron deficiency and gap-polymerase chain reaction (gap-PCR) revealed a heterozygosity for the common -alpha(3.7) thalassemia deletion, partially justifying the hematological picture. The Hb pattern on alkaline electrophoresis and capillary electrophoresis was normal, while a fraction of 9% preceding the Hb A peak, remained visible on different high performance liquid chromatography (HPLC) devices. This fraction, located in front of the Hb A peak, is usually considered as a Hb A derivate that becomes more expressed in older samples. However, the sample was freshly collected and the peak unusually evident. Therefore, direct sequencing of the alpha-globin genes was performed revealing a GTG-->CTG transversion at codon 1 of the alpha1-globin gene or of the hybrid gene. This point mutation induces a single amino acid substitution from valine to leucine. Electrospray-mass spectrometry (ES-MS) analysis revealed, in addition to this substitution, that the N-terminal methionine was retained and that about 20% of the variant was acetylated. As expected for an association with a -alpha(3.7)-thalassemia (thal) deletion, the non acetylated and acetylated abnormal alpha chain amounted to 32% of the total alpha chains. Family studies revealed that the mutated codon was located in cis of the deletion. PMID:17654068

  2. HbA1c and Risks of All-Cause and Cause-Specific Death in Subjects without Known Diabetes: A Dose-Response Meta-Analysis of Prospective Cohort Studies

    PubMed Central

    Zhong, Guo-Chao; Ye, Ming-Xin; Cheng, Jia-Hao; Zhao, Yong; Gong, Jian-Ping

    2016-01-01

    Whether HbA1c levels are associated with mortality in subjects without known diabetes remains controversial. Moreover, the shape of the dose–response relationship on this topic is unclear. Therefore, a dose–response meta-analysis was conducted. PubMed and EMBASE were searched. Summary hazard ratios (HRs) were calculated using a random-effects model. Twelve studies were included. The summary HR per 1% increase in HbA1c level was 1.03 [95% confidence interval (CI) = 1.01–1.04] for all-cause mortality, 1.05 [95% CI = 1.02–1.07) for cardiovascular disease (CVD) mortality, and 1.02 (95% CI = 0.99–1.07) for cancer mortality. After excluding subjects with undiagnosed diabetes, the aforementioned associations remained significant for CVD mortality only. After further excluding subjects with prediabetes, all aforementioned associations presented non-significance. Evidence of a non-linear association between HbA1c and mortality from all causes, CVD and cancer was found (all Pnon-linearity < 0.05). The dose–response curves were relatively flat for HbA1c less than around 5.7%, and rose steeply thereafter. In conclusion, higher HbA1c level is associated with increased mortality from all causes and CVD among subjects without known diabetes. However, this association is driven by those with undiagnosed diabetes or prediabetes. The results regarding cancer mortality should be treated with caution due to limited studies. PMID:27045572

  3. Active Well Neutron Coincidence Assays for U-235 Content in HB-Line Desicooler Repackage Campaign at the Savannah River Site

    SciTech Connect

    DEWBERRY, RAYMOND

    2004-07-15

    At HB-Line of the Savannah River Site, 4.3 kg of U-235 have been repackaged from FB-Line Desicooler material into a cement matrix in individual one-gallon paint cans for disposition as solid waste. The 4.3 kg of U-235 material were packaged into 172 paint cans with U-235 contents ranging from 8.9 g up to 32 g. Prior to transfer to the Solid Waste Facilities, verification measurements of selected cans were performed to assure valid control of the solid waste. The HB-Line-DOE Sampling Plan designated confirmatory assays, and a total of 67 paint cans were assayed to verify the contents. The Analytical Development Section of the Savannah River National Laboratory selected an active well coincidence neutron counter as the best instrument available to accomplish the assays. The instrument was set up at-line in the thermal excitation mode, and three standard samples that contained 8.9-, 28.5-, and 32.4-g of U-235 were counted for twenty hours of acquisition time each. A linear calibration based on the observed doubles rates was installed in the instrument. Subsequent verification measurements were performed on the selected samples using fifteen one-minute active acquisitions. Of the 67 samples assayed, 53 verification measurements were within the limits greater than or less than 32 per cent prescribed by the sample plan. Eleven samples had results that were biased low by as much as 95 percent, and three samples had results that were biased high and outside of the prescribed range. Because of the extremely variable nature of the cement matrix these results were not unexpected. From the observed data we were able to use the singles rates to develop a correction factor that we could apply to the doubles rates of the eleven negatively biased results that brought each verification measurement back into the prescribed range. The three samples that had large positive biases in the verification measurements were observed in the passive acquisition mode to confirm contributions

  4. Study of microdefects and their distribution in dislocation-free Si-doped HB GaAs by X-ray diffuse scattering on triple-crystal diffractometer

    NASA Astrophysics Data System (ADS)

    Charniy, L. A.; Morozov, A. N.; Bublik, V. T.; Scherbachev, K. D.; Stepantsova, I. V.; Kaganer, V. M.

    1992-03-01

    Microdefects in dislocation-free Si-doped (n = (1-3) × 10 18cm-3) HB GaAs crystals were studied by X-ray diffuse scattering measured with the help of a triple-crystal diffractometer. The intensity of the diffuse scattering as well as the isointensity contours around different reciprocal lattice points were analysed. A comparison of the measured isointensity contours with the theoretically calculated ones showed that the microdefects detected are interstitial dislocation loops with the Burgers vectors b = {1}/{2}<110 #3862;; lying in the planes #38;{110} and {111}. The mean radius of the dislocation loops R0 was determined using the wave vector q0 alpha; R-10 corresponding to the transmition point where the Huang diffuse scattering I( q) alpha q-2 ( q < q0) changed to the asymptotic scattering I( q) alpha q-4 ( q #62 q0). The analysis of a D-shaped cross-sectional (111) wafer cut from the end part of the HB ingot showed that R0 changed smoothly along the [ overline211] symmetry axis of the wafer. The highly inhomogeneous "new-moon"-like distribution of the non-dislocational etch-pits was also obtained. The maximal loop radius obtained at the edges of the wafer, R 0 = 1 μm, corresponds to the wafer area enriched with etch-pits and the minimal one, R 0 = 0.3 μm, corresponds to the bound of the new-moon-like area denuded from etch-pits. Microdefects of a new type were detected in the denuded area. These microdefects consist of nuclei, 0.1 μm in radius, and an extended atmosphere of interstitials. The minimal microdefect radius in the centre of the wafer corresponds to the maximum local value of the lattice parameter a = 5.655380 Å, and the minimum local value a = 5.65372 Å was obtained at the wafer edges enriched with microdefect-related etch-pits. Absolute X-ray diffuse intensity measurements were used for microdefect concentration determination. Normalization of I( q) was based on the comparison of the Huang intensity with the thermal diffuse scattering

  5. Clinical Severity of β-thalassaemia/Hb E Disease Is Associated with Differential Activities of the Calpain-Calpastatin Proteolytic System

    PubMed Central

    Sukati, Suriyan; Svasti, Saovaros; Stifanese, Roberto; Averna, Monica; Panutdaporn, Nantika; Penglong, Tipparat; Melloni, Edon; Fucharoen, Suthat; Katzenmeier, Gerd

    2012-01-01

    Earlier observations in the literature suggest that proteolytic degradation of excess unmatched α-globin chains reduces their accumulation and precipitation in β-thalassaemia erythroid precursor cells and have linked this proteolytic degradation to the activity of calpain protease. The aim of this study was to correlate the activity of calpain and its inhibitor, calpastatin, with different degrees of disease severity in β-thalassaemia. CD34+ cells were enriched from peripheral blood of healthy individuals (control group) and patients with mild and severe clinical presentations of β0-thalassaemia/Hb E disease. By ex vivo cultivation promoting erythroid cell differentiation for 7 days, proerythroblasts, were employed for the functional characterization of the calpain-calpastatin proteolytic system. In comparison to the control group, enzymatic activity and protein amounts of μ-calpain were found to be more than 3-fold increased in proerythroblasts from patients with mild clinical symptoms, whereas no significant difference was observed in patients with severe clinical symptoms. Furthermore, a 1.6-fold decrease of calpastatin activity and 3.2-fold accumulation of a 34 kDa calpain-mediated degradation product of calpastatin were observed in patients with mild clinical symptoms. The increased activity of calpain may be involved in the removal of excess α-globin chains contributing to a lower degree of disease severity in patients with mild clinical symptoms. PMID:22615919

  6. Optimal Conditions for Continuous Immobilization of Pseudozyma hubeiensis (Strain HB85A) Lipase by Adsorption in a Packed-Bed Reactor by Response Surface Methodology.

    PubMed

    Bussamara, Roberta; Dall'agnol, Luciane; Schrank, Augusto; Fernandes, Kátia Flávia; Vainstein, Marilene Henning

    2012-01-01

    This study aimed to develop an optimal continuous process for lipase immobilization in a bed reactor in order to investigate the possibility of large-scale production. An extracellular lipase of Pseudozyma hubeiensis (strain HB85A) was immobilized by adsorption onto a polystyrene-divinylbenzene support. Furthermore, response surface methodology (RSM) was employed to optimize enzyme immobilization and evaluate the optimum temperature and pH for free and immobilized enzyme. The optimal immobilization conditions observed were 150 min incubation time, pH 4.76, and an enzyme/support ratio of 1282 U/g support. Optimal activity temperature for free and immobilized enzyme was found to be 68°C and 52°C, respectively. Optimal activity pH for free and immobilized lipase was pH 4.6 and 6.0, respectively. Lipase immobilization resulted in improved enzyme stability in the presence of nonionic detergents, at high temperatures, at acidic and neutral pH, and at high concentrations of organic solvents such as 2-propanol, methanol, and acetone. PMID:22315670

  7. Simeprevir and Sofosbuvir Combination Treatment in a Patient with HCV Cirrhosis and HbS Beta 0-Thalassemia: Efficacy and Safety despite Baseline Hyperbilirubinemia

    PubMed Central

    Deutsch, Melanie; Georgalas, Athanasios; Poulakidas, Helias; Karnesis, Lazaros

    2016-01-01

    Hyperbilirubinemia is an adverse reaction of simeprevir (SMV). The majority of these patients were taking concurrent ribavirin presenting elevated unconjugated hyperbilirubinemia due to hemolysis. However, cases of hepatic failure with elevated bilirubin level have also been reported in patients with decompensated cirrhosis. We describe a 51-year-old female patient with HbS beta 0-thalassemia and recently diagnosed compensated cirrhosis due to chronic hepatitis C infection. Laboratory evaluation revealed total bilirubin: 2.7 mg/dL and serum HCV-RNA 137.204 IU/mL. HCV was genotyped as 4. A FibroScan revealed 35.3 kPa. She was considered as illegible for pegylated-interferon-free treatment with direct acting antivirals and a course with simeprevir and sofosbuvir (SOF) combination for twelve weeks was planned. Hyperbilirubinemia developed from the beginning with peak values during the 3rd month of treatment. However, no findings of liver decompensation were noticed. Hyperbilirubinemia was benign and fully reversible and our patient finally achieved sustained virological response 24 weeks after the end of treatment. PMID:27042368

  8. Simeprevir and Sofosbuvir Combination Treatment in a Patient with HCV Cirrhosis and HbS Beta 0-Thalassemia: Efficacy and Safety despite Baseline Hyperbilirubinemia.

    PubMed

    Papadopoulos, Nikolaos; Deutsch, Melanie; Georgalas, Athanasios; Poulakidas, Helias; Karnesis, Lazaros

    2016-01-01

    Hyperbilirubinemia is an adverse reaction of simeprevir (SMV). The majority of these patients were taking concurrent ribavirin presenting elevated unconjugated hyperbilirubinemia due to hemolysis. However, cases of hepatic failure with elevated bilirubin level have also been reported in patients with decompensated cirrhosis. We describe a 51-year-old female patient with HbS beta 0-thalassemia and recently diagnosed compensated cirrhosis due to chronic hepatitis C infection. Laboratory evaluation revealed total bilirubin: 2.7 mg/dL and serum HCV-RNA 137.204 IU/mL. HCV was genotyped as 4. A FibroScan revealed 35.3 kPa. She was considered as illegible for pegylated-interferon-free treatment with direct acting antivirals and a course with simeprevir and sofosbuvir (SOF) combination for twelve weeks was planned. Hyperbilirubinemia developed from the beginning with peak values during the 3rd month of treatment. However, no findings of liver decompensation were noticed. Hyperbilirubinemia was benign and fully reversible and our patient finally achieved sustained virological response 24 weeks after the end of treatment. PMID:27042368

  9. Differential domain accessibility to monoclonal antibodies in three different morphological assemblies built up by the S-layer protein of Thermus thermophilus HB8.

    PubMed Central

    Castón, J R; Olabarría, G; Lasa, I; Carrascosa, J L; Berenguer, J

    1996-01-01

    A collection of 27 monoclonal antibodies (MAbs) against the S-layer protein (P100) of Thermus thermophilus HB8 has been obtained. They have been classified according to their ability to recognize S-layer regions expressed in E. coli from plasmids containing different fragments of its coding gene, slpA. The accessibility of the binding sites in hexagonal, trigonal, or tetragonal assemblies of P100 was analyzed by enzyme-linked immunosorbent assays with six of these MAbs and their respective Fab fragments. When packed hexagonally as the native S-layer (S1 assemblies), only a small region located near the amino terminus of the P1OO was accessible. However, when P1OO was assembled into trigonal (pS2 assemblies) or tetragonal (S2 assemblies) arrays, most of the protein domains analyzed were easily detected, thus suggesting that P1OO is assembled in S2 and pS2 in a similar way and that these two arrangements are quite different from the S1 assembly. Relationships between accessibility and sequence predictions are discussed. PMID:8655568

  10. Optimal Conditions for Continuous Immobilization of Pseudozyma hubeiensis (Strain HB85A) Lipase by Adsorption in a Packed-Bed Reactor by Response Surface Methodology

    PubMed Central

    Bussamara, Roberta; Dall'Agnol, Luciane; Schrank, Augusto; Fernandes, Kátia Flávia; Vainstein, Marilene Henning

    2012-01-01

    This study aimed to develop an optimal continuous process for lipase immobilization in a bed reactor in order to investigate the possibility of large-scale production. An extracellular lipase of Pseudozyma hubeiensis (strain HB85A) was immobilized by adsorption onto a polystyrene-divinylbenzene support. Furthermore, response surface methodology (RSM) was employed to optimize enzyme immobilization and evaluate the optimum temperature and pH for free and immobilized enzyme. The optimal immobilization conditions observed were 150 min incubation time, pH 4.76, and an enzyme/support ratio of 1282 U/g support. Optimal activity temperature for free and immobilized enzyme was found to be 68°C and 52°C, respectively. Optimal activity pH for free and immobilized lipase was pH 4.6 and 6.0, respectively. Lipase immobilization resulted in improved enzyme stability in the presence of nonionic detergents, at high temperatures, at acidic and neutral pH, and at high concentrations of organic solvents such as 2-propanol, methanol, and acetone. PMID:22315670

  11. Identification of the -α(2.4) Deletion in One Family and in One Hb H Disease Patient in Guangxi, People's Republic of China.

    PubMed

    Pang, Wanrong; Sun, Lei; Long, Ju; Weng, Xunjin; Ye, Xuehe; Wang, Junjie; Liao, Yan; Tang, Weijun; Fan, Zuqian; Wu, Suping; Song, Chuanlu; Wei, Xiaoying; Zhang, Chenghong

    2016-06-01

    The 2.4 kb (or -α(2.4)) deletion in the α-globin gene cluster (NG_000006.1) is an α(+)-thalassemia (α(+)-thal) allele. The molecular basis of -α(2.4) is a deletion from 36860 to 39251 of the α-globin gene cluster. It was reported by three research groups in 2005, 2012 and 2014, respectively. In routine thalassemia screening studies by this research group, we found an individual with the -α(2.4)/αα genotype and an Hb H (β4) disease patient whose genotype was - -(SEA)/-α(2.4). Samples from the parents of the carrier of the -α(2.4)/αα genotype were collected to perform pedigree analysis, and the proband's mother's genotype was diagnosed to be - -(SEA)/-α(2.4). The research revealed that the -α(2.4) allele exists in the population of southern Guangxi, People's Republic of China. PMID:26984456

  12. Intake of Vitamin and Mineral Supplements and Longitudinal Association with HbA1c Levels in the General Non-Diabetic Population—Results from the MONICA/KORA S3/F3 Study

    PubMed Central

    Schwab, Sigrid; Zierer, Astrid; Heier, Margit; Fischer, Beate; Huth, Cornelia; Baumert, Jens; Meisinger, Christa; Peters, Annette; Thorand, Barbara

    2015-01-01

    Background Lower levels of hemoglobin A1c (HbA1c) are associated with a decreased risk of cardiovascular complications in diabetic and non-diabetic individuals. The aim of the study was to longitudinally investigate the association between the use of 11 vitamins and minerals (vitamins E, C, D, B1, folic acid, carotenoids, calcium, magnesium, zinc, iron, and selenium) and change in HbA1c levels over 10 years in non-diabetic individuals drawn from the general population. Methods Baseline data were available from 4447 subjects included in the population-based “Monitoring of Trends and Determinants in Cardiovascular Diseases” (MONICA) Augsburg S3 survey (1994/95). Follow-up data were derived from 2774 participants in the follow-up survey named “Cooperative Health Research in the Region of Augsburg” (KORA) F3 (2004/05). Vitamin/mineral intake from supplements and medications was assessed in a personal interview, where participants were asked to bring product packages of preparations that had been ingested during the last 7 days prior to the examination. Associations between regular vitamin/mineral intake amounts and HbA1c levels measured at baseline and follow-up were investigated using generalized estimating equation models. For carotenoids, analyses were stratified by smoking status. Results None of the investigated nutrients except for carotenoids was significantly associated with changes in HbA1c levels after 10 years. Regular intake of carotenoids from supplements and medications in amounts > 6.8mg/d (upper tertile) was associated with an absolute –0.26% (95% CI: –0.43 to –0.08) lower increase in HbA1c levels compared with no intake of carotenoids. An inverse association was observed in those who never smoked but not in (former) smokers. Conclusion Larger prospective and intervention studies in non-diabetic/non-smoking individuals are needed to confirm the results and to assess whether the observed associations between carotenoid intake and change in

  13. slpM, a gene coding for an "S-layer-like array" overexpressed in S-layer mutants of Thermus thermophilus HB8.

    PubMed Central

    Olabarría, G; Fernández-Herrero, L A; Carrascosa, J L; Berenguer, J

    1996-01-01

    S-layer deletion mutants of Thermus thermophilus HB8 overproduce a regular array which surrounds groups of several cells. Averages of two-dimensional projections revealed a detailed architecture similar in general morphology and unit cell dimensions to that of the S-layer but having a different mass distribution. The structural components of these "S-layer-like arrays" are a group of three proteins of 52 (P52), 50 (P50), and 36 (P36) kDa, which are overexpressed in S-layer mutants. These three proteins specifically bind antibodies against P52, suggesting that the smaller proteins correspond to fragments derived from P52. This hypothesis was demonstrated by the identity of the trypsin digestion products of P52 and P50. The gene slpM, responsible for the synthesis of P52, was cloned by using synthetic oligonucleotides designed from partial amino acid sequences of P52 and P50. When slpM was expressed in Escherichia coli, proteins specifically recognized by anti-P52 antiserum whose electrophoretic mobilities were similar to those of P52 and P36 were detected. The sequence of slpM revealed the existence of an open reading frame in which the amino termini of P52, P50, and P36 were identified. The unprocessed product of slpM is a 469-amino-acid-long polypeptide whose theoretical M(r) (52,131) was in good agreement with the electrophoretic mobility of P52. The properties deduced for the product of slpM are very different from those of any S-layer protein so far sequenced. The possible roles of SlpM in wild-type cells are discussed. PMID:8550453

  14. On the Thermus thermophilus HB8 potential pathogenicity triggered from rhamnolipids secretion: morphological alterations and cytotoxicity induced on fibroblastic cell line.

    PubMed

    Pantazaki, A A; Choli-Papadopoulou, T

    2012-05-01

    A limited number of bacterial strains usually grown under nutrient limitation secrete rhamnolipids (RLs), which are recorded as virulence factors that are implicated in the pathogenicity of a microorganism. The non-pathogenic T. thermophilus HB8 produces extracellular rhamnolipids (TthRLs) under defined cultivation conditions using sunflower seed oil and sodium gluconate as carbon sources. In particular, the secreted TthRLs have been isolated, purified and identified with ATR-FTIR. Their effects on the cells' viability were examined when they were supplemented in a culture of human skin fibroblasts. Purified TthRLs triggered a sequence of rapid and pronounced morphological alterations characterized by transformation of fibroblast shape from polygonal to fusiform; retraction with cytoplasm condensation, rounding up, distortion of nuclei and loss of lamellar processes, and finally disruption of membrane. The addition of TthRLs in the cultured fibroblasts caused cytotoxicity, in contrast to that of rhamnose that stimulated viability, as it was assessed by MTT test. These results revealed that among the constituents of RLs that are implicated in the cytotoxicity, it has to be attributed to the lipidic chain variation and not to the carbohydrate part. TthRLs cytotoxicity on fibroblasts is comparable, and provoked similar effects, to that caused by saponin white, a known surfactant. TthRLs secretion might be a crucial point for the transformation of a non-pathogenic bacterium to a pathogenic one under certain environmental conditions favoring their secretion. RLs secretion in the microorganism's world might be a general route for the passage in the pathogenicity to ensure their survival under nutrient limitation conditions. PMID:21611776

  15. Presence of immunoglobulins, C3 and cytolytic C5b-9 complement components on the surface of erythrocytes from patients with beta-thalassaemia/HbE disease.

    PubMed

    Malasit, P; Mahasorn, W; Mongkolsapaya, J; Singhathong, B; Fucharoen, S; Wasi, P; Bhakdi, S

    1997-03-01

    The occurrence of IgG, IgM, IgA, C3 and C5b-9 complement complexes on erythrocytes from 43 patients with beta-thalassaemia HbE disease was investigated. Indirect immunoradiometric assays using radioiodinated protein A were employed to quantify the individual components. We confirmed that circulating erythrocytes from thalassaemic patients contained elevated amounts of IgG, and small but significant amounts of C3. In addition, small but significant amounts of C5b-9 were detected. Levels of cell-bound IgG, C3 and C5b-9 were higher in splenectomized versus non-splenectomized patients. The presence of C5b-9 on circulating cells from five splenectomized patients was confirmed by an ELISA employing a monoclonal antibody specific for a C5b-9 neoantigen. When C5b-9 positive cells from two patients were solubilized with detergent and subjected to sucrose density gradient centrifugation, the terminal complexes sedimented as 25-40S macromolecules, thus behaving as membrane C5b-9 complexes. The presence of C8 and C9 in these high molecular weight fractions was directly demonstrated by Western blotting. These results constitute the first demonstration that circulating diseased erythrocytes may carry low numbers of potentially cytolytic C5b-9 complement complexes which may be partly responsible for the known ionic disturbances found in thalassaemic cells. Both bound C3 and C5b-9 could promote removal of diseased cells in the reticuloendothelial system. PMID:9054657

  16. Crystal structures of shikimate dehydrogenase AroE from Thermus thermophilus HB8 and its cofactor and substrate complexes: insights into the enzymatic mechanism.

    PubMed

    Bagautdinov, Bagautdin; Kunishima, Naoki

    2007-10-19

    Shikimate dehydrogenase (EC 1.1.1.25) catalyses the fourth step of the shikimate pathway which is required for the synthesis of the aromatic amino acids and other aromatic compounds in bacteria, microbial eukaryotes, and plants. The crystal structures of the shikimate dehydrogenase AroE from Thermus thermophilus HB8 in its ligand-free form, binary complexes with cofactor NADP+ or substrate shikimate, and the ternary complex with both NADP(H) and shikimate were determined by X-ray diffraction method at atomic resolutions. The crystals are nearly isomorphous with the asymmetric unit containing a dimer, each subunit of which has a bi-domain structure of compact alpha/beta sandwich folds. The two subunits of the enzyme display asymmetry in the crystals due to different relative orientations between the N- and C-terminal domains resulting in a slightly different closure of the interdomain clefts. NADP(H) is bound to the more closed form only. This closed conformation with apparent higher affinity to the cofactor is also observed in the unliganded crystal form, indicating that the NADP(H) binding to TtAroE may follow the selection mode where the cofactor binds to the subunit that happens to be in the closed conformation in solution. Crystal structures of the closed subunits with and without NADP(H) show no significant structural difference, suggesting that the cofactor binding to the closed subunit corresponds to the lock-and-key model in TtAroE. On the other hand, shikimate binds to both open and closed subunit conformers of both apo and NADP(H)-liganded holo enzyme forms. The ternary complex TtAroE:NADP(H):shikimate allows unambiguous visualization of the SDH permitting elucidation of the roles of conserved residues Lys64 and Asp100 in the hydride ion transfer between NADP(H) and shikimate. PMID:17825835

  17. Characterization of Hb Calvino (HBB: c.406G > A): a new silent β-globin gene variant found in coexistence with α-thalassemia in a family of African origin.

    PubMed

    Marsella, Maria; Salvagno, Gianluca; Dolcini, Bernadetta; Ferlini, Alessandra; Ravani, Anna; Harteveld, Cornelis L; Giordano, Piero C; Borgna-Pignatti, Caterina

    2014-01-01

    We report a new silent β-globin gene variant found in a family from Angola living in the north eastern Italian city of Ferrara. The probands, two young sisters, presented with hematological parameters compatible with a β-thalassemia (β-thal) minor but with normal Hb A₂ levels and normal hemoglobin (Hb) separation on high performance liquid chromatography (HPLC). Molecular analyses revealed a homozygosity for the common -α(3.7) (rightward) deletion and heterozygosity for a novel transition (GCT > ACT) at codon 135 of the β-globin gene, leading to an Ala → Thr single amino acid substitution that was inherited from the healthy father. PMID:25222042

  18. Insulin induces a transcriptional activation of epiregulin, HB-EGF and amphiregulin, by a PI3K-dependent mechanism: Identification of a specific insulin-responsive promoter element

    SciTech Connect

    Ornskov, Dorthe; Nexo, Ebba; Sorensen, Boe S. . E-mail: boess@as.aaa.dk

    2007-03-23

    Previously we have shown that insulin-stimulation of RT4 bladder cancer cells leads to increased proliferation, which require HER1 activation, and is accompanied by increased mRNA expression of the EGF-ligands heparin-binding EGF-like growth factor (HB-EGF), amphiregulin (AR), and epiregulin (EPI) [D. Ornskov, E. Nexo, B.S. Sorensen, Insulin-induced proliferation of bladder cancer cells is mediated through activation of the epidermal growth factor system, FEBS J. 273 (2006) 5479-5489]. In the present paper, we have investigated the molecular mechanism leading to this insulin-induced expression. We monitored the decay of mRNA after inhibiting transcription with Actinomycin D and demonstrated that the insulin-mediated increase was not caused by enhanced mRNA stability. In untreated cells, HB-EGF mRNA was the least stable, whereas AR and EPI mRNA decayed with slower kinetics. However, promoter analysis of HB-EGF and EPI demonstrated that insulin stimulated transcription. Studies on the EPI promoter identified the insulin-responsive element to be located in the region -564 to -365 bp. This region contains potential binding sites for the transcription factors SP1, AP1, and NF-{kappa}B. Interestingly, all three transcription factors can be activated by PI3K. We demonstrate that the insulin-induced expression of HB-EGF, AR, and EPI mRNA is completely prevented by the specific PI3K inhibitor Wortmannin, suggesting an involvement of the PI3K.

  19. Minimal impact of an iron-fortified lipid-based nutrient supplement on Hb and iron status: a randomised controlled trial in malnourished HIV-positive African adults starting antiretroviral therapy.

    PubMed

    James, Philip; Friis, Henrik; Woodd, Susannah; Rehman, Andrea M; PrayGod, George; Kelly, Paul; Koethe, John R; Filteau, Suzanne

    2015-08-14

    Anaemia, redistribution of Fe, malnutrition and heightened systemic inflammation during HIV infection confer an increased risk of morbidity and mortality in HIV patients. We analysed information on Fe status and inflammation from a randomised, double blind, controlled phase-III clinical trial in Lusaka, Zambia and Mwanza, Tanzania. Malnourished patients (n 1815) were recruited at referral to antiretroviral therapy (ART) into a two-stage nutritional rehabilitation programme, randomised to receive a lipid-based nutrient supplement with or without added micronutrients. Fe was included in the intervention arm during the second stage, given from 2 to 6 weeks post-ART. Hb, serum C-reactive protein (CRP), serum ferritin and soluble transferrin receptor (sTfR) were measured at recruitment and 6 weeks post-ART. Multivariable linear regression models were used to assess the impact of the intervention, and the effect of reducing inflammation from recruitment to week 6 on Hb and Fe status. There was no effect of the intervention on Hb, serum ferritin, sTfR or serum CRP. A one-log decrease of serum CRP from recruitment to week 6 was associated with a 1.81 g/l increase in Hb (95% CI 0.85, 2.76; P< 0.001), and a 0.11 log decrease in serum ferritin (95% CI - 0.22, 0.03; P= 0.012) from recruitment to week 6. There was no association between the change in serum CRP and the change in sTfR over the same time period (P= 0.78). In malnourished, HIV-infected adults receiving dietary Fe, a reduction in inflammation in the early ART treatment period appears to be a precondition for recovery from anaemia. PMID:26179616

  20. Impact of age, BMI and HbA1c levels on the genome-wide DNA methylation and mRNA expression patterns in human adipose tissue and identification of epigenetic biomarkers in blood.

    PubMed

    Rönn, Tina; Volkov, Petr; Gillberg, Linn; Kokosar, Milana; Perfilyev, Alexander; Jacobsen, Anna Louisa; Jørgensen, Sine W; Brøns, Charlotte; Jansson, Per-Anders; Eriksson, Karl-Fredrik; Pedersen, Oluf; Hansen, Torben; Groop, Leif; Stener-Victorin, Elisabet; Vaag, Allan; Nilsson, Emma; Ling, Charlotte

    2015-07-01

    Increased age, BMI and HbA1c levels are risk factors for several non-communicable diseases. However, the impact of these factors on the genome-wide DNA methylation pattern in human adipose tissue remains unknown. We analyzed the DNA methylation of ∼480 000 sites in human adipose tissue from 96 males and 94 females and related methylation to age, BMI and HbA1c. We also compared epigenetic signatures in adipose tissue and blood. Age was significantly associated with both altered DNA methylation and expression of 1050 genes (e.g. FHL2, NOX4 and PLG). Interestingly, many reported epigenetic biomarkers of aging in blood, including ELOVL2, FHL2, KLF14 and GLRA1, also showed significant correlations between adipose tissue DNA methylation and age in our study. The most significant association between age and adipose tissue DNA methylation was found upstream of ELOVL2. We identified 2825 genes (e.g. FTO, ITIH5, CCL18, MTCH2, IRS1 and SPP1) where both DNA methylation and expression correlated with BMI. Methylation at previously reported HIF3A sites correlated significantly with BMI in females only. HbA1c (range 28-46 mmol/mol) correlated significantly with the methylation of 711 sites, annotated to, for example, RAB37, TICAM1 and HLA-DPB1. Pathway analyses demonstrated that methylation levels associated with age and BMI are overrepresented among genes involved in cancer, type 2 diabetes and cardiovascular disease. Our results highlight the impact of age, BMI and HbA1c on epigenetic variation of candidate genes for obesity, type 2 diabetes and cancer in human adipose tissue. Importantly, we demonstrate that epigenetic biomarkers in blood can mirror age-related epigenetic signatures in target tissues for metabolic diseases such as adipose tissue. PMID:25861810

  1. Association of Exposure to Radio-Frequency Electromagnetic Field Radiation (RF-EMFR) Generated by Mobile Phone Base Stations with Glycated Hemoglobin (HbA1c) and Risk of Type 2 Diabetes Mellitus

    PubMed Central

    Meo, Sultan Ayoub; Alsubaie, Yazeed; Almubarak, Zaid; Almutawa, Hisham; AlQasem, Yazeed; Muhammed Hasanato, Rana

    2015-01-01

    Installation of mobile phone base stations in residential areas has initiated public debate about possible adverse effects on human health. This study aimed to determine the association of exposure to radio frequency electromagnetic field radiation (RF-EMFR) generated by mobile phone base stations with glycated hemoglobin (HbA1c) and occurrence of type 2 diabetes mellitus. For this study, two different elementary schools (school-1 and school-2) were selected. We recruited 159 students in total; 96 male students from school-1, with age range 12–16 years, and 63 male students with age range 12–17 years from school-2. Mobile phone base stations with towers existed about 200 m away from the school buildings. RF-EMFR was measured inside both schools. In school-1, RF-EMFR was 9.601 nW/cm2 at frequency of 925 MHz, and students had been exposed to RF-EMFR for a duration of 6 h daily, five days in a week. In school-2, RF-EMFR was 1.909 nW/cm2 at frequency of 925 MHz and students had been exposed for 6 h daily, five days in a week. 5–6 mL blood was collected from all the students and HbA1c was measured by using a Dimension Xpand Plus Integrated Chemistry System, Siemens. The mean HbA1c for the students who were exposed to high RF-EMFR was significantly higher (5.44 ± 0.22) than the mean HbA1c for the students who were exposed to low RF-EMFR (5.32 ± 0.34) (p = 0.007). Moreover, students who were exposed to high RF-EMFR generated by MPBS had a significantly higher risk of type 2 diabetes mellitus (p = 0.016) relative to their counterparts who were exposed to low RF-EMFR. It is concluded that exposure to high RF-EMFR generated by MPBS is associated with elevated levels of HbA1c and risk of type 2 diabetes mellitus. PMID:26580639

  2. Association of Exposure to Radio-Frequency Electromagnetic Field Radiation (RF-EMFR) Generated by Mobile Phone Base Stations with Glycated Hemoglobin (HbA1c) and Risk of Type 2 Diabetes Mellitus.

    PubMed

    Meo, Sultan Ayoub; Alsubaie, Yazeed; Almubarak, Zaid; Almutawa, Hisham; AlQasem, Yazeed; Hasanato, Rana Muhammed

    2015-11-01

    Installation of mobile phone base stations in residential areas has initiated public debate about possible adverse effects on human health. This study aimed to determine the association of exposure to radio frequency electromagnetic field radiation (RF-EMFR) generated by mobile phone base stations with glycated hemoglobin (HbA1c) and occurrence of type 2 diabetes mellitus. For this study, two different elementary schools (school-1 and school-2) were selected. We recruited 159 students in total; 96 male students from school-1, with age range 12-16 years, and 63 male students with age range 12-17 years from school-2. Mobile phone base stations with towers existed about 200 m away from the school buildings. RF-EMFR was measured inside both schools. In school-1, RF-EMFR was 9.601 nW/cm² at frequency of 925 MHz, and students had been exposed to RF-EMFR for a duration of 6 h daily, five days in a week. In school-2, RF-EMFR was 1.909 nW/cm² at frequency of 925 MHz and students had been exposed for 6 h daily, five days in a week. 5-6 mL blood was collected from all the students and HbA1c was measured by using a Dimension Xpand Plus Integrated Chemistry System, Siemens. The mean HbA1c for the students who were exposed to high RF-EMFR was significantly higher (5.44 ± 0.22) than the mean HbA1c for the students who were exposed to low RF-EMFR (5.32 ± 0.34) (p = 0.007). Moreover, students who were exposed to high RF-EMFR generated by MPBS had a significantly higher risk of type 2 diabetes mellitus (p = 0.016) relative to their counterparts who were exposed to low RF-EMFR. It is concluded that exposure to high RF-EMFR generated by MPBS is associated with elevated levels of HbA1c and risk of type 2 diabetes mellitus. PMID:26580639

  3. The Association between HbA1c, Fasting Glucose, 1-Hour Glucose and 2-Hour Glucose during an Oral Glucose Tolerance Test and Cardiovascular Disease in Individuals with Elevated Risk for Diabetes

    PubMed Central

    Lind, Marcus; Tuomilehto, Jaakko; Uusitupa, Matti; Nerman, Olle; Eriksson, Johan; Ilanne-Parikka, Pirjo; Keinänen-Kiukaanniemi, Sirkka; Peltonen, Markku; Pivodic, Aldina; Lindström, Jaana

    2014-01-01

    Objective To determine the association between HbA1c, fasting plasma glucose (FPG), 1-hour (1 hPG) and 2-hour (2 hPG) glucose after an oral glucose tolerance test (OGTT) and cardiovascular disease in individuals with elevated risk for diabetes. Design We studied the relationship between baseline, updated mean and updated (last) value of HbA1c, FPG, 1 hPG and 2 hPG after an oral 75 g glucose tolerance test (OGTT) and acute CVD events in 504 individuals with impaired glucose tolerance (IGT) at baseline enrolled in the Finnish Diabetes Prevention Study. Setting Follow-up of clinical trial. Participants 504 individuals with IGT were followed with yearly evaluations with OGTT, FPG and HbA1c. Main Outcome Measure Relative risk of CVD. Results Over a median follow-up of 9.0 years 34 (6.7%) participants had a CVD event, which increased to 52 (10.3%) over a median follow-up of 13.0 years when including events that occurred among participants following a diagnosis of diabetes. Updated mean HbA1c, 1 hPG and 2 hPG, HR per 1 unit SD of 1.57 (95% CI 1.16 to 2.11), p = 0.0032, 1.51 (1.03 to 2.23), p = 0.036 and 1.60 (1.10 to 2.34), p = 0.014, respectively, but not FPG (p = 0.11), were related to CVD. In analyses of the last value prior to the CVD event the same three glycaemic measurements were associated with the CVD events, with HRs per 1 unit SD of 1.45 (1.06 to 1.98), p = 0.020, 1.55 (1.04 to 2.29), p = 0.030 and 2.19 (1.51 to 3.18), p<0.0001, respectively but only 2 hPG remained significant in pairwise comparisons. Including the follow-up period after diabetes onset updated 2 hPG (p = 0.003) but not updated mean HbA1c (p = 0.08) was related to CVD. Conclusions and Relevance Current 2 hPG level in people with IGT is associated with increased risk of CVD. This supports its use in screening for prediabetes and monitoring glycaemic levels of people with prediabetes. PMID:25285769

  4. APPLICATION OF COLUMN EXTRACTION METHOD FOR IMPURITIES ANALYSIS ON HB-LINE PLUTONIUM OXIDE IN SUPPORT OF MOX FEED PRODUCT SPECIFICATIONS

    SciTech Connect

    Jones, M.; Diprete, D.; Wiedenman, B.

    2012-03-20

    The current mission at H-Canyon involves the dissolution of an Alternate Feedstocks 2 (AFS-2) inventory that contains plutonium metal. Once dissolved, HB-Line is tasked with purifying the plutonium solution via anion exchange, precipitating the Pu as oxalate, and calcining to form plutonium oxide (PuO{sub 2}). The PuO{sub 2} will provide feed product for the Mixed Oxide (MOX) Fuel Fabrication Facility, and the anion exchange raffinate will be transferred to H-Canyon. The results presented in this report document the potential success of the RE resin column extraction application on highly concentrated Pu samples to meet MOX feed product specifications. The original 'Hearts Cut' sample required a 10000x dilution to limit instrument drift on the ICP-MS method. The instrument dilution factors improved to 125x and 250x for the sample raffinate and sample eluent, respectively. As noted in the introduction, the significantly lower dilutions help to drop the total MRL for the analyte. Although the spike recoveries were half of expected in the eluent for several key elements, they were between 94-98% after Nd tracer correction. It is seen that the lower ICD limit requirements for the rare earths are attainable because of less dilution. Especially important is the extremely low Ga limit at 0.12 {mu}g/g Pu; an ICP-MS method is now available to accomplish this task on the sample raffinate. While B and V meet the column A limits, further development is needed to meet the column B limits. Even though V remained on the RE resin column, an analysis method is ready for investigation on the ICP-MS, but it does not mean that V cannot be measured on the ICP-ES at a low dilution to meet the column B limits. Furthermore, this column method can be applicable for ICP-ES as shown in Table 3-2, in that it trims the sample of Pu, decreasing and sometimes eliminating Pu spectral interferences.

  5. Stellar abundances and ages for metal-rich Milky Way globular clusters. Stellar parameters and elemental abundances for 9 HB stars in NGC 6352

    NASA Astrophysics Data System (ADS)

    Feltzing, S.; Primas, F.; Johnson, R. A.

    2009-01-01

    Context: Metal-rich globular clusters provide important tracers of the formation of our Galaxy. Moreover, and not less important, they are very important calibrators for the derivation of properties of extra-galactic metal-rich stellar populations. Nonetheless, only a few of the metal-rich globular clusters in the Milky Way have been studied using high-resolution stellar spectra to derive elemental abundances. Additionally, Rosenberg et al. identified a small group of metal-rich globular clusters that appeared to be about 2 billion years younger than the bulk of the Milky Way globular clusters. However, it is unclear if like is compared with like in this dataset as we do not know the enhancement of α-elements in the clusters and the amount of α-elements is well known to influence the derivation of ages for globular clusters. Aims: We derive elemental abundances for the metal-rich globular cluster NGC 6352 and we present our methods to be used in up-coming studies of other metal-rich globular clusters. Methods: We present a study of elemental abundances for α- and iron-peak elements for nine HB stars in the metal-rich globular cluster NGC 6352. The elemental abundances are based on high-resolution, high signal-to-noise spectra obtained with the UVES spectrograph on VLT. The elemental abundances have been derived using standard LTE calculations and stellar parameters have been derived from the spectra themselves by requiring ionizational as well as excitational equilibrium. Results: We find that NGC 6352 has [Fe/H] = -0.55, is enhanced in the α-elements to about +0.2 dex for Ca, Si, and Ti relative to Fe. For the iron-peak elements we find solar values. Based on the spectroscopically derived stellar parameters we find that an E(B-V) = 0.24 and (m-M) ≃ 14.05 better fits the data than the nominal values. An investigation of log gf-values for suitable Fe i lines lead us to the conclusion that the commonly used correction to the May et al. (1974) data should not be

  6. Exenatide once weekly improved glycaemic control, cardiometabolic risk factors and a composite index of an HbA1c < 7%, without weight gain or hypoglycaemia, over 52 weeks

    PubMed Central

    Bergenstal, R M; Li, Y; Porter, T K Booker; Weaver, C; Han, J

    2013-01-01

    Aims Type 2 diabetes mellitus (T2DM) is often associated with cardiovascular (CV) risk factors such as obesity, hypertension and dyslipidemia. The objective of this analysis was to evaluate potential effects of exenatide once weekly (ExQW), a GLP-1 receptor agonist, on glycaemic control and CV risk factors. Methods This analysis included 675 Intent-to-Treat patients with T2DM [baseline (mean ± SD) HbA1c, 8.1 ± 1.2%; fasting blood glucose (FBG), 166 ± 48 mg/dl; weight, 94.3 ± 19.4 kg; systolic/diastolic blood pressure (SBP/DBP), 129 ± 15/78 ± 9 mm Hg; total cholesterol, 178.5 ± 41.9 mg/dl; low-density lipoprotein (LDL), 100.1 ± 35.0 mg/dl; high-density lipoprotein (HDL), 44.5 ± 11.6 mg/dl; triglycerides, 155.6 ± 3.3 mg/dl; alanine aminotransferase (ALT), 32.1 ± 19.5 U/l] treated with diet and exercise alone or in combination with metformin, sulfonylurea, and/or thiazolidinedione who received 52 weeks of ExQW in four clinical trials. Results At 52 weeks, ExQW significantly improved HbA1c [mean (SE) change from baseline, −1.3 (0.05)%], FBG [−36.3 (2.02) mg/dl], body weight [−2.6 (0.19) kg], SBP/DBP [−3.6 (0.56) mm Hg/−1.2 (0.34) mm Hg], total cholesterol, −4.4 (1.33) mg/dl; LDL, −2.6 (1.08) mg/dl; HDL, 1.1 (0.31) mg/dl; triglycerides, −7 (1.6)%], and ALT [−4.3 (0.71) IU/l] concentrations, with greater improvements in patients with elevated analyte levels at baseline. Improvements were observed across a range of background antihyperglycaemia therapies. Of patients completing 52 weeks, 19% achieved the composite American Diabetes Association goal (HbA1c < 7.0%, BP < 130/80 mm Hg, LDL < 100 mg/dl), compared to 1% at baseline. Nearly half (48%) achieved HbA1c < 7.0% without weight gain or major/minor hypoglycaemia. Nausea was the most frequent adverse event and was predominantly mild. Hypoglycaemia was infrequent, and more common with a sulfonylurea. Conclusions With 52 weeks of ExQW, patients experienced sustained improvements in glycaemic

  7. TECHNICAL BASIS FOR DOE STANDARD 3013 EQUIVALENCY SUPPORTING REDUCED TEMPERATURE STABILIZATION OF OXALATE-DERIVED PLUTONIUM OXIDE PRODUCED BY THE HB-LINE FACILITY AT SAVANNAH RIVER SITE

    SciTech Connect

    Duffey, J.; Livingston, R.; Berg, J.; Veirs, D.

    2012-07-02

    The HB-Line (HBL) facility at the Savannah River Site (SRS) is designed to produce high-purity plutonium dioxide (PuO{sub 2}) which is suitable for future use in production of Mixed Oxide (MOX) fuel. The MOX Fuel Fabrication Facility (MFFF) requires PuO{sub 2} feed to be packaged per the U.S. Department of Energy (DOE) Standard 3013 (DOE-STD-3013) to comply with the facility's safety basis. The stabilization conditions imposed by DOE-STD-3013 for PuO{sub 2} (i.e., 950 C for 2 hours) preclude use of the HBL PuO{sub 2} in direct fuel fabrication and reduce the value of the HBL product as MFFF feedstock. Consequently, HBL initiated a technical evaluation to define acceptable operating conditions for production of high-purity PuO{sub 2} that fulfills the DOE-STD-3013 criteria for safe storage. The purpose of this document is to demonstrate that within the defined operating conditions, the HBL process will be equivalent for meeting the requirements of the DOE-STD-3013 stabilization process for plutonium-bearing materials from the DOE complex. The proposed 3013 equivalency reduces the prescribed stabilization temperature for high-purity PuO{sub 2} from oxalate precipitation processes from 950 C to 640 C and places a limit of 60% on the relative humidity (RH) at the lowest material temperature. The equivalency is limited to material produced using the HBL established flow sheet, for example, nitric acid anion exchange and Pu(IV) direct strike oxalate precipitation with stabilization at a minimum temperature of 640 C for four hours (h). The product purity must meet the MFFF acceptance criteria of 23,600 {micro}g/g Pu (i.e., 2.1 wt %) total impurities and chloride content less than 250 {micro}g/g of Pu. All other stabilization and packaging criteria identified by DOE-STD-3013-2012 or earlier revisions of the standard apply. Based on the evaluation of test data discussed in this document, the expert judgment of the authors supports packaging the HBL product under a 3013

  8. The Role of Metformin Response in Lipid Metabolism in Patients with Recent-Onset Type 2 Diabetes: HbA1c Level as a Criterion for Designating Patients as Responders or Nonresponders to Metformin

    PubMed Central

    Kashi, Zahra; Mahrooz, Abdolkarim; Kianmehr, Anvarsadat; Alizadeh, Ahad

    2016-01-01

    Background In this study, we investigated whether response to metformin, the most frequently drug for diabetes treatment, influences the therapeutic effects of antilipidemic medication in newly diagnosed patients with type 2 diabetes mellitus (T2DM). Methods A total of 150 patients with T2DM were classified into two groups following 3 months of metformin therapy (1000 mg twice daily): responders (patients showing ≥1% reduction in HbA1c from baseline) and nonresponders (patients showing <1% reduction in HbA1c from baseline). The patients received atorvastatin 20 mg, gemfibrozil 300 mg, or atorvastatin 20 mg and gemfibrozil 300 mg daily. Principal Findings HbA1c and fasting glucose levels were significantly different between baseline and 3 months among responders receiving atorvastatin; however, these differences were not statistically significant in nonresponders. Atherogenic ratios of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C; p = 0.002), total cholesterol to HDL-C (TC/HDL-C; p<0.001) and AIP (the atherogenic index of plasma; p = 0.004) decreased significantly in responders receiving atorvastatin than in nonresponders. Moreover, responders receiving atorvastatin showed a significant increase in HDL-C levels but nonresponders receiving atorvastatin did not (p = 0.007). The multivariate model identified a significant association between metformin response (as the independent variable) and TG, TC, HDL-C and LDL-C (dependent variables; Wilk's λ = 0.927, p = 0.036). Conclusions Metformin response affects therapeutic outcomes of atorvastatin on atherogenic lipid markers in patients newly diagnosed with T2DM. Metformin has a greater impact on BMI in responders of metformin compared to nonresponders. Adoption of better therapeutic strategies for reducing atherogenic lipid markers may be necessary for metformin nonresponders. PMID:26978661

  9. One center in Brussels has consistently had the lowest HbA1c values in the 4 studies (1994-2009) by the Hvidoere International Study Group on Childhood Diabetes: What are the "recipes"?

    PubMed Central

    Dorchy, Harry

    2015-01-01

    The principal aims of therapeutic management of the child, adolescent and adult with type 1 diabetes are to allow good quality of life and to avoid long-term complications (retinopathy, neuropathy, nephropathy, cardiovascular disease, etc.) by maintaining blood glucose concentrations close to normal level. Glycated hemoglobin levels (HbA1c) provide a good criterion of overall glycemic control. The Hvidoere Study Group (HSG) on Childhood Diabetes, founded in 1994, is an international group representing about twenty highly experienced pediatric centers from Europe, North America, Japan and Australia. Four international comparisons of metabolic control (1995, 1998, 2005, 2009) have been performed. The one center that has consistently had the lowest HbA1c values (approximate 7.3% or 56.3 mmol/mol) is my center in Brussels. This is more often obtained with a twice-daily free-mixed regimen with additional supplemental fast insulins ad hoc. The so-called “Dorchy’s recipes” are summarized. The conclusion is that the number of daily insulin injections, 2 or ≥ 4, or the use of pumps, by itself does not necessarily give better results. Intensified therapy should not depend upon the number of insulin doses per day, by syringe, pen or pump but rather should be redefined as to intent-to-treat ascertainment (i.e., goals). When there are no mutually agreed upon goals for BG and/or HbA1c, when there is insufficient education and psychosocial support by the medical team or at home, there is likely to be poor outcomes, as shown by the HSG. One of our recipes is not to systematically replace rapid-acting human insulins by fast-acting analogues. Because the multicenter studies of the HSG, performed in developed countries without financial restriction, show that treatment of childhood diabetes is inadequate in general and that levels of HbA1c are very different, diabetes treatment teams should individually explore the reasons for failure, without any prejudice or bias. Any

  10. One center in Brussels has consistently had the lowest HbA1c values in the 4 studies (1994-2009) by the Hvidoere International Study Group on Childhood Diabetes: What are the "recipes"?

    PubMed

    Dorchy, Harry

    2015-02-15

    The principal aims of therapeutic management of the child, adolescent and adult with type 1 diabetes are to allow good quality of life and to avoid long-term complications (retinopathy, neuropathy, nephropathy, cardiovascular disease, etc.) by maintaining blood glucose concentrations close to normal level. Glycated hemoglobin levels (HbA1c) provide a good criterion of overall glycemic control. The Hvidoere Study Group (HSG) on Childhood Diabetes, founded in 1994, is an international group representing about twenty highly experienced pediatric centers from Europe, North America, Japan and Australia. Four international comparisons of metabolic control (1995, 1998, 2005, 2009) have been performed. The one center that has consistently had the lowest HbA1c values (approximate 7.3% or 56.3 mmol/mol) is my center in Brussels. This is more often obtained with a twice-daily free-mixed regimen with additional supplemental fast insulins ad hoc. The so-called "Dorchy's recipes" are summarized. The conclusion is that the number of daily insulin injections, 2 or ≥ 4, or the use of pumps, by itself does not necessarily give better results. Intensified therapy should not depend upon the number of insulin doses per day, by syringe, pen or pump but rather should be redefined as to intent-to-treat ascertainment (i.e., goals). When there are no mutually agreed upon goals for BG and/or HbA1c, when there is insufficient education and psychosocial support by the medical team or at home, there is likely to be poor outcomes, as shown by the HSG. One of our recipes is not to systematically replace rapid-acting human insulins by fast-acting analogues. Because the multicenter studies of the HSG, performed in developed countries without financial restriction, show that treatment of childhood diabetes is inadequate in general and that levels of HbA1c are very different, diabetes treatment teams should individually explore the reasons for failure, without any prejudice or bias. Any dogmatism

  11. The Multi-Center Randomized Controlled Trial (RCT) Published by the Journal of the American Medical Association (JAMA) on the Effect of Periodontal Therapy on Glycated Hemoglobin (HbA1c) Has Fundamental Problems

    PubMed Central

    Borgnakke, Wenche S.; Chapple, Iain L.C.; Genco, Robert J.; Armitage, Gary; Bartold, P. Mark; D’Aiuto, Francesco; Eke, Paul I.; Giannobile, William V.; Kocher, Thomas; Kornman, Kenneth S.; Lang, Niklaus P.; Madianos, Phoebus N.; Murakami, Shinya; Nishimura, Fusanori; Offenbacher, Steven; Preshaw, Philip M.; Rahman, Amin ur; Sanz, Mariano; Slots, Jørgen; Tonetti, Maurizio S.; Van Dyke, Thomas E.

    2015-01-01

    SUMMARY Subject Participants had type 2 diabetes, were on stable medication regimens, had HbA1c levels between 7% and <9%, retained at least 16 natural teeth, and had untreated chronic periodontitis. A total of 514 participants were enrolled between November 2009 and March 2012 from diabetes and dental clinics and communities affiliated with five participating academic medical centers. They were randomized with half (n = 257) allocated to a treatment group and the other half (n = 257) to a control group. Key Exposure/Study Factor The exposure was non-surgical periodontal treatment comprising scaling and root planing, oral hygiene instruction, and oral rinsing with chlorhexidine provided to the treatment group at baseline. Supportive periodontal therapy was also provided at 3 and 6 months. The control group received no treatment for the 6-month duration of the study. Main Outcome Measure The primary outcome measure was “the difference in change in HbA1c level from baseline between the two groups at 6 months.” Secondary outcomes included changes in periodontal probing depth (PPD), clinical attachment loss, bleeding on probing (BOP), gingival index, fasting glucose level, and Homeostasis Model Assessment (HOMA2) score. Main Results The authors report that enrollment into their Diabetes and Periodontal Therapy Trial (DPTT) was terminated early due to futility. At 6 months, mean HbA1c levels in the periodontal therapy group increased 0.17 (±1.0)%, compared with 0.11 (±1.0)% in the control group, with no significant difference between groups based on a linear regression model adjusting for clinical site (mean difference, −0.05% [95% CI: −0.23% to 0.12%]; p = 0.55). Periodontal measures improved in the treatment group compared with the control group at 6 months, with adjusted between-group differences of 0.28 mm (95% CI: 0.18–0.37) for PPD; 0.25 mm (95% CI: 0.14–0.36) for clinical attachment loss; 13.1% (95% CI: 8.1%–18.1%) for BOP; and 0.27 (95% CI: 0.17

  12. Stress-induced ligand field distribution and consequent multi-mode spin crossover in Fe II(phen) 2(NCS) 2 and Fe II[HB(pz) 3] 2

    NASA Astrophysics Data System (ADS)

    Tsuchiya, Naoko; Tsukamoto, Atsushi; Ohshita, Tadashi; Isobe, Tetsuhiko; Senna, Mamoru; Yoshioka, Naoki; Inoue, Hidenari

    2001-09-01

    Changes in the nature of spin crossover caused by mechanical stressing exerted on the crystalline powders were studied for Fe II(phen) 2(NCS) 2 (phen = 1,10-phenanthroline) and Fe II[HB(pz) 3] 2 (pz = pyrazol-1-yl) by means of a multi-component fitting of the temperature dependence of magnetic susceptibility. The analysis revealed the development and broadening of the ligand field distribution as a consequence of mechanical stressing. This was confirmed by the broadening of Mössbauer and far-infrared spectra.

  13. A randomized Phase I/II Trial of HQK-1001, an oral fetal globin gene inducer, in β–thalassaemia intermedia and HbE/β–thalassaemia

    PubMed Central

    Fucharoen, Suthat; Inati, Adlette; Siritanaratku, Noppadol; Thein, Swee Lay; Wargin, William C.; Koussa, Suzanne; Taher, Ali; Chaneim, Nattawara; Boosalis, Michael; Berenson, Ronald; Perrine, Susan P.

    2014-01-01

    β–thalassemia intermedia syndromes (BTI) cause hemolytic anemia, ineffective erythropoiesis, and widespread complications. Higher fetal globin expression within genotypes reduces globin imbalance and ameliorates anemia. Sodium 2,2 dimethylbutyrate (HQK-1001), an orally bioavailable short-chain fatty acid derivative, induces γ-globin expression experimentally and is well-tolerated in normal subjects. Accordingly, a randomized, blinded, placebo-controlled, Phase I/II trial was performed in 21 adult BTI patients (14 with HbE/β0 thalassemia and 7 with β+/β0 thalassemia intermedia, to determine effective doses for fetal globin induction, safety, and tolerability. HQK-1001 or placebo were administered once daily for 8 weeks at four dose levels (10, 20, 30, or 40 mg/kg/day), and subjects were monitored for laboratory and clinical events. Pharmacokinetic profiles demonstrated a t1/2 of 10–12 hours. Adverse events with HQK-1001 treatment were not significantly different from placebo treatment. Median HbF increased with the 20 mg/kg treatment doses above baseline levels by 6.6% and 0.44 g/dL (p <0.01) in 8/9 subjects; total hemoglobin (Hgb) increased by a mean of 1.1 gm/dL in 4/9 subjects. These findings identify a safe oral therapeutic which induces fetal globin in BTI. Further investigation of HQK-1001 with longer dosing to definitively evaluate its hematologic potential appears warranted. PMID:23530969

  14. Diagnostic Accuracy of the HemoCue Hb 301, STAT-Site MHgb and URIT-12 Point-of-Care Hemoglobin Meters in a Central Laboratory and a Community Based Clinic in Durban, South Africa

    PubMed Central

    Jaggernath, Manjeetha; Naicker, Rumallen; Madurai, Savathree; Brockman, Mark A.; Ndung’u, Thumbi; Gelderblom, Huub C.

    2016-01-01

    In South Africa, various point-of-care hemoglobin meters are used. However, the regulatory framework for approval, implementation and oversight of use of point-of-care hemoglobin meters is suboptimal. We assessed the diagnostic accuracy of the HemoCue Hb 301, STAT-Site MHgb and URIT-12 point-of-care hemoglobin meters, compared to a central laboratory based reference assay, in a central laboratory and a community based clinic in Durban, South Africa. Differences in performance of the point-of-care assays, compared to the reference assay, were more pronounced in the community based clinic. Results were reasonable for the HemoCue Hb 301, but poor for the STAT-Site MHgb and the URIT-12. Poor test performance of point-of-care hemoglobin meters, and inadequate evaluations and oversight in South Africa, leads to suboptimal clinical care and clinical research, and increased costs. There is a need for proper evaluation and quality assurance of point-of-care tests, the results of which should be made widely available to key stakeholders. PMID:27046200

  15. The difference between oats and beta-glucan extract intake in the management of HbA1c, fasting glucose and insulin sensitivity: a meta-analysis of randomized controlled trials.

    PubMed

    He, Li-Xia; Zhao, Jian; Huang, Yuan-Sheng; Li, Yong

    2016-03-16

    Increasing oats and beta-glucan extract intake has been associated with improved glycemic control, which is associated with the reduction in the development of diabetes. This study aims to assess the different effects between oat (whole and bran) and beta-glucan extract intake on glycemic control and insulin sensitivity. PubMed, Embase, Medline, The Cochrane Library, CINAHL and Web of Science were searched up to February 2014. We included randomized controlled trials with interventions that lasted at least four weeks that compared oats and beta-glucan (extracted from oats or other sources) intake with a control. A total of 1351 articles were screened for eligibility, and relevant data were extracted from 18 studies (n = 1024). Oat product dose ranged from 20 g d(-1) to 136 g d(-1), and beta-glucan extract dose ranged from 3 g d(-1) to 10 g d(-1). Compared with the control, oat intake resulted in a greater decrease in fasting glucose and insulin of subjects (P < 0.05), but beta-glucan extract intake did not. Furthermore, oat intake resulted in a greater decrease in glycosylated hemoglobin (HbA1c) (P < 0.001, I(2) = 0%) and fasting glucose (P < 0.001, I(2) = 68%) after removing one study using a concentrate and a different design and fasting insulin of type 2 diabetes (T2D) (P < 0.001, I(2) = 0%). The intake of oats and beta-glucan extracted from oats were effective in decreasing fasting glucose (P = 0.007, I(2) = 91%) and fasting insulin of T2D (P < 0.001, I(2) = 0%) and tented to lower HbA1c (P = 0.09, I(2) = 92%). Higher consumption of whole oats and oat bran, but not oat or barley beta-glucan extracts, are associated with lower HbA1c, fasting glucose and fasting insulin of T2D, hyperlipidaemic and overweight subjects, especially people with T2D, which supports the need for clinical trials to evaluate the potential role of oats in approaching to the management of glycemic control and insulin sensitivity of diabetes or metabolic syndrome subjects. PMID:26840185

  16. The cell-penetrating peptide domain from human heparin-binding epidermal growth factor-like growth factor (HB-EGF) has anti-inflammatory activity in vitro and in vivo

    SciTech Connect

    Lee, Jue-Yeon; Seo, Yoo-Na; Park, Hyun-Jung; Park, Yoon-Jeong; Chung, Chong-Pyoung

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer HBP sequence identified from HB-EGF has cell penetration activity. Black-Right-Pointing-Pointer HBP inhibits the NF-{kappa}B dependent inflammatory responses. Black-Right-Pointing-Pointer HBP directly blocks phosphorylation and degradation of I{kappa}B{alpha}. Black-Right-Pointing-Pointer HBP inhibits nuclear translocation of NF-{kappa}B p65 subunit. -- Abstract: A heparin-binding peptide (HBP) sequence from human heparin-binding epidermal growth factor-like growth factor (HB-EGF) was identified and was shown to exhibit cell penetration activity. This cell penetration induced an anti-inflammatory reaction in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. HBP penetrated the cell membrane during the 10 min treatment and reduced the LPS-induced production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), and cytokines (TNF-{alpha} and IL-6) in a concentration-dependent manner. Additionally, HBP inhibited the LPS-induced upregulation of cytokines, including TNF-{alpha} and IL-6, and decreased the interstitial infiltration of polymorphonuclear leukocytes in a lung inflammation model. HBP inhibited NF-{kappa}B-dependent inflammatory responses by directly blocking the phosphorylation and degradation of I{kappa}B{alpha} and by subsequently inhibiting the nuclear translocation of the p65 subunit of NF-{kappa}B. Taken together, this novel HBP may be potentially useful candidate for anti-inflammatory treatments and can be combined with other drugs of interest to transport attached molecules into cells.

  17. Effect of long-term intermittent supplementation with multiple micronutrients compared with iron-and-folic acid supplementation on Hb and micronutrient status of non-anaemic adolescent schoolgirls in rural Bangladesh.

    PubMed

    Ahmed, Faruk; Khan, Moududur R; Akhtaruzzaman, Mohammad; Karim, Rezaul; Williams, Gail; Banu, Cadi P; Nahar, Badrun; Darnton-Hill, Ian

    2012-10-28

    The present study examined whether long-term supplementation with once- and twice-weekly multiple micronutrients (MMN-1 and MMN-2) can improve Hb and micronutrient status more than twice-weekly Fe-folic acid (IFA-2) supplementation in non-anaemic adolescent girls in Bangladesh. An equal number of 324 rural schoolgirls aged 11-17 years were given MMN-1 or MMN-2 or IFA-2 supplements for 52 weeks in a randomised, double-blind trial. Blood samples were collected at baseline, and at 26 and 52 weeks of supplementation. The girls receiving IFA-2 supplements were more likely to be anaemic than the girls receiving MMN-2 supplements for 26 weeks (OR 5·1, 95% CI 1·3, 19·5; P = 0·018). All three supplements reduced Fe deficiency effectively. Both the MMN-1 and MMN-2 groups showed significantly greater improvements in vitamins A, B(2) and C status than the girls in the IFA-2 group, as might be expected. Receiving a MMN-1 supplement was found to be less effective than MMN-2 supplement in improving Fe, vitamins A, B(2) and folic acid status. Receiving micronutrient supplements beyond 26 weeks showed little additional benefit in improving micronutrient status. In conclusion, given twice-weekly for 26 weeks, MMN supplements can improve micronutrient status effectively with no significant increase in Hb concentration compared with IFA supplements in non-anaemic Bangladeshi adolescent girls. However, it significantly reduces the risk of anaemia. Before any recommendations can be made, further research, including into cost-effectiveness, is needed to see whether MMN supplementation has any additional longer-term health benefits over that of IFA supplementation in this population. PMID:22244349

  18. Crystal structure of a hypothetical protein, TTHA0829 from Thermus thermophilus HB8, composed of cystathionine-β-synthase (CBS) and aspartate-kinase chorismate-mutase tyrA (ACT) domains.

    PubMed

    Nakabayashi, Makoto; Shibata, Naoki; Ishido-Nakai, Emi; Kanagawa, Mayumi; Iio, Yota; Komori, Hirofumi; Ueda, Yasufumi; Nakagawa, Noriko; Kuramitsu, Seiki; Higuchi, Yoshiki

    2016-05-01

    TTHA0829 from Thermus thermophilus HB8 has a molecular mass of 22,754 Da and is composed of 210 amino acid residues. The expression of TTHA0829 is remarkably elevated in the latter half of logarithmic growth phase. TTHA0829 can form either a tetrameric or dimeric structure, and main-chain folding provides an N-terminal cystathionine-β-synthase (CBS) domain and a C-terminal aspartate-kinase chorismate-mutase tyrA (ACT) domain. Both CBS and ACT are regulatory domains to which a small ligand molecule can bind. The CBS domain is found in proteins from organisms belonging to all kingdoms and is observed frequently as two or four tandem copies. This domain is considered as a small intracellular module with a regulatory function and is typically found adjacent to the active (or functional) site of several enzymes and integral membrane proteins. The ACT domain comprises four β-strands and two α-helices in a βαββαβ motif typical of intracellular small molecule binding domains that help control metabolism, solute transport and signal transduction. We discuss the possible role of TTHA0829 based on its structure and expression pattern. The results imply that TTHA0829 acts as a cell-stress sensor or a metabolite acceptor. PMID:26936147

  19. Enhanced haemolysis with beta-thalassaemia trait due to the unstable beta chain variant, Hb Gunma, accompanied by hereditary elliptocytosis due to protein 4.1 deficiency in a Japanese family.

    PubMed

    Maehara, Tadashi; Tsukamoto, Norifumi; Nojima, Yoshihisa; Karasawa, Masamitsu; Murakami, Hirokazu; Hattori, Yukio; Ideguchi, Hiroshi

    2002-04-01

    We identified a Japanese family with a beta-thalassaemia trait and hereditary elliptocytosis (HE). We studied five members of this family. One was normal, one had only the beta-thalassaemia trait, one had heterozygous HE, and two had compound heterozygous beta-thalassaemia trait and HE. The last two had already undergone splenectomy. The molecular profile of beta-thalassaemia was consistent with that of Hb Gunma: codon 127/128CAGGCT(Gln-Ala)--> CCT(Pro). Analysis of erythrocyte membrane proteins revealed a partial deficiency of protein 4.1 in all those with HE, whereas the spectrin content was within the normal range. Each heterozygous family member with either the beta-thalassaemia trait or HE was asymptomatic, whereas the two with both beta-thalassaemia and HE had marked red blood cell deformities and haemolysis. The abnormalities of the red blood cells in patients with the beta-thalassaemia trait might be enhanced by association with HE owing to a protein 4.1 deficiency. PMID:11918554

  20. The freeware AIDA interactive educational diabetes simulator--http://www.2aida.org--(2). Simulating glycosylated haemoglobin (HbA1c) levels in AIDA v4.3.

    PubMed

    Lehmann, E D

    2001-01-01

    In 1996 an interactive educational diabetes simulator called AIDA was released without charge on the Internet as a non-commercial contribution to continuing diabetes education. Over the past 4+ years over 74,000 people have visited the AIDA Web pages at http://www.2aida.org and over 20,000 copies of the program have been downloaded from there free-of-charge. This article builds on the experience gained from the AIDA development, and the World Wide Web distribution of the software, and highlights some of the problems which users have reported with the program. An updated release of the software (AIDA v4.3) is described and the method applied for modelling glycosylated haemoglobin (HbA1c) levels within this new version of AIDA is documented. An overview is provided of the trialling and beta-testing of this latest release of the program, and the general concept of a 'virtual diabetic patient' that provides an electronic representation of a patient with diabetes--and which can be used for self-learning/teaching/demonstration purposes--is highlighted. PMID:11386034

  1. Active G protein-coupled receptors (GPCR), matrix metalloproteinases 2/9 (MMP2/9), heparin-binding epidermal growth factor (hbEGF), epidermal growth factor receptor (EGFR), erbB2, and insulin-like growth factor 1 receptor (IGF-1R) are necessary for trenbolone acetate-induced alterations in protein turnover rate of fused bovine satellite cell cultures.

    PubMed

    Thornton, K J; Kamanga-Sollo, E; White, M E; Dayton, W R

    2016-06-01

    Trenbolone acetate (TBA), a testosterone analog, increases protein synthesis and decreases protein degradation in fused bovine satellite cell (BSC) cultures. However, the mechanism through which TBA alters these processes remains unknown. Recent studies indicate that androgens improve rate and extent of muscle growth through a nongenomic mechanism involving G protein-coupled receptors (GPCR), matrix metalloproteinases (MMP), heparin-binding epidermal growth factor (hbEGF), the epidermal growth factor receptor (EGFR), erbB2, and the insulin-like growth factor-1 receptor (IGF-1R). We hypothesized that TBA activates GPCR, resulting in activation of MMP2/9 that releases hbEGF, which activates the EGFR and/or erbB2. To determine whether the proposed nongenomic pathway is involved in TBA-mediated alterations in protein turnover, fused BSC cultures were treated with TBA in the presence or absence of inhibitors for GPCR, MMP2/9, hbEGF, EGFR, erbB2, or IGF-1R, and resultant protein synthesis and degradation rates were analyzed. Assays were replicated at least 9 times for each inhibitor experiment utilizing BSC cultures obtained from at least 3 different steers that had no previous exposure to steroid compounds. As expected, fused BSC cultures treated with 10 n TBA exhibited increased ( < 0.05) protein synthesis rates and decreased ( < 0.05) protein degradation rates when compared to control cultures. Treatment of fused BSC cultures with 10 n TBA in the presence of inhibitors for GPCR, MMP2/9, hbEGF, EGFR, erbB2, or IGF-1R suppressed ( < 0.05) TBA-mediated increases in protein synthesis rate. Alternatively, inhibition of GPCR, MMP2/9, hbEGF, EGFR, erbB2, or IGF-1R in the presence of 10 n TBA each had no ( > 0.05) effect on TBA-mediated decreases in protein degradation. However, inhibition of both EGFR and erbB2 in the presence of 10 n TBA resulted in decreased ( < 0.05) ability of TBA to decrease protein degradation rate. Additionally, fused BSC cultures treated with 10 n

  2. Highly tunable fluorinated trispyrazolylborates [HB(3-CF3-5-{4-RPh}pz)3](-) (R = NO2, CF3, Cl, F, H, OMe and NMe2) and their copper(I) complexes.

    PubMed

    van Dijkman, Thomas F; Siegler, Maxime A; Bouwman, Elisabeth

    2015-12-28

    The ethene and carbon monoxide adducts of copper(I) with seven trispyrazolylborate ligands ([HB(3-CF3-5-{4-RPh}pz)3](-); R = NO2 (4a), CF3 (4b), Cl (4c), F (4d), H (4e), OMe (4f) and NMe2 (4g)) were synthesized and characterized. The ligands were synthesized from their corresponding pyrazoles and sodium tetrahydridoborate and were obtained as solvent adducts of their sodium salts after workup. When the pyrazole with the most electron-withdrawing substituent (R = NO2) is used the asymmetric ligand [HB(3-CF3-5-{4-NO2Ph}pz)2(3-{4-NO2Ph}-5-CF3pz)](-) (4a') is formed as the major product. Copper(I) complexes with ethene or CO as a co-ligand were prepared in good yields and were structurally characterized using (1)H NMR, (13)C NMR and infrared spectroscopy. Single crystal X-ray crystallography analyses revealed the structures of Na4a', Na4b, four copper ethene complexes and four copper carbonyl complexes. The structures of the copper(I) complexes show Cu(I) ions in pseudo-tetrahedral coordination environments consisting of three nitrogen atoms of the trispyrazolylborate ligand and the carbonyl or η(2)-coordinated ethene ligands, with nearly identical coordination environments around the Cu(I) ion. The compound [Na(4a')(H2O)]n crystallizes as one-dimensional chains with intermolecular NaO2N interactions. The sodium ions were found in severely distorted octahedral geometries with three nitrogen atoms from the trispyrazolylborate ligand, one aqua ligand and two oxygen atoms from the nitro group of an adjacent molecule. The compound [Na2(4b)2(μ-H2O)2] crystallizes as a centrosymmetric water-bridged dimer: two five-coordinate square-pyramidal sodium ions each are coordinated facially by three nitrogen atoms from a trispyrazolylborate ligand and two bridging water ligands. Below the base of the pyramidal structure one intermolecular and two intramolecular NaF short contacts are present. The (1)H and (13)C NMR spectra of the copper-ethene complexes show signals for the ethene

  3. THE AGES OF 55 GLOBULAR CLUSTERS AS DETERMINED USING AN IMPROVED ΔV{sup HB}{sub TO} METHOD ALONG WITH COLOR-MAGNITUDE DIAGRAM CONSTRAINTS, AND THEIR IMPLICATIONS FOR BROADER ISSUES

    SciTech Connect

    VandenBerg, Don A.; Brogaard, K.; Leaman, R.; Casagrande, L. E-mail: kfb@phys.au.dk E-mail: luca@mso.anu.edu.au

    2013-10-01

    Ages have been derived for 55 globular clusters (GCs) for which Hubble Space Telescope Advanced Camera for Surveys photometry is publicly available. For most of them, the assumed distances are based on fits of theoretical zero-age horizontal-branch (ZAHB) loci to the lower bound of the observed distributions of HB stars, assuming reddenings from empirical dust maps and metallicities from the latest spectroscopic analyses. The age of the isochrone that provides the best fit to the stars in the vicinity of the turnoff (TO) is taken to be the best estimate of the cluster age. The morphology of isochrones between the TO and the beginning part of the subgiant branch (SGB) is shown to be nearly independent of age and chemical abundances. For well-defined color-magnitude diagrams (CMDs), the error bar arising just from the 'fitting' of ZAHBs and isochrones is ≈ ± 0.25 Gyr, while that associated with distance and chemical abundance uncertainties is ∼ ± 1.5-2 Gyr. The oldest GCs in our sample are predicted to have ages of ≈13.0 Gyr (subject to the aforementioned uncertainties). However, the main focus of this investigation is on relative GC ages. In conflict with recent findings based on the relative main-sequence fitting method, which have been studied in some detail and reconciled with our results, ages are found to vary from mean values of ≈12.5 Gyr at [Fe/H] ∼< – 1.7 to ≈11 Gyr at [Fe/H] ∼> –1. At intermediate metallicities, the age-metallicity relation (AMR) appears to be bifurcated: one branch apparently contains clusters with disk-like kinematics, whereas the other branch, which is displaced to lower [Fe/H] values by ≈0.6 dex at a fixed age, is populated by clusters with halo-type orbits. The dispersion in age about each component of the AMR is ∼ ± 0.5 Gyr. There is no apparent dependence of age on Galactocentric distance (R{sub G}) nor is there a clear correlation of HB type with age. As previously discovered in the case of M3 and M13

  4. The Ages of 55 Globular Clusters as Determined Using an Improved \\Delta V^HB_TO Method along with Color-Magnitude Diagram Constraints, and Their Implications for Broader Issues

    NASA Astrophysics Data System (ADS)

    VandenBerg, Don A.; Brogaard, K.; Leaman, R.; Casagrande, L.

    2013-10-01

    Ages have been derived for 55 globular clusters (GCs) for which Hubble Space Telescope Advanced Camera for Surveys photometry is publicly available. For most of them, the assumed distances are based on fits of theoretical zero-age horizontal-branch (ZAHB) loci to the lower bound of the observed distributions of HB stars, assuming reddenings from empirical dust maps and metallicities from the latest spectroscopic analyses. The age of the isochrone that provides the best fit to the stars in the vicinity of the turnoff (TO) is taken to be the best estimate of the cluster age. The morphology of isochrones between the TO and the beginning part of the subgiant branch (SGB) is shown to be nearly independent of age and chemical abundances. For well-defined color-magnitude diagrams (CMDs), the error bar arising just from the "fitting" of ZAHBs and isochrones is ≈ ± 0.25 Gyr, while that associated with distance and chemical abundance uncertainties is ~ ± 1.5-2 Gyr. The oldest GCs in our sample are predicted to have ages of ≈13.0 Gyr (subject to the aforementioned uncertainties). However, the main focus of this investigation is on relative GC ages. In conflict with recent findings based on the relative main-sequence fitting method, which have been studied in some detail and reconciled with our results, ages are found to vary from mean values of ≈12.5 Gyr at [Fe/H] <~ - 1.7 to ≈11 Gyr at [Fe/H] >~ -1. At intermediate metallicities, the age-metallicity relation (AMR) appears to be bifurcated: one branch apparently contains clusters with disk-like kinematics, whereas the other branch, which is displaced to lower [Fe/H] values by ≈0.6 dex at a fixed age, is populated by clusters with halo-type orbits. The dispersion in age about each component of the AMR is ~ ± 0.5 Gyr. There is no apparent dependence of age on Galactocentric distance (R G) nor is there a clear correlation of HB type with age. As previously discovered in the case of M3 and M13, subtle variations have

  5. Simultaneous Expression of Abiotic Stress Responsive Transcription Factors, AtDREB2A, AtHB7 and AtABF3 Improves Salinity and Drought Tolerance in Peanut (Arachis hypogaea L.)

    PubMed Central

    Pruthvi, Vittal; Narasimhan, Rama; Nataraja, Karaba N.

    2014-01-01

    Drought, salinity and extreme temperatures are the most common abiotic stresses, adversely affecting plant growth and productivity. Exposure of plants to stress activates stress signalling pathways that induce biochemical and physiological changes essential for stress acclimation. Stress tolerance is governed by multiple traits, and importance of a few traits in imparting tolerance has been demonstrated. Under drought, traits linked to water mining and water conservation, water use efficiency and cellular tolerance (CT) to desiccation are considered to be relevant. In this study, an attempt has been made to improve CT in drought hardy crop, peanut (Arachis hypogaea L., cv. TMV2) by co-expressing stress-responsive transcription factors (TFs), AtDREB2A, AtHB7 and AtABF3, associated with downstream gene expression. Transgenic plants simultaneously expressing these TFs showed increased tolerance to drought, salinity and oxidative stresses compared to wild type, with an increase in total plant biomass. The transgenic plants exhibited improved membrane and chlorophyll stability due to enhanced reactive oxygen species scavenging and osmotic adjustment by proline synthesis under stress. The improvement in stress tolerance in transgenic lines were associated with induced expression of various CT related genes like AhGlutaredoxin, AhAldehyde reductase, AhSerine threonine kinase like protein, AhRbx1, AhProline amino peptidase, AhHSP70, AhDIP and AhLea4. Taken together the results indicate that co-expression of stress responsive TFs can activate multiple CT pathways, and this strategy can be employed to improve abiotic stress tolerance in crop plants. PMID:25474740

  6. Simultaneous expression of abiotic stress responsive transcription factors, AtDREB2A, AtHB7 and AtABF3 improves salinity and drought tolerance in peanut (Arachis hypogaea L.).

    PubMed

    Pruthvi, Vittal; Narasimhan, Rama; Nataraja, Karaba N

    2014-01-01

    Drought, salinity and extreme temperatures are the most common abiotic stresses, adversely affecting plant growth and productivity. Exposure of plan